Vascular Medicine Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic Angina A Randomized Sham-Controlled Study

Background—Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. Methods and Results—Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n 28) or sham EECP (n 14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F1 , endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial ( 51% versus 2%) and femoral ( 30% versus 3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite ( 36% versus 2%), and 6-keto-prostaglandin F1 ( 71% versus 1%), whereas it decreased endothelin-1 ( 25% versus 5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine ( 28% versus 0.2%) in treatment versus sham groups, respectively (all P 0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor( 16% versus 12%), monocyte chemoattractant protein-1 ( 13% versus 0.2%), soluble vascular cell adhesion molecule-1 ( 6% versus 1%), high-sensitivity C-reactive protein ( 32% versus 5%), and the lipid peroxidation marker 8-isoprostane ( 21% versus 1.3%) in treatment versus sham groups, respectively (all P 0.05). EECP reduced angina classification ( 62% versus 0%; P 0.001) in treatment versus sham groups, respectively. Conclusions—Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease. (Circulation. 2010;122:1612-1620.)