Journal
AMERICAN JOURNAL OF CARDIOLOGY
Volume 167, Issue -, Pages 43-53Publisher
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI: 10.1016/j.amjcard.2021.11.041
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Funding
- NIH [4R61HL138657-04, U54AG062334-01, 1P30DK11102403S1, 15SFCRN23910003, 5P01HL086773-09, 1R01HL141205-01, 5P01HL101398-05, 1P20HL113451-04, 3RF1AG051633-01S2]
- American Heart Association [15SFCRN23910003]
- Abraham J. and Phyllis Katz Foundation (Atlanta, Georgia)
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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.
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.
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