High-sensitivity C-reactive protein mediates age-related vascular dysfunction: the Rotterdam study

Area of Science:

• Cardiovascular Research
• Aging Biology
• Inflammation Science

Background:

• Aging is associated with increased vascular dysfunction.
• Chronic low-grade systemic inflammation is implicated in aging processes.
• High-sensitivity C-reactive protein (hsCRP) is a key inflammatory marker.

Purpose of the Study:

• To investigate the mediating role of hsCRP in the relationship between aging and vascular dysfunction.
• To compare the causal contribution of hsCRP versus lipid metabolism in this association.
• To examine sex-specific differences in inflammatory pathways related to vascular aging.

Main Methods:

• Analysis of data from the Rotterdam Study (N=7,591 for cIMT, N=6,488 for PWV).
• Mediation analysis assessing hsCRP, total cholesterol, and HDL in the age-vascular dysfunction link, with sex-stratification.
• Two-sample Mendelian Randomization (MR) to explore causal effects of hsCRP on vascular outcomes.

Main Results:

• hsCRP significantly mediated the effect of age on carotid intima-media thickness (cIMT) and pulse wave velocity (PWV).
• Mediation by hsCRP was comparable to lipid markers and stronger in men than women.
• MR analyses supported a potential causal link between hsCRP and PWV, but not cIMT.

Conclusions:

• Systemic inflammation (hsCRP) mediates and potentially causally contributes to age-related vascular stiffness, particularly in men.
• Findings highlight inflammation's role in functional vascular aging.
• Anti-inflammatory strategies may complement lipid-lowering therapies for cardiovascular risk reduction.