Pathophysiology of Hypercholesterolemia and Cardiovascular Disease

Keith C. Ferdinand, MD: Hello and welcome to HCPLive® Peer Exchange titled Paradigm Shifts in Lipid Lowering. I'm Dr Keith C. Ferdinand from Tulane University School of Medicine in New Orleans, Louisiana, and I have some very experienced clinicians and researchers.

We are joined by Dr Linda Hemphill from Massachusetts General Hospital in Boston. How are you doing, Linda? Dr Dean Karalis from Thomas Jefferson University Hospital in Philadelphia, PA. Dr Norman Lepor, Cedars Sinai Medical Center, Los Angeles, California. And Dr Manesh Patel from Duke University School of Medicine in Durham, North Carolina.

In today's discussion we will provide a brief overview of the standards of care for lipid management, and focus on a rapidly emerging, newer treatment as an option for managing dyslipidemia. Let us get started.

Manesh, I know you do a lot of interventions and you see patients who are at high risk, but what is the pathophysiology of the relationship between hypercholesterolemia and cardiovascular disease? How is it actually related?

Manesh Patel, MD: Yeah, thanks, Keith, and thanks for having me on this program. This is potentially, and I think we've all now learned the single most common pathophysiological process that's leading to morbidity and mortality worldwide, even unfortunately in the setting of global pandemics and other things, heart disease is still the #1 killer through atherosclerosis. 

I often tell my patients the process is actually, we know from childbirth to, unfortunately, throughout our age of life that atherosclerosis happens as we start to have lipid plaques, and we'll go into sort of the particles of lipids with HDL, LDL, total cholesterol, but the cholesterol gets put down into the vessel. Over time, that cholesterol that has put down into the vessel actually incorporates sometimes into the wall under the endothelium and leads to narrowings. They don't have to actually narrow the entire artery. That leads to some inflammation as your body responds to that atherosclerosis, and that inflammation sometimes leads to occasionally plaque ruptures where some of that material is made evident in the blood vessel and leads to thrombosis. And some people have used the terms atherothrombosis when people have these events.

The risk factors, in addition to just sort of saying our diet and things that lead to how we manage that cholesterol also include high blood pressure, sort of our classical atherosclerotic cardiovascular disease respecters, diabetes, hypertension, the cholesterol level itself, your age, your sex, if you smoke tobacco. Those things go into something we have our patients do to calculate the ASCVD [atherosclerotic cardiovascular disease] risk score.

Keith C. Ferdinand, MD: The two points that you made that I want to highlight, if you may, one is you said lifelong, because we think this is an adult disease since we are an adult patient population that we deal with. But it really starts in teenage years or before that.

Manesh Patel, MD: Yeah, I think we're learning more and more about primordial prevention to primary prevention to secondary prevention, and unfortunately, we know, as we've seen more recently, a lot of adverse childhood events and other things affect how our bodies are shaped during development, and then in addition to that, both habits, genetics, environmental influences affect what's happening, and I'm sure we're going to talk some about that.

Those lead to this atherosclerosis that is a lifelong process that often presents itself, as an interventional cardiologist, for me, sometimes when somebody is 50 or sometimes when they're 80, unfortunately sometimes when they're even younger these days. And those atherosclerotic events that people have are led to where those plaques have built up.

I tell our patients there's sort of the big three: the brain. We all care about the brain, and so atherosclerosis in the vessels that go to the brain leading to stroke or cerebrovascular events. Obviously, the heart, we think a lot about cardiovascular events that lead to the heart. And then what I call our peripheral extremities, the lower extremities and peripheral artery disease, and atherosclerotic events that lead to, eventually in life, limb limitation or limb loss.

So those are sort of the ways in which I describe the biology of that and to the clinical events. And there's chronic biology and then there's acute biology, when an acute event happens on top of that chronic, lifelong process.

Keith C. Ferdinand, MD: If you enjoyed watching this HCPLive® Peer Exchange, if you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right in your inbox.

Thank you very much for listening to this program.

Transcript Edited for Clarity