This 6-month, randomized, double-blind, placebo-controlled pilot study investigates whether high-dose resveratrol (500 mg/day), when added to standard therapy, can improve endothelial function and reduce inflammation in patients with stable ischemic heart disease. While preclinical data and small trials have shown promising effects on vascular health and inflammation, larger studies have lacked consistent results. This study aims to provide more robust clinical evidence by assessing flow-mediated dilation (FMD) and high-sensitivity C-reactive protein (hs-CRP) as primary outcomes in a well-defined patient group.

This study is a 6-month, double-blind, placebo-controlled pilot randomized clinical trial designed to evaluate the effects of high-dose resveratrol (500 mg/day) on endothelial function and systemic inflammation in patients with stable ischemic heart disease (IHD). Despite widespread interest in resveratrol's cardioprotective potential, there remains limited high-quality clinical evidence supporting its benefit in established cardiovascular disease. Preclinical and small human studies suggest that resveratrol may enhance endothelial function via eNOS activation and oxidative stress reduction, reduce inflammation by lowering pro-inflammatory markers like CRP and cytokines, and mimic caloric restriction pathways through sirtuin activation. However, its clinical efficacy may be hindered by factors such as poor bioavailability, heterogeneous patient populations, and overlapping effects of standard cardiovascular drugs. This trial will randomize eligible participants, aged 45 to 75 with stable IHD and elevated inflammation or impaired endothelial function, to receive either resveratrol or placebo alongside their regular medication. The primary endpoints are changes in flow-mediated dilation (FMD) and high-sensitivity C-reactive protein (hs-CRP) from baseline to six months. Secondary outcomes include changes in inflammatory biomarkers, lipid profile, arterial stiffness, blood pressure, quality of life, and exercise tolerance. The study also assesses the safety and tolerability of long-term high-dose supplementation. With an estimated 70 participants (35 per arm), the study aims to detect a clinically meaningful 3% improvement in FMD with 80% power, contributing valuable data to guide future larger-scale investigations.

Inclusion Criteria:

• Men and women aged 45-75 years.
• Clinically documented stable ischemic heart disease (≥6 months post-myocardial infarction or post-revascularization).
• On stable, guideline-recommended cardiac medications (e.g., statins, beta-blockers, ACE inhibitors).
• Elevated hs-CRP (>2 mg/L) or impaired endothelial function (FMD <7%) at baseline (optional enrichment criterion).
• Able and willing to give written informed consent.

Exclusion Criteria:

• Heart failure with reduced ejection fraction <30% or New York Heart Association (NYHA) class III-IV.
• Severe hepatic or renal dysfunction.
• Decompensated diabetes (e.g., HbA1c >10%).
• Current or recent (past 3 months) use of high-dose antioxidant/anti-inflammatory supplements (other than a standard multivitamin).
• Known allergy or intolerance to resveratrol.