High 'Good' Cholesterol Linked to Lower Statin Use in At-Risk Adults, Raising Concerns Over Missed Prevention: Study

The findings were published online in JACC: Advances on April 30, 2025.

The analysis, based on data from the National Health and Nutrition Examination Survey (NHANES) collected between 2013 and early 2020, included adults aged 40 to 75 years who had no history of ASCVD, diabetes, or markedly elevated low-density lipoprotein cholesterol (LDL-C ≥190 mg/dL). All participants had an estimated 10-year ASCVD risk between 7.5% and 20%, categorizing them as having an "intermediate risk" and making them eligible for moderate-intensity statin therapy under current guidelines.

Traditionally dubbed the "good cholesterol," HDL-C has long been associated with reduced cardiovascular risk. However, emerging research suggests that the functionality of HDL particles, rather than their quantity, may hold greater significance in atherosclerosis. Despite this shift in understanding, the long-held perception of HDL-C as protective may still be influencing clinical decisions.

In the study, Alexander R. Zheutlin, Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA, and colleagues stratified participants by HDL-C levels: low (<40 mg/dL), normal (40–60 mg/dL), and high (≥60 mg/dL).

The key findings of the study were as follows:

• Individuals with high HDL-C levels were significantly less likely to be prescribed statins than those with normal HDL-C levels.
• Those with low HDL-C levels were slightly more likely to receive statin therapy than individuals with normal HDL-C.
• Adjusted analysis showed that high HDL-C was linked to a 15% lower likelihood of statin use.
• Low HDL-C was associated with a modest increase in statin prescriptions.
• The study analyzed data from over 900 participants, representing nearly 23.7 million U.S. adults with intermediate 10-year ASCVD risk.
• No significant interaction was found between sex and HDL-C levels concerning statin use.
• The findings suggest that lower statin use among individuals with high HDL-C may reflect prevailing clinical perceptions rather than evidence-based, sex-specific prescribing patterns.

The authors emphasized that while HDL-C is included in risk assessment models, it is not considered a risk-enhancing factor in current cholesterol guidelines. Both low and excessively high HDL-C levels have been linked to increased ASCVD risk in other studies.

The cross-sectional analysis cannot establish causality but raises important concerns about possible undertreatment among adults with high HDL-C who otherwise qualify for preventive statin therapy. The findings stress the need for improved education around the complex role of HDL-C in cardiovascular health and suggest a reevaluation of how lipid profiles influence statin prescribing in clinical practice.

Reference:

Zheutlin AR, Jacobs JA, Bress AP. High-density lipoprotein cholesterol and statin use among U.S. adults with intermediate 10-year predicted ASCVD risk. JACC Adv. 2025; Epub ahead of print.