Background: Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta-analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow-mediated dilation (FMD), and reactive hyperemia--peripheral arterial tonometry (RH-PAT) for future cardiovascular events.

Methods and results: Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH-PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH-PAT index (Ln_RHI) using random-effects models. Thirty-five FMD studies of 17 280 participants and 6 RH-PAT studies of 1602 participants were included in the meta-analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84-0.91], P<0.001, 0.1 increase in Ln_RHI 0.79 [0.71-0.87], P<0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk.

Conclusions: Noninvasive peripheral endothelial function tests, FMD and RH-PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function-guided strategy can provide benefit in improving cardiovascular outcomes.