Strategies Used to Treat Hypercholesterolemia

Dhiren Patel, PharmD, CDCES, BC-ADM, BCACP: Dr Bhatt, maybe before we dive into how we can play a role and what tools we have in our toolbox, walk us through the pathophysiology of hypercholesterolemia and cardiovascular disease to get us started.

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC: Yes, absolutely. This is really an important topic. I recall a time when there was some controversy around the role of cholesterol and atherosclerosis, but that time has well past. At this point, there’s no credible voice out there that’s debating the point that cholesterol is directly causal in terms of atherosclerosis. This is true of coronary atherosclerosis, peripheral cerebrovascular disease, and LDL [low-density lipoprotein] cholesterol in particular, an elevation in that, is a potent risk marker for the development of cardiovascular diseases, and it’s a modifiable risk factor. And there’s no question that LDL cholesterol, especially more atherogenic forms, such as when it gets oxidized, is really toxic to blood vessels. The good news is there’s something we can do about that. The first line of attack is lifestyle modification, and diets that are healthy. I would in particular endorse a plant-based diet to the extent one can adhere to that. And by that, I mean a diet that’s high in fresh fruit and vegetables and whole grain intake, to the extent that that forms the majority of a diet, that’s better for retarding atherosclerosis. Not just in terms of only trying to lower cholesterol, but also other beneficial cardiovascular effects.

Beyond diet, regular daily physical activity, even exercise I’ll say, can be usefulin terms of maintaining one’s cholesterol, but other associated risk factors like blood pressure, weight, glucose, etc. And when those measures aren’t enough, then pharmacotherapy is certainly indicated. We’re lucky that we’ve got generic statins and generic ezetimibe, relatively safe, well-tolerated, inexpensive ways to lower LDL cholesterol when lifestyle management is not enough. One concept that’s been introduced into the literature, in fact Mike Shapiro, [DO,] and I wrote an editorial on this in the Journal of the American College of Cardiology recently, is the idea of cholesterol years.

I think most folks, at least in health care, are aware of the concept of pack years of tobacco exposure. The more pack years, the worse off someone is in terms of their cardiovascular, and in that case, also cancer risk. Cholesterol years is similar. It’s looking at the number of years that someone has cholesterol elevation, and the degree of elevation of cholesterol, and that product, or the area under the curve, essentially represents their cumulative risk for atherosclerosis, at least attributable to LDL cholesterol. And thinking about it that way then forces us to realize, well, for some people, you really do want to start therapy, at minimum lifestyle modification recommendations, but potentially pharmacotherapy much earlier in life if their LDL is extremely high, such as someone with a genetic disorder or familial hypercholesterolemia. Whereas for someone who has good LDL cholesterol due to diet, genetics, nature, whatever, that sort of person perhaps they don’t need pharmacotherapy until maybe much later in life when their cardiovascular risk is higher, and perhaps their LDL cholesterol has drifted higher.

So, the pathophysiology and the epidemiology, I think, are quite interlinked, but importantly, in a way that’s actionable. And for myself, in cardiology, of course, I’m always thinking about cardiovascular risk. But these are lessons that can apply at the many points where we may touch a patient. That is, they might show up for their screening before their knee surgery at a relatively young age, maybe. But if they’ve got identified cardiovascular risk factors, well, that provides an opportunity to act, even though they’re not there at that exact moment to get cholesterol management advice.

Dhiren Patel, PharmD, CDCES, BC-ADM, BCACP: That makes sense, and those are all great points.

Transcript edited for clarity.