Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease

Abstract

Background— There is an ongoing debate as to whether the gastrointestinal safety of COX-2 inhibition compared with nonsteroidal antiinflammatory drugs (NSAIDs) may come at the cost of increased cardiovascular events. In view of the large number of patients at cardiovascular risk requiring chronic analgesic therapy with COX-2 inhibitors for arthritic and other inflammatory conditions, the effects of selective COX-2 inhibition on clinically useful surrogates for cardiovascular disease, particularly endothelial function, need to be determined. Methods and Results— Fourteen male patients (mean age, 66±3 years) with severe coronary artery disease (average of 2.6 vessels with stenosis >75%) undergoing stable background therapy with aspirin and statins were included. The patients received celecoxib (200 mg BID) or placebo for a duration of 2 weeks in a double-blind, placebo-controlled, crossover fashion. After each treatment period, flow-mediated dilation of the brachial artery, high-sensitivity C-reactive protein, oxidized LDL, and prostaglandins were measured. Celecoxib significantly improved endothelium-dependent vasodilation compared with placebo (3.3±0.4% versus 2.0±0.5%, P =0.026), whereas endothelium-independent vasodilation, as assessed by nitroglycerin, remained unchanged (9.0±1.6% versus 9.5±1.3%, P =0.75). High-sensitivity C-reactive protein was significantly lower after celecoxib (1.3±0.4 mg/L) than after placebo (1.8±0.5 mg/L, P =0.019), as was oxidized LDL (43.6±2.4 versus 47.6±2.6 U/L, P =0.028), whereas prostaglandins did not change. Conclusions— This is the first study to demonstrate that selective COX-2 inhibition improves endothelium-dependent vasodilation and reduces low-grade chronic inflammation and oxidative stress in coronary artery disease. Thus, selective COX-2 inhibition holds the potential to beneficially impact outcome in patients with cardiovascular disease.

Xuezhikang, an Extract of Cholestin, Protects Endothelial Function Through Antiinflammatory and Lipid-Lowering Mechanisms in Patients With Coronary Heart Disease

“…26 Interestingly, reducing CRP levels over time is associated with improvement of endothelium-dependent vasodilation in patients with coronary artery disease. 25,27 In this study, xuezhikang had a potent effect on lowering CRP, which was associated with improvement of fasting FMD. This supports the hypothesis that xuezhikang may protect endothelial function partly through an antiinflammatory mechanism.…”

Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects

“…Investigation of possible mechanisms, by which low-dose aspirin can influence on BP of patients with AH and hypercholesterolaemia Improvement of endothelial function was shown in acute studies, 28,29 while results of chronic trials are conflicting [30][31][32] Our study demonstrates that addition of low-dose aspirin in hypertensive and hypercholesterolaemic subjects on top of antihypertensive and statins improves endothelial function and reduces BP Homogeneity of the studied population. Demonstration of synergistic interactions between aspirin and statins on BP reduction via improvement of NOmediated endothelial function Small study.…”

“…29 Results of chronic trials are conflicting. [30][31][32] Since other COX inhibitors showed no beneficial vascular effects, aspirin might exhibit a vasculoprotective, COX-independent mechanism. Recently, Taubert et al 33 demonstrated that therapeutically relevant concentrations of aspirin elicit nitric oxide (NO) release from vascular endothelium due to a direct acetylation of the eNOS protein, but is independent of COX inhibition or inhibition of superoxidemediated NO degradation.…”

Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II–Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats

“…This is the first report showing that rofecoxib possesses antioxidative property and inhibits Ang II-induced cardiovascular alterations. Recent data indicated that selective COX-2 inhibition by celecoxib reduces oxidized LDL in patients with coronary artery disease, 15 slightly decreased salt-induced hypertension, and normalized the indicator of oxidative stress, 8-isoprostane, in hypertensive rats. 16 However, different from our result, rofecoxib (2 mg/kg per day) treatment did not show any antioxidative effect in those salt-induced hypertensive rats.…”