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Published on: October 12, 2017
Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor? New Insights From the
Jacquelaine Bartlett1, Irene M Predazzi2, Scott M Williams1
1Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover, NH.
Insights
Low high-density lipoprotein cholesterol (HDL-C) may still increase cardiovascular disease (CVD) risk even with normal low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). HDL-C
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Preventive Cardiology
Background:
- The established inverse relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) risk is being re-evaluated.
- Recent studies question if HDL-C is an independent CVD predictor, particularly when low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) are within normal ranges.
Purpose of the Study:
- To investigate whether low HDL-C poses a CVD risk independently of LDL-C and TG levels.
- To assess the impact of different HDL-C phenotypes on CVD risk in conjunction with varying LDL-C and TG levels.
Main Methods:
- Analysis of 3590 participants from the Framingham Heart Study offspring cohort without prior CVD (1987-2011).
- Defined low HDL-C (<40 mg/dL men, <50 mg/dL women) as isolated when TG and LDL-C were low (<100 mg/dL).
- Utilized logistic regression to compare CVD risk across different HDL-C, TG, and LDL-C phenotypes, including higher thresholds for TG (150 mg/dL) and LDL-C (130 mg/dL).
Main Results:
- Low HDL-C, even with normal LDL-C and TG, was associated with increased CVD risk.
- CVD risk was significantly higher when low HDL-C co-occurred with elevated LDL-C and/or TG compared to isolated low HDL-C.
- High HDL-C was generally associated with lower CVD risk, except when accompanied by elevated TG and LDL-C.
Conclusions:
- Cardiovascular disease risk associated with HDL-C levels is significantly influenced by concurrent levels of LDL-C and triglycerides.
- The independent predictive value of HDL-C for CVD may be context-dependent on the overall lipid profile.
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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