To investigate the role of chronic low-grade systemic inflammation, specifically high-sensitivity C-reactive protein (hsCRP), in mediating the relationship between ageing and vascular dysfunction, and to assess its causal contribution relative to lipid metabolism, particularly focusing on sex-specific differences.
Key Findings:
hsCRP significantly mediated the effect of age on cIMT (2.66%, P = 0.001) and PWV (2.56%, P = 4.95 × 10−9), indicating a notable role in vascular ageing.
Mediation effects were stronger in men compared to women, highlighting potential sex differences in inflammatory pathways.
MR analyses provided genetic support for a potential causal relationship between hsCRP and PWV, but not cIMT, suggesting targeted interventions may be necessary.
Interpretation:
Systemic inflammation indexed by hsCRP appears to mediate and potentially contribute causally to age-related vascular stiffness, particularly in men, suggesting inflammation plays a critical role in functional vascular ageing and may inform future therapeutic strategies.
Limitations:
Observational nature of the study limits causal inference, and potential confounding factors such as lifestyle and genetic predispositions were not fully accounted for.
Conclusion:
Findings support the role of inflammation in vascular ageing and suggest that anti-inflammatory strategies may complement lipid-lowering approaches in reducing cardiovascular risk, emphasizing the need for integrated treatment strategies.
