High HDL Cholesterol...Is too much of a good thing bad?

Updated: Jul 12

There is not a week that goes by that I don’t hear from family, friends, patients, and even other doctors that they “ have perfect cholesterol” because their HDL-C (good cholesterol) is high. Unfortunately, nothing could be further from the truth. There is little evidence that raising one’s good cholesterol protects from having a cardiovascular event or death. When the good cholesterol is measured, we are just measuring a quantitative number that tells us nothing about how well it functions. This is called the functionality of HDL-C. There is no way to measure the functionality. There has never been any prospective randomized human study that shows that a person who has a higher HDL-C has fewer events than a person with a lower HDL-C? In scientific terms, this is referred to as a lack of Level 1 evidence. There is only data in epidemiological and retrospective studies that has shown that the higher the HDL-C, the lower the cardiovascular event rate.

We do know, however, that a low HDL-C is a major risk factor for cardiovascular morbidity and mortality. Like almost everything else in medicine, there is a caveat to this. There is a group of people who are referred to as ApoA1 Milano and are all originally from Limone, Italy. Approximately 3.5% of this population has very low HDL-C levels, below 10mg/dl, and have no evidence of significant cardiovascular disease whatsoever. They have what I refer to as a “Supercharged” good cholesterol in the way that it functions.

I will put another twist in this discussion. There is a level at which one’s HDL-C becomes too high, dysfunctional, and can be harmful to the arteries. In fact a new study that was published on May 18 in JAMA Cardiology suggests that very high levels of high-density lipoprotein cholesterol (HDL-C) may be associated with higher mortality risk in patients with coronary artery disease (CAD). Investigators studied close to 10,000 patients with CAD in two separate cohorts. After adjusting for an array of covariates, they found that individuals with HDL-C levels greater than 80 mg/dL had a 96% higher risk for all-cause mortality and a 71% higher risk for cardiovascular mortality than those with HDL-C levels between 40 and 60 mg/dL. The senior author of the article from Emory University stated that "Very high HDL levels are associated with increased risk of adverse outcomes, not lower risk, as previously thought. This is true not only in the general population, but also in people with known coronary artery disease.” He went on to state "Physicians have to be cognizant of the fact that, at levels of HDL-C above 80 mg/dL, they should be more aggressive with risk reduction and not believe that the patient is at 'low risk' because of high levels of 'good' cholesterol”. The potential mechanism through which very high HDL-C might cause adverse cardiovascular outcomes in patients with CAD needs to be studied. I think the most important point of the study is to identify people with very high HDL-C.

The major theme of this review should be that in most people, a low HDL-C is bad and is a major risk factor for cardiovascular events and death. High HDL-C levels should not automatically be assumed to be protective. The name of the game is to get the bad cholesterol down. That is why I believe that it is essential that everyone have their lipoprotein particles measured. These are the particles that actually drive the cholesterol into the walls of the arteries and cause plaque formation, which is know as Atherosclerosis.

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