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Arterial Stiffness May Predict Risk for Glaucoma
TOPLINE:
Arterial stiffness increases the risk for developing glaucoma, a new study found.
METHODOLOGY:
- To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
- They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
- The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.
TAKEAWAY:
- Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
- Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
- The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).
IN PRACTICE:
“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.
SOURCE:
This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.
LIMITATIONS:
The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.
DISCLOSURES:
The study did not receive any funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Arterial stiffness increases the risk for developing glaucoma, a new study found.
METHODOLOGY:
- To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
- They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
- The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.
TAKEAWAY:
- Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
- Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
- The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).
IN PRACTICE:
“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.
SOURCE:
This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.
LIMITATIONS:
The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.
DISCLOSURES:
The study did not receive any funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Arterial stiffness increases the risk for developing glaucoma, a new study found.
METHODOLOGY:
- To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
- They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
- The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.
TAKEAWAY:
- Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
- Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
- The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).
IN PRACTICE:
“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.
SOURCE:
This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.
LIMITATIONS:
The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.
DISCLOSURES:
The study did not receive any funding. The authors declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Calcium and CV Risk: Are Supplements and Vitamin D to Blame?
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff.
Matthew J. Budoff, MD: Thank you.
Dietary Calcium vs Coronary Calcium
Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?
Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease.
As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on.
Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods?
Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
Does Vitamin D Exacerbate Risk?
Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?
Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.
Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk.
Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews.
Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system.
Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic.
Ms. Ward: With the vitamin D?
Dr. Budoff: With the vitamin D.
Diabetes and Renal Function
Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?
Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression.
We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes.
Avoid Supratherapeutic Vitamin D Levels
Ms. Ward:: What are you telling your patients?
Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements.
I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe.
Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?
Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast.
For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place.
Ms. Ward: Is there anything else you want to add?
Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation.
Ms. Ward: Thank you very much for joining me today.
Dr. Budoff: It’s a pleasure. Thanks for having me.
Dr. Budoff disclosed being a speaker for Amarin Pharma.
A version of this article appeared on Medscape.com.
Another Reason to Control Lp(a): To Protect the Kidneys Too
LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.
There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.
Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).
“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).
Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes.
The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.
The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.
Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
Lp(a) and Chronic Kidney Disease
When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.
Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.
Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.
The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.
The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.
A version of this article appeared on Medscape.com.
LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.
There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.
Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).
“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).
Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes.
The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.
The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.
Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
Lp(a) and Chronic Kidney Disease
When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.
Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.
Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.
The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.
The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.
A version of this article appeared on Medscape.com.
LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.
There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.
Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).
“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).
Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes.
The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.
The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.
Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
Lp(a) and Chronic Kidney Disease
When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.
Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.
Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.
The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.
The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.
A version of this article appeared on Medscape.com.
Colchicine: A New Tool for Ischemic Stroke, CVD Event Recurrence?
BASEL, SWITZERLAND — However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.
“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.
The results were presented at the European Stroke Organization Conference (ESOC) 2024.
Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.
Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.
The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.
Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.
Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.
The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.
Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.
Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.
In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
A Novel Target for Stroke Treatment
In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.
In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).
“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.
He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.
“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.
Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.
“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.
“I think we have a new tool, but of course we need further trials to confirm that,” she added.
The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
BASEL, SWITZERLAND — However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.
“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.
The results were presented at the European Stroke Organization Conference (ESOC) 2024.
Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.
Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.
The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.
Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.
Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.
The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.
Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.
Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.
In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
A Novel Target for Stroke Treatment
In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.
In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).
“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.
He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.
“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.
Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.
“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.
“I think we have a new tool, but of course we need further trials to confirm that,” she added.
The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
BASEL, SWITZERLAND — However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.
“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.
The results were presented at the European Stroke Organization Conference (ESOC) 2024.
Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.
Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.
The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.
Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.
Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.
The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.
Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.
Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.
In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
A Novel Target for Stroke Treatment
In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.
In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).
“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.
He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.
“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.
Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.
“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.
“I think we have a new tool, but of course we need further trials to confirm that,” she added.
The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ESOC 2024
Counting Steps or Watching the Clock for a Longer Life?
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.
“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
The 10,000-Step Recommendation
However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.
The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.
The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
Risk Reduction With Both Parameters
Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.
Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.
Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.
For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
More Ways to Reach the Goal
Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”
For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.
“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
This story was translated from Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Gene Tests Could Predict if a Drug Will Work for a Patient
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
What if there were tests that could tell you whether the following drugs were a good match for your patients: Antidepressants, statins, painkillers, anticlotting medicines, chemotherapy agents, HIV treatments, organ transplant antirejection drugs, proton pump inhibitors for heartburn, and more?
That’s quite a list. And that’s pharmacogenetics, testing patients for genetic differences that affect how well a given drug will work for them and what kind of side effects to expect.
“About 9 out of 10 people will have a genetic difference in their DNA that can impact how they respond to common medications,” said Emily J. Cicali, PharmD, a clinical associate at the University of Florida College of Pharmacy, Gainesville.
Dr. Cicali is the clinical director of UF Health’s MyRx, a virtual program that gives Florida and New Jersey residents access to pharmacogenetic (PGx) tests plus expert interpretation by the health system’s pharmacists. Genetic factors are thought to contribute to about 25% or more of inappropriate drug responses or adverse events, said Kristin Wiisanen, PharmD, dean of the College of Pharmacy at Rosalind Franklin University of Medicine and Science in North Chicago.
Dr. Cicali said.
Through a cheek swab or blood sample, the MyRx program — and a growing number of health system programs, doctors’ offices, and home tests available across the United States — gives consumers a window on inherited gene variants that can affect how their body activates, metabolizes, and clears away medications from a long list of widely used drugs.
Why PGx Tests Can Have a Big Impact
These tests work by looking for genes that control drug metabolism.
“You have several different drug-metabolizing enzymes in your liver,” Dr. Cicali explained. “Pharmacogenetic tests look for gene variants that encode for these enzymes. If you’re an ultrarapid metabolizer, you have more of the enzymes that metabolize certain drugs, and there could be a risk the drug won’t work well because it doesn’t stay in the body long enough. On the other end of the spectrum, poor metabolizers have low levels of enzymes that affect certain drugs, so the drugs hang around longer and cause side effects.”
While pharmacogenetics is still considered an emerging science, it’s becoming more mainstream as test prices drop, insurance coverage expands, and an explosion of new research boosts understanding of gene-drug interactions, Dr. Wiisanen said.
Politicians are trying to extend its reach, too. The Right Drug Dose Now Act of 2024, introduced in Congress in late March, aims to accelerate the use of PGx by boosting public awareness and by inserting PGx test results into consumers’ electronic health records. (Though a similar bill died in a US House subcommittee in 2023.)
“The use of pharmacogenetic data to guide prescribing is growing rapidly,” Dr. Wiisanen said. “It’s becoming a routine part of drug therapy for many medications.”
What the Research Shows
When researchers sequenced the DNA of more than 10,000 Mayo Clinic patients, they made a discovery that might surprise many Americans: Gene variants that affect the effectiveness and safety of widely used drugs are not rare glitches. More than 99% of study participants had at least one. And 79% had three or more.
The Mayo-Baylor RIGHT 10K Study — one of the largest PGx studies ever conducted in the United States — looked at 77 gene variants, most involved with drug metabolism in the liver. Researchers focused closely on 13 with extensively studied, gene-based prescribing recommendations for 21 drugs including antidepressants, statins, pain killers, anticlotting medications for heart conditions, HIV treatments, chemotherapy agents, and antirejection drugs for organ transplants.
When researchers added participants’ genetic data to their electronic health records, they also sent semi-urgent alerts, which are alerts with the potential for severe harm, to the clinicians of 61 study volunteers. Over half changed patients’ drugs or doses.
The changes made a difference. One participant taking the pain drug tramadol turned out to be a poor metabolizer and was having dizzy spells because blood levels of the drug stayed high for long periods. Stopping tramadol stopped the dizziness. A participant taking escitalopram plus bupropion for major depression found out that the combo was likely ineffective because they metabolized escitalopram rapidly. A switch to a higher dose of bupropion alone put their depression into full remission.
“So many factors play into how you respond to medications,” said Mayo Clinic pharmacogenomics pharmacist Jessica Wright, PharmD, BCACP, one of the study authors. “Genetics is one of those pieces. Pharmacogenetic testing can reveal things that clinicians may not have been aware of or could help explain a patient’s exaggerated side effect.”
Pharmacogenetics is also called pharmacogenomics. The terms are often used interchangeably, even among PGx pharmacists, though the first refers to how individual genes influence drug response and the second to the effects of multiple genes, said Kelly E. Caudle, PharmD, PhD, an associate member of the Department of Pharmacy and Pharmaceutical Sciences at St. Jude Children’s Research Hospital in Memphis, Tennessee. Dr. Caudle is also co-principal investigator and director of the National Institutes of Health (NIH)-funded Clinical Pharmacogenetics Implementation Consortium (CPIC). The group creates, publishes, and posts evidence-based clinical practice guidelines for drugs with well-researched PGx influences.
By any name, PGx may help explain, predict, and sidestep unpredictable responses to a variety of drugs:
- In a 2023 multicenter study of 6944 people from seven European countries in The Lancet, those given customized drug treatments based on a 12-gene PGx panel had 30% fewer side effects than those who didn’t get this personalized prescribing. People in the study were being treated for cancer, heart disease, and mental health issues, among other conditions.
- In a 2023 from China’s Tongji University, Shanghai, of 650 survivors of strokes and transient ischemic attacks, those whose antiplatelet drugs (such as clopidogrel) were customized based on PGx testing had a lower risk for stroke and other vascular events in the next 90 days. The study was published in Frontiers in Pharmacology.
- In a University of Pennsylvania of 1944 adults with major depression, published in the Journal of the American Medical Association, those whose antidepressants were guided by PGx test results were 28% more likely to go into remission during the first 24 weeks of treatment than those in a control group. But by 24 weeks, equal numbers were in remission. A 2023 Chinese of 11 depression studies, published in BMC Psychiatry, came to a similar conclusion: PGx-guided antidepressant prescriptions may help people feel better quicker, perhaps by avoiding some of the usual trial-and-error of different depression drugs.
PGx checks are already strongly recommended or considered routine before some medications are prescribed. These include abacavir (Ziagen), an antiviral treatment for HIV that can have severe side effects in people with one gene variant.
The US Food and Drug Administration (FDA) recommends genetic testing for people with colon cancer before starting the drug irinotecan (Camptosar), which can cause severe diarrhea and raise infection risk in people with a gene variant that slows the drug’s elimination from the body.
Genetic testing is also recommended by the FDA for people with acute lymphoblastic leukemia before receiving the chemotherapy drug mercaptopurine (Purinethol) because a gene variant that affects drug processing can trigger serious side effects and raise the risk for infection at standard dosages.
“One of the key benefits of pharmacogenomic testing is in preventing adverse drug reactions,” Dr. Wiisanen said. “Testing of the thiopurine methyltransferase enzyme to guide dosing with 6-mercaptopurine or azathioprine can help prevent myelosuppression, a serious adverse drug reaction caused by lower production of blood cells in bone marrow.”
When, Why, and How to Test
“A family doctor should consider a PGx test if a patient is planning on taking a medication for which there is a CPIC guideline with a dosing recommendation,” said Teri Klein, PhD, professor of biomedical data science at Stanford University in California, and principal investigator at PharmGKB, an online resource funded by the NIH that provides information for healthcare practitioners, researchers, and consumers about PGx. Affiliated with CPIC, it’s based at Stanford University.
You might also consider it for patients already on a drug who are “not responding or experiencing side effects,” Dr. Caudle said.
Here’s how four PGx experts suggest consumers and physicians approach this option.
Find a Test
More than a dozen PGx tests are on the market — some only a provider can order, others a consumer can order after a review by their provider or by a provider from the testing company. Some of the tests (using saliva) may be administered at home, while blood tests are done in a doctor’s office or laboratory. Companies that offer the tests include ARUP Laboratories, Genomind, Labcorp, Mayo Clinic Laboratories, Myriad Neuroscience, Precision Sciences Inc., Tempus, and OneOme, but there are many others online. (Keep in mind that many laboratories offer “lab-developed tests” — created for use in a single laboratory — but these can be harder to verify. “The FDA regulates pharmacogenomic testing in laboratories,” Dr. Wiisanen said, “but many of the regulatory parameters are still being defined.”)
Because PGx is so new, there is no official list of recommended tests. So you’ll have to do a little homework. You can check that the laboratory is accredited by searching for it in the NIH Genetic Testing Laboratory Registry database. Beyond that, you’ll have to consult other evidence-based resources to confirm that the drug you’re interested in has research-backed data about specific gene variants (alleles) that affect metabolism as well as research-based clinical guidelines for using PGx results to make prescribing decisions.
The CPIC’s guidelines include dosing and alternate drug recommendations for more than 100 antidepressants, chemotherapy drugs, the antiplatelet and anticlotting drugs clopidogrel and warfarin, local anesthetics, antivirals and antibacterials, pain killers and anti-inflammatory drugs, and some cholesterol-lowering statins such as lovastatin and fluvastatin.
For help figuring out if a test looks for the right gene variants, Dr. Caudle and Dr. Wright recommended checking with the Association for Molecular Pathology’s website. The group published a brief list of best practices for pharmacogenomic testing in 2019. And it keeps a list of gene variants (alleles) that should be included in tests. Clinical guidelines from the CPIC and other groups, available on PharmGKB’s website, also list gene variants that affect the metabolism of the drug.
Consider Cost
The price tag for a test is typically several hundred dollars — but it can run as high as $1000-$2500. And health insurance doesn’t always pick up the tab.
In a 2023 University of Florida study of more than 1000 insurance claims for PGx testing, the number reimbursed varied from 72% for a pain diagnosis to 52% for cardiology to 46% for psychiatry.
Medicare covers some PGx testing when a consumer and their providers meet certain criteria, including whether a drug being considered has a significant gene-drug interaction. California’s Medi-Cal health insurance program covers PGx as do Medicaid programs in some states, including Arkansas and Rhode Island. You can find state-by-state coverage information on the Genetics Policy Hub’s website.
Understand the Results
As more insurers cover PGx, Dr. Klein and Dr. Wiisanen say the field will grow and more providers will use it to inform prescribing. But some health systems aren’t waiting.
In addition to UF Health’s MyRx, PGx is part of personalized medicine programs at the University of Pennsylvania in Philadelphia, Endeavor Health in Chicago, the Mayo Clinic, the University of California, San Francisco, Sanford Health in Sioux Falls, South Dakota, and St. Jude Children’s Research Hospital in Memphis, Tennessee.
Beyond testing, they offer a very useful service: A consult with a pharmacogenetics pharmacist to review the results and explain what they mean for a consumer’s current and future medications.
Physicians and curious consumers can also consult CPIC’s guidelines, which give recommendations about how to interpret the results of a PGx test, said Dr. Klein, a co-principal investigator at CPIC. CPIC has a grading system for both the evidence that supports the recommendation (high, moderate, or weak) and the recommendation itself (strong, moderate, or optional).
Currently, labeling for 456 prescription drugs sold in the United States includes some type of PGx information, according to the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling and an annotated guide from PharmGKB.
Just 108 drug labels currently tell doctors and patients what to do with the information — such as requiring or suggesting testing or offering prescribing recommendations, according to PharmGKB. In contrast, PharmGKB’s online resources include evidence-based clinical guidelines for 201 drugs from CPIC and from professional PGx societies in the Netherlands, Canada, France, and elsewhere.
Consumers and physicians can also look for a pharmacist with pharmacogenetics training in their area or through a nearby medical center to learn more, Dr. Wright suggested. And while consumers can test without working with their own physician, the experts advise against it. Don’t stop or change the dose of medications you already take on your own, they say . And do work with your primary care practitioner or specialist to get tested and understand how the results fit into the bigger picture of how your body responds to your medications.
A version of this article appeared on Medscape.com.
Roche Blood Test for Lp(a) Designated Breakthrough Device
The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development.
Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.
Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.
Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test.
If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.
Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.
There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development.
One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.
Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.
Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
A version of this article appeared on Medscape.com.
The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development.
Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.
Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.
Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test.
If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.
Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.
There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development.
One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.
Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.
Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
A version of this article appeared on Medscape.com.
The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development.
Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.
Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.
Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test.
If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.
Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.
There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development.
One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.
Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.
Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
A version of this article appeared on Medscape.com.
Right heart catheterization practice patterns in pulmonary hypertension in the US
PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK
Pulmonary Vascular Disease Section
While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.
A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.2 Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.
About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.
This study provides the largest reported data on real-world RHC practices by PH physicians in the US. We found significant variability in hemodynamic interpretation. Standardization of RHC performance and hemodynamic evaluation is crucial to ensure appropriate PH management.
– Abubakr A. Bajwa, MBBS, FCCP
Member-at-Large
– Samantha Pettigrew, MD
Fellow-in-Training
– Francisco J. Soto, MD, MS, FCCP
Section Vice Chair
References
1. Simonneau et al. Eur Resp J. 2019;53(1):1801913
2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834
PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK
Pulmonary Vascular Disease Section
While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.
A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.2 Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.
About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.
This study provides the largest reported data on real-world RHC practices by PH physicians in the US. We found significant variability in hemodynamic interpretation. Standardization of RHC performance and hemodynamic evaluation is crucial to ensure appropriate PH management.
– Abubakr A. Bajwa, MBBS, FCCP
Member-at-Large
– Samantha Pettigrew, MD
Fellow-in-Training
– Francisco J. Soto, MD, MS, FCCP
Section Vice Chair
References
1. Simonneau et al. Eur Resp J. 2019;53(1):1801913
2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834
PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK
Pulmonary Vascular Disease Section
While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.
A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.2 Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.
About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.
This study provides the largest reported data on real-world RHC practices by PH physicians in the US. We found significant variability in hemodynamic interpretation. Standardization of RHC performance and hemodynamic evaluation is crucial to ensure appropriate PH management.
– Abubakr A. Bajwa, MBBS, FCCP
Member-at-Large
– Samantha Pettigrew, MD
Fellow-in-Training
– Francisco J. Soto, MD, MS, FCCP
Section Vice Chair
References
1. Simonneau et al. Eur Resp J. 2019;53(1):1801913
2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834
Risk Screening Tool Helped Identify Pregnant Patients Previously Undiagnosed With CVD
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
FROM ACOG 2024
Statins Show ‘Remarkable’ CVD Benefit in Oldest Patients
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE