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

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.