Is Isolated Low HDL-C a CVD Risk Factor?: New Insights from the Framingham Offspring Study
Jacquelaine Bartlett, MS,#1 Irene M. Predazzi, PhD,#2 Scott M. Williams, PhD,1 William S. Bush, PhD, MS,3Yeunjung Kim, MD, MPH,4 Stephen Havas, MD, MPH, MS,5 Peter P. Toth, MD, PhD,6 Sergio Fazio, MD, PhD,2 andMichael Miller, MD7
Abstract
Background—
While the inverse association between high-density lipoprotein cholesterol (HDLC) and risk of (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 HDLC 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 to isolated low HDL-C, CVD risks were higher when low HDLC was accompanied by LDL-C ≥100 mg/dL and TG <100 mg/dL (OR 1.3 [1.0, 1.6]), TG ≥100mg/dL and LDL-C <100 mg/dL (OR 1.3 [1.1, 1.5]), or TG and LDL-C ≥ 100 mg/dL (OR 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/or LDL-C (≥130 mg/dL) results were essentially the same. In contrast,compared to isolated low HDL-C, high HDL-C was associated with 20-40% 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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