Cardiology News

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.

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.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. 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 — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. 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 — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. 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.

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.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

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.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” 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.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” 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.

“Pharmacogenetics helps consumers avoid drugs that may not work well for them or could cause serious adverse events. It’s personalized medicine,” 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.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

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.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

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.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

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.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with axial spondyloarthritis (axSpA) who reported high nonsteroidal anti-inflammatory drug (NSAID) use did not have a higher risk for hypertension than those who reported low NSAID use.

METHODOLOGY:

• NSAIDs are first-line therapy for axSpA and are associated with a high risk for hypertension in the general population, but it’s unknown whether NSAID use increases the risk for hypertension in patients with axSpA, who are already at higher risk for cardiovascular disease and hypertension than the general population
• This study used the DESIR cohort, a multicenter cohort of patients with recent-onset axSpA in France, including 631 individuals aged 18-50 years who did not have hypertension at baseline and had 6 years of follow-up.
• NSAID use was evaluated at each follow-up visit, using the Assessment of Spondyloarthritis International Society NSAID index.
• A score ≥ 50 was categorized as high use, and a score < 50 was considered low use.
• The primary outcome was hypertension, defined by the use of antihypertensive medication, self-reported hypertension, and/or systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on at least two visits.

TAKEAWAY:

• A total of 39% of patients were categorized as high NSAID users.
• Over 6 years of follow-up, 70 patients (11%) developed hypertension.
• There was no significant association between high NSAID use and the risk for hypertension.

IN PRACTICE:

The study is too preliminary to have practice application.

SOURCE:

The research was led and presented by Jose Meade-Aguilar, MD, of Boston University School of Medicine, at the Spondyloarthritis Research and Treatment Network (SPARTAN) 2024 annual meeting in Cleveland.

LIMITATIONS:

The study had a low number of hypertension events, which could be due to the younger age of participants and earlier disease stage. The study was observational, so residual or unmeasured confounding is possible.

DISCLOSURES:

The DESIR cohort study is financially supported by unrestricted grants from both the French Society for Rheumatology and Pfizer France. One coauthor reported receiving research grants and/or consultancy fees from AbbVie, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, UCB, and Sanofi. Another coauthor reported receiving research grants from UCB and consulting fees from Eli Lilly, Novartis, Pfizer, and UCB. The remaining authors had no financial, relational, or commercial conflicts to disclose.
 

A version of this article appeared on Medscape.com.

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.

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .

Welcome everyone. I’m Dr. John White. I’m the chief medical officer at WebMD. Does your biologic sex impact your health? Does it have any play in how you’re diagnosed, how you’re treated in terms of what symptoms you have? Of course it does. We all know that. But that’s not something that many people believed 5, 10 years ago, certainly not 20 years ago. And it was only because of leaders like my guest today, Phyllis Greenberger, who really championed the need for research on women’s health. She has a new book out, which I love. It’s called Sex Cells: the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Please welcome my very good friend, Phyllis Greenberger.

Thank you.

Phyllis, It’s great to see you today.

It’s great to see you as well.

Now, you and I have been talking about this for easily 2 decades.

At least.

And some people think, oh, of course it makes sense. Although I saw you disagreeing that not everyone still believes that. But what has been that journey? Why has it been so hard to make people understand, as you point out early on in your book, women are not smaller men?

I think the basic reason was that it was just believed that men and women were the same except for their reproductive organs. So minus the reproductive organs, whether it was a device, a diagnostic, or therapeutic, if it was used and successful on a male, that it would be successful on a female. We’re really very far from understanding the differences, and there’s still a lot of distrust and disbelief and ignorance about it. And so there’s still a long way to go.

But you talk about that in the book, that there’s still a long way to go. Why is that? What’s the biggest obstacle? Is it just misinformation, lack of information? People don’t understand the science? There’s still resistance in some areas. Why is that?

I think it’s misinformation, and I gave a presentation, I don’t know how many years ago, at least 20 years ago, about the curriculum. And at the time, there was no women’s health in the curriculum. It was health. So if it was on cardiovascular issues or on osteoporosis, it was sort of the basic. And at the time, there would maybe be one woman whose job was women’s health, and she’d have an office, and otherwise there was nothing. And maybe they talked about breast cancer, who knows. But I spoke to someone just the other day, in view of all the attention that the book is getting now, whether that’s changed, whether it’s necessary and required. And she said it’s not. So, it’s not necessarily on the curriculum of all research and medical institutions, and even if women’s health, quote unquote, is on the curriculum, it doesn’t mean that they’re really looking at sex differences. And the difference is obvious. I mean, gender is really, it’s a social construct, but biological sex is how disease occurs and develops. And so if you’re not looking, and because there’s so little research now on sex differences that I don’t even know, I mean, how much you could actually teach.

So what needs to change? This book is a manifesto in many ways in how we need to include women; we need to make research more inclusive of everyone. But we’re not there yet. So what needs to change, Phyllis?

During this whole saga of trying to get people to listen to me and to the society, we really started out just looking at clinical trials and that, as you mentioned, I mean, there are issues in rural communities. There’s travel issues for women and child care. There’s a lot of disbelief or fear of clinical trials in some ethnicities. I do think, going to the future, that technology can help that. I mean, if people have broadband, which of course is also an issue in rural areas.

What could women do today? What should women listeners hear and then be doing? Should they be saying something to their doctor? Should they be asking specific questions? When they interact with the health care system, how can they make sure they’re getting the best care that’s appropriate for them when we know that sex cells matter?

Well, that’s a good question. It depends on, frankly, if your doctor is aware of this, if he or she has learned anything about this in school, which, I had already said, we’re not sure about that because research is still ongoing and there’s so much we don’t know. So I mean, you used to think, or I used to think, that you go to, you want a physician who’s older and more experienced. But now I think you should be going to a physician who’s younger and hopefully has learned about this, because the physicians that were educated years ago and have been practicing for 20, 30 years, I don’t know how much they know about this, whether they’re even aware of it.

Phyllis, you are a woman of action. You’ve lived in the DC area. You have championed legislative reforms, executive agendas. What do you want done now? What needs to be changed today? The curriculum is going to take time, but what else needs to change?

That’s a good question. I mean, if curriculum is going to take a while and you can ask your doctor if he prescribes the medication, whether it’s been tested on women, but then if it hasn’t been tested on women, but it’s the only thing that there is for your condition, I mean, so it’s very difficult. The Biden administration, as you know, just allocated a hundred million dollars for women’s health research.

What do you hope to accomplish with this book?

Well, what I’m hoping is that I spoke to someone at AMWA and I’m hoping — and AMWA is an association for women medical students. And I’m hoping that’s the audience. The audience needs to be. I mean, obviously everybody that I know that’s not a doctor that’s read it, found it fascinating and didn’t know a lot of the stuff that was in it. So I think it’s an interesting book anyway, and I think women should be aware of it. But really I think it needs to be for medical students.

And to your credit, you built the Society for Women’s Health Research into a powerful force in Washington under your tenure in really promoting the need for Office of Women’s Health and Research in general. The book is entitled Sex Cells, the Fight to Overcome Bias and Discrimination in Women’s Healthcare. Phyllis Greenberger, thank you so much for all that you’ve done for women’s health, for women’s research. We wouldn’t be where we are today if it wasn’t for you. So thanks.

Thank you very much, John. Thank you. I appreciate the opportunity.

Dr. Whyte, is chief medical officer, WebMD, New York, NY. He has disclosed no relevant financial relationships. Ms. Greenberger is a women’s health advocate and author of “Sex Cells: The Fight to Overcome Bias and Discrimination in Women’s Healthcare”

This interview originally appeared on WebMD on May 23, 2024. A version of this article appeared on Medscape.com .