Very High High-Density Lipoprotein Cholesterol Levels and Cardiovascular Mortality

Previous studies have shown reduced cardiovascular risk with increasing high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high concentrations of HDL-C. Thus, we aimed to study the gender-specific relation between very high HDL-C levels (> 80, > 100 mg/100 ml) and adverse cardiovascular outcomes and the genetic basis in the general population enrolled in the United Kingdom Biobank. A total of 415,416 participants enrolled in the United Kingdom Biobank without coronary artery disease were included in this prospective cohort study, with a median follow-up of 9 years. A high HDL-C level > 80 mg/100 ml was associated with increased risk of all-cause death (Hazard ratio [HR] 1.11, confidence interval [CI] 1.03 to 1.20, p = 0.005) and cardiovascular death (HR 1.24, CI 1.05 to 1.46, p = 0.01) after adjustment for age, gender, race, body mass index, hypertension, smoking, triglycerides, LDL-C, stroke history, heart attack history, diabetes, eGFR, and frequent alcohol use (defined as >= 3 times/week) using Cox proportional hazard and Fine and Gray's subdistribution hazard models, respectively. In gender-stratified analyses, such associations were only observed in men (all-cause death HR 1.79, CI 1.59 to 2.02, p < 0.0001; cardiovascular death HR 1.92, CI 1.52 to 2.42, p < 0.0001), but not in women (all-cause death HR 0.97, CI 0.88 to 1.06, p = 0.50; cardio-vascular death HR 1.04, CI 0.83 to 1.31, p = 0.70). The findings persisted after adjusting for the genetic risk score comprised of known HDL-C-associated single nucleotide poly-morphisms. Very high HDL-C levels are associated with an increased risk of all-cause death and cardiovascular death among men but not in women in the general population free of coronary artery disease. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The study found that very high levels of HDL-C are associated with an increased risk of all-cause death and cardiovascular death among men, but not women, in the general population.