Time to Tell the Truth About HDL Cholesterol

Updated: Jan 25

I hear almost daily from family, friends, and other doctors that they are in great shape because their HDL-C (the good cholesterol) is high and that is the most important number to look at in a cholesterol panel. Unfortunately this statement is false, and I will explain why.

We know that low HDL cholesterol (good cholesterol) is a risk factor for cardiovascular morbidity and mortality. It is included in both the well known risk factor scoring systems to determine cardiovascular risk, called the Framingham Risk Score and the

Reynold’s Risk Factor Scoring System. Surprisingly, there is little clinical evidence that therapies directed at raising HDL cholesterol reduces one’s risk. I will say that again, there is little evidence that raising one’s good cholesterol number protects them from having a heart attack, a stroke, or dying.

For this reason, the National Cholesterol Education Panel (NCEP) did not specify a number that would be the “optimal” HDL level of therapy. NCEP also stated that raising one’s HDL is not a primary or secondary goal of therapy in order to reduce cardiovascular events or death. NCEP ATP-III statements about low HDL cholesterol were published in the journal titled Circulation in 2002. Here are some random quotes from the article:

a) A categorical low HDL-C should be defined as a level of <40 mg/dL, in both men and women

b) Whether raising HDL per se will reduce risk for CHD has not been resolved. (Still true in 2022)

c) Some persons with severe deficiency of HDL do not manifest premature coronary heart disease; this suggests that HDL is not uniquely involved in atherogenesis (clogging of the arteries), as is LDL cholesterol (the bad cholesterol).

d) A specific HDL cholesterol goal level to reach with HDL raising therapy is not identified.

Over the past decade, four different pharmaceutical companies developed a class of medicines called CETP Inhibitors which were supposed to raise one’s HDL cholesterol and hopefully reduce the rate of cardiovascular events and deaths. While all the drugs did raise one’s HDL-C, all the trials were failures except for the REVEAL trial, but Merck decided that the results were not that impressive and abandoned further study in 2017.

In summary, when we measure HDL cholesterol, we are just measuring a number that tells us nothing about how well it functions. There is no way yet to measure how well one’s HDL functions, and thus, if one’s level is within normal limits, does the person with a higher HDL number have fewer events than a person with lower HDL number? This has never shown to be true in any randomized prospective human studies. This is also defined in scientific terms as no Level 1 evidence. There is only data in retrospective and epidemiological studies that show that the higher the HDL cholesterol number the lower the cardiovascular event rate.

I will put another twist in the HDL discussion. There is a level at which the HDL cholesterol in some people may be too high and dysfunctional, and actually be harmful. A recent study published in The American Journal of Cardiology concluded this finding in men. I will summarize the findings:

  • Researchers examined data from 415,416 patients, including more than 227,000 women and more than 187,000 men, who participated in the UK Biobank database. Patients with a history of coronary artery disease were excluded.

  • Nearly 7% of patients had an HDL-C level above 80 mg/100 ml. These patients were mostly women and more likely to be older and present with a lower BMI. They also tended to have higher total cholesterol levels, and a history of stroke or myocardial infarction were uncommon.

  • After a median follow-up period of nine years, the all-cause mortality rate was 4%. The cardiovascular mortality rate was 0.9%.

  • Overall, women with very high HDL-C levels do not face a heightened risk of cardiovascular mortality. Men with very high HDL-C levels, however, see their risk of cardiovascular death nearly double.

These findings, the group noted, “highlight the limitation of high HDL-C levels as a marker of atheroprotection as currently employed in clinical practice.” This might explain why pharmaceutic interventions aimed at boosting HDL-C levels have failed to make much of an impact on patient outcomes.

The take away message of this review article should be that low HDL cholesterol is bad and is a risk factor for cardiovascular events and death, but a high level may not be protective.The name of the game is drive one’s LDL-P down as these are the vehicles that drive the cholesterol into the wall of the arteries and cause Atherosclerosis.

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