High Molecular Weight Adiponectin Is Not Associated with Incident Coronary Heart Disease in Older Women: A Nested Prospective Case-Control Study

CONTEXT: Adiponectin levels appear weakly linked to incident vascular disease, but the high molecular weight (HMW) fraction may be more relevant. OBJECTIVE: Our objective was to test whether HMW adiponectin, the key biologically active fraction, is linked to incident coronary heart disease (CHD) events. DESIGN, PARTICIPANTS, AND MAIN OUTCOME MEASURES: We assessed the association between HMW adiponectin (measured by ELISA) and CHD risk in a prospective (4-yr) case-control study nested within the British Women's Heart and Health Study. All women were postmenopausal. SETTING: Women were seen in a primary care setting. RESULTS: Among both cases (n = 167) and controls (n = 333), HMW adiponectin positively correlated with age and high-density lipoprotein cholesterol and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, homeostasis model assessment for insulin resistance scores, C-reactive protein, and triglycerides, in similar fashion to total adiponectin. The age-adjusted relative risk ratio for a doubling of HMW adiponectin was 0.96 (95% confidence interval, 0.78-1.18), and adjustment for any of the potential confounding or mediating variables did not substantively alter this. Additional adjustments for childhood social class, alcohol consumption, hormone replacement therapy use, statin, aspirin, or blood pressure medication did not alter the null association. When we examined the effect of HMW adiponectin by quarters of its distribution, there was no evidence of any associations (P trend = 0.71). There was also no association of the ratio of HMW adiponectin to total adiponectin with CHD risk; age-adjusted relative risk per doubling of the ratio was 1.10 (95% confidence interval, 0.80-1.50). CONCLUSIONS: Despite associations with total adiponectin and insulin resistance, our data go against any apparent association between HMW adiponectin levels and incident CHD events.