Jacquelaine Bartlett1, Irene M Predazzi2, Scott M Williams1, William S Bush3, Yeunjung Kim4, Stephen Havas5, Peter P Toth6, Sergio Fazio2, Michael Miller7. 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.
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.
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.
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