Nancy A. Melville

New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.

“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.

“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”

MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.

However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.

Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.

To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.

However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.

The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.

“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.

One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.

“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.

Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”

“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.

Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.

And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.

“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.

The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.

However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.

Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.

“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.

“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”

In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.

The authors of the guidelines have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.

“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.

“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”

MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.

However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.

Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.

To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.

However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.

The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.

“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.

One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.

“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.

Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”

“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.

Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.

And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.

“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.

The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.

However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.

Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.

“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.

“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”

In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.

The authors of the guidelines have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New consensus guidelines from a multispecialty working group of the Pelvic Floor Disorders Consortium (PFDC) clear up inconsistencies in the use of magnetic resonance defecography (MRD) and provide universal recommendations on MRD technique, interpretation, reporting, and other factors.

“The consensus language used to describe pelvic floor disorders is critical, so as to allow the various experts who treat these patients [to] communicate and collaborate effectively with each other,” coauthor Liliana Bordeianou, MD, MPH, an associate professor of surgery at Harvard Medical School and chair of the Massachusetts General Hospital Colorectal and Pelvic Floor Centers, told this news organization.

“These diseases do not choose an arbitrary side in the pelvis,” she noted. “Instead, these diseases affect the entire pelvis and require a multidisciplinary and collaborative solution.”

MRD is a key component in that solution, providing dynamic evaluation of pelvic floor function and visualization of the complex interaction in pelvic compartments among patients with defecatory pelvic floor disorders, such as vaginal or uterine prolapse, constipation, incontinence, or other pelvic floor dysfunctions.

However, a key shortcoming has been a lack of consistency in nomenclature and the reporting of MRD findings among institutions and subspecialties.

Clinicians may wind up using different definitions for the same condition and different thresholds for grading severity, resulting in inconsistent communication not only between clinicians across institutions but even within the same institution, the report notes.

To address the situation, radiologists with the Pelvic Floor Dysfunction Disease Focused Panel of the Society of Abdominal Radiology (SAR) published recommendations on MRD protocol and technique in April.

However, even with that guidance, there has been significant variability in the interpretation and utilization of MRD findings among specialties outside of radiology.

The new report was therefore developed to include input from the broad variety of specialists involved in the treatment of patients with pelvic floor disorders, including colorectal surgeons, urogynecologists, urologists, gynecologists, gastroenterologists, radiologists, physiotherapists, and other advanced care practitioners.

“The goal of this effort was to create a universal set of recommendations and language for MRD technique, interpretation, and reporting that can be utilized and carry the same significance across disciplines,” write the authors of the report, published in the American Journal of Roentgenology.

One key area addressed in the report is a recommendation that MRD can be performed in either the upright or supine position, which has been a topic of inconsistency, said Brooke Gurland, MD, medical director of the Pelvic Health Center at Stanford University, California, a co-author on the consensus statement.

“Supine versus upright position was a source of debate, but ultimately there was a consensus that supine position was acceptable,” she told said in an interview.

Regarding positioning, the recommendations conclude that “given the variable results from different studies, consortium members agreed that it is acceptable to perform MRD in the supine position when upright MRD is not available.”

“Importantly, consortium experts stressed that it is very important that this imaging be performed after proper patient education on the purpose of the examination,” they note.

Other recommendations delve into contrast medium considerations, such as the recommendation that MRD does not require the routine use of vaginal contrast medium for adequate imaging of pathology.

And guidance on the technique and grading of relevant pathology include a recommendation to use the pubococcygeal line (PCL) as a point of reference to quantify the prolapse of organs in all compartments of the pelvic floor.

“There is an increasing appreciation that most patients with pelvic organ prolapse experience dual or even triple compartment pathology, making it important to describe the observations in all three compartments to ensure the mobilization of the appropriate team of experts to treat the patient,” the authors note.

The consensus report features an interpretative template providing synopses of the recommendations, which can be adjusted and modified according to additional radiologic information, as well as individualized patient information or clinician preferences.

However, “the suggested verbiage and steps should be advocated as the minimum requirements when performing and interpreting MRD in patients with evacuation disorders of the pelvic floor,” the authors note.

Dr. Gurland added that, in addition to providing benefits in the present utilization of MRD, the clearer guidelines should help advance its use to improve patient care in the future.

“Standardizing imaging techniques, reporting, and language is critical to improving our understanding and then developing therapies for pelvic floor disorders,” she said.

“In the future, correlating MRD with surgical outcomes and identifying modifiable risk factors will improve patient care.”

In addition to being published in the AJR, the report was published concurrently in the journals Diseases of the Colon & Rectum, International Urogynecology Journal, and Female Pelvic Medicine and Reconstructive Surgery.

The authors of the guidelines have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.

“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.

In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.

“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”

Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.

“For me, this paper is rather reassuring of the safety of the therapy,” he added.

Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.

However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.

For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.

Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).

There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).

Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).

Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”

“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.

Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.

“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.

“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.

Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.

Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.

“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.

In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.

“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.

“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”

The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.

Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.

“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.

In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.

“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”

Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.

“For me, this paper is rather reassuring of the safety of the therapy,” he added.

Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.

However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.

For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.

Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).

There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).

Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).

Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”

“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.

Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.

“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.

“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.

Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.

Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.

“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.

In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.

“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.

“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”

The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.

Amid ongoing debate over potential adverse effects of radioactive iodine (RAI) in the treatment of hyperthyroidism, a new meta-analysis shows no significant increase in the risk of cancer or cancer mortality in the vast majority of cases, with an increased dose-response risk with higher doses shown in some studies.

“These findings suggest that radiation-induced cancer risks following RAI therapy for hyperthyroidism are small and, in observational studies, may only be detectable at higher levels of administered dose,” report the authors of the analysis, published Sept. 27 in JAMA Network Open.

In a commentary published along with the study, Bernadette Biondi, MD, noted that, despite some limitations, “the current analysis from recent literature studies is reassuring on the potential negative effects of RAI”.

“These data can help reduce anxiety in both patients and clinicians as to the risk of cancer after RAI.”

Martin A. Walter, MD, agreed. “When including nearly a half-million patients into the analysis, there is no significant increase of risk for secondary cancers after radioiodine therapy for hyperthyroidism,” Dr. Walter, who was a coauthor on the American Thyroid Association’s guidelines for the diagnosis and management of hyperthyroidism (Thyroid. 2016 Oct;26:1343-421), told this news organization.

“For me, this paper is rather reassuring of the safety of the therapy,” he added.

Though used in the treatment of hyperthyroidism for more than 7 decades, the frequent use of RAI continues to generate concern of potential carcinogenic effects, with some previous studies linking the treatment with subsequent malignant neoplasms, while others have shown no risk.

However, the potential role of a dose-response effect on the cancer risk has not been well explored, the authors note.

For their meta-analysis, Sung Ryul Shim, PhD, of the department of preventive medicine, Korea University, Seoul, South Korea, and colleagues identified 12 studies including 479,452 participants that involved evaluation of cancer incidence and mortality with exposure versus nonexposure to RAI therapy for hyperthyroidism.

Overall, the results showed no significant difference in the pooled cancer incidence ratio between those who were and were not exposed to RAI therapy (incidence ratio, 1.02), and there also were no significant differences in mortality (IR, 0.98).

There were no increases in the risk of any specific cancers with the exception of thyroid cancer, which had a higher incidence among those with RAI treatment (1.86), and more than twice the risk of mortality (2.22).

Two studies did report a linear dose-response association between RAI for hyperthyroidism and breast cancer mortality (1.35 per 370 MBq; P = .03) and solid cancer mortality (1.14 per 370 MBq; P = .01).

Among them was a 2019 study, using data on nearly 19,000 patients from the multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study, showing a dose-response effect on solid-cancer mortality that the study authors described as “modest.”

“For every 1,000 patients with hyperthyroidism receiving typical doses to the stomach (150-250 mGy), an estimated lifetime excess of 19-32 solid cancer deaths could occur,” the study concluded.

Caveats surrounding the issue include that hyperthyroidism itself has been associated with an increased risk of cancer, suggesting a potential role of an excess of thyroid hormone excess on cancer risk.

“The underlying conditions of the thyroid gland could be another possible reason for the increased risk of malignant thyroid tumor after RAI for hyperthyroidism,” the investigators of the current study write.

“Thyroid-stimulating hormone and thyroid-stimulating antibodies, present in Graves disease, may play a role in carcinogenesis and tumoral growth, and hyperthyroidism is associated with a high incidence of thyroid carcinoma,” they add.

Tumors developing from hyperthyroid tissue show aggressive behavior, they add, and note that an increased overall risk of cancer and greater cancer mortality has been also reported with the alternative of antithyroid drug therapy when compared with RAI.

Nevertheless, considering the dose-response risk observed in the two studies, the authors and Dr. Bondi agree that more rigorous studies are needed to investigate the issue.

“The limited quality of the evidence in the literature on the adverse effects of RAI underlines the need for future randomized clinical trials in this area,” writes Dr. Bondi, of the department of clinical medicine and surgery, University of Naples (Italy) Federico II, in her editorial.

In further commenting, Dr. Walter, of the department of nuclear medicine, University Hospital, University of Geneva, agreed that the benefits of treatment need to be weighed against the risks.

“There is always caution used when deciding for a medical therapy, including radioiodine therapy,” he added. “It has to be emphasized though, that poorly controlled hyperthyroidism is a serious condition that, for instance, can lead to arrhythmia, and that in elderly patients is associated with increased mortality,” Dr, Walter cautioned.

“Statistically significant does not always mean clinically relevant, and the benefits clearly outweigh the risks.”

The authors, Dr. Bondi, and Dr. Walter had no disclosures to report.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

A version of this article first appeared on Medscape.com.

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a “new paradigm” in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of Herbert Wertheim College of Medicine, Florida International University, Miami, said in an interview.

“The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we’ve been long using it based on the assumption that the majority of high-risk tumors respond to RAI,” he explained. 

“But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment.”

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.
 

Avoid unnecessary treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer – the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system – in the immediate perioperative period, which is well established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

“Traditional risk stratification systems can be further refined by ... judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions,” the authors wrote.

Dr. Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

“The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it,” he said in an interview.

“For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy,” Dr. Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Dr. Gulec has  reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts – compared with higher amounts or binge drinking, given similar weekly levels.

“The novel finding of the current study is that frequent drinking may be more dangerous than binge drinking with regard to GI cancers. Alcohol use is a known risk factor for gastrointestinal (GI) cancers. Now, new research indicates that this risk is more associated with frequent drinking – even in smaller amounts -- compared with higher amounts or binge drinking, given similar weekly levels.” first author Jung Eun Yook, MD, of Seoul (South Korea) National University Hospital, and colleagues reported in an article published Aug. 18, 2021, in JAMA Network Open (doi: 10.1001/jamanetworkopen.2021.20382).

“This finding suggests that repeated alcohol consumption events even at lower amounts of alcohol may have a greater carcinogenic effect on GI organs than the consumption of larger amounts of alcohol at a lower frequency,” the investigators wrote.

A possible reason behind the difference in risk may be that the chronic “carcinogenic insult” from regular alcohol use may promote cancer development, whereas less frequent, episodic alcohol exposures may allow physiologic recovery, said the authors.

The results are from a population-based study that involved 11,737,467 participants in the Korean National Health System database who did not have cancer and who took part in a national screening program between January 2009 and December 2010.

They were followed from the year after their screening until either they had received a diagnosis of a GI cancer, death occurred, or the end of December 2017.

During a median follow-up of 6.4 years, 319,202 (2.7%) of those in the study developed a GI cancer.

The increase in the risk associated with alcohol consumption was dose dependent.

Compared with those who did not consume alcohol, the risk of developing GI cancer was higher for mild drinkers (adjusted hazard ratio, 1.04; 95% confidence interval, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29), after adjusting for age, sex, income, smoking status with intensity, regular exercise, body mass index, diabetes, hypertension, and dyslipidemia.

There was a linear association between the frequency of drinking and GI cancer risk, with an aHR of 1.39 for individuals who reported drinking every day (95% CI, 1.36-1.41). The risk for GI cancer increased with consumption of five to seven units per occasion (aHR, 1.15). Notably, there were no similar increases with higher intake, including intake of 8-14 units per occasion (aHR, 1.11; 95% CI, 1.09-1.12), and even up to more than 14 units per occasion (aHR, 1.11; 95%CI, 1.08-1.14), in comparison with an intake of 5-7 units per occasion.

“Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion,” the authors write.

“Most previous studies just assess alcohol consumption as a total amount, [such as] drinks per occasion times occasion per week equals drinks per week [and] grams per week,” coauthor Dong Wook Shin, MD, DrPH, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, said in an interview.

“But it was not known whether frequent drinking with small amount is more harmful than binge drinking, given a similar level of total drinking,” Dr. Shin said.

The increased risk associated with frequent drinking was generally similar with respect to esophageal, gastric, colorectal, biliary, and pancreatic cancer.

An exception was liver cancer, which showed a slightly decreased risk among mild drinkers (aHR, 0.91; 95% CI, 0.89-0.93).

Of note, the association between alcohol intake and the incidence of GI cancer was lower among women than men in terms of weekly consumption, frequency, and amount of alcohol consumed per occasion.

The associations between drinking and cancer type in terms of esophageal and liver cancers were similar between men and women. However, the alcohol-related risk for colorectal, biliary, and pancreatic cancers was less prominent for women.

Possible mechanisms related to regular drinking

A factor that might account for the increase in GI cancer risk with frequent drinking is that regular alcohol consumption “promotes the accumulation of cell divisions in the stem cells that maintain tissues in homeostasis,” the authors explained.

Another possible explanation is that long-term alcohol exposure may promote carcinogenesis, whereas less frequent exposure might allow “physiological homeostasis,” the authors wrote, adding that in vivo experiments have shown that duration and dose of alcohol exposure have been linked to cancer development.

Importantly, the findings support the importance of reducing the frequency of alcohol use to prevent cancer, the authors noted.

“Alcohol users who have a glass of wine or beer during dinner every day may develop more cancer than people who occasionally consume several drinks,” they cautioned.
 

Genetics, self-reporting considerations

In a related commentary, John D. Potter, MBBS, PhD, of the Research Center for Hauora and Health, Massey University, Wellington, New Zealand, noted that, in addition to supporting the known link between alcohol and cancers of the esophagus, colorectum, and liver, the study “strengthens evidence for a role of alcohol in stomach, biliary tract, and pancreas cancers.”

In comparison with nondrinkers, those who reported heavy drinking were much more likely to be smokers (51.6% vs. 9.0%); however, the study adjusted for smoking.

“Because the researchers were able to control for tobacco, this last finding [regarding the association with cancers of the stomach, biliary tract, and pancreas] is particularly informative,” Dr. Potter noted.

An important caveat is that more than a quarter of the Korean population is known to have an inactive form of the aldehyde dehydrogenase gene (ALDH2), which could have effects on alcohol metabolism as well as the risk for cancer, Dr. Potter wrote.

“This common polymorphism in ALDH2 (ALDH2 rs671 [c.1510G>A (Glu504Lys)]) has paradoxical effects,” he wrote.

“It increases the level of acetaldehyde in the blood of drinkers, which in turn increases the risk of cancer because acetaldehyde is a key player in the carcinogenicity of alcoholic beverages,” Dr. Potter explained. “On the other hand, the accumulation of acetaldehyde and the resultant flushing response are sufficiently unpleasant that they tend to reduce alcohol consumption among those with the Lys allele.”

The study results may therefore not be generalizable to a population in which the distribution of the variation in the ALDH2 enzyme differs, Dr. Potter added.

The lower prevalence of the inactive form (in North America, for instance) would mean that this lower prevalence was not a constraint on individuals’ drinking behavior as it is for some in Korea, Dr. Potter explained.

He noted another consideration: the underreporting of alcohol use is a well-known limitation of studies involving the assessment of alcohol consumption.

Dr. Shin agreed that underreporting is a limitation.

“People tend to underestimate their alcohol use,” Dr. Shin said in an interview.

However, he noted that “our study participants are health-screening participants aged 40 years and older, [and] people who participate in health screening tend to have higher awareness and better health behavior than nonparticipants.”

The authors and Dr. Potter disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The United States Preventive Services Task Force has updated its recommendation on the age of screening for prediabetes and type 2 diabetes in the primary care setting – lowering the age from 40 to 35 years for asymptomatic patients who are overweight or obese and encouraging greater interventions when patients do show a risk.

KatarzynaBialasiewicz/Thinkstock

“The USPSTF concludes with moderate certainty that screening for prediabetes and type 2 diabetes and offering or referring patients with prediabetes to effective preventive interventions has a moderate net benefit,” the task force concludes in its recommendation, published Aug. 24 in JAMA.

“Clinicians should offer or refer patients with prediabetes to effective preventive interventions,” they write.

Experts commenting on the issue strongly emphasize that it’s not just the screening, but the subsequent intervention that is needed to make a difference.

“If young adults newly identified with abnormal glucose metabolism do not receive the needed intensive behavioral change support, screening may provide no benefit,” write Richard W. Grant, MD, MPH, and colleagues in an editorial published with the recommendation.

“Given the role of our obesogenic and physically inactive society in the shift toward earlier onset of diabetes, efforts to increase screening and recognition of abnormal glucose metabolism must be coupled with robust public health measures to address the underlying contributors.”
 

BMI cutoff lower for at-risk ethnic populations

The recommendation, which updates the task force’s 2015 guideline, carries a “B” classification, meaning the USPSTF has high certainty that the net benefit is moderate. It now specifies screening from age 35to 70 for persons classified as overweight (body mass index at least 25) or obese (BMI at least 30) and recommends referral to preventive interventions when patients are found to have prediabetes.

In addition to recommendations of lifestyle changes, such as diet and physical activity, the task force also endorses the diabetes drug metformin as a beneficial intervention in the prevention or delay of diabetes, while noting fewer overall health benefits from metformin than from the lifestyle changes.

A lower BMI cutoff of at least 23 is recommended for diabetes screening of Asian Americans, and, importantly, screening for prediabetes and diabetes should be considered at an even earlier age if the patient is from a population with a disproportionately high prevalence of diabetes, including American Indian/Alaska Native, Black, Hawaiian/Pacific Islander, Hispanic/Latino, the task force recommends.

Screening tests should include fasting plasma glucose, hemoglobin A1c, or an oral glucose tolerance test. Although screening every 3 years “may be a reasonable approach for adults with normal blood glucose levels,” the task force adds that “the optimal screening interval for adults with an initial normal glucose test result is uncertain.”
 

Data review: Few with prediabetes know they have it

The need for the update was prompted by troubling data showing increasing diabetes rates despite early signs that can and should be identified and acted upon in the primary care setting to prevent disease progression.

Data from the Centers for Disease Control and Prevention, for instance, show that while 13% of all U.S. adults 18 years or older have diabetes and 35% meet criteria for prediabetes, as many as 21% of those with diabetes were not aware of or did not report having the disease. Furthermore, only a small fraction – 15% of those with prediabetes – said they had been told by a health professional that they had this condition, the task force notes.

The task force’s final recommendation was based on a systematic review of evidence regarding the screening of asymptomatic, nonpregnant adults and the harms and benefits of interventions, such as physical activity, behavioral counseling, or pharmacotherapy.

Among key evidence supporting the lower age was a 2014 study showing that the number of people necessary to obtain one positive test for diabetes with screening sharply drops from 80 among those aged 30-34 years to just 31 among those aged 36-39.

Opportunistic universal screening of eligible people aged 35 and older would yield a ratio of 1 out of just 15 to spot a positive test, the authors of that study reported.

In addition, a large cohort study in more than 77,000 people with prediabetes strongly links the risk of developing diabetes with increases in A1c level and with increasing BMI.
 

ADA recommendations differ

The new recommendations differ from American Diabetes Association guidelines, which call for diabetes screening at all ages for people who are overweight or obese and who have one or more risk factors, such as physical inactivity or a first-degree relative with diabetes. If results are normal, repeat screening at least every 3 years is recommended.

The ADA further recommends universal screening for all adults 45 years and older, regardless of their risk factors.

For the screening of adults over 45, the ADA recommends using a fasting plasma glucose level, 2-hour plasma glucose level during a 75-g oral glucose tolerance test, or A1c level, regardless of risk factors.

The American Association of Clinical Endocrinology also recommends universal screening for prediabetes and diabetes for all adults 45 years or older, regardless of risk factors, and also advises screening those who have risk factors for diabetes regardless of age.
 

Screening of little benefit without behavior change support

In an interview, Dr. Grant added that broad efforts are essential as those at the practice level have clearly not succeeded.

“The medical model of individual counseling and referral has not really been effective, and so we really need to think in terms of large-scale public health action,” said Dr. Grant, of the division of research, Kaiser Permanente Northern California, Oakland.

His editorial details the sweeping, multifactorial efforts that are needed.

“To turn this recommendation into action – that is, to translate screening activities into improved clinical outcomes – change is needed at the patient-clinician level (recognizing and encouraging eligible individuals to be screened), health care system level (reducing screening barriers and ensuring access to robust lifestyle programs), and societal level (applying effective public health interventions to reduce obesity and increase exercise),” they write.

A top priority has to be a focus on individuals of diverse backgrounds and issues such as access to healthy programs in minority communities, Dr. Grant noted.

“Newly diagnosed adults are more likely to be African-American and Latinx,” he said.

“We really need to invest in healthier communities for low-income, non-White communities to reverse the persistent health care disparities in these communities.”

While the challenges may appear daunting, history shows they are not necessarily insurmountable – as evidenced in the campaign to discourage tobacco smoking.

“National smoking cessation efforts are one example of a mostly successful public health campaign that has made a difference in health behaviors,” Grant noted.

The recommendation is also posted on the USPSTF web site .

Dr. Grant reports receiving grants from the National Institutes of Health and the Patient-Centered Outcomes Research Institute.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

The potential of polygenic risk scores (PRSs) to become key components in the assessment of individual risk for disease in the clinical setting is inching closer to fruition; however, the technology is plagued by one glaring omission of most existing PRSs – the lack of applicability to those of non-European ancestry.

Polygenic risk scores predict an individual’s risk of disease based on common genetic variants identified in large genomewide association studies (GWASs). They have gained ground in research, as well as in the unregulated realm of the direct-to-consumer market where they are sold as add-ons to DNA ancestry kits such as 23andMe and MyHeritage.com.

While the risk scores show strong validation in estimating risk among people of European descent, their striking caveat is the lack of applicability to other ancestries, particularly African, and their use in practice outside of clinical trials is discouraged in National Comprehensive Cancer Network guidelines.

Study underscores need for ethnically diverse datasets

In a recent study published in JAMA Network Open, researchers evaluated the use of polygenic risk scores’ models in a clinical setting. Researchers tested 7 PRSs models for breast cancer risk against the medical records data of 39,591 women of European, African, and Latinx ancestry.

The PRSs models – all used only for research purposes – included three models involving European ancestry cohorts, two from Latinx cohorts, and two from women African descent.

After adjusting for factors including age, breast cancer family history, and ancestry, the PRSs from women with European ancestry highly corresponded to breast cancer risk, with a mean odds ratio of 1.46 per standard deviation increase in the score.

PRSs were also generalized relatively well among women of Latinx ancestry with a mean OR of 1.31. The authors noted that association is likely caused by Latinx individuals in the United States having a greater proportion of European ancestry than individuals with African ancestry. Importantly, however, the effect size was lower for women of African ancestry with a highest OR of 1.19 per standard deviation.

In the highest percentiles of breast cancer risk, women of European descent had odds ratio as high as 2.19-2.48, suggesting a statistically significant association with overall breast cancer risk. No statistically significant associations were found among women of Latinx and African-ancestry.

The PRSs models were smaller for women of non-European ancestry and included fewer genetic variants for women of non-European ancestry were notably smaller and hence reflected fewer genetic variants. Of the two risk scores involving African ancestry, the Women’s Health Initiative for Women with African ancestry risk score had just 75 variants, while the African diaspora study (ROOT) had 34 variants, compared with 3,820 and 5,218 in the two largest European ancestry PRSs, the Breast Cancer Association Consortium and the UK Biobank, respectively.

“These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts,” the authors wrote.

First author, Cong Liu, PhD, of Columbia University Irving Medical Center, New York, said that efforts are underway to improve the inclusivity in the Electronic Medical Records and Genomics network data set used in this study.

“Until well-developed and validated PRSs for women with non-European ancestry become available, the current PRSs based on cohorts with European ancestry could be adapted for Latinx women, but not women with African ancestry until additional data sets become available in this important and high-risk group,” Dr. Liu and colleagues wrote.

In a commentary published with the study, Payal D. Shah, MD, of the Basser Center for BRCA at the University of Pennsylvania, Philadelphia, said that PRSs are “disproportionately applicable to patients with European ancestry and are insufficiently vetted and developed in other populations. If an instrument exists that has clinical utility in informing effective cancer risk mitigation strategies, then we must strive to ensure that it is available and applicable to all.”

Higher morality among African American women

While American Cancer Society data shows women with African ancestry generally have incidence rates of breast cancer similar to White women, they have significantly higher mortality from the disease in part because of later-stage diagnosis and health care barriers.

Anne Marie McCarthy, PhD, of the University of Pennsylvania, and Katrina Armstrong, MD, of Harvard Medical School, Boston, wrote in the Journal of the National Cancer Institute that African American women “have 42% higher breast cancer mortality than white women, despite having lower disease incidence, and are more likely to be diagnosed with triple-negative breast cancer, which has poorer prognosis than other molecular subtypes.”

Dr. McCarthy and Dr. Armstrong wrote that African American women are chronically underrepresented in breast cancer studies. And as such, it is impossible to know the extent of the prevalence of mutations and risk.

Failing to address the lack of diversity in genomic studies may worsen health disparities for women with African ancestry, Dr. Liu and colleagues wrote. The higher mortality “underscores the urgent need to increase diversity in genomic studies so that future clinical applications of the PRS do not exacerbate existing health disparities. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.”
 

Potential PRS benefits underscore need to eliminate bias

The potentially important benefits of PRSs as risk prediction tools used in combination with family history, reproductive history and other factors, should provide strong incentive to push for improvement, Dr. Shah wrote.

For instance, if an individual is estrogen receptor positive and shows elevations in breast cancer risk on a reliable PRS, “this may inform antiestrogen chemoprevention strategies,” she wrote.

A risk score could furthermore influence the age at which breast cancer screening should begin or factor into whether a patient should also receive surveillance breast MRI.

Importantly, PRSs could also add to other risk factors to provide more precise risk estimates and inform management of women with a pathogenic variant in a breast cancer risk predisposition gene, Dr. Shah wrote.

Confluence project

Among the most promising developments in research is the National Cancer Institute’s Confluence Project, a large research resource aiming to include approximately 300,000 breast cancer cases and 300,000 controls of different races/ethnicities, utilizing the confluence of existing GWAS and new genomewide genotyping data.

Having started enrollment in 2018, the project is approaching implementation, said Montserrat García-Closas, MD, MPH, DrPH, deputy director of cancer epidemiology and genetics with the National Cancer Institute.

“We expect genotyping to be completed by the end of 2022 and for the data to be made available to the research community soon after that,” she said.

Among the project’s key objectives are the development of PRSs to be integrated with known risk factors to provide a personalized risk assessment for breast cancer, overall and by ancestral subtype.

“We plan to apply novel methods to derive multiancestry PRS that will account for differences and similarities in genetic architecture across ethnic/racial groups to develop breast cancer PRSs that can be applied in multiethnic/racial populations,” she said.

NCI is working with investigators in Africa, Central and South America, and Asia, and reaching out to non-European organizations such as AORTIC for studies of African populations.

Direct-to-consumer global PRS

In the commercial PRS market, efforts to address diversity shortcomings are also gaining momentum, with Myriad Genetics touting a first-of-its kind “global PRS.”

The PRS, a recalibrated version the company’s riskScore PRS, sold as part of its Myriad myRisk Hereditary Cancer test, will reportedly apply to all ethnicities in estimating an individual’s 5-year and lifetime risk of breast cancer.

A study presented in June at the American Society of Clinical Oncology meeting, describes the development of the model with the use of three large ancestry-specific PRSs based on African American, Asian, and European cohorts, with the system including a total of 149 single-nucleotide polymorphisms, including 93 well established for breast cancer and 56 that are ancestry specific.

In validation of the data in an independent cohort of 62,707 individuals, the global PRS was strongly associated with breast cancer in the full combined validation cohort as well as in all three of the ancestry subcohorts.

However, the effect size among women with African ancestry was still the lowest of all of the groups, with a mean OR of 1.24 per standard deviation, versus the highest rate of mixed ancestry (OR, 1.59).

According to senior author Holly Pederson, MD, director of medical breast services at the Cleveland Clinic, the applicability of the PRS to women with African ancestry is expected to further improve as additional data become available.

“The discriminatory power in women of African descent was significantly improved but still suboptimal,” she said. “The need for more data, particularly in Black women, is challenging not only because there is likely more diversity in the genomic landscape of women of African descent, but also because the barriers created by historical, cultural, institutional and interpersonal dynamics result in the paucity of this data.”

“We must be committed to ending bias resulting in health care disparities,” Dr. Pederson said. She noted that the global PRS is nevertheless “still clinically useful in Black women,” and recommended that clinicians be up front with patients on the status of the research challenges.

“As with any clinical shared decision-making conversation between a patient and her provider, it is important for Black women to know that data is limited in the African American population, particularly given the vast genomic diversity of the African continent,” she said. “This model, as models that have gone before it, will improve with additional data, particularly in this population.”

Commercial PRSs may benefit research

While the commercial marketing of PRSs in a direct-to-consumer fashion have raised some concerns, such as how individuals respond to their risk scores, there could be important benefits as well, commented Megan C. Roberts, PhD.

“There may be an opportunity to learn from these companies about how to engage diverse communities in genomic testing,” said Dr. Roberts, an assistant professor and director of implementation science in precision health and society at the University of North Carolina at Chapel Hill. “Moreover, the data they collect from their customers often can be used for research purposes as well.”

In a recent perspective, Dr. Roberts and colleagues addressed the role of health disparities in PRSs. She’ll be joining international precision public health researchers in October in hosting a free virtual conference at UNC on the topic.

“There is a huge need to improve racial and ethnic diversity in our genomic datasets,” Dr. Roberts said. “Without this, we will not be able to return on the promise of precision medicine and prevention for improving the health of our whole population.”

Dr. Pederson disclosed that she is a consultant for Myriad Genetics.

Despite ongoing pandemic-related economic challenges, endocrinologists report stability in their overall wealth in the past year, with more than a third of the specialists having a net worth between $1 million and $5 million, according to the Medscape Endocrinologist Wealth & Debt Report 2021.

South_agency/Getty Images

The findings regarding wealth and debt among endocrinologists, along with 28 other specialties, were reported as part of Medscape’s Physician Compensation Report 2021, which included nearly 18,000 physicians.

According to the report, endocrinologists had an upswing in their income, compared with the prior year, with average annual earnings of $245,000 versus $236,000 in 2020. The earnings tie them with infectious disease specialists at fourth from the bottom of the list of specialties.

In the latest report, 38% reported a net worth between $1 million and $5 million, down 1% from 39% in last year’s report.

Nine percent of endocrinologists had a net worth of over $5 million, matching last year’s rate.

That puts endocrinologists and rheumatologists near the middle of specialists earning more than $5 million. Dermatologists rank the highest, with 28% worth over $5 million. Allergy and immunology specialists are at the bottom of the list, with just 2%.

Joel Greenwald, MD, a wealth management advisor to physicians based in St. Louis Park, Minn., said the reasons for the stability in wealth are multifactorial.

“The rise in home prices is certainly a factor,” he said. “Definitely the rise in the stock market played a large role; the S&P 500 finished the year up over 18%.

“I’ve seen clients accumulate cash, which has added to their net worth,” Dr. Greenwald added. “They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on [during lockdowns].”

The percentage of endocrinologists reporting a net worth below $500,000 decreased from 37% in 2020 to 31% for the current report, placing them fifth from the top of the list of specialists with a net worth below $500,000. Family medicine was at the top of the list, at 40%.
 

Gender disparities in net worth are striking

The gender disparities in net worth among endocrinologists are substantial. Although only 15% of male endocrinologists have a net worth of less than $500,000, that rate is nearly three times higher – 44% – for female endocrinologists.

Twenty-seven percent of male endocrinologists have a net worth between $1 million and $2 million, compared with just 13% among women. Although 14% of men have a net worth of more than $5 million, only 4% of female endocrinologists fall in that category.

Of note, 61% of those who responded to the poll were men; 36% were women.
 

Expenses, savings

Only 6% of endocrinologists reported being unable to pay their mortgage as a result of the pandemic; 8% said they were unable to pay other bills because of COVID-19.

The vast majority, however – 91% – said the pandemic did not affect their ability to pay bills or their mortgage. U.S. Census Bureau data from last July show that about a quarter of adults (25.3%) missed a mortgage or rent payment because of challenges related to COVID-19.

Approximately three-quarters of endocrinologists (72%) reported having not made any changes to reduce major expenses in 2020, despite the pandemic. About 25% took significant measures to reduce expenses, including refinancing their house or moving to a different home.

Seventeen percent say they are still paying off their school loans, similar to the rate last year.

The report notes that, according to the Association of American Medical Colleges, the average medical school debt for students who graduated in 2019 was $201,490, compared with an average student loan debt for all graduating students in the same year of $28,950.

Although 65% of endocrinologists said they added the same amount to their 401(k) plan in the past year, 28% put less into their fund, and although 53% put the same amount into their taxable savings account, 23% reported not using the taxable savings accounts at all.

Although earnings were steady in the past year, 12% of endocrinologists report having losses from practice problems, compared with 5% the previous year. COVID-19 was the most common cause. The proportion reporting no financial losses declined to 65%, versus 75% in the last report.

A version of this article first appeared on Medscape.com.

Despite ongoing pandemic-related economic challenges, endocrinologists report stability in their overall wealth in the past year, with more than a third of the specialists having a net worth between $1 million and $5 million, according to the Medscape Endocrinologist Wealth & Debt Report 2021.

South_agency/Getty Images

The findings regarding wealth and debt among endocrinologists, along with 28 other specialties, were reported as part of Medscape’s Physician Compensation Report 2021, which included nearly 18,000 physicians.

According to the report, endocrinologists had an upswing in their income, compared with the prior year, with average annual earnings of $245,000 versus $236,000 in 2020. The earnings tie them with infectious disease specialists at fourth from the bottom of the list of specialties.

In the latest report, 38% reported a net worth between $1 million and $5 million, down 1% from 39% in last year’s report.

Nine percent of endocrinologists had a net worth of over $5 million, matching last year’s rate.

That puts endocrinologists and rheumatologists near the middle of specialists earning more than $5 million. Dermatologists rank the highest, with 28% worth over $5 million. Allergy and immunology specialists are at the bottom of the list, with just 2%.

Joel Greenwald, MD, a wealth management advisor to physicians based in St. Louis Park, Minn., said the reasons for the stability in wealth are multifactorial.

“The rise in home prices is certainly a factor,” he said. “Definitely the rise in the stock market played a large role; the S&P 500 finished the year up over 18%.

“I’ve seen clients accumulate cash, which has added to their net worth,” Dr. Greenwald added. “They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on [during lockdowns].”

The percentage of endocrinologists reporting a net worth below $500,000 decreased from 37% in 2020 to 31% for the current report, placing them fifth from the top of the list of specialists with a net worth below $500,000. Family medicine was at the top of the list, at 40%.
 

Gender disparities in net worth are striking

The gender disparities in net worth among endocrinologists are substantial. Although only 15% of male endocrinologists have a net worth of less than $500,000, that rate is nearly three times higher – 44% – for female endocrinologists.

Twenty-seven percent of male endocrinologists have a net worth between $1 million and $2 million, compared with just 13% among women. Although 14% of men have a net worth of more than $5 million, only 4% of female endocrinologists fall in that category.

Of note, 61% of those who responded to the poll were men; 36% were women.
 

Expenses, savings

Only 6% of endocrinologists reported being unable to pay their mortgage as a result of the pandemic; 8% said they were unable to pay other bills because of COVID-19.

The vast majority, however – 91% – said the pandemic did not affect their ability to pay bills or their mortgage. U.S. Census Bureau data from last July show that about a quarter of adults (25.3%) missed a mortgage or rent payment because of challenges related to COVID-19.

Approximately three-quarters of endocrinologists (72%) reported having not made any changes to reduce major expenses in 2020, despite the pandemic. About 25% took significant measures to reduce expenses, including refinancing their house or moving to a different home.

Seventeen percent say they are still paying off their school loans, similar to the rate last year.

The report notes that, according to the Association of American Medical Colleges, the average medical school debt for students who graduated in 2019 was $201,490, compared with an average student loan debt for all graduating students in the same year of $28,950.

Although 65% of endocrinologists said they added the same amount to their 401(k) plan in the past year, 28% put less into their fund, and although 53% put the same amount into their taxable savings account, 23% reported not using the taxable savings accounts at all.

Although earnings were steady in the past year, 12% of endocrinologists report having losses from practice problems, compared with 5% the previous year. COVID-19 was the most common cause. The proportion reporting no financial losses declined to 65%, versus 75% in the last report.

A version of this article first appeared on Medscape.com.

Despite ongoing pandemic-related economic challenges, endocrinologists report stability in their overall wealth in the past year, with more than a third of the specialists having a net worth between $1 million and $5 million, according to the Medscape Endocrinologist Wealth & Debt Report 2021.

South_agency/Getty Images

The findings regarding wealth and debt among endocrinologists, along with 28 other specialties, were reported as part of Medscape’s Physician Compensation Report 2021, which included nearly 18,000 physicians.

According to the report, endocrinologists had an upswing in their income, compared with the prior year, with average annual earnings of $245,000 versus $236,000 in 2020. The earnings tie them with infectious disease specialists at fourth from the bottom of the list of specialties.

In the latest report, 38% reported a net worth between $1 million and $5 million, down 1% from 39% in last year’s report.

Nine percent of endocrinologists had a net worth of over $5 million, matching last year’s rate.

That puts endocrinologists and rheumatologists near the middle of specialists earning more than $5 million. Dermatologists rank the highest, with 28% worth over $5 million. Allergy and immunology specialists are at the bottom of the list, with just 2%.

Joel Greenwald, MD, a wealth management advisor to physicians based in St. Louis Park, Minn., said the reasons for the stability in wealth are multifactorial.

“The rise in home prices is certainly a factor,” he said. “Definitely the rise in the stock market played a large role; the S&P 500 finished the year up over 18%.

“I’ve seen clients accumulate cash, which has added to their net worth,” Dr. Greenwald added. “They cut back on spending because they were worried about big declines in income and also because there was simply less to spend money on [during lockdowns].”

The percentage of endocrinologists reporting a net worth below $500,000 decreased from 37% in 2020 to 31% for the current report, placing them fifth from the top of the list of specialists with a net worth below $500,000. Family medicine was at the top of the list, at 40%.
 

Gender disparities in net worth are striking

The gender disparities in net worth among endocrinologists are substantial. Although only 15% of male endocrinologists have a net worth of less than $500,000, that rate is nearly three times higher – 44% – for female endocrinologists.

Twenty-seven percent of male endocrinologists have a net worth between $1 million and $2 million, compared with just 13% among women. Although 14% of men have a net worth of more than $5 million, only 4% of female endocrinologists fall in that category.

Of note, 61% of those who responded to the poll were men; 36% were women.
 

Expenses, savings

Only 6% of endocrinologists reported being unable to pay their mortgage as a result of the pandemic; 8% said they were unable to pay other bills because of COVID-19.

The vast majority, however – 91% – said the pandemic did not affect their ability to pay bills or their mortgage. U.S. Census Bureau data from last July show that about a quarter of adults (25.3%) missed a mortgage or rent payment because of challenges related to COVID-19.

Approximately three-quarters of endocrinologists (72%) reported having not made any changes to reduce major expenses in 2020, despite the pandemic. About 25% took significant measures to reduce expenses, including refinancing their house or moving to a different home.

Seventeen percent say they are still paying off their school loans, similar to the rate last year.

The report notes that, according to the Association of American Medical Colleges, the average medical school debt for students who graduated in 2019 was $201,490, compared with an average student loan debt for all graduating students in the same year of $28,950.

Although 65% of endocrinologists said they added the same amount to their 401(k) plan in the past year, 28% put less into their fund, and although 53% put the same amount into their taxable savings account, 23% reported not using the taxable savings accounts at all.

Although earnings were steady in the past year, 12% of endocrinologists report having losses from practice problems, compared with 5% the previous year. COVID-19 was the most common cause. The proportion reporting no financial losses declined to 65%, versus 75% in the last report.

A version of this article first appeared on Medscape.com.

A diet rich in vegetables and low in carbs – a so-called low glycemic index (GI) diet – is associated with clinically significant benefits beyond those provided by existing medications for people with type 1 and type 2 diabetes, compared with a higher glycemic diet, findings from a new meta-analysis show.

marilyna/iStock/Getty Images Plus

“Although the effects were small, which is not surprising in clinical trials in nutrition, they were clinically meaningful improvements for which our certainty in the effects were moderate to high,” first author Laura Chiavaroli, PhD, of the department of nutritional sciences, Temerty Faculty of Medicine, University of Toronto, said in an interview.

The GI rates foods on the basis of how quickly they affect blood glucose levels.

Fruits, vegetables, and whole grains have a low GI. They also help to regulate blood sugar levels. Such foods are linked to a reduced risk for heart disease among people with diabetes.

But guidelines on this – such as those from the European Association for the Study of Diabetes – reflect research published more than 15 years ago, before several key trials were published.

Dr. Chiavaroli and colleagues identified 27 randomized controlled trials – the most recent of which was published in May 2021 – that involved a total of 1,617 adults with type 1 or 2 diabetes. For the patients in these trials, diabetes was moderately controlled with glucose-lowering drugs or insulin. All of the included trials examined the effects of a low GI diet or a low glycemic load (GL) diet for people with diabetes over a period 3 or more weeks. The majority of patients in the studies were overweight or had obesity, and they were largely middle-aged.

The meta-analysis, which included new data, was published Aug. 5 in The BMJ. The study “expands the number of relevant intermediate cardiometabolic outcomes, and assesses the certainty of the evidence using GRADE [grading of recommendations assessment, development, and evaluation],” Dr. Chiavaroli and colleagues noted.

“The available evidence provides a good indication of the likely benefit in this population and supports existing recommendations for the use of low GI dietary patterns in the management of diabetes,” they emphasized.
 

Improvements in A1c, fasting glucose, cholesterol, and triglycerides

Overall, compared with people who consumed diets with higher GI/GL ratings, for those who consumed lower glycemic diets, glycemic control was significantly improved, as reflected in A1c level, which was the primary outcome of the study (mean difference, –0.31%; P < .001).

This “would meet the threshold of ≥ 0.3% reduction in HbA1c proposed by the European Medicines Agency as clinically relevant for risk reduction of diabetic complications,” the authors noted.

Those who consumed low glycemic diets also showed improvements in secondary outcomes, including fasting glucose level, which was reduced by 0.36 mmol/L (–6.5 mg/dL), a 6% reduction in low-density cholesterol (LDL-C) (–0.17 mmol/L), and a fall in triglyceride levels (–0.09 mmol/L).

They also lost marginally more body weight, at –0.66 kg (–1.5 pounds). Body mass index was lower by –0.38, and inflammation was reduced (C-reactive protein, –.41 mg/L; all P < .05).

No significant differences were observed between the groups in blood insulin level, high-density lipoprotein cholesterol level, waist circumference, or blood pressure.

Three of the studies showed that participants developed a preference for the low GI diet. “In recent years, there has been a growing interest in whole-food plant-based diets, and there are more options, for example, for pulse-based products,” Dr. Chiavaroli said.

This meta-analysis should support the recommendation of the low-glycemic diet, particularly among people with diabetes, she reiterated.
 

Will larger randomized trial show effect on outcomes?

The authors noted, however, that to determine whether these small improvements in intermediate cardiometabolic risk factors observed with low GI diets translate to reductions in cardiovascular disease, nephropathy, and retinopathy among people with diabetes, larger randomized trials are needed.

One such trial, the Low Glycemic Index Diet for Type 2 Diabetics, includes 169 high-risk patients with type 2 diabetes and subclinical atherosclerosis. The investigators are evaluating the effect of a low GI diet on the progression of atherosclerosis, as assessed by vascular MRI over 3 years.

“We await the results,” they said.

The study received funding from the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes (EASD) as part of the development of the EASD Clinical Practice Guidelines for Nutrition Therapy. The study was also supported by the Canadian Institutes of Health Research through the Canada-wide Human Nutrition Trialists’ Network. The Diet, Digestive Tract, and Disease (3D) Center, which is funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the study.

A version of this article first appeared on Medscape.com.

A diet rich in vegetables and low in carbs – a so-called low glycemic index (GI) diet – is associated with clinically significant benefits beyond those provided by existing medications for people with type 1 and type 2 diabetes, compared with a higher glycemic diet, findings from a new meta-analysis show.

marilyna/iStock/Getty Images Plus

“Although the effects were small, which is not surprising in clinical trials in nutrition, they were clinically meaningful improvements for which our certainty in the effects were moderate to high,” first author Laura Chiavaroli, PhD, of the department of nutritional sciences, Temerty Faculty of Medicine, University of Toronto, said in an interview.

The GI rates foods on the basis of how quickly they affect blood glucose levels.

Fruits, vegetables, and whole grains have a low GI. They also help to regulate blood sugar levels. Such foods are linked to a reduced risk for heart disease among people with diabetes.

But guidelines on this – such as those from the European Association for the Study of Diabetes – reflect research published more than 15 years ago, before several key trials were published.

Dr. Chiavaroli and colleagues identified 27 randomized controlled trials – the most recent of which was published in May 2021 – that involved a total of 1,617 adults with type 1 or 2 diabetes. For the patients in these trials, diabetes was moderately controlled with glucose-lowering drugs or insulin. All of the included trials examined the effects of a low GI diet or a low glycemic load (GL) diet for people with diabetes over a period 3 or more weeks. The majority of patients in the studies were overweight or had obesity, and they were largely middle-aged.

The meta-analysis, which included new data, was published Aug. 5 in The BMJ. The study “expands the number of relevant intermediate cardiometabolic outcomes, and assesses the certainty of the evidence using GRADE [grading of recommendations assessment, development, and evaluation],” Dr. Chiavaroli and colleagues noted.

“The available evidence provides a good indication of the likely benefit in this population and supports existing recommendations for the use of low GI dietary patterns in the management of diabetes,” they emphasized.
 

Improvements in A1c, fasting glucose, cholesterol, and triglycerides

Overall, compared with people who consumed diets with higher GI/GL ratings, for those who consumed lower glycemic diets, glycemic control was significantly improved, as reflected in A1c level, which was the primary outcome of the study (mean difference, –0.31%; P < .001).

This “would meet the threshold of ≥ 0.3% reduction in HbA1c proposed by the European Medicines Agency as clinically relevant for risk reduction of diabetic complications,” the authors noted.

Those who consumed low glycemic diets also showed improvements in secondary outcomes, including fasting glucose level, which was reduced by 0.36 mmol/L (–6.5 mg/dL), a 6% reduction in low-density cholesterol (LDL-C) (–0.17 mmol/L), and a fall in triglyceride levels (–0.09 mmol/L).

They also lost marginally more body weight, at –0.66 kg (–1.5 pounds). Body mass index was lower by –0.38, and inflammation was reduced (C-reactive protein, –.41 mg/L; all P < .05).

No significant differences were observed between the groups in blood insulin level, high-density lipoprotein cholesterol level, waist circumference, or blood pressure.

Three of the studies showed that participants developed a preference for the low GI diet. “In recent years, there has been a growing interest in whole-food plant-based diets, and there are more options, for example, for pulse-based products,” Dr. Chiavaroli said.

This meta-analysis should support the recommendation of the low-glycemic diet, particularly among people with diabetes, she reiterated.
 

Will larger randomized trial show effect on outcomes?

The authors noted, however, that to determine whether these small improvements in intermediate cardiometabolic risk factors observed with low GI diets translate to reductions in cardiovascular disease, nephropathy, and retinopathy among people with diabetes, larger randomized trials are needed.

One such trial, the Low Glycemic Index Diet for Type 2 Diabetics, includes 169 high-risk patients with type 2 diabetes and subclinical atherosclerosis. The investigators are evaluating the effect of a low GI diet on the progression of atherosclerosis, as assessed by vascular MRI over 3 years.

“We await the results,” they said.

The study received funding from the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes (EASD) as part of the development of the EASD Clinical Practice Guidelines for Nutrition Therapy. The study was also supported by the Canadian Institutes of Health Research through the Canada-wide Human Nutrition Trialists’ Network. The Diet, Digestive Tract, and Disease (3D) Center, which is funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the study.

A version of this article first appeared on Medscape.com.

A diet rich in vegetables and low in carbs – a so-called low glycemic index (GI) diet – is associated with clinically significant benefits beyond those provided by existing medications for people with type 1 and type 2 diabetes, compared with a higher glycemic diet, findings from a new meta-analysis show.

marilyna/iStock/Getty Images Plus

“Although the effects were small, which is not surprising in clinical trials in nutrition, they were clinically meaningful improvements for which our certainty in the effects were moderate to high,” first author Laura Chiavaroli, PhD, of the department of nutritional sciences, Temerty Faculty of Medicine, University of Toronto, said in an interview.

The GI rates foods on the basis of how quickly they affect blood glucose levels.

Fruits, vegetables, and whole grains have a low GI. They also help to regulate blood sugar levels. Such foods are linked to a reduced risk for heart disease among people with diabetes.

But guidelines on this – such as those from the European Association for the Study of Diabetes – reflect research published more than 15 years ago, before several key trials were published.

Dr. Chiavaroli and colleagues identified 27 randomized controlled trials – the most recent of which was published in May 2021 – that involved a total of 1,617 adults with type 1 or 2 diabetes. For the patients in these trials, diabetes was moderately controlled with glucose-lowering drugs or insulin. All of the included trials examined the effects of a low GI diet or a low glycemic load (GL) diet for people with diabetes over a period 3 or more weeks. The majority of patients in the studies were overweight or had obesity, and they were largely middle-aged.

The meta-analysis, which included new data, was published Aug. 5 in The BMJ. The study “expands the number of relevant intermediate cardiometabolic outcomes, and assesses the certainty of the evidence using GRADE [grading of recommendations assessment, development, and evaluation],” Dr. Chiavaroli and colleagues noted.

“The available evidence provides a good indication of the likely benefit in this population and supports existing recommendations for the use of low GI dietary patterns in the management of diabetes,” they emphasized.
 

Improvements in A1c, fasting glucose, cholesterol, and triglycerides

Overall, compared with people who consumed diets with higher GI/GL ratings, for those who consumed lower glycemic diets, glycemic control was significantly improved, as reflected in A1c level, which was the primary outcome of the study (mean difference, –0.31%; P < .001).

This “would meet the threshold of ≥ 0.3% reduction in HbA1c proposed by the European Medicines Agency as clinically relevant for risk reduction of diabetic complications,” the authors noted.

Those who consumed low glycemic diets also showed improvements in secondary outcomes, including fasting glucose level, which was reduced by 0.36 mmol/L (–6.5 mg/dL), a 6% reduction in low-density cholesterol (LDL-C) (–0.17 mmol/L), and a fall in triglyceride levels (–0.09 mmol/L).

They also lost marginally more body weight, at –0.66 kg (–1.5 pounds). Body mass index was lower by –0.38, and inflammation was reduced (C-reactive protein, –.41 mg/L; all P < .05).

No significant differences were observed between the groups in blood insulin level, high-density lipoprotein cholesterol level, waist circumference, or blood pressure.

Three of the studies showed that participants developed a preference for the low GI diet. “In recent years, there has been a growing interest in whole-food plant-based diets, and there are more options, for example, for pulse-based products,” Dr. Chiavaroli said.

This meta-analysis should support the recommendation of the low-glycemic diet, particularly among people with diabetes, she reiterated.
 

Will larger randomized trial show effect on outcomes?

The authors noted, however, that to determine whether these small improvements in intermediate cardiometabolic risk factors observed with low GI diets translate to reductions in cardiovascular disease, nephropathy, and retinopathy among people with diabetes, larger randomized trials are needed.

One such trial, the Low Glycemic Index Diet for Type 2 Diabetics, includes 169 high-risk patients with type 2 diabetes and subclinical atherosclerosis. The investigators are evaluating the effect of a low GI diet on the progression of atherosclerosis, as assessed by vascular MRI over 3 years.

“We await the results,” they said.

The study received funding from the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes (EASD) as part of the development of the EASD Clinical Practice Guidelines for Nutrition Therapy. The study was also supported by the Canadian Institutes of Health Research through the Canada-wide Human Nutrition Trialists’ Network. The Diet, Digestive Tract, and Disease (3D) Center, which is funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the study.

A version of this article first appeared on Medscape.com.

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

A version of this article first appeared on Medscape.com.

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

A version of this article first appeared on Medscape.com.

In the largest comparison of angiotensin receptor blockers (ARBs) and ACE inhibitors to date, a study of nearly 2.3 million patients starting the drugs as monotherapy shows no significant differences between the two in the long-term prevention of hypertension-related cardiovascular events.

However, side effects were notably lower with ARBs.

“This is a very large, well-executed observational study that confirms that ARBs appear to have fewer side effects than ACE inhibitors, and no unexpected ARB side effects were detected,” senior author George Hripcsak, MD, professor and chair of biomedical informatics at Columbia University, New York, told this news organization.

“Despite being equally guideline-recommended first-line therapies for hypertension, these results support preferentially starting ARBs rather than ACE inhibitors when initiating treatment for hypertension for physicians and patients considering renin-angiotensin system (RAS) inhibition,” the authors added in the study, published online July 26, 2021, in the journal Hypertension.

They noted that both drug classes have been on the market a long time, with proven efficacy in hypertension and “a wide availability of inexpensive generic forms.”

They also stressed that their findings only apply to patients with hypertension for whom a RAS inhibitor would be the best choice of therapy.

Commenting on the research, George Bakris, MD, of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago, said the findings were consistent with his experience in prescribing as well as researching the two drug classes.

“I have been in practice for over 30 years and studied both classes, including head-to-head prospective trials to assess blood pressure, and found in many cases better blood pressure lowering by some ARBs and always better tolerability,” he told this news organization. “I think this study confirms and extends my thoughts between the two classes of blood pressure–lowering agents.”
 

Head-to-head comparisons of ACE inhibitors and ARBs limited to date

ACE inhibitors and ARBs each have extensive evidence supporting their roles as first-line medications in the treatment of hypertension, and each have the strongest recommendations in international guidelines.

However, ACE inhibitors are prescribed more commonly than ARBs as the first-line drug for lowering blood pressure, and head-to-head comparisons of the two are limited, with conflicting results.

For the study, Dr. Hripcsak and colleagues evaluated data on almost 3 million patients starting monotherapy with an ACE inhibitor or ARB for the first time between 1996 and 2018 in the United States, Germany, and South Korea, who had no history of heart disease or stroke.

They identified a total of 2,297,881 patients initiating ACE inhibitors and 673,938 starting ARBs. Among new users of ACE inhibitors, most received lisinopril (80%), followed by ramipril and enalapril, while most patients prescribed ARBs received losartan (45%), followed by valsartan and olmesartan.

With follow-up times ranging from about 4 months to more than 18 months, the data show no statistically significant differences between ACE inhibitors versus ARBs in the primary outcomes of acute myocardial infarction (hazard ratio, 1.11), heart failure (HR, 1.03), stroke (HR, 1.07), or composite cardiovascular events (HR, 1.06).

For secondary and safety outcomes, including an analysis of 51 possible side effects, ACE inhibitors, compared with ARBs, were associated with a significantly higher risk of angioedema (HR, 3.31; P < .01), cough (HR, 1.32; P < .01), acute pancreatitis (HR, 1.32; P = .02), gastrointestinal bleeding (HR, 1.18; P = .04), and abnormal weight loss (HR, 1.18; P = .04).

While the link between ACE inhibitors and pancreatitis has been previously reported, the association with GI bleeding may be a novel finding, with no prior studies comparing those effects in the two drug classes, the authors noted.

Despite most patients taking just a couple of drugs in either class, Dr. Hripcsak said, “we don’t expect that other drugs from those classes will have fewer differences. It is possible, of course, but that is not our expectation.”
 

Results only applicable to those starting therapy with RAS inhibitors

First author RuiJun Chen, MD, added that, importantly, the results may not apply to patients switching therapies or adding on therapy, “such as for the patient whose hypertension is not effectively controlled with one drug and requires the addition of a second medication,” he said in an interview.

“Also, the suggestion of preferentially prescribing ARBs only applies to those patients and providers intending to control blood pressure through RAS inhibition,” said Dr. Chen, an assistant professor in translational data science and informatics at Geisinger Medical Center in Danville, Pa., who was a National Library of Medicine postdoctoral fellow at Columbia University at the time of the study.

Hence, he stressed the results do not extend to other classes of recommended first-line blood pressure medications.

“Essentially, since this is an ACE inhibitor versus ARB study, we would not claim that ARBs are preferred over all other types of hypertension medications which were not studied here,” the researchers emphasize.

In addition to ARBs and ACE inhibitors, other medications recommended by the AHA/American College of Cardiology in the 2017 “Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults” for the primary treatment of hypertension include thiazide diuretics and calcium channel blockers.

The study received support from the National Library of Medicine and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; the National Science Foundation; and the Ministries of Health & Welfare and of Trade, Industry & Energy of the Republic of Korea. Dr. Hripcsak reported receiving grants from the National Library of Medicine during the study and grants from Janssen Research outside the submitted work. Dr. Bakris reported being a consultant for Merck, KBP Biosciences, and Ionis.

A version of this article first appeared on Medscape.com.