Evolving Strategies for Cholesterol Management and Atherosclerotic Cardiovascular Disease Risk Reduction - Episode 2

Risk Enhancing Factors in ASCVD

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A panel of experts comments on the importance of risk assessment in ASCVD as well as factors that contribute to risks.

Erin D. Michos, MD, MHS, FACC, FASPC: Diabetes and kidney disease are not the only risk-enhancing factors, there are other ones that may have been underappreciated until recent times. Dr Bailey was a coauthor on the ACC/AHA [American College of Cardiology/American Heart Association] cholesterol guidelines. An important addition to the guidelines is the emphasis on risk-enhancing factors if present, put someone into a higher cardiovascular risk category they might be considering about statins and primary prevention. Maybe you can discuss a little more about these risk enhancers?

Alison Bailey, MD, FACC: Yes, thank you so much, Erin. When assessing any patient when we first look at them, we think of primary prevention or secondary prevention. In our primary prevention cohort, we know there are different groups of patients who are at higher risk that we can’t quite put our finger on. That’s one of the things we wanted to come up with in the guidelines. Obviously, we do pooled cohort equations, 10-year risk for everyone over age 40, but then we talk about these risk-enhancing factors. The risk-enhancing factors include premature atherosclerotic disease in the family, primary hypercholesterolemia that doesn’t quite meet that 190 mg/dL LDL [low-density lipoprotein] threshold, metabolic syndrome or that conglomeration of factors that was just mentioned, chronic kidney disease, chronic inflammatory conditions such as lupus, rheumatoid arthritis, HIV. Then for the first time, we talked about conditions specific to women, so adverse pregnancy outcomes or preeclampsia, premature menopause. Then high-risk ethnicity, specifically South Asians. Also abnormal lipids; we all know that lipoprotein(a) increases risk, but exactly how much, and which individuals, and things like persistently elevated triglycerides. It’s important that we think about that.

Then in our secondary prevention cohort, we need to think about that very high-risk patient, or that just plain old high-risk patient. The very high-risk patient is one who has multiple major ASCVD [atherosclerotic cardiovascular disease] risk events, something such as an acute coronary syndrome, prior heart attack, peripheral arterial disease, and ischemic stroke. Two of those will get you into that category. Or if you have one of those along with some other high-risk features, like age over 65, diabetes, hyperlipidemia, hypertension, chronic kidney disease, you’re a current smoker, or persistently elevated LDL or triglycerides, or history of heart failure. All of those things should help us amplify the risk and be even more aggressive. One other point I wanted to make that ties back to what Pam was saying, when I see a primary prevention patient coming into the clinic, I always look at their prior imaging. Because now we have the opportunity to see lots of calcium or plaque in the aorta or in the coronaries that maybe somebody didn’t mention on the CTPA [CT pulmonary angiography] protocol they had in the ED [emergency department]. That also makes me be a little more aggressive, although not quite in these guidelines.

Jorge Plutzky, MD: One of the things about risk-enhancing factors that I find so important in practice is that we have so much evidence, but it’s usually broadly applied. To wait for a trial in each of these areas, and hopefully that will come, and we’ll have those data and get that insight. But being able to leverage what we know about what may be enhancing risk allows you, in an appropriate way, to apply more aggressive strategies to someone who has more risk, and not say I need to wait for a trial showing a very specific condition or scenario that there’s benefit. There’s so much evidence for benefit through modifying risk factors, in particular LDL.

Erin D. Michos, MD, MHS, FACC, FASPC: We’ve been having a great discussion about risk assessment. This is an important consideration because we’re going to move into our next session soon talking about LDL lowering. But the intensity of LDL lowering depends on the recommendations based on the absolute risk of the patient, for higher risk patients we recommend even more intensive LDL lowering. Risk assessment is not only in primary prevention with those factors that Dr Bailey mentioned that are considered after you estimate risk with something like the pooled cohort equations. Also, as you mentioned in secondary prevention, there are tiers of secondary prevention with certain patients being at very high risk who need the most aggressive LDL lowering. Does anyone else have any other comments about risk assessment?

Jorge Plutzky, MD: I think we have a lot more tools. I agree completely with the comment about looking for calcification. How often do you go back and see someone who’s had prior imaging in their abdomen, and they have a calcification in their aorta and it’s possible to say, “Well, I‘m done now.” I think there are a lot of patients we miss by not thinking about additional ways to consider, like what does it mean to have a prior history of cigarette smoking, or even exposure to passive cigarette smoke? We have a lot of new mechanisms that may contribute to that, epigenetic and otherwise. The deeper dive into assessing risk, especially in the challenging situation where someone hasn’t had an event, that’s where there’s such a potential for an upside. Thinking about prediabetes is something we’re moving toward; we were just talking about that. There’s an artificiality to say you need to cross a certain A1C [glycated hemoglobin] level where I’m going to label you as having diabetes, but we know those drivers for atherosclerosis are already there. That combines with the risk-enhancing factors and what we already know about what is not just a targeted LDL, but an optimal LDL. I think it reshapes that focus and it is a message that we really have to get, I think not just our cardiology colleagues, endocrinology colleagues are paying attention, but also the internists and primary care physicians. To have them really thinking that this is the real opportunity to keep an event from happening subsequently and changing someone’s life by having them undergo either an event, sometimes catastrophic, or an intervention, which still really changes things.

Erin D. Michos, MD, MHS, FACC, FASPC: We’re going to talk a little more about coronary calcium scores in a later segment, but I just want to echo that because it’s something we do a lot of in our program. Including in the guidelines, the guidelines say that even after you estimate the pooled cohort equations and consider these risk-enhancing factors, there can still be uncertainty about a patient’s risk. A coronary calcium score, now with a 2A indication, can be considered to help refine risk estimation and guide shared decision-making around statin therapy. Also, potentially nonstatin therapy, which we’re going to talk more about. In fact, the NLA [National Lipid Association] recently released a coronary calcium statement, where they indicated that for very high calcium score, such as above 300, these individuals have a risk similar to a stable secondary prevention patient, where you’d want to consider a similar degree of intensity of LDL lowering, getting the LDL to a greater than 50% reduction from baseline. As well as trying to achieve a threshold of less than 70 mg/dL, and if that cannot be achieved with statin therapy, then consider the role of nonstatins for these individuals.

Transcript edited for clarity