Flow-mediated dilation, carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia

Area of Science:

• Cardiovascular Medicine
• Lipidology
• Genetics

Background:

• The association between very high plasma high-density lipoprotein cholesterol (HDLc) and subclinical atherosclerosis remains debated.
• Primary hyperalphalipoproteinemia (HAL) is characterized by elevated HDLc without secondary causes.

Purpose of the Study:

• To investigate the relationship between very high HDLc levels in HAL subjects and markers of subclinical atherosclerosis.
• To explore the role of HDL particle characteristics, cholesterol efflux capacity (CEC), and specific gene variants in this relationship.

Main Methods:

• Compared 20 HAL subjects (highest 10th percentile HDLc) with 20 age/sex-matched controls.
• Assessed lipid profiles, lipoprotein particle distribution, CEC (ABCA1, ABCG1 pathways), adhesion molecules, CETP, SRB1, LIPG gene variants, ankle-brachial index (ABI), carotid intima-media thickness (cIMT), and flow-mediated dilation (FMD).

Main Results:

• HAL subjects had 40 mg/dl higher HDLc; LDLc levels were similar to controls.
• HAL subjects exhibited larger, more buoyant HDL particles.
• No significant differences were found in ABI, cIMT, arterial plaques, or FMD between HAL and control groups.
• CEC via ABCA1 and ABCG1 pathways did not differ, though ABCG1 showed a slight relation to arterial reactivity.

Conclusions:

• HDL particle size, function, and genetics appear to have limited association with subclinical atherosclerosis and vascular reactivity in middle-aged HAL subjects.
• Very high HDLc levels in HAL may not confer protection against early vascular disease in this cohort.