Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease - Additive value of flow-mediated dilation to ankle-brachial pressure index

Background - Endothelial dysfunction plays a key role in atherogenesis. We prospectively investigated the impact of noninvasive measurement of endothelial function on cardiovascular risk in peripheral arterial disease (PAD). The study was specially aimed at assessing whether brachial artery flow-mediated dilation (FMD) added to the predictive value of ankle-brachial pressure index (ABPI). Methods and Results - Of 131 patients monitored for a mean of 23 +/- 10 months, 18 had a coronary event, 12 a cerebrovascular event, and 9 a peripheral event. The median FMD was lower in patients with an event than in those without (5.8% versus 7.6%, P < 0.05), whereas vasodilation to nitroglycerin was similar in the two groups. The cardiovascular event rate was higher in patients with FMD below the median versus those with FMD above the median (P < 0.001 by log-rank test). In a Cox proportion hazard model, independent predictors of events were FMD below the median (P < 0.01), ABPI below the median (P < 0.01), and previous stroke (P < 0.02). Similar results were obtained when peripheral events were excluded from the analysis. Below-median ABPI and FMD combined was more accurate in predicting risk (relative risk [RR] 13.0; 95% CI, 3.0 to 56.2; P < 0.01) than ABPI (RR, 6.4; 95% CI, 1.4 to 29.1; P < 0.02) and FMD (RR, 4.8; 95% CI, 1.1 to 23.3; P < 0.05) alone. Conclusions - A low brachial artery FMD is an independent predictor of cardiovascular risk in patients with PAD and adds to the prognostic value of ABPI, which is currently the most powerful prognostic indicator in PAD.