title: Metabolic syndrome, inflammation, and risk of symptomatic peripheral artery disease in women: a prospective study.
abstract: BACKGROUND
  The metabolic syndrome (MetS) is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation; however, prospective data pertaining to MetS and future peripheral artery disease (PAD) are sparse, with few studies examining the role of inflammation. We therefore evaluated the relationship between MetS, inflammation, and incident PAD.
  
  
  RESULTS
  We conducted a prospective cohort study among 27 111 women free of baseline cardiovascular disease who were participating in the Women's Health Study. Subjects were followed for incident symptomatic PAD (n=114; median cohort follow-up 13.3 years). We used Cox proportional hazards models to compare PAD risk among women with and without MetS. We also evaluated relationships between MetS and subclinical inflammation as measured by high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 and adjusted for these biomarkers in multivariable models. Women with MetS had a 62% increased risk of future PAD (hazard ratio 1.62, 95% confidence interval 1.10 to 2.38). After multivariable adjustment, MetS remained significantly associated with PAD (adjusted hazard ratio 1.48, 95% confidence interval 1.01 to 2.18), with a 21% risk increase per additional MetS-defining trait (adjusted hazard ratio 1.21, 95% confidence interval 1.06 to 1.39). In women with and without MetS, respectively, median levels of high-sensitivity C-reactive protein were 4.0 versus 1.5 mg/L (P<0.0001), and median levels of soluble intercellular adhesion molecule-1 were 374 versus 333 ng/mL (P<0.0001). When high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 were added to multivariable models, risk associated with MetS was substantially attenuated and no longer significant (hazard ratio 1.14, 95% confidence interval 0.75 to 1.73).
  
  
  CONCLUSIONS
  MetS is associated with an increased risk of future symptomatic PAD in women. This risk appears to be mediated largely by the effects of inflammation and endothelial activation.
authors.affiliation: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Conen
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Aruna D
authors.initials: AD
authors.lastname: Pradhan
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000209:etiology*; D011446:Prospective Studies; D012306:Risk
chemical_list: D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein