Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.
Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes.
Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included. Associations of HDL-P, HDL-size, HDL-C, and HDL-C/HDL-P with risk of overall HF, HF with reduced and preserved ejection fraction were assessed using adjusted Cox models.
Results: Among 16,925 participants (53.5% women; 21.8% Black), there were 612 incident HF events (3.6%) (HF with reduced ejection fraction, 309 [50.5%]; HF preserved ejection fraction, 303 [49.5%]) over median follow-up of 11.4 years. In adjusted models, higher HDL-P was significantly associated with lower HF risk (HR of highest vs lowest tertile of HDL-P: 0.76 [95% CI: 0.62-0.93]). Larger HDL-size was significantly associated with higher overall HF risk (HR of largest vs smallest tertile of HDL-size: 1.27 [95% CI: 1.03-1.58]). HF risk associated with HDL-P and HDL-size was similar for HF subtypes. In adjusted analyses, there was no significant association between HDL-C and HF risk. Higher HDL-C/HDL-P was significantly associated with higher overall HF risk (HR of highest vs lowest tertile of HDL-C/HDL-P: 1.29 [95% CI: 1.04-1.60]).
Conclusions: Higher HDL-P was associated with a lower risk of HF. In contrast, larger HDL-size was associated with higher risk of HF and there was no significant association observed between HDL-C and HF risk after accounting for cardiovascular risk factors.
Competing Interests: Funding Support and Author Disclosures The ARIC study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I. The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. The Multi-Ethnic Study of Atherosclerosis was supported by the National Heart, Lung, and Blood Institute (R01 HL071739 and contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, and N01-C-95169). The PREVEND cohort study was supported by The Dutch Kidney Foundation which supported the infrastructure of the PREVEND program from 1997 to 2003 (Grant E.033). The University Medical Center Groningen supported the infrastructure from 2003 to 2006. Dr Pandey is supported by the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, the National Institute of Aging GEMSSTAR Grant (1R03AG067960-01), and Applied Therapeutics; has served on the advisory board for Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. Dr Patel has served as a consultant to Novo Nordisk. Dr Segar has received speaker fees from Merck and is on the advisory board of descendantsDNA. Dr Shapiro has received grants from Amgen, Boehringer Ingelheim, 89Bio, Esperion, Novartis, Ionis, Merck, and New Amsterdam; has served on scientific advisory boards for Amgen, Agepha, Ionis, Novartis, Precision BioScience, New Amsterdam, and Merck; and has served as a consultant to Ionis, Novartis, Regeneron, Aidoc, Shanghai Pharma Biotherapeutics, Kaneka, and Novo Nordisk. Dr Connelly is an employee of Labcorp. Dr Rohatgi has received a research grant from CSL Behring; has served as a collaborator to Quest; has served as a consultant to HDL Diagnostics, JP Morgan, Johnson and Johnson, and Raydel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024. Published by Elsevier Inc.)