High-molecular-weight and total adiponectin levels and incident symptomatic peripheral artery disease in women: a prospective investigation.

BACKGROUND Adiponectin is linked to reduced diabetes risk and may be antiatherogenic, yet clinical data show no consistent relationship with incident cardiovascular events, especially among women. To our knowledge, no prior prospective studies have evaluated adiponectin, including high-molecular-weight (HMW) adiponectin, and incident peripheral artery disease (PAD). METHODS AND RESULTS We evaluated the relationship of total adiponectin, HMW adiponectin, and the HMW-to-total adiponectin ratio with incident symptomatic PAD in a prospective, nested case-control study conducted within the Women's Health Study (n=110 cases, n=230 controls, frequency matched in strata defined by 5-year age categories, smoking, fasting status, and follow-up time; median cohort follow-up=13.2 years). Baseline median levels of HMW and total adiponectin were significantly lower in women developing PAD than in those remaining event free (HMW: 3.3 versus 3.8 μg/mL, P=0.0005; total: 5.6 versus 7.4 μg/mL, P<0.0001). The ratio did not differ significantly between groups. Age-adjusted PAD odds ratios (95% confidence intervals) across tertiles were 1.0, 0.66 (0.39-1.13), and 0.40 (0.22-0.74) for HMW and 1.0, 0.74 (0.43-1.25), and 0.35 (0.18-0.65) for total adiponectin (P(trend)=0.004 and 0.001, respectively). Results were similar after adjustment for traditional cardiovascular risk factors, use of postmenopausal hormone therapy, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, leptin, hemoglobin A(1c), and fasting insulin (adjusted odds ratio and 95% confidence interval for HMW: 1.0, 0.62 [0.29-1.34], 0.30 [0.12-0.74]; total: 1.0, 0.46 [0.22-1.00], 0.30 [0.12-0.76]; P(trend)=0.01 for both). CONCLUSIONS Total and HMW adiponectin are inversely associated with incident PAD among initially healthy women. These prospective data support a protective role for this adipokine in peripheral atherosclerosis development.