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Is very high HDL cholesterol risky in heart patients?

JAMA Cardiology
Reuters Health - 20/05/2022  - In patients with coronary-artery disease (CAD), very high levels of HDL cholesterol above 80 mg/dL were paradoxically associated with greater mortality risk in two secondary-prevention studies.

"High HDL-C levels should not automatically be assumed to be protective," write the authors of an editor's note published with the study in JAMA Cardiology.

"Clinicians should use HDL-C levels as a surrogate marker with very low and very high levels as a red flag to target for more intensive primary and secondary prevention, as the maxim for HDL-C as 'good' cholesterol only holds for HDL-C levels of 80 mg/dL or less," say Dr. Sadiya Khan with Northwestern University, Chicago, and Dr. Gregg Fonarow with University of California, Los Angeles.

The findings of Dr. Arshed Quyyumi with Emory University, Atlanta, and colleagues are based on two independent groups of CAD patients: 14,478 (mean age, 62; 76% men) from the UK Biobank (UKB) and 5,467 (mean age, 64; 66% men) from the Emory Cardiovascular Biobank (EmCAB).

In the UKB, compared with adults with HDL-C levels in the range of 40 to 60 mg/dL, peers with HDL-C levels above 80 mg/dL had a 96% higher risk of dying from any cause and a 71% higher risk of cardiovascular mortality after adjusting for confounding factors, the study team says.

These findings were replicated in patients with CAD from the EmCAB cohort.

The association of very high HDL-C with mortality was independent of common polymorphisms associated with high HDL-C.

In sensitivity analyses, the risk increase for all-cause mortality with very high HDL-C was higher in men than women in the UKB cohort, with hazard ratios of 2.63 (P<0.001) and 1.39 (P=0.23), respectively.

The findings add to recent data from the general population suggesting an increased risk of adverse outcomes at very high HDL-C levels.

The researchers say their study "addresses an important knowledge gap as current risk calculators used in the general population input high HDL-C level as a protective factor, whereas at very high levels, this protective effect does not appear to hold true and, in fact, may confer increased risk."

Support for the study was provided by National Institutes of Health, the American Heart Association and the Abraham J. & Phyllis Katz Foundation. The authors have no relevant disclosures.

SOURCE: https://bit.ly/3yLPXqh and shttps://bit.ly/3yKTZ28 JAMA Cardiology, online May 18, 2022.

By Reuters Staff

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