Comparison of metabolic vasodilation in response to exercise and ischemia and endothelium-dependent flow-mediated dilation in African-American versus non-African-American patients with chronic heart failure.

Race-related disparities in response to therapy and clinical outcomes have been reported in patients with chronic heart failure (HF). Vascular dysfunction is an important determinant of therapeutic response and clinical outcomes in chronic HF, but race-related differences of vasodilator responses in those with chronic HF have not been previously characterized. We assessed metabolic vasodilation in response to exercise and ischemia and endothelium-dependent flow-mediated dilation in conduit and resistance vessels with strain gauge venous occlusion plethysmography and high-resolution ultrasound imaging in the forearm circulation of 69 African-American and 188 non-African-American patients with chronic HF.

Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure.

Background: Endothelial function is known to be impaired in subjects with chronic heart failure (CHF), but the association between endothelial function and subsequent mortality risk in CHF has not been previously reported.

Methods And Results: Biomarkers of endothelial function in the systemic arterial circulation (flow-mediated dilation [FMD] in the brachial artery) and the pulmonary circulation (exhaled nitric oxide [NO] production during submaximal exercise) were prospectively assessed in 259 subjects with New York Heart Association class II-III CHF. In subjects with FMD measurements (n=149), there were 12 deaths and 5 urgent transplantations over a median follow-up period of 841 days.

Comparison of suppression of the circulating and vascular renin-angiotensin system by enalapril versus trandolapril in chronic heart failure.

Experimental studies suggest that angiotensin-converting enzyme (ACE) inhibitors with high tissue affinity confer a greater degree of vascular renin-angiotensin system suppression than those with low tissue affinity despite similar suppression of the circulating renin-angiotensin system. To test this hypothesis in a clinical setting, we randomized subjects with chronic heart failure to receive the low tissue affinity ACE inhibitor enalapril or the high tissue affinity ACE inhibitor trandolapril, and assessed the degree of circulating and vascular renin-angiotensin system suppression. Vascular renin-angiotensin system suppression was determined by measuring the pressor response to intravenous injections of angiotensin I.

Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure.

ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner.

High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort.

Objectives: This study sought to determine the effect of lipoprotein(a), or Lp(a), levels and apolipoprotein(a), or apo(a), sizes on endothelial function and to explore ethnic differences in their effects.

Background: Although high levels of Lp(a) have been shown to confer increased cardiovascular risk in Caucasians, its significance in non-Caucasian populations is uncertain. The pathogenic role of the apo(a) component of Lp(a) is also unclear.

Effect of dexrazoxane on homocysteine-induced endothelial dysfunction in normal subjects.

Objective: Dexrazoxane is an antioxidant prodrug that on hydrolysis is converted into an intracellular iron chelator. We hypothesized that the antioxidant effects of dexrazoxane would prevent homocysteine-induced endothelial dysfunction in the brachial artery of normal human subjects.

Methods And Results: Ten healthy volunteers completed a randomized, double-blind, crossover study.