Penson, P, Long, L, Howard, G, Howard, VJ, Jones, SR, Martin, SS, Mikhailidis, DP, Muntner, P, Rizzo, M, Rader, DJ, Safford, MM, Sahebkar, A, Toth, PP and Banach, M (2018) Associations between cardiovascular disease, cancer and very low HDL cholesterol in the REasons for Geographical And Racial Differences in Stroke (REGARDS) study. Cardiovascular Research, 115 (1). pp. 204-212. ISSN 0008-6363

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Abstract

AIMS: Relatively little is known about the health outcomes associated with very low plasma concentrations of high density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We therefore investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart disease (CHD) in individuals from the Reasons for Geographical And Racial Differences in Stroke (REGARDS) study. METHODS AND RESULTS: Analysis was based on 21,751 participants from the REGARDS study who were free of CHD, other cardiovascular disease and cancer at baseline and were categorized by baseline HDL-C into <30 mg/dL (very low), 30 -<40 mg/dL (low), and ≥40 mg/dL (reference). A series of incremental Cox proportional hazards models were employed to assess the association between the HDL-C categories and outcomes. Statistical analysis was performed using both complete case methods and multiple imputations with chained equations. After adjustment for age, race and sex, the hazard ratios (HRs) comparing the lowest and highest HDL-C categories were 1.48 (95% confidence interval [CI]: 1.28, 1.73) for all-cause mortality, 1.35 (95%Cl: 1.03, 1.77) for cancer-specific mortality and 1.39 (95%Cl: 0.99, 1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors and treatment for dyslipidemia. We found evidence for an ‘HDL paradox’ whereby low HDL (30-<40 mg/dL) was associated with reduced risk of incident CHD in black participants in a fully-adjusted complete case model (HR 0.63; 95%CI: 0.46, 0.88) and after multiple imputation analyses (HR 0.76; 95%CI 0.58, 0.98). HDL-C (<30 mg/dL) was significantly associated with poorer outcomes in women for all outcomes, especially with respect to cancer mortality (HR 2.31; 95%Cl: 1.28, 4.16) in a fully-adjusted complete case model, replicated using multiple imputation (HR 1.81; 95%CI 1.03, 3.20). CONCLUSIONS: Low HDL-C was associated with reduced risk of incident CHD in black participants suggesting a potential HDL paradox for incident CHD. Very low HDL-C in women was significantly associated with cancer mortality in a fully-adjusted complete case model.

Item Type:	Article
Additional Information:	This is a pre-copyedited, author-produced version of an article accepted for publication in Cardiovascular Research following peer review. The version of record [Peter Penson, D Leann Long, George Howard, Virginia J Howard, Steven R Jones, Seth S Martin, Dimitri P Mikhailidis, Paul Muntner, Manfredi Rizzo, Daniel J Rader, Monika M Safford, Amirhossein Sahebkar, Peter P Toth, Maciej Banach, Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study, Cardiovascular Research, Volume 115, Issue 1, January 2019, Pages 204–212 is available online at: https://doi.org/10.1093/cvr/cvy198
Uncontrolled Keywords:	1102 Cardiovascular Medicine And Haematology
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Oxford University Press (OUP)
Date Deposited:	31 Jul 2018 08:18
Last Modified:	04 Sep 2021 10:16
DOI or ID number:	10.1093/cvr/cvy198
URI:	https://researchonline.ljmu.ac.uk/id/eprint/9044

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