High density lipoprotein and cardiovascular diseases

Area of Science:

• Cardiovascular Medicine
• Biochemistry
• Epidemiology

Background:

• Low high density lipoprotein cholesterol (HDL-C) is recognized as a cardiovascular disease (CVD) risk factor.
• The causal link between HDL-C levels and CVD risk remains uncertain.
• HDL particles possess anti-atherosclerotic properties, including anti-inflammatory and cholesterol efflux activities.

Purpose of the Study:

• To investigate the causal association between HDL-C concentration and CVD risk.
• To evaluate the impact of increased HDL-C levels on myocardial infarction risk.
• To explore the relationship between HDL particle structure, functionality, and CVD risk.

Main Methods:

• Two Mendelian randomization analyses were conducted.
• Review of epidemiological studies on HDL-C and CVD.
• Analysis of findings from terminated clinical trials (AIM-HIGH) and discontinued drug development (dalcetrapib).

Main Results:

• Increased HDL-C levels were not associated with a reduced risk of myocardial infarction.
• Clinical trial outcomes (AIM-HIGH) and drug discontinuation (dalcetrapib) challenge the benefit of raising HDL-C.
• HDL particle heterogeneity in size, structure, composition, and metabolism is significant.

Conclusions:

• The assumption that raising plasma HDL-C uniformly reduces CVD risk is challenged.
• HDL functionality, rather than just HDL-C levels, may be more critical for CVD risk.
• Further research is required to understand HDL particle structure, functionality, and metabolism in relation to CVD.