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Circ Cardiovasc Qual Outcomes. 2016 May;9(3):206-212. doi: 10.1161/CIRCOUTCOMES.115.002436. Epub 2016 May 10.

Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the Framingham Offspring Study.

Author information

1
Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH.
2
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
3
Institute for Computational Biology, Case Western Reserve University, Cleveland, OH.
4
Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
5
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
6
CGH Medical Center, Sterling, Illinois, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD.
7
Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD.
#
Contributed equally

Abstract

BACKGROUND:

Although the inverse association between high-density lipoprotein cholesterol (HDL-C) and risk of cardiovascular disease (CVD) has been long established, it remains unclear whether low HDL-C remains a CVD risk factor when levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are not elevated. This is a timely issue because recent studies have questioned whether HDL-C is truly an independent predictor of CVD.

METHODS AND RESULTS:

3590 men and women from the Framingham Heart Study offspring cohort without known CVD were followed between 1987 and 2011. Low HDL-C (<40 mg/dL in men and <50 mg/dL in women) was defined as isolated if TG and LDL-C were both low (<100 mg/dL). We also examined higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL) and compared low versus high HDL-C phenotypes using logistic regression analysis to assess association with CVD. Compared with isolated low HDL-C, CVD risks were higher when low HDL-C was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (odds ratio 1.3 [1.0, 1.6]), TG ≥100 mg/dL and LDL-C <100 mg/dL (odds ratio 1.3 [1.1, 1.5]), or TG and LDL-C ≥100 mg/dL (odds ratio 1.6, [1.2, 2.2]), after adjustment for covariates. When low HDL-C was analyzed with higher thresholds for TG (≥150 mg/dL) and LDL-C (≥130 mg/dL), results were essentially the same. In contrast, compared with isolated low HDL-C, high HDL-C was associated with 20% to 40% lower CVD risk except when TG and LDL-C were elevated.

CONCLUSIONS:

CVD risk as a function of HDL-C phenotypes is modulated by other components of the lipid panel.

KEYWORDS:

coronary heart disease risk; epidemiology; high-density lipoprotein cholesterol; low-density lipoprotein cholesterol; triglycerides

PMID:
27166203
PMCID:
PMC4871717
DOI:
10.1161/CIRCOUTCOMES.115.002436
[Indexed for MEDLINE]
Free PMC Article

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