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


Bartlett J, Predazzi IM, Williams SM, Bush WS, Kim Y, Havas S, Toth PP, Fazio S, Miller M,.

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

Posted in Publications, Will Bush.

Will Bush

William S. Bush, Ph.D., is a human geneticist and bioinformatician, and Assistant Professor within the Cleveland Institute for Computational Biology and the Department of Population and Quantitative Health Sciences at Case Western Reserve University.