Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study
- PMID: 30576432
- PMCID: PMC6302258
- DOI: 10.1093/cvr/cvy198
Associations between cardiovascular disease, cancer, and very low high-density lipoprotein cholesterol in the REasons for Geographical and Racial Differences in Stroke (REGARDS) study
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% CI 1.03-1.77) for cancer-specific mortality and 1.39 (95% CI 0.99-1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors, and treatment for dyslipidaemia. 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% CI 1.28-4.16) in a fully adjusted complete case model, replicated using multiple imputation (HR 1.81; 95% CI 1.03-3.20).
Conclusion: 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.
Figures
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Comment in
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High-density lipoprotein cholesterol levels, cardiovascular disease risk, and cancer: a relation which does not apply to all?Cardiovasc Res. 2019 Jan 1;115(1):6-7. doi: 10.1093/cvr/cvy247. Cardiovasc Res. 2019. PMID: 30295742 No abstract available.
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References
-
- Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR.. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977;62:707–714. - PubMed
-
- Glomset JA. The plasma lecithins: cholesterol acyltransferase reaction. J Lipid Res 1968;9:155–167. - PubMed
-
- Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J.. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999;341:410–418. - PubMed
-
- Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B; ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109–2122. - PubMed
-
- Toth PP, Barylski M, Nikolic D, Rizzo M, Montalto G, Banach M.. Should low high-density lipoprotein cholesterol (HDL-C) be treated? Best Pract Res Clin Endocrinol Metab 2014;28:353–368. - PubMed
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