Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort

Abstract

Background and Purpose - Leptin, important for body weight regulation, may be involved in the pathogenesis of the insulin resistance syndrome, associated with cardiovascular disease. We tested to determine whether leptin is a risk marker for first-ever stroke in a nested case-referent study. Methods - We identified 113 patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke) who, before the stroke, had participated in population-based health surveys in northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographic region. Blood pressure (BP), body mass index (BMI), and presence f smoking, diabetes, and hypertension were recorded. Total cholesterol, insulin, and leptin were analyzed in stored samples. Risk markers for first-ever stroke were analyzed by conditional logistic regression analysis. Results - Patients with hemorrhagic stroke had higher levels of BMI and systolic and diastolic BPs. Leptin levels were 72% and 59% higher in males and females, respectively, with hemorrhagic stroke versus referents. Patients with ischemic stroke more often had hypertension, diabetes mellitus, and higher fasting glucose and insulin levels. A diagnosis of hypertension and elevated systolic and diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels together with hypertension (OR = 16.28; 95% CI, 1.49 to 177.3) remained as significant risk markers in a multivariate model. The combination of high leptin and high systolic or diastolic BP were associated with a profoundly increased risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes, hypertension, and obesity (BMI ≥27), together with high levels of insulin, glucose, systolic and diastolic BP, were significant risk markers for first-ever ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to 3.86) remained as an independent risk marker in a multivariate model. Conclusions - Plasma leptin is strongly associated with an increased risk for first-ever hemorrhagic stroke, independent of other risk markers for cardiovascular disease. Leptin may be an important link in the development of cardiovascular disease in obesity.