Atherosclerosis and its Pharmacology

Upcoming Series

One of my goals with this page is to assess the evidence base underlying commonly prescribed medications. This post will serve as a brief introduction and an outline for what I anticipate will be a many-part series. We will eventually review physiology, pathophysiology, and clinical trials supporting the various medications used to reduce the risk of atherosclerosis and its complications.

Today, we start with the concept of atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is a lifelong process that occurs within our blood vessels. Autopsy studies of young adults who have died from non-cardiovascular causes show that this process begins as early as adolescence. Various factors (eg, endothelial dysfunction, dyslipidemia, inflammation, hypertension, smoking) play a role in the pathogenesis.

The figure below provides a helpful model to understand the problem. Don’t get caught up with the details at this point if they are unfamiliar.

Over time there is narrowing of the lumen, and if the lesion ruptures, as pictured at the bottom of the figure, the blood vessel can become occluded. If that blood vessel is a major coronary artery, you get a myocardial infarction (MI), a heart attack.

The term cardiovascular disease (CVD) includes MI, cerebrovascular disease (read: strokes), peripheral artery disease (PAD) and other non-coronary atherosclerosis. CVD is the number one cause of death both in the United States and globally.

Who gets CVD?- Read the caption of the figure below, from this paper, it does a good job of showing the incidence of cardiovascular disease in broad terms.

Risk Factors: There are many, but we will stick to some of the big ones. Risk factors are often put into two categories, either modifiable or non-modifiable.

• Non-modifiable- Age and male sex are the two big ones

• Modifiable- Hypertension, hyperlipidemia, diabetes mellitus, obesity, and cigarette smoking

Medical Approach

We can target modifiable risk factors in the hope that improving along those dimensions will lead to improved cardiovascular health. A simple example is smoking cessation. By far the best way to improve the other risk factors and live a healthy life is through a good diet and regular exercise.

In this series we will zoom in on individual risk factors, going over relevant physiology and the major medications that are used to reduce risk. Below are some big buckets:

• Hyperlipidemia- Colloquially, “high cholesterol” is a major risk factor, the next post in this series will review the basics, including population studies (Framingham, MESA, etc.) and an introduction to statins.

• Hypertension- Elevated blood pressure is another crucial player, it is consistently screened for and managed fairly aggressively, if guidelines are followed. In future posts we will review some of these medications and major clinical trials.

• Diabetes Mellitus- We will compare/contrast type 1 and type 2, and probably spend a lot of time on the medications. This may be its own off-shoot series, down the road.

This kind of turned into a teaser for future posts, mostly because I realized it would take me all day to even start to do justice to any one of these topics. The good thing is sending this out will pressure me to follow through, and once June is over I won’t have to be studying all the time.