This study examined the relationship between the metabolic syndrome, inflammation and incident peripheral artery disease (PAD) in women. A total of 27 111 women of the Women’s Health Study were followed for incident symptomatic PAD. During a median 13.3-year follow-up, women who had 1 or 2 metabolic syndrome criteria had a 2.5 fold increased PAD risk whereas women with established metabolic syndrome had a 3 fold increased risk independent of age, smoking, total cholesterol and physical activity. Women with the metabolic syndrome had a median CRP level of 4.0 ml/L and sICAM-1 concentration of 374 ng/mL compared to 1.5 mg/L and 333 ng/mL among women without the metabolic syndrome. After inclusion of CRP and ICAM-1 into multivariable models, the risk associated with the metabolic syndrome was substantially attenuated and no longer significant. In conclusion, the metabolic syndrome is associated with an increased risk of future PAD in women and this risk appears to be largely mediated by the effect of inflammation and endothelial activation.
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