Background:
In population studies leptin is directly associated with coronary heart disease (CHD) and ischemic stroke, but leptin’s proatherogenic properties in animal models are not clear. Opposite to leptin, adiponectin is atheroprotective in animal models but epidemiological investigations evaluating its role in cardiovascular disease (CVD) have been contradictory. Because the predictive significance of previously reported racial differences in adipokine levels remains unclear, we assessed the prospective association of the two adipokines with the risk of incident CVD events in African Americans (AA), known to have a high prevalence of cardiometabolic risk factors.
Methods:
Serum specimens from 5,108 AA Jackson Heart Study (JHS) participants without prevalent CVD at baseline examination (2000-2004) were analyzed by ELISA for adiponectin levels and by a radioimmunoassay method for leptin levels. Age-adjusted correlation coefficients and Cox proportional hazards regression models were used to estimate the associations of the two adipokines with incident CHD and incident ischemic stroke.
Results:
During 6.2 years average of follow-up, 164 incident CHD and 122 incident ischemic stroke events were documented. Among our study participants (63% women; mean age 54 ± 13 years), the mean (standard deviation, SD) was 6.14 (4.55) μg/mL in women and 4.19 (3.51) μg/mL in men for adiponectin and 37.54 (24.02) ng/mL in women and 11.30 (10.36) ng/mL in men for leptin. Adiponectin statistically significantly correlated with insulin resistance, as measured continuously by the homeostasis assessment model for insulin resistance, HOMA-IR (r = - 0.41 in women and r = - 0.30 in men) and with high-density lipoprotein cholesterol, HDL-cholesterol (r = 0.37 in women and r = 0.39 in men). Leptin significantly correlated with body mass index, BMI (r = 0.66 in women and r = 0.73 in men) and with HOMA-IR (r = 0.38 in women and r = 0.50 in men). After multivariate adjustment that included age, BMI, HDL-cholesterol, triglycerides, HOMA-IR, systolic blood pressure, hypertension medication, smoking and physical activity, adiponectin was marginally directly associated among women with incident CHD (HR = 1.27, 95% CI = 1.00 - 1.61 per 1 SD; p = 0.05), but not among men (p = 0.29). It was associated among women with incident stroke, HR = 1.36 (1.05 - 1.76) per 1 SD (p = 0.02), but not among men (p = 0.09). Leptin was not associated with incident CHD nor incident stroke.
Conclusion:
In the largest community-based cohort of African Americans, a higher adiponectin level was associated among women with a higher risk of incident stroke and marginally with a higher risk of incident coronary heart disease. Whether adiponectin harbors harmful properties, or it is produced in response to vascular inflammation to counter the atherosclerotic process, or the putative ’adiponectin resistance’ phenomenon acts, should be further investigated.
Associations of Adiponectin and Leptin with Incident Coronary Heart Disease and Ischemic Stroke in African Americans: The Jackson Heart Study
