Isolated Low HDL Cholesterol and CV Disease Risk

Study Questions:

Are high-density lipoprotein cholesterol (HDL-C) levels inversely associated with cardiovascular disease (CVD) risk?


Data from the Framingham Heart Study offspring cohort were used for the present study. Only participants without known CVD, who were followed between 1987 and 2011, were included. Low HDL-C (<40 mg/dl in men and <50 mg/dl in women) was defined as isolated if triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C) were both low (<100 mg/dl). Low versus high HDL-C phenotypes were also compared using higher thresholds for TGs (150 mg/dl) and LDL-C (130 mg/dl).


A total of 3,590 men and women were included in the analysis. In general, the baseline characteristics of participants with isolated high and low HDL-C groups were similar, regardless of TG and LDL-C measures. Participants with isolated low HDL-C were characterized by a relatively normal mean body mass index, systolic blood pressure, and a low prevalence of diabetes mellitus (6%) in contrast to low HDL-C groups with a higher TG phenotype (≥100 mg/dl). Compared with isolated low HDL-C, CVD risks were higher when low HDL-C was accompanied by LDL-C ≥100 mg/dl and TGs <100 mg/dl (odds ratio [OR], 1.3 [1.0, 1.6]), TGs ≥100 mg/dl and LDL-C <100 mg/dl (OR, 1.3 [1.1, 1.5]), or TGs and LDL-C ≥100 mg/dl (OR, 1.6 [1.2, 2.2]), after adjustment for covariates. Similar associations were observed when low HDL-C was analyzed with higher thresholds for TGs (≥150 mg/dl) and LDL-C (≥130 mg/dl). In contrast, compared with isolated low HDL-C, high HDL-C was associated with 20-40% lower CVD risk except when TGs and LDL-C were elevated.


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


These data suggest that HDL-C levels may be clinically useful in identifying higher-risk patients, but only in relation to other factors such as LDL-C and TG levels.

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