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

Soroush Mohammadi Jouabadi1,2, Annique Claringbould1, A H Jan Danser1

  • 1Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.

European Journal of Preventive Cardiology
|June 25, 2025
PubMed
Summary
This summary is machine-generated.

Chronic inflammation, measured by high-sensitivity C-reactive protein (hsCRP), significantly mediates age-related vascular dysfunction, especially in men. This suggests anti-inflammatory treatments could aid cardiovascular health alongside lipid management.

Keywords:
Genetic analysisInflammationLipid metabolismMendelian RandomizationPWVVascular ageingcIMThsCRP

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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.