Scott Webb (Host): Welcome to Addressing Treatment Disparities to Reduce Risk and Improve Cardiovascular Outcomes Among Women and People from Various Racial and Ethnic Groups, a Spotlight on LDL-C Lowering. I'm Scott Webb, and I'm joined today by two esteemed faculty members. I'm joined by Dr. Deepak L. Bhatt, Director of the Mount Sinai Fuster Heart Hospital, and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine in New York. I'm also joined by Dr. Kevin C. Maki, President and Chief Scientist at Midwest Biomedical Research in Addison, Illinois, Adjunct Professor and Dean's Eminent Scholar at the Indiana University School of Public Health in Bloomington, Indiana, and Co-Editor in Chief for the Journal of Clinical Lipidology. For full relevant financial disclosure information, please see iridiumce.com/lipidsinwomen.

This educational activity is supported by an independent educational grant from Aspirian. We want to thank them for their support for this initiative. Learning objectives for this program are to identify factors contributing to the risk of atherosclerotic cardiovascular disease, ASCVD, in women and people from various racial and ethnic groups, and describe reasons for lower rates of hypocholesterolemia treatment and control in women and people from various racial and ethnic groups.

Dr. Maki, I'm going to start with you. I want to have you start off our discussion by describing the trends for CVD incidents and mortality in the United States.

Kevin Maki, PhD: Thank you. It's a pleasure to be here and I wish I were able to give better news. When it comes to cardiovascular disease mortality, for years, I used to show a slide that indicated that cardiovascular disease mortality was declining. From the 1970s on, we saw this steady decline. But recently, starting in about 2015, that trend has reversed in both men and women. And we see cardiovascular disease mortality heading in the wrong direction. There are probably a number of contributing factors, increased obesity, type 2 diabetes. But one factor that I think is especially important is inadequate management of LDL cholesterol. And there are a variety of reasons that that is the case. But we have very good evidence from randomized controlled trials, also from studies of genetic variants that influence LDL cholesterol levels, that when it comes to LDL cholesterol, lower for longer is better for preventing cardiovascular disease and its outcomes like heart attacks and strokes.

But when we look at large healthcare systems, for instance, in one recent survey of more than 600,000 patients With known cardiovascular disease, what we saw is that only about half were taking a statin. And the cornerstone of managing elevated LDL cholesterol is lifestyle and statin therapy. We have other tools in the toolbox available. They're not being used as often as they should. And so we're seeing high rates of inadequate control of LDL cholesterol. And that's true in people with known cardiovascular disease. And it's also true when it comes to primary prevention. What we see is that among people with high enough estimated risk to qualify for statin therapy, in all major groups, fewer than half are receiving statin therapy. And when we look at some subgroups like African Americans and Hispanic Latino Americans, the situation's even worse with fewer than a quarter of those who qualify for statin therapy actually receiving it. So, there's a lot of work to do in order to have better identification and management of increased cardiovascular risk related to elevated LDL cholesterol.

Host: Dr. Bhatt, Dr. Maki provided a good foundation for how uncontrolled hypercholesterolemia contributes to ASCVD risk. So, what are the factors that contribute to the risk of ASCVD that are specific to women?

Deepak Bhatt, MD: It's a great question and part of it, I think, is lack of physician and nurse and patient awareness of this increased risk of atherosclerotic cardiovascular disease in women. I do think there's been some progress that's been made over the past couple of decades along those lines, but still a ways to go. And that sometimes can tie into a lack of urgency as well. For example, when a woman's presenting to the emergency department with a potential acute coronary syndrome, there's also, in general, a misperception of a higher risk of cancers, especially breast cancer versus cardiovascular disease, and that's not to say breast cancer isn't important. Of course, it's important. Screening for it appropriately with mammography and so forth, very important and evidence-based. But in terms of the numbers, cardiovascular disease remains the leading killer.

And another troublesome thing has been an increasing rate of myocardial infarction, especially among young women. It's true of young people in general. It's a bit perplexing exactly why that's happening. In young women specifically, part of it might be greater awareness of the possibilities of cardiovascular disease, even in that demographic. But I think part of it is actual increases, not just due to better detection or better awareness. So, we've got to sort out what's going there and maybe some of it is post-pandemic related, or hard to say. There were certainly some setbacks in preventive care that happened during the pandemic. It seemed to have persisted even post-pandemic. Maybe that has something to do with it, too.

It's also important to be aware of female-specific cardiovascular disease risk factors. Actually, some couple years ago, I'd written an editorial along with Anne Marie Valente and Abbi Lane-Cordova. We titled it Pregnancy is a Cardiac Stress Test: Time to Include Obstetric History in Cardiac Risk Assessment. This was published in the Journal of the American College of Cardiology, I think it was in 2020. And we listed there are a number of different sex-specific cardiovascular risk factors that were pertinent to women. Things like, well, probably everyone will know of this one, pre-eclampsia, but there are other things too. Just having a premature infant, for example, in fact, is associated with higher cardiovascular risk in the mother. Early menarche, something else to be aware of as a potential cardiovascular risk factor. Hormonal contraceptive use, I think lots of folks know of that association, especially the older generation versions with things like DVT and PE. Early menopause or premature ovarian failure, hormone replacement therapy, as well as a risk factor for certain cardiovascular diseases. So, some of these are known, I think, others are not so well appreciated, but in particular adverse pregnancy outcomes, such as preeclampsia, but even preterm or early term births, various hypertensive disorders in pregnancy, small for gestational age infants, gestational diabetes, all these things are associated with greater cardiovascular risk in the future for that woman. So, important to be aware of that and probably does make sense to take an obstetric history, even in someone that is past the childbearing years to assess for cardiovascular risk.

Host: Yeah. And Dr. Maki, what are some of the factors that contribute to the risk of ASCVD for people in various racial and ethnic groups?

Kevin Maki, PhD: Well, I think clinicians should be aware that prevalence of various risk factors differs across racial and ethnic subgroups. So, in people of South Asian ancestry, for instance, there's a higher prevalence of insulin resistance, central adiposity. In African Americans, you have an increased prevalence of hypertension and type 2 diabetes, and in Hispanic Latino Americans, and I should emphasize that all of these groups encompass, you know, large subsets. And so, I make general statements about large groups. But within those groups, there's a lot of variation, but clinicians should be aware of differences in risk factors. So in Hispanic, Latino Americans, high prevalence of type 2 diabetes, as an example. And so, the key element is to identify what is driving the risk in a particular patient or in a particular subgroup in the population, and then address those risk factors.

And for all of the subgroups, elevated LDL cholesterol is an important risk factor that we have lots of tools to manage now. But in addition, there are contributing factors like those with lower socioeconomic status or lower educational attainment may have limited access to affordable care. They may have difficulty navigating the healthcare system, and may live in unhealthy environments where they don't have safe and convenient places to exercise. They don't have access to affordable, healthy dietary options. And so, these are things that should be identified and addressed to the degree possible because, again, within all of these subgroups, cardiovascular disease is the leading cause of mortality.

Scott Webb (Host): Dr. Bhatt, what are your thoughts on how to address these various contributing factors for the increased ASCVD risk among women and people from various racial and ethnic groups?

Deepak Bhatt, MD: That's a tricky question. There's really a lot of different things one could consider. There are patient related factors, factors related to physicians and nurses, factors related to the health care system. So, part of the efforts could be trying to improve health literacy and risk factor awareness among patients, being aware of cultural norms that's something really that physicians and nurses should strive to do to make sure that risk assessment is optimal and that care is consistent for everybody. And the healthcare system, it's been discussed quite a bit how it's fragmented and there are various barriers to access to care. There's payer coverage issues, insurance issues, and all these sorts of factors contribute, I think, to some of these disparities in care. I think quality metrics can sometimes be useful to see if care is hopefully good and uniform across various demographic groups. So, I think those are all potential things that could be done.

An interesting analysis that came out of the AHA Get With The Guidelines program a few years ago was a mediation analysis. That's just some fancy statistics to see whether differences in care between men and women and among various racial and ethnic groups, you know, what was it actually due to? And the findings of that mediation analysis showed that a good chunk of the difference in outcomes between men and women could be at least theoretically abolished by just providing guideline concordant care in women to the same extent that it was being provided to men. So, in theory, that is an easy fix, that is just apply the professional society guidelines to the right patients irrespective of their sex. So, that was an encouraging, in some ways, part of the analysis.

But interestingly, that wasn't as true for racial and ethnic minorities. There wasn't just a matter of decreased guideline adherence and the implication being if you fix that, you can eliminate the disparity. There were other factors that we could characterize in that study that went beyond just less adherence to the guidelines, so probably a bit more complex really to tease out what was going on there with respect to disparities on the basis of race and ethnicity.

Host: Yeah. And Dr. Maki, can you describe some of the factors that contribute to lower rates of optimal hypercholesterolemia management in these patient populations?

Kevin Maki, PhD: Sure. I think there's a lack of Patient awareness about the importance of dyslipidemia management. And among clinicians, there's been a shift in the last 10 or 12 years away from goals for levels of LDL cholesterol and toward a focus more on whether or not someone is receiving statin therapy. And of course, statin therapy is one of the cornerstones of management. But in the intervening years, we've had more evidence develop for the efficacy of other lipid-lowering drug therapies and so, lifestyle, statin therapy, and then additional lipid-lowering therapies as needed. And we have lots of data from surveys and registries to show that most patients at high risk and very high risk are not achieving recommended levels of LDL cholesterol. And unlike hypertension and type 2 diabetes, where you very often see combination pharmacotherapy being used, you see that much less often in lipid management. So, these are some of the factors.

Also, you have the challenge of statin intolerance. We know that many patients report statin intolerance. We also have a good sense that much of what patients attribute to statin therapy is not truly statin intolerance, but muscle symptoms in particular are common. And so, if someone is taking a statin and has muscle aches and pains, they often attribute it to the statin. So, it's important for clinicians to understand that for people with statin intolerance, most can tolerate some degree of statin therapy. And then, other medications are available to act as an adjunct or as an alternative to statin therapy if the patient has statin intolerance and is not able to tolerate a sufficient amount of statin in order to reach the therapeutic objectives for LDL cholesterol.

And then, you have other issues, cultural and language barriers, and social determinants of health that are more challenging. And as Dr. Bhatt mentioned, that in racial and ethnic subgroups like African Americans, Hispanic, Latino Americans, there are probably additional factors that are contributing to increased risk. And some of those factors are things that the healthcare system isn't well equipped to really address. But no matter what is driving the risk, I think it's important to understand that maintaining a low level of LDL cholesterol will help reduce the risk, even if that isn't the primary driver of risk. So again, lower for longer is better when it comes to LDL cholesterol. I would like to defer to Dr. Bhatt to discuss some of the other issues, especially around women and cardiovascular risk and LDL cholesterol management.

Deepak Bhatt, MD: Yeah. I mean, I think you've given a really great summary of the situation. It's really tricky, I think, with respect to some of the reasons for undertreatment in women. I think that is a core issue, actual undertreatment, say, of elevated LDL cholesterol. So, that can sometimes be a lack of awareness on the part of the patient, could also be a lack of awareness on the part of the physician. So, it goes both ways there. Beyond just that sort of lack awareness in women, the same sort of thing is playing out at times in various racial and ethnic groups. And on top of that, there do appear to be increased rates of statin intolerance and other adverse events, particular in some racial and ethnic groups. And there can also be cultural and language barriers superimposed between the physician and the nurse or the patient. And you alluded to social determinants of health. These are increasingly recognized as playing a role in how patients do. I don't think many of us that went to medical school, when I went to medical school, really ever thought about social determinants of health. Certainly, those with a public health background might have been educated in that, but this is really referring to things like socioeconomic status, education, access to affordable care, and the ability to navigate the healthcare system, which can be really tough, even for people that are in the healthcare system. So, these different social determinants can really adversely affect health in general, but this is certainly pertinent to cardiovascular disease and cardiovascular prevention.

Kevin Maki, PhD: And maybe I'll add just one more item, and that is that clinicians are often hesitant to prescribe statin or other drug therapies for dyslipidemia to women of childbearing potential because they're concerned about the possibility of birth defects. And I think that it would be useful for clinicians to look up the FDA statement that came out a couple of years ago, with regard to the potential for birth defects in women who are taking statin therapy. And this is especially important for women with, for instance, familial hypercholesterolemia, who may be starting statin therapy earlier in life. And so, there's a balance between the removal of statin therapy if someone wants to try and get pregnant, for instance and then during pregnancy and breastfeeding, and the lifetime exposure to elevated levels of LDL cholesterol.

Host: Dr. Maki, as we get close to wrapping up here, focusing on the healthcare system standpoint more, what can be done to increase awareness of addressing risk factors in women and people from various racial and ethnic groups?

Kevin Maki, PhD: Well, one thing that was alluded to earlier is LDL cholesterol measurement and control as a quality metric for healthcare systems. Again, we've moved away from that after the 2013 guideline came out about cholesterol management. That was really focused on who qualifies for statin therapy. And since then, we've had a lot more evidence become available about the usefulness of other medications for LDL cholesterol lowering to reduce cardiovascular risk.

And so, I think the focus should really be on identifying those people with risk related to elevated LDL cholesterol, and then using the tools that are available to manage that risk, but then also having feedback with LDL cholesterol measurement and control as quality metrics. Right now, they are not in the formal quality metrics. And so, we hope to change that going forward so that clinicians and healthcare systems are getting graded essentially on how well they're managing LDL cholesterol, not just whether or not a patient is receiving statin therapy.

Host: And Dr. Bhatt, I'll give last word to you.

Deepak Bhatt, MD: Well, you know, the American Society of Preventive Cardiology and the National Lipid Association wrote a joint clinical perspective on the importance of low-density lipoprotein cholesterol measurement and control as performance measures, in which they outlined that lipid monitoring is essential for assessing lipid-lowering pharmacotherapy, and that the evidence favors LDL cholesterol measurement to improve population-wide lipid control.

Host: Well, excellent points by both of you. We've reached the end of this episode. I want to thank our esteemed faculty for this engaging discussion, and we'd also like to thank Aspirian for their support for this program. Be sure to claim your CME credit by filling out the evaluation and post-test. Don't miss the next episode in this two-part series. And be sure to follow Iridium on X, Facebook, and LinkedIn to see the corresponding MedEd threads.