Vascular aging biomarkers and mortality and cardiovascular outcomes: a systematic review and meta-analysis

Background Vascular aging is associated with cardiovascular disease and mortality, but the evidence supporting candidate biomarkers varies. We assessed associations between vascular aging biomarkers and clinical outcomes across prospective studies. Methods We searched CENTRAL, MEDLINE and EMBASE and additional sources for prospective studies with at least six months of follow-up. We evaluated 16 biomarker categories and five outcomes using random-effects meta-analysis of risk estimates and event counts, trial sequential analysis, subgroup analyses and sensitivity analyses. The review was registered in PROSPERO (CRD42022377292). Results Across 223 studies involving 1,325,186 participants, a coronary artery calcium score above zero, a low ankle-brachial index and shorter leucocyte telomere length are associated with both mortality outcomes. Their pooled hazard ratios for all-cause mortality are 1.59 (95% confidence interval 1.35–1.87), 1.82 (1.66–2.01) and 1.13 (1.09–1.18), respectively; corresponding estimates for cardiovascular mortality are 1.13 (1.04–1.22), 2.28 (1.91–2.74) and 1.11 (1.04–1.18). Trial sequential analyses support these associations, and sensitivity analyses do not materially change the main findings. Associations with stroke, myocardial infarction and major adverse cardiovascular events vary by biomarker. Conclusions These findings identify candidate biomarkers for further vascular aging research. Heterogeneity and residual confounding limit clinical interpretation. Their combined predictive value and usefulness for guiding interventions require prospective validation.