Abstract

Background Metabolic syndrome (MetS) includes a number of cardiovascular risk factors known to predict vascular disease. Little is known, however, about the interrelationships between MetS, inflammation and the risk of incident peripheral artery disease (PAD). Methods We conducted a prospective cohort study among 27111 women participating in the Women’s Health Study. Subjects were free of cardiovascular disease at baseline and followed for the incidence of symptomatic PAD (n=114) over a follow-up period of 13.3 years. We used Cox proportional-hazards models to compare the risk of PAD among women with and without the MetS. We also evaluated relationships between MetS and markers of subclinical inflammation including high sensitivity C-reactive protein (hsCRP) and soluble intercellular adhesion molecule-1 (sICAM-1) and adjusted for these biomarker levels in multivariable models. Results At study entry, 25.5% of participants had the MetS. Women with the MetS had a 62% increased risk of incident PAD (HR 1.62; 95% CI 1.10 –2.38). After multivariable adjustment, MetS remained significantly associated with incident PAD (Table ). Similar results were obtained when we assessed the risk of PAD according to the number of MetS defining traits (21% risk increase per additional trait) (Table ). Median plasma levels of hsCRP and sICAM-1 were 4.0 mg/L versus 1.53 mg/L (p<0.0001) and 374 ng/mL versus 333 ng/mL (p<0.0001) in women with and without MetS, respectively. From 0 to 5 MetS defining traits, median hsCRP levels gradually increased from 1.0 to 5.9 mg/L (p<0.0001) and median sICAM-1 levels increased from 321 to 413 ng/mL (p<0.0001). When hsCRP and sICAM-1 were added to multivariable models for incident PAD, risk estimates for the MetS were substantially attenuated and became non-significant (Table ). Conclusion Women with the MetS have an increased risk of incident PAD. This increased risk may be largely mediated by the effects of inflammation and/or endothelial activation. Metabolic Syndrome and Risk of PAD

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