Context: Adiponectin levels appear weakly linked to incident vascular disease but the HMW fraction may be more relevant.

Objective: To test whether high molecular weight (HMW) adiponectin, the key biologically active fraction, is linked to incident 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 year) case control study nested within the British Women's Heart and Health Study. All women were postmenopausal.

Setting: Primary care

Results: Among both cases (n = 167) and controls (n = 333), HMW adiponectin positively correlated with age and HDL-C and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, HOMA-IR scores, CRP and triglycerides, in similar fashion to total adiponectin. The age-adjusted relative risk ratio for a doubling of HMW adiponectin was 0.96 (95% CI: 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, HRT 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:total adiponectin with CHD risk: age-adjusted relative risk per doubling of the ratio 1.10 (95%CI: 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.