Pauline Anderson

TOPLINE:

Mortality in patients with takotsubo syndrome (TTS), sometimes called broken heart syndrome or stress-induced cardiomyopathy is substantially higher than that in the general population and comparable with that in patients having myocardial infarction (MI), results of a new case-control study showed. The rates of medication use are similar for TTS and MI, despite no current clinical trials or recommendations to guide such therapies, the authors noted.

METHODOLOGY:

• The study included 620 Scottish patients (mean age, 66 years; 91% women) with TTS, a potentially fatal condition that mimics MI, predominantly affects middle-aged women, and is often triggered by stress.
• The analysis also included two age-, sex-, and geographically matched control groups: Representative participants from the general Scottish population (1:4) and patients with acute MI (1:1).
• Using comprehensive national data sets, researchers extracted information for all three cohorts on prescribing of cardiovascular and noncardiovascular medications, including the duration of dispensing and causes of death, and clustered the major causes of death into 17 major groups.
• At a median follow-up of 5.5 years, there were 722 deaths (153 in patients with TTS, 195 in those with MI, and 374 in the general population cohort).

TAKEAWAY:

• and slightly lower than that in patients having MI (HR, 0.76; 95% CI, 0.62-0.94; P = .012), with cardiovascular causes, particularly heart failure, being the most strongly associated with TTS (HR, 2.47; 95% CI, 1.81-3.39; P < .0001 vs general population), followed by pulmonary causes. Noncardiovascular mortality was similar in TTS and MI.
• Prescription rates of cardiovascular and noncardiovascular medications were similar between patients with TTS and MI.
• The only cardiovascular therapy associated with lower mortality in patients with TTS was angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (P = .0056); in contrast, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, antiplatelet agents, and statins were all associated with improved survival in patients with MI.
• Diuretics were associated with worse outcomes in both patients with TTS and MI, as was psychotropic therapy.

IN PRACTICE:

“These findings may help to lay the foundations for further exploration of potential mechanisms and treatments” for TTS, an “increasingly recognized and potentially fatal condition,” the authors concluded.

In an accompanying comment, Rodolfo Citro, MD, PHD, Cardiovascular and Thoracic Department, San Giovanni di Dio e Ruggi d’ Aragona University Hospital, Salerno, Italy, and colleagues said the authors should be commended for providing data on cardiovascular mortality “during one of the longest available follow-ups in TTS,” adding the study “suggests the importance of further research for more appropriate management of patients with acute and long-term TTS.”

SOURCE:

The research was led by Amelia E. Rudd, MSC, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen and NHS Grampian, Aberdeen, Scotland. It was published online in the Journal of the American College of Cardiology.

LIMITATIONS:

Complete alignment of all variables related to clinical characteristics of patients with TTS and MI wasn’t feasible. During the study, TTS was still relatively unfamiliar to clinicians and underdiagnosed. As the study used a national data set of routinely collected data, not all desirable information was available, including indications of why drugs were prescribed or discontinued, which could have led to imprecise results. As the study used nonrandomized data, causality can’t be assumed.

DISCLOSURES:

Dr. Rudd had no relevant conflicts of interest. Study author Dana K. Dawson, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Scotland, declared receiving the Chief Scientist Office Scotland award CGA-16-4 and the BHF Research Training Fellowship. Commentary authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mortality in patients with takotsubo syndrome (TTS), sometimes called broken heart syndrome or stress-induced cardiomyopathy is substantially higher than that in the general population and comparable with that in patients having myocardial infarction (MI), results of a new case-control study showed. The rates of medication use are similar for TTS and MI, despite no current clinical trials or recommendations to guide such therapies, the authors noted.

METHODOLOGY:

• The study included 620 Scottish patients (mean age, 66 years; 91% women) with TTS, a potentially fatal condition that mimics MI, predominantly affects middle-aged women, and is often triggered by stress.
• The analysis also included two age-, sex-, and geographically matched control groups: Representative participants from the general Scottish population (1:4) and patients with acute MI (1:1).
• Using comprehensive national data sets, researchers extracted information for all three cohorts on prescribing of cardiovascular and noncardiovascular medications, including the duration of dispensing and causes of death, and clustered the major causes of death into 17 major groups.
• At a median follow-up of 5.5 years, there were 722 deaths (153 in patients with TTS, 195 in those with MI, and 374 in the general population cohort).

TAKEAWAY:

• and slightly lower than that in patients having MI (HR, 0.76; 95% CI, 0.62-0.94; P = .012), with cardiovascular causes, particularly heart failure, being the most strongly associated with TTS (HR, 2.47; 95% CI, 1.81-3.39; P < .0001 vs general population), followed by pulmonary causes. Noncardiovascular mortality was similar in TTS and MI.
• Prescription rates of cardiovascular and noncardiovascular medications were similar between patients with TTS and MI.
• The only cardiovascular therapy associated with lower mortality in patients with TTS was angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (P = .0056); in contrast, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, antiplatelet agents, and statins were all associated with improved survival in patients with MI.
• Diuretics were associated with worse outcomes in both patients with TTS and MI, as was psychotropic therapy.

IN PRACTICE:

“These findings may help to lay the foundations for further exploration of potential mechanisms and treatments” for TTS, an “increasingly recognized and potentially fatal condition,” the authors concluded.

In an accompanying comment, Rodolfo Citro, MD, PHD, Cardiovascular and Thoracic Department, San Giovanni di Dio e Ruggi d’ Aragona University Hospital, Salerno, Italy, and colleagues said the authors should be commended for providing data on cardiovascular mortality “during one of the longest available follow-ups in TTS,” adding the study “suggests the importance of further research for more appropriate management of patients with acute and long-term TTS.”

SOURCE:

The research was led by Amelia E. Rudd, MSC, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen and NHS Grampian, Aberdeen, Scotland. It was published online in the Journal of the American College of Cardiology.

LIMITATIONS:

Complete alignment of all variables related to clinical characteristics of patients with TTS and MI wasn’t feasible. During the study, TTS was still relatively unfamiliar to clinicians and underdiagnosed. As the study used a national data set of routinely collected data, not all desirable information was available, including indications of why drugs were prescribed or discontinued, which could have led to imprecise results. As the study used nonrandomized data, causality can’t be assumed.

DISCLOSURES:

Dr. Rudd had no relevant conflicts of interest. Study author Dana K. Dawson, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Scotland, declared receiving the Chief Scientist Office Scotland award CGA-16-4 and the BHF Research Training Fellowship. Commentary authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Mortality in patients with takotsubo syndrome (TTS), sometimes called broken heart syndrome or stress-induced cardiomyopathy is substantially higher than that in the general population and comparable with that in patients having myocardial infarction (MI), results of a new case-control study showed. The rates of medication use are similar for TTS and MI, despite no current clinical trials or recommendations to guide such therapies, the authors noted.

METHODOLOGY:

• The study included 620 Scottish patients (mean age, 66 years; 91% women) with TTS, a potentially fatal condition that mimics MI, predominantly affects middle-aged women, and is often triggered by stress.
• The analysis also included two age-, sex-, and geographically matched control groups: Representative participants from the general Scottish population (1:4) and patients with acute MI (1:1).
• Using comprehensive national data sets, researchers extracted information for all three cohorts on prescribing of cardiovascular and noncardiovascular medications, including the duration of dispensing and causes of death, and clustered the major causes of death into 17 major groups.
• At a median follow-up of 5.5 years, there were 722 deaths (153 in patients with TTS, 195 in those with MI, and 374 in the general population cohort).

TAKEAWAY:

• and slightly lower than that in patients having MI (HR, 0.76; 95% CI, 0.62-0.94; P = .012), with cardiovascular causes, particularly heart failure, being the most strongly associated with TTS (HR, 2.47; 95% CI, 1.81-3.39; P < .0001 vs general population), followed by pulmonary causes. Noncardiovascular mortality was similar in TTS and MI.
• Prescription rates of cardiovascular and noncardiovascular medications were similar between patients with TTS and MI.
• The only cardiovascular therapy associated with lower mortality in patients with TTS was angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy (P = .0056); in contrast, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, antiplatelet agents, and statins were all associated with improved survival in patients with MI.
• Diuretics were associated with worse outcomes in both patients with TTS and MI, as was psychotropic therapy.

IN PRACTICE:

“These findings may help to lay the foundations for further exploration of potential mechanisms and treatments” for TTS, an “increasingly recognized and potentially fatal condition,” the authors concluded.

In an accompanying comment, Rodolfo Citro, MD, PHD, Cardiovascular and Thoracic Department, San Giovanni di Dio e Ruggi d’ Aragona University Hospital, Salerno, Italy, and colleagues said the authors should be commended for providing data on cardiovascular mortality “during one of the longest available follow-ups in TTS,” adding the study “suggests the importance of further research for more appropriate management of patients with acute and long-term TTS.”

SOURCE:

The research was led by Amelia E. Rudd, MSC, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen and NHS Grampian, Aberdeen, Scotland. It was published online in the Journal of the American College of Cardiology.

LIMITATIONS:

Complete alignment of all variables related to clinical characteristics of patients with TTS and MI wasn’t feasible. During the study, TTS was still relatively unfamiliar to clinicians and underdiagnosed. As the study used a national data set of routinely collected data, not all desirable information was available, including indications of why drugs were prescribed or discontinued, which could have led to imprecise results. As the study used nonrandomized data, causality can’t be assumed.

DISCLOSURES:

Dr. Rudd had no relevant conflicts of interest. Study author Dana K. Dawson, Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Scotland, declared receiving the Chief Scientist Office Scotland award CGA-16-4 and the BHF Research Training Fellowship. Commentary authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

In addition to better known risk factors such as diabetes, stroke, heart disease, and depression, findings of a large study suggested vitamin D deficiency, elevated C-reactive protein (CRP) levels, and social isolation increase the risk for young-onset dementia (YOD).

METHODOLOGY:

• The study included 356,052 participants younger than 65 years (mean baseline age, 54.6 years) without dementia from the UK Biobank, an ongoing prospective cohort study.
• Participants underwent a comprehensive baseline assessment, provided biological samples, completed touch screen questionnaires, and underwent a physical examination.
• Researchers identified incident all-cause YOD cases from hospital inpatient registers or death register linkage.
• The researchers detected 39 potential risk factors and grouped them into domains of sociodemographic, genetic, lifestyle, environmental, vitamin D and CRP levels, cardiometabolic, psychiatric, and other factors.
• Researchers analyzed incidence rates of YOD for 5-year age bands starting at age 40 years and separately for men and women.

TAKEAWAY:

• During a mean follow-up of 8.12 years, there were 485 incident YOD cases (incidence rate of 16.8 per 100,000 person-years; 95% CI 15.4-18.3).
• The final analysis identified 15 risk factors associated with significantly higher incidence of YOD, including traditional factors like stroke (hazard ratio [HR], 2.07), heart disease (HR, 1.61), diabetes (HR, 1.65), and depression (HR, 3.25) but also less-recognized risk factors like vitamin D deficiency (< 10 ng/mL; HR, 1.59), high CRP levels (> 1 mg/dL; HR, 1.54), and social isolation (infrequent visits to friends or family; HR, 1.53), with lower socioeconomic status (HR, 1.82), having two apolipoprotein E epsilon-4 alleles (HR, 1.87), orthostatic hypotension, which the authors said may be an early sign of Parkinson dementia or Lewy body dementia (HR, 4.20), and hearing impairment (HR, 1.56) also increasing risk.
• Interestingly, some alcohol use seemed to be protective (moderate or heavy alcohol use had a lower association with YOD than alcohol abstinence, possibly due to the “healthy drinker effect” where people who drink are healthier than abstainers who may have illnesses preventing them from drinking, said the authors), as was higher education level and higher than normative handgrip strength (less strength is a proxy for physical frailty).
• Men with diabetes had higher YOD risk than those without diabetes, while there was no association with diabetes in women; on the other hand, women with high CRP levels had greater YOD risk than those with low levels, while there was no association with CRP in men.

IN PRACTICE:

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing YOD and can be readily integrated in current dementia prevention initiatives,” the investigators wrote.

SOURCE:

The study was led by Stevie Hendriks, PhD, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands. It was published online in JAMA Neurology.

LIMITATIONS:

The study was observational and so can’t infer causality. Several factors were based on self-reported data, which might be a source of response bias. Factors not considered in the study, for example, family history of dementia and drug (other than alcohol) use disorder, may have confounded associations. Some factors including orthostatic hypotension had few exposed cases, leading to decreased power to detect associations. Hospital and death records may not have captured all YOD cases. The UK Biobank is overrepresented by healthy and White participants, so results may not be generalizable to other racial and ethnic groups. The analyses only focused on all-cause dementia.

DISCLOSURES:

The study was supported by Alzheimer Netherlands. Hendriks has no relevant conflicts of interest; see paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A digital stethoscope that uses artificial intelligence (AI) is better at detecting heart murmurs associated with clinically significant valvular heart disease (VHD) than is a primary care physician (PCP) using a traditional stethoscope, a new study shows.

The results suggest collecting relevant sounds through a stethoscope (auscultation) using AI-powered technology is an important primary care tool to detect VHD, study author Moshe A. Rancier, MD, medical director, Massachusetts General Brigham Community Physicians, Lawrence, Massachusetts, said in an interview.

“Incorporating this AI-assisted device into the primary care exam will help identify patients at risk for VHD earlier and eventually decrease costs in our healthcare system,” he said, because timely detection could avoid emergency room visits and surgeries.

The findings were presented at the annual scientific sessions of the American Heart Association.
 

VHD Common

Clinically significant VHD, indicating structural damage to heart valves, affects 1 in 10 adults older than 65 years. Patients may be asymptomatic or present to their PCP with an unspecific symptom like fatigue or malaise.

If VHD is undiagnosed and left untreated, patients could develop more severe symptoms, even be at risk for death, and their quality of life is significantly affected, said Dr. Rancier.

Cardiac auscultation, the current point-of-care clinical standard, has relatively low sensitivity for detecting VHD, leaving most patients undiagnosed.

The deep learning–based AI tool uses sound data to detect cardiac murmurs associated with clinically significant VHD. The device used in the study (Eko; Eko Health) is approved by the US Food and Drug Administration and is on the market.

The tool identifies background sounds that might affect the evaluation. “If there’s any noise or breath sounds, it tells me this is not a good heart sound, and asks me to record again,” said Dr. Rancier.

A doctor using the AI-assisted stethoscope carries out the auscultation exam with the sound data captured by a smartphone or tablet and sent to the AI server. “I get an answer in a second as to if there’s a murmur or not,” said Dr. Rancier.

Not only that, but the tool can determine if it’s a systolic or diastolic murmur, he added.
 

Real-World Population

The study enrolled a “real-world” population of 368 patients, median age 70 years, 61% female, 70% White, and 18% Hispanic without a prior VHD diagnosis or history of murmur, from three primary care clinics in Queens, New York, and Lawrence and Haverhill, Massachusetts. 

About 79% of the cohort had hypertension, 68% had dyslipidemia, and 38% had diabetes, “which aligns with the population in the US,” said Dr. Rancier.

Each study participant had a regular exam carried out by Dr. Rancier using a traditional stethoscope to detect murmurs and an exam by a technician with a digital stethoscope that collected phonocardiogram (PCG) data for analysis by AI.

In addition, each patient received an echocardiogram 1-2 weeks later to confirm whether clinically significant VHD was present. An expert panel of cardiologists also reviewed the patient’s PCG recordings to confirm the presence of audible murmurs.

Dr. Rancier and the expert panel were blinded to AI and echocardiogram results.

Researchers calculated performance metrics for both PCP auscultation and the AI in detecting audible VHD.

The study showed that AI improved sensitivity to detect audible VHD by over twofold compared with PCP auscultation (94.1% vs 41.2%), with limited impact on specificity (84.5% vs 95.5%).

Dr. Rancier stressed the importance of sensitivity because clinicians tend to under-detect murmurs. “You don’t want to miss those patients because the consequences of undiagnosed VHD are dire.”

The AI tool identified 22 patients with moderate or greater VHD who were previously undiagnosed, whereas PCPs identified eight previously undiagnosed patients with VHD.

Dr. Rancier sees this tool being used beyond primary care, perhaps by emergency room personnel.

The authors plan to follow study participants and assess outcomes at for 6-12 months. They also aim to include more patients to increase the study’s power.
 

Expanding the Technology

They are also interested to see whether the technology can determine which valve is affected; for example, whether the issue is aortic stenosis or mitral regurgitation.

A limitation of the study was its small sample size.

Commenting on the findings, Dan Roden, MD, professor of medicine, pharmacology, and biomedical informatics, senior vice president for personalized medicine at Vanderbilt University Medical Center, Nashville, Tennessee, and chair of the American Heart Association Council on Genomic and Precision Medicine, noted that it demonstrated the AI-based stethoscope “did extraordinarily well” in predicting VHD. 

“I see this as an emerging technology — using an AI-enabled stethoscope and perhaps combining it with other imaging modalities, like an AI-enabled echocardiogram built into your stethoscope,” said Dr. Roden.

“Use of these new tools to detect the presence of valvular disease, as well as the extent of valvular disease and the extent of other kinds of heart disease, will likely help to transform CVD care.” 

The study was funded by Eko Health Inc. Dr. Rancier and Dr. Roden have no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

ORLANDO — A new review adds to growing evidence that the modified Atkins diet (MAD) significantly reduces seizures in adults with drug-resistant epilepsy.

The results of the small new review and meta-analysis suggest that “the MAD may be an effective adjuvant therapy for older patients who have failed anti-seizure medications,” study investigator Aiswarya Raj, MBBS, Aster Malabar Institute of Medical Sciences, Kerala, India, said in an interview.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Paucity of Adult Data 

The MAD is a less restrictive hybrid of the ketogenic diet that limits carbohydrate intake and encourages fat consumption. It does not restrict fluids, calories, or proteins and does not require fats to be weighed or measured.

The diet includes fewer carbohydrates than the traditional Atkins diet and places more emphasis on fat intake. Dr. Raj said that the research suggests that the MAD “is a promising therapy in pediatric populations, but there’s not a lot of data in adults.”

Dr. Raj noted that this diet type has not been that popular in patients who clinicians believe might be better treated with drug therapy, possibly because of concern about the cardiac impact of consuming high-fat foods.

After conducting a systematic literature review assessing the efficacy of MAD in adults, the researchers included three randomized controlled trials and four observational studies published from January 2000 to May 2023 in the analysis.

The randomized controlled trials in the review assessed the primary outcome, a greater than 50% seizure reduction, at the end of 2 months, 3 months, and 6 months. In the MAD group, 32.5% of participants had more than a 50% seizure reduction vs 3% in the control group (odds ratio [OR], 12.62; 95% CI, 4.05-39.29; P < .0001).

Four participants who followed the diet achieved complete seizure-freedom compared with no participants in the control group (OR, 16.20; 95% CI, 0.82-318.82; P = .07).

The prospective studies examined this outcome at the end of 1 month or 3 months. In these studies, 41.9% of individuals experienced more than a 50% seizure reduction after 1 month of following the MAD, and 34.2% experienced this reduction after 3 months (OR, 1.41; 95% CI, 0.79-2.52; P = .24), with zero heterogeneity across studies.

It’s difficult to interpret the difference in seizure reduction between 1 and 3 months of therapy, Dr. Raj noted, because “there’s always the issue of compliance when you put a patient on a long-term diet.”

Positive results for MAD in adults were shown in another recent systematic review and meta-analysis published in Seizure: European Journal of Epilepsy.

That analysis included six studies with 575 patients who were randomly assigned to MAD or usual diet (UD) plus standard drug therapy. After an average follow-up of 12 weeks, MAD was associated with a higher rate of 50% or greater reduction in seizure frequency (relative risk [RR], 6.28; 95% CI, 3.52-10.50; P < .001), both in adults with drug-resistant epilepsy (RR, 6.14; 95% CI, 1.15-32.66; P = .033) and children (RR, 6.28; 95% CI, 3.43-11.49; P < .001).

MAD was also associated with a higher seizure freedom rate compared with UD (RR, 5.94; 95% CI, 1.93-18.31; P = .002).
 

Cholesterol Concern

In Dr. Raj’s analysis, there was an increment in blood total cholesterol level after 3 months of MAD (standard mean difference, -0.82; 95% CI, -1.23 to -0.40; P = .0001).

Concern about elevated blood cholesterol affecting coronary artery disease risk may explain why doctors sometimes shy away from recommending the MAD to their adult patients. “Some may not want to take that risk; you don’t want patients to succumb to coronary artery disease,” said Dr. Raj.

She noted that 3 months “is a very short time period,” and studies looking at cholesterol levels at the end of at least 1 year are needed to determine whether levels return to normal.

“We’re seeing a lot of literature now that suggests dietary intake does not really have a link with cholesterol levels,” she said. If this can be proven, “then this is definitely a great therapy.” 

The evidence of cardiovascular safety of the MAD includes a study of 37 patients who showed that although total cholesterol and low-density lipoprotein (LDL) cholesterol increased over the first 3 months of MAD treatment, these values normalized within 1 year of treatment, including in patients treated with MAD for more than 3 years.
 

Primary Diet Recommendation

This news organization asked one of the authors of that study, Mackenzie C. Cervenka, MD, professor of neurology and medical director of the Adult Epilepsy Diet Center, Johns Hopkins Hospital, Baltimore, Maryland, to comment on the new research.

She said that she was “thrilled” to see more evidence showing that this diet therapy can be as effective for adults as for children. “This is a really important message to get out there.”

At her adult epilepsy diet center, the MAD is the “primary” diet recommended for patients who are resistant to seizure medication, not tube fed, and are keen to try diet therapy, said Dr. Cervenka.

In her experience, the likelihood of having a 50% or greater seizure reduction is about 40% among medication-resistant patients, “so very similar to what they reported in that review,” she said.

However, she noted that she emphasizes to patients that “diet therapy is not meant to be monotherapy.”

Dr. Cervenka’s team is examining LDL cholesterol levels as well as LDL particle size in adults who have been on the MAD for 2 years. LDL particle size, she noted, is a better predictor of long-term cardiovascular health. 

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

ORLANDO — A new review adds to growing evidence that the modified Atkins diet (MAD) significantly reduces seizures in adults with drug-resistant epilepsy.

The results of the small new review and meta-analysis suggest that “the MAD may be an effective adjuvant therapy for older patients who have failed anti-seizure medications,” study investigator Aiswarya Raj, MBBS, Aster Malabar Institute of Medical Sciences, Kerala, India, said in an interview.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Paucity of Adult Data 

The MAD is a less restrictive hybrid of the ketogenic diet that limits carbohydrate intake and encourages fat consumption. It does not restrict fluids, calories, or proteins and does not require fats to be weighed or measured.

The diet includes fewer carbohydrates than the traditional Atkins diet and places more emphasis on fat intake. Dr. Raj said that the research suggests that the MAD “is a promising therapy in pediatric populations, but there’s not a lot of data in adults.”

Dr. Raj noted that this diet type has not been that popular in patients who clinicians believe might be better treated with drug therapy, possibly because of concern about the cardiac impact of consuming high-fat foods.

After conducting a systematic literature review assessing the efficacy of MAD in adults, the researchers included three randomized controlled trials and four observational studies published from January 2000 to May 2023 in the analysis.

The randomized controlled trials in the review assessed the primary outcome, a greater than 50% seizure reduction, at the end of 2 months, 3 months, and 6 months. In the MAD group, 32.5% of participants had more than a 50% seizure reduction vs 3% in the control group (odds ratio [OR], 12.62; 95% CI, 4.05-39.29; P < .0001).

Four participants who followed the diet achieved complete seizure-freedom compared with no participants in the control group (OR, 16.20; 95% CI, 0.82-318.82; P = .07).

The prospective studies examined this outcome at the end of 1 month or 3 months. In these studies, 41.9% of individuals experienced more than a 50% seizure reduction after 1 month of following the MAD, and 34.2% experienced this reduction after 3 months (OR, 1.41; 95% CI, 0.79-2.52; P = .24), with zero heterogeneity across studies.

It’s difficult to interpret the difference in seizure reduction between 1 and 3 months of therapy, Dr. Raj noted, because “there’s always the issue of compliance when you put a patient on a long-term diet.”

Positive results for MAD in adults were shown in another recent systematic review and meta-analysis published in Seizure: European Journal of Epilepsy.

That analysis included six studies with 575 patients who were randomly assigned to MAD or usual diet (UD) plus standard drug therapy. After an average follow-up of 12 weeks, MAD was associated with a higher rate of 50% or greater reduction in seizure frequency (relative risk [RR], 6.28; 95% CI, 3.52-10.50; P < .001), both in adults with drug-resistant epilepsy (RR, 6.14; 95% CI, 1.15-32.66; P = .033) and children (RR, 6.28; 95% CI, 3.43-11.49; P < .001).

MAD was also associated with a higher seizure freedom rate compared with UD (RR, 5.94; 95% CI, 1.93-18.31; P = .002).
 

Cholesterol Concern

In Dr. Raj’s analysis, there was an increment in blood total cholesterol level after 3 months of MAD (standard mean difference, -0.82; 95% CI, -1.23 to -0.40; P = .0001).

Concern about elevated blood cholesterol affecting coronary artery disease risk may explain why doctors sometimes shy away from recommending the MAD to their adult patients. “Some may not want to take that risk; you don’t want patients to succumb to coronary artery disease,” said Dr. Raj.

She noted that 3 months “is a very short time period,” and studies looking at cholesterol levels at the end of at least 1 year are needed to determine whether levels return to normal.

“We’re seeing a lot of literature now that suggests dietary intake does not really have a link with cholesterol levels,” she said. If this can be proven, “then this is definitely a great therapy.” 

The evidence of cardiovascular safety of the MAD includes a study of 37 patients who showed that although total cholesterol and low-density lipoprotein (LDL) cholesterol increased over the first 3 months of MAD treatment, these values normalized within 1 year of treatment, including in patients treated with MAD for more than 3 years.
 

Primary Diet Recommendation

This news organization asked one of the authors of that study, Mackenzie C. Cervenka, MD, professor of neurology and medical director of the Adult Epilepsy Diet Center, Johns Hopkins Hospital, Baltimore, Maryland, to comment on the new research.

She said that she was “thrilled” to see more evidence showing that this diet therapy can be as effective for adults as for children. “This is a really important message to get out there.”

At her adult epilepsy diet center, the MAD is the “primary” diet recommended for patients who are resistant to seizure medication, not tube fed, and are keen to try diet therapy, said Dr. Cervenka.

In her experience, the likelihood of having a 50% or greater seizure reduction is about 40% among medication-resistant patients, “so very similar to what they reported in that review,” she said.

However, she noted that she emphasizes to patients that “diet therapy is not meant to be monotherapy.”

Dr. Cervenka’s team is examining LDL cholesterol levels as well as LDL particle size in adults who have been on the MAD for 2 years. LDL particle size, she noted, is a better predictor of long-term cardiovascular health. 

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.

ORLANDO — A new review adds to growing evidence that the modified Atkins diet (MAD) significantly reduces seizures in adults with drug-resistant epilepsy.

The results of the small new review and meta-analysis suggest that “the MAD may be an effective adjuvant therapy for older patients who have failed anti-seizure medications,” study investigator Aiswarya Raj, MBBS, Aster Malabar Institute of Medical Sciences, Kerala, India, said in an interview.

The findings were presented at the annual meeting of the American Epilepsy Society.
 

Paucity of Adult Data 

The MAD is a less restrictive hybrid of the ketogenic diet that limits carbohydrate intake and encourages fat consumption. It does not restrict fluids, calories, or proteins and does not require fats to be weighed or measured.

The diet includes fewer carbohydrates than the traditional Atkins diet and places more emphasis on fat intake. Dr. Raj said that the research suggests that the MAD “is a promising therapy in pediatric populations, but there’s not a lot of data in adults.”

Dr. Raj noted that this diet type has not been that popular in patients who clinicians believe might be better treated with drug therapy, possibly because of concern about the cardiac impact of consuming high-fat foods.

After conducting a systematic literature review assessing the efficacy of MAD in adults, the researchers included three randomized controlled trials and four observational studies published from January 2000 to May 2023 in the analysis.

The randomized controlled trials in the review assessed the primary outcome, a greater than 50% seizure reduction, at the end of 2 months, 3 months, and 6 months. In the MAD group, 32.5% of participants had more than a 50% seizure reduction vs 3% in the control group (odds ratio [OR], 12.62; 95% CI, 4.05-39.29; P < .0001).

Four participants who followed the diet achieved complete seizure-freedom compared with no participants in the control group (OR, 16.20; 95% CI, 0.82-318.82; P = .07).

The prospective studies examined this outcome at the end of 1 month or 3 months. In these studies, 41.9% of individuals experienced more than a 50% seizure reduction after 1 month of following the MAD, and 34.2% experienced this reduction after 3 months (OR, 1.41; 95% CI, 0.79-2.52; P = .24), with zero heterogeneity across studies.

It’s difficult to interpret the difference in seizure reduction between 1 and 3 months of therapy, Dr. Raj noted, because “there’s always the issue of compliance when you put a patient on a long-term diet.”

Positive results for MAD in adults were shown in another recent systematic review and meta-analysis published in Seizure: European Journal of Epilepsy.

That analysis included six studies with 575 patients who were randomly assigned to MAD or usual diet (UD) plus standard drug therapy. After an average follow-up of 12 weeks, MAD was associated with a higher rate of 50% or greater reduction in seizure frequency (relative risk [RR], 6.28; 95% CI, 3.52-10.50; P < .001), both in adults with drug-resistant epilepsy (RR, 6.14; 95% CI, 1.15-32.66; P = .033) and children (RR, 6.28; 95% CI, 3.43-11.49; P < .001).

MAD was also associated with a higher seizure freedom rate compared with UD (RR, 5.94; 95% CI, 1.93-18.31; P = .002).
 

Cholesterol Concern

In Dr. Raj’s analysis, there was an increment in blood total cholesterol level after 3 months of MAD (standard mean difference, -0.82; 95% CI, -1.23 to -0.40; P = .0001).

Concern about elevated blood cholesterol affecting coronary artery disease risk may explain why doctors sometimes shy away from recommending the MAD to their adult patients. “Some may not want to take that risk; you don’t want patients to succumb to coronary artery disease,” said Dr. Raj.

She noted that 3 months “is a very short time period,” and studies looking at cholesterol levels at the end of at least 1 year are needed to determine whether levels return to normal.

“We’re seeing a lot of literature now that suggests dietary intake does not really have a link with cholesterol levels,” she said. If this can be proven, “then this is definitely a great therapy.” 

The evidence of cardiovascular safety of the MAD includes a study of 37 patients who showed that although total cholesterol and low-density lipoprotein (LDL) cholesterol increased over the first 3 months of MAD treatment, these values normalized within 1 year of treatment, including in patients treated with MAD for more than 3 years.
 

Primary Diet Recommendation

This news organization asked one of the authors of that study, Mackenzie C. Cervenka, MD, professor of neurology and medical director of the Adult Epilepsy Diet Center, Johns Hopkins Hospital, Baltimore, Maryland, to comment on the new research.

She said that she was “thrilled” to see more evidence showing that this diet therapy can be as effective for adults as for children. “This is a really important message to get out there.”

At her adult epilepsy diet center, the MAD is the “primary” diet recommended for patients who are resistant to seizure medication, not tube fed, and are keen to try diet therapy, said Dr. Cervenka.

In her experience, the likelihood of having a 50% or greater seizure reduction is about 40% among medication-resistant patients, “so very similar to what they reported in that review,” she said.

However, she noted that she emphasizes to patients that “diet therapy is not meant to be monotherapy.”

Dr. Cervenka’s team is examining LDL cholesterol levels as well as LDL particle size in adults who have been on the MAD for 2 years. LDL particle size, she noted, is a better predictor of long-term cardiovascular health. 

No conflicts of interest were reported.
 

A version of this article appeared on Medscape.com.