Endothelial Dysfunction, Oxidative Stress, and Risk of Cardiovascular Events in Patients With Coronary Artery Disease

Abstract

Background Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease. Methods and Results Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine ( P <0.001) and sodium nitroprusside ( P <0.05), but greater benefit from vitamin C ( P <0.01). The Cox proportional regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation ( P =0.001), the effect of vitamin C ( P =0.001), and age ( P =0.016) remained independent predictors of cardiovascular events. Conclusions Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribute not only to endothelial dysfunction but also to coronary artery disease activity.

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

“…Endothelial dysfunction has been shown to be a good predictor of cardiovascular events [19][20][21][22][23][24] and has been described as a 'barometer for cardiovascular risk' [25]. We were therefore somewhat surprised by our previous study, which showed that in a normotensive population of patients with type 2 diabetes, spironolactone actually worsened the key prognostic marker of endothelial function [10].…”

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

“…Endothelial dysfunction is the major antecedent to atherosclerosis, a predictor of clinical CVD risk, and is linked to many common disorders of aging including cognitive impairments, Alzheimer's disease, motor dysfunction, insulin resistance, and sarcopenia (Heitzer et al ., 2001; Gokce et al ., 2002; Lakatta & Levy, 2003; Widlansky et al ., 2003; Seals et al ., 2011, 2014). We have previously demonstrated that arterial SIRT1 activity is reduced with aging and contributes to the age‐related impairment in endothelial function (Donato et al ., 2011; Gano et al ., 2014).…”

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

“…Similarly, abnormal vasomotion occurs in subjects with uncomplicated hypertension (71), diabetes (72)(73)(74)(75), cigarette smoking (76,77) and low levels of high density lipoprotein (78,79). Oxidized low density lipoprotein plays an important role in abnormal endothelial vasorelaxation, leukocyte adhesion and endothelin production (80)(81)(82)(83). In addition, oxygen free radicals impair endothelial function through direct inactivation of NO (84).…”