HDL Cholesterol Levels May Sway Statin Decisions in Primary Prevention

HDL, the so-called good cholesterol, appears to influence treatment decisions around statin therapy, according to an analysis in JACC: Advances.

Compared with people who have normal HDL-cholesterol levels (40-60 mg/dL), those with high concentrations are less likely to be treated with a statin, investigators reported this week.

With preventive therapies, including statins, there are many factors involved in making the decision to start treatment, but “anything that nudges people away from doing something tends to win out,” lead investigator Alexander Zheutlin, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), told TCTMD.

However, if someone has an indication to address cardiovascular risk, “HDL cholesterol should not be used in that decision-making process,” he added. “We may get to a point where we can really look at HDL functionality, and whether or not that HDL cholesterol means anything, but right now we should move away from looking at HDL [as part of] our clinical decision-making.”

For many clinicians, as well as the lay public, HDL cholesterol has long been regarded as cardioprotective. Epidemiologic studies have shown an inverse association between HDL and atherosclerotic cardiovascular disease (ASCVD), a relationship that spurred research into therapies aimed at boosting HDL. Those studies failed to bear fruit, however. Niacin, which raises HDL cholesterol by 30% to 50%, didn’t lower the risk of major ASCVD events in AIM-HIGH or HPS2-THRIVE, while raising HDL cholesterol with apolipoprotein A-1 and several CETP inhibitors also flamed out in large trials. 

For adults without diabetes, those with a 10-year risk of ASCVD ranging from 7.5% to less than 20% (intermediate risk) can consider starting a moderate-intensity statin, according to US cholesterol guidelines. To help make the call on treatment, there are several risk-enhancing factors that can influence the decision, but HDL cholesterol is not one.

To look into the role HDL potentially might play in treatment decisions, the researchers checked on statin use by HDL levels among intermediate-risk adults using data from the National Health and Nutrition Examination Survey.

Among 999 adults (mean age 63.2 years; 36.6% female), the unadjusted percentage of statin use was 27.4% among adults with low HDL cholesterol, 25.8% in those with normal HDL, and 31.6% in those with high HDL cholesterol. However, in an adjusted model, those with high HDL cholesterol had a significantly lower prevalence of statin use than those with normal HDL levels (prevalence ratio [PR] 0.85; 95% CI 0.63-0.88). Those with low HDL cholesterol had a higher prevalence of statin use (PR 1.14; 95% CI 1.01-1.18).

To TCTMD, Zheutlin cautioned this is an observational, cross-sectional study subject to several limitations, and that as a result it can’t be concluded that high HDL is what caused the lower usage of statins. However, it does suggest that those with elevated HDL cholesterol may be treated less aggressively than those at similar ASCVD risk with normal HDL levels.  

“It seemed to have some sort of role here,” he said, noting that he continues to hear HDL referred to as “good” cholesterol. “I still hear it clinically. A lot of us learned in medical school that HDL cholesterol is good cholesterol, and that sticks. It takes a number of years or decades for the science to [alter] clinical practice.”

Regarding other risk-enhancing factors, Zheutlin said apolipoprotein B, which can be checked with a simple blood test, “is probably one of the best” additional markers that can be used to stratify a patient’s risk.