Resveratrol as an Anti-inflammatory Agent in Coronary Artery Disease:A Systematic Review, Meta-Analysis and Meta-Regression

Background: Resveratrol is a non-flavonoid polyphenol that shows promise in reducing proinflammatory factors and maintaining endothelial function, which hints at its potential role in slowing atherosclerosis and preventing acute coronary events. Objective: To study the cardioprotective effects of resveratrol on inflammatory mediators and endothelial function in patients with coronary artery disease(CAD). Methods: A thorough search was conducted in databases(Cochrane Library, Pro Quest, Pub Med, LILACS, Science Direct, Springer, Taylor&Francis, CNKI, Wanfang, and Weipu) until September 24, 2023. The vasopro-inflammatory mediators, endothelial function and outcomes related to cardiovascular events were observed. Titles and abstracts were assessed, and bias was evaluated with Cochrane Ro B 2.0. Heterogeneity of results was explored by metaregression, certainty of evidence was assessed by the GRADE system, and conclusive evidence was enhanced by trial sequence analysis. Results: Ten randomized controlled trials and 3 animal studies investigated resveratrol's impact on inflammatory mediators and endothelial function. In primary prevention studies, meta-analysis showed a significant reduction(95% CI: –0.73 to –0.20; P=0.0005) in tumor necrosis factor-α(TNF-α) expression with resveratrol, demonstrating a dose-dependent relationship. No significant difference was observed in interleukin-6(IL-6) expression with P=0.58 for primary prevention and P=0.57 for secondary prevention. Vascular endothelial nitric oxide synthase(e NOS) expression was significantly increased after resveratrol pre-treatment following CAD events. Secondary prevention studies yielded no significant results; however, meta-regression identified associations between age, hypertension, and lower doses with the extent of TNF-α alterations. High certainty of evidence supported TNF-α reduction, while evidence for IL-6 reduction and e NOS elevation was deemed low. Conclusions: Resveratrol reduces TNF-α in individuals at risk for CAD, specifically 15 mg per day. However, its usefulness in patients with confirmed CAD is limited due to factors such as age, high blood pressure, and insufficient dosage. Due to the small sample size, the reduction of IL-6 is inconclusive. Animal studies suggest that resveratrol enhances endothelial function by increasing e NOS.(PROSPERO registration No. CRD42023465234)