Blood pressure, proteomic vascular ageing, and incident cardiovascular disease

AIMS: Blood proteomic profiling may model vascular biological ageing with high precision. This study aimed to assess the association between blood pressure and proteomic vascular ageing, and its potential mediation role in the relationship between high blood pressure and incident cardiovascular events. METHODS AND RESULTS: Among 45 387 UK Biobank participants, we developed a proteomic vascular ageing signature (vascular age gap) using 21 heart- and artery-enriched proteins via a LightGBM model. Associations with vascular age gap were evaluated for blood pressure categories and continuous systolic/diastolic blood pressure (SBP/DBP). Mediation analyses examined the role of proteomic vascular ageing in the link between high blood pressure and cardiovascular events. Compared to normotensive participants, the vascular age gap was significantly higher in those with high-normal blood pressure (0.122 ± 0.048 years, P = 0.011), Grade 1 hypertension (0.266 ± 0.049 years, P < 0.001), and Grade 2 hypertension (0.494 ± 0.071 years, P < 0.001). Non-linear associations were observed for both SBP and DBP, with thresholds near 120/80 mmHg. The associations were stronger in midlife adults. The vascular age gap may mediate 3.73-10.59% of the association between Grade 2 hypertension and cardiovascular events. No mediation was observed for peripheral artery disease in Grade 2 hypertension. The most influential proteins exhibited potential mediation effects, with TNFRSF11B and CRLF1 consistently contributing to mediation across blood pressure categories and outcomes. CONCLUSION: High blood pressure is associated with accelerated proteomic vascular ageing, which potentially mediates its link to cardiovascular events. This supports vascular age gap as a modest but significant marker of blood pressure-related cardiovascular risk.