Endothelial dysfunction, measured by reactive hyperaemia using strain‐gauge plethysmography, is an independent predictor of adverse outcome in heart failure

Abstract

AimsIn congestive heart failure (CHF), arterial response is regulated by endothelial molecules. The aim of this study was to evaluate whether endothelial dysfunction (ED) was a predictor of outcome in a cohort of patients with heart failure. Methods and resultsEndothelial function was assessed in 242 patients with CHF by forearm reactive hyperaemia measured with intermittent venous occlusion plethysmography using a mercury strain gauge. The main endpoints were: 'total events' (death, heart attack, angina, stroke, NYHA class IV, or hospitalization due to heart failure) analysed using Cox regression for repeated events and 'death'. Patients were followed-up for 5 years. Post-hyperaemia forearm blood flow (PHFABF) was an independent predictor of total events [P ¼ 0.01; hazard ratio [Exp(B)] 0.665, standard error (SE) 0.182]. Risk stratification by basal forearm blood flow (BFABF) showed that patients with basal blood flow above the median (3.03 mL min 21 100 mL 21 ) benefited from an increase in PHFABF, whereas in patients with a BFABF below the median, the increase in PHFABF did not diminish the risk of events. There was no relation between variations in PHFABF and death. ConclusionPost-hyperaemia forearm blood flow, as a measure of ED, is an independent predictor of major events in patients with CHF. A BFABF below the median is more predictive of an increased risk of complications.-Heart failure † Endothelial function † Strain gauge plethysmography † Reactive hyperaemia † Post-hyperaemia forearm blood flow

Endothelial Dysfunction, Arterial Stiffness, and Heart Failure

“…The degree of endothelial dysfunction correlates with HF severity and functional capacity (54,148). Endothelial dysfunction independently predicts major clinical events in HF (147), including mortality risk (141,146,149,150). In patients with and without coronary artery disease, presence of epicardial or microvascular endothelial dysfunction predicts death (151)(152)(153)(154)(155)(156).…”

Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation

“…While lower levels of constitutively produced NO are involved in the regulation of mitochondrial activity by competing with oxygen at the level of complex IV of the respiratory chain (Erusalimsky & Moncada, 2007), higher concentrations of NO have been shown to persistently inhibit mitochondrial function by nitrosylation of electron chain complexes, in particular complex I (Clementi et al, 1998), and to cause DNA damage (Delaney et al, 1993;deRojas-Walker et al, 1995). Endothelial dysfunction is apparent in conditions such as hypertension, heart failure, coronary artery disease, and atherosclerosis (Cai & Harrison, 2000;Vanhoutte, 2009;de Berrazueta et al, 2010). During these pathophysiological conditions, eNOS-dependent conversion of L-arginine to NO is impaired and thus NO bioavailability is reduced, concurrent with decrease in NO-mediated vasorelaxation (Shimokawa et al, 1991;Pou et al, 1992;Harrison, 1997;Wilcox et al, 1997).…”

Endothelial dysfunction as a nexus for endothelial cell-cardiomyocyte miscommunication

“…Independently of the initial underlying pathology of HF, EC dysfunction plays a major role in the progression of the disease and has important prognostic value on clinical outcomes (Fischer et al, 2005; Shechter et al, 2009; De Berrazueta et al, 2010). …”