Abstract 10013: Total and High Molecular Weight Adiponectin and Future Risk of Ischemic Stroke and Coronary Heart Disease in Older Adults
Background: Total circulating adiponectin (APN) has shown an inverse association with incident cardiovascular disease (CVD) in healthy middle-aged cohorts. In older adults, however, the relation has been directionally opposite, with higher levels predicting increased CVD risk. Data on high molecular weight (HMW) APN, which may have stronger insulin-sensitizing properties, are sparse.
Methods: We investigated the associations of total and HMW APN with first-ever CVD (ischemic stroke & coronary heart disease) in the Cardiovascular Health Study, a large prospective cohort of older adults. Total and HMW APN were measured by ELISA in participants free of prevalent CVD at the 1992-93 exam with available serum (n=3,290; age 74.4±5.1; 63.3% women).
Results: During median follow-up of 16 yrs, 1314 CVD events occurred. Adjusted cubic spline analyses revealed that the associations of total & HMW APN with CVD were U-shaped, with inflection points at 20 and 10 mg/L (∼75iles), respectively. After adjustment for age, sex, race, SES, center, HTN, smoking, alcohol, estrogen Rx, aspirin Rx, eGFR, health status, & BMI, levels of total APN up to 20 mg/L were significantly inversely associated with incident CVD (HR=0.87 [95% CI=0.79-0.97] per SD [7.8 mg/L] increase), though this was not significant for HMW APN levels <10 mg/L (HR=0.90 [0.79-1.02] per SD [5.8 mg/L] increase). These associations became or remained null with inclusion of mediators (diabetes, LDL, HDL, triglycerides, CRP). For levels above these cutpoints, total APN was significantly positively associated with CVD after adjustment for confounders, and both total (HR=1.23 [1.09-1.40]) and HMW APN (HR=1.12 [1.00-1.25]) exhibited significant positive associations after adjustment for mediators.
Conclusions: In this large older cohort, total and HMW APN exhibited similar U-shaped relationships with CVD. The inverse relation in the lower range was abolished, while the positive association in the higher range was unchanged or strengthened, by inclusion of mediators, suggesting that higher values in the upper range reflect adverse processes separate from adiponectin's beneficial glycometabolic properties. These findings help explain the paradoxical associations of total APN with CVD reported previously.
- © 2011 by American Heart Association, Inc.