Very High HDL Associated With CV Mortality in CAD

Coronary artery disease (CAD) is a common heart condition. The major blood vessels that supply the heart (coronary arteries) struggle to send enough blood, oxygen and nutrients to the heart muscle. Cholesterol deposits (plaques) in the heart arteries and inflammation are usually the cause of CAD.

High-density lipoprotein (HDL) cholesterol is known as the "good" cholesterol because it helps remove other forms of cholesterol from your bloodstream. Higher levels of HDL cholesterol are associated with a lower risk of heart disease. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations.

Cardiologists at the Emory University School of Medicine (Atlanta, Georgia) and their colleagues studied the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with CAD and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes. In a prospective study, they analyzed data from patients with confirmed CAD and high HDL, defined as at least 80 mg/dL, using UK Biobank (2006-present; n = 14,478; mean age, 62 years; 76.2% men) and Emory Cardiovascular Biobank (2003-present; n = 5,467; mean age, 64 years; 66.4% men).

During a median follow-up of 8.9 years in the UK Biobank and 6.7 years in the Emory Cardiovascular Biobank, the scientists observed a U-shaped association between HDL level, all-cause death and CV death, with higher risk among patients with low and very high HDL versus patients with midrange values. For the UK Biobank analysis, compared with patients with an HDL between 40 mg/dL and 60 mg/dL, patients with an HDL of at least 80 mg/dL were nearly twice as likely to die of any cause during follow-up, with a HR of 1.96 and 71% more likely to die of CV causes, with an HR of 1.71. Results persisted after adjustment for other CV risk factors, including hypertension, diabetes and smoking. In sensitivity analyses, all-cause death risk among patients from the UK Biobank with very high HDL was greater among men (HR = 2.63) compared with women (HR = 1.39).

Arshed A. Quyyumi, MD, FRCP, a Professor of Medicine and senior author of the study, said, “Very high HDL levels are associated with increased risk for 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. The higher risk with very high HDL levels is particularly seen in men, although women also have higher risk at very high HDL levels.”

The authors concluded that results of their cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels. The study was published on May 18, 2022 in the journal JAMA Cardiology.

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Emory University School of Medicine