Abstract 1582: Hyperleptinemia is Associated with Vascular Dysfunction in Patients with Coronary Artery Disease
Purpose: Increased body mass is an important risk factor for adverse prognosis in patients with coronary heart disease. The mechanisms responsible for this association are poorly understood. The adipokine, leptin is a pro-inflammatory mediator that has a direct effect on the vascular endothelium. We assessed the relationship between leptin concentrations and vascular function in patients with coronary artery disease.
Methods: We recruited 84 patients with a typical cardiovascular risk factor profile and a mean body-mass index (BMI) of 29±0.5 kg/m2. Bilateral forearm blood flow, plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured before and during intra-brachial infusion of substance P (2, 4, and 8 pmol/min). Endothelium independent vasodilatation was measured in response to sodium nitroprusside (2, 4, 8 mcg/min). Patients were stratified into tertiles according to plasma leptin concentrations (4.1±0.2, 9.2±0.5, 26.3±2.6 ng/mL).
Results: Plasma leptin concentrations correlated with BMI (r=0.636, P<0.0001), C-reactive protein (r=0.310, P<0.005) and plasma PAI-1 antigen concentrations (r=0.381, P<0.001). There were no differences between resting arterial pressure or forearm blood flow between groups. Patients with elevated leptin concentrations had impaired endothelium-dependent vasodilatation during substance P infusion (9.2±0.7 vs. 11.3±0.6 ml/100ml of tissue/min, peak dose, P<0.02), whereas the response to sodium nitroprusside did not differ. Substance P caused a dose-dependent increase in plasma t-PA concentrations (P<0.001), with this response augmented in patients with the highest leptin concentrations (16.0±2.8 vs. 9.7±1.6 ng/100ml of tissue/min, P=0.01).
Conclusions: The adipokine leptin is associated with systemic inflammation, altered fibrinolytic response and endothelial dysfunction in patients with coronary artery disease. This provides a potentially important mechanism whereby obesity and increased plasma leptin concentrations increase risk in patients with coronary artery disease.