title: Metabolic syndrome and incident peripheral artery disease - the Multi-Ethnic Study of Atherosclerosis.
abstract: OBJECTIVE
  We evaluated whether metabolic syndrome (MetS) is associated with an increased incidence of lower extremity peripheral artery disease (PAD) in community dwelling people free of clinical cardiovascular disease at baseline. We assessed whether higher levels of inflammatory biomarkers may mediate the association of MetS with incident PAD.
  
  
  METHODS
  MetS was defined at baseline as the presence of three or more of the following components: elevated waist circumference, triglycerides ≥150 mg/dL, reduced high-density lipoprotein (HDL) cholesterol, blood pressure ≥130/85 mm Hg or taking blood pressure medication, and fasting glucose ≥100 mg/dL and <126 mg/dL. People with diabetes were excluded. Incident New PAD was defined among people with a normal ankle brachial index (ABI) at baseline (i.e. baseline ABI of 0.90 to 1.40) and consisted of one of the following outcomes during 3-year follow-up: ABI decline to < 0.90 combined with a decline ≥0.15 or medical record confirmed PAD outcome. Multivariable Poisson regression was used to estimate the association between MetS and incident PAD.
  
  
  RESULTS
  Among 4817 participants without PAD at baseline, 1382 (29%) had MetS. Adjusting for age, sex, race, smoking, physical activity, low-density lipoprotein cholesterol, baseline ABI, and other confounders, 23/1382 (1.7%) people with MetS developed PAD vs. 30/3435 (0.87%) people without MetS (risk ratio = 1.78 [95% Confidence Interval (CI), 1.04 to 2.82], P = 0.031). Adjusting for C-reactive protein, fibrinogen, or interleukin-6 did not attenuate this association.
  
  
  CONCLUSIONS
  People free of clinical cardiovascular disease with MetS are at increased risk for PAD. Our findings suggest that this association is not mediated by inflammation.
authors.affiliation: University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Himabindu
authors.initials: H
authors.lastname: Vidula
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, 750 N Lake Shore Drive, 10th Floor, Chicago, IL 60611, USA.
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Family and Preventive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Criqui
authors.affiliation: Department of Epidemiology, John Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Moyses
authors.initials: M
authors.lastname: Szklo
authors.affiliation: Department of Family and Preventive Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.affiliation: Knight Cardiovascular Institute, Oregon Health and Science University, 3181 South West Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Sibley
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Baltimore, MD 21224, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ouyang
authors.affiliation: Departments of Pathology and Biochemistry, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA.
authors.forename: Cheeling
authors.initials: C
authors.lastname: Chan
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USA; Department of Medicine, Northwestern University Feinberg School of Medicine, 750 N Lake Shore Drive, 10th Floor, Chicago, IL 60611, USA. Electronic address: mdm608@northwestern.edu.
authors.forename: Mary M
authors.initials: MM
authors.lastname: McDermott
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D050197:Atherosclerosis / Q000150:complications / Q000208:ethnology; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005006:Ethnicity; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000150:complications*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008078:Cholesterol, LDL; C508600:IL6 protein, human; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein; D003404:Creatinine
keywords: Cardiovascular disease; Metabolic syndrome; Peripheral artery disease