Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis

Abstract

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.

Keywords: cardiovascular diseases; endothelium; meta‐analysis; prognosis.

Figure 1

Scheme of risk bias assessment.

Figure 2

Flow chart of the study selection procedure. FMD indicates flow‐mediated dilation; RH‐PAT, reactive hyperemia–peripheral arterial tonometry.

Figure 3

Forest plot of unadjusted risk ratio of FMD for cardiovascular events. CV indicates cardiovascular; FMD, flow‐mediated dilation; RR, risk ratio.

Figure 4

Forest plot of adjusted risk ratio of FMD for cardiovascular events. CV indicates cardiovascular; FMD, flow‐mediated dilation; RR, risk ratio.

Figure 5

Forest plot of unadjusted risk ratio of Ln_RHI for cardiovascular events. CV indicates cardiovascular; Ln_RHI, logarithmic value of reactive hyperemia index; RR, risk ratio.

Figure 6

Forest plot of adjusted risk ratio of Ln_RHI for cardiovascular events. CV indicates cardiovascular; Ln_RHI, logarithmic value of reactive hyperemia index; RR, risk ratio.

Figure 7

Relative risk for FMD and Ln_RHI values. (A) Univariate relative risk and (B) Multivariate relative risk. The relative risk for cardiovascular events in each FMD or Ln_RHI value is relative to the expected event rate with the median value of FMD or Ln_RHI. CV indicates cardiovascular; FMD, flow‐mediated dilation; Ln_RHI, logarithmic value of reactive hyperemia index; RR, risk ratio.

Figure 8

Funnel plot of flow‐mediated vasodilation (FMD) studies. Funnel plot of univariate (A) and multivariate (B) risk ratio of FMD.

Figure 9

Funnel plot of RH‐PAT studies. Funnel plot of univariate (A) and multivariate (B) risk ratio of Ln_RHI. Ln_RHI indicates logarithmic value of reactive hyperemia index; RH‐PAT, reactive hyperemia–peripheral arterial tonometry.