HDL-C: Good or Bad

Is “Good” Cholesterol Actually Bad?

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Remember when we learned that hormone replacement therapy might harm—rather than help—postmenopausal women? Or when the new PSA testing guidelines turned conventional wisdom on its head? Remember the droves of anxious patients who worried that they had been mistreated, over treated, or misled?

Be prepared for another round of anxiety in response to yet another purported contradiction that hit the news late last week. Many of your patients have probably heard the story about new genetic research that failed to support a causal association between higher concentrations of high-density lipoprotein (HDL) cholesterol and a lower risk of heart attack. The findings, published in The Lancet[1], challenge the established view that raising HDL cholesterol will uniformly translate into reductions in heart attack risk.

Epidemiologic studies have shown that elevated levels of LDL are strongly associated with an increased risk of heart attack; drugs that lower LDL, such as statins, have been shown definitively to reduce that risk. Similar epidemiologic studies have shown that above-normal levels of HDL are associated with a decreased risk of heart attack. But because there are no drugs that raise HDL, researchers have been unable to prove that the high HDL levels are the cause of the reduced risk.

The Lancet study analyzed 20,913 patients who had a heart attack and 95,407 controls from 20 studies. Findings showed that people with a genetically programmed tendency for higher HDL cholesterol concentrations did not have a lower susceptibility to heart attack.

The researchers were able to construct a genetic risk score testing for 14 common genetic variants exclusively associated with higher HDL cholesterol in nearly 12,500 people with a history of heart attack and over 41,000 controls. The researchers calculated that people with the genetic defect would have a 13% decreased risk of heart attack. But despite their HDL levels, their genetic risk score was not associated with a decreased risk of heart attack, “suggesting that some genetic mechanisms that raise HDL cholesterol do not lower risk of myocardial infarction.”[1]

So what does this mean, exactly?

These new data suggest that there may be no direct relationship between HDL cholesterol and coronary heart disease, and, therefore, that other factors must be involved. However, the results don’t provide the whole answer as to whether HDL cholesterol has an effect on heart disease, and how this effect might be mediated. Only a few gene variants were examined; it may be that there are subtypes of HDL that do confer cardiovascular protection while others put patients at risk for cardiovascular disease. A recent study[2] suggests that at least one HDL subtype is a risk factor for heart disease.

As we learn more about these various HDL subtypes and their role in heart disease, it is likely that clinicians will be able to “tease out” a patient’s HDL profile and determine which—if any—medications are appropriate to prevent heart disease. But in the meantime, nothing in the Lancet paper suggests that raising HDL is detrimental to your patients’ health—and it may still provide a hedge against cardiovascular risk. Remind patients that some of the best ways to raise their HDL also provide other benefits: maintaining an ideal body weight, eating a healthful diet, and exercising regularly. For those disgruntled patients who grouse because scientists “always change their mind” relative to health and medicine, remind them that science is an ever-evolving process. As the data sets become more complete, the measurements more certain, and more scientists bring their points of view to the problem, the hypotheses evolve. Researchers should be prepared to modify or abandon hypotheses when they no longer validate key observations. In other words, “changing their minds” is exactly what scientists are supposed to do as they expand their observations and understanding of medical science.


Jill Shuman, MS, ELS
Published May 22, 2012



  1. Voight BF, Peloso GM, Orho-Melander M, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study [published online before print May 17, 2012]. Lancet. doi:10.1016/S0140-6736(12)60312-2 .
  2. Jensen MK, Rimm EB, Furtado JD, Sacks FM. Apolipoprotein C-III as a potential modulator of the association between HDL-cholesterol and incidence coronary heart disease. J Amer Heart Assoc. 2012. doi:10.1161/JAHA.111:000232.