title: Soluble P-selectin predicts lower extremity peripheral artery disease incidence and change in the ankle brachial index: the Multi-Ethnic Study of Atherosclerosis (MESA).
abstract: OBJECTIVE
  To determine the association of circulating P-selectin with prevalent and incident peripheral artery disease (PAD), the ankle brachial index (ABI), and change in the ABI.
  
  
  METHODS
  The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort study including 6814 European descent, African American, Hispanic and Chinese men and women aged 45-84 at baseline. Four clinical exams took place after the baseline exam. After excluding those with ABI>1.4, prevalent and incident PAD were defined as an ABI≤0.90. ABI progression was defined as progression from a normal ABI (0.91-1.4) to abnormal (≤0.90 or >1.4) at a later exam.
  
  
  RESULTS
  In adjusted models, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((-0.011, -0.004)), p < 0.001), and an average change in the ABI of -0.006 ((-0.010, -0.003, p < 0.001). P-selectin was significantly associated with a 1.17-fold greater odds of prevalent PAD ((1.02, 1.33), p = 0.03), and a 30% greater risk of incident PAD ((1.11, 1.53), p = 0.001), as well as progression from a normal ABI to an ABI≤ 0.90 (p = 0.003), but not to an ABI>1.4 (p = 0.96). Addition of P-selectin to models containing traditional PAD risk factors and markers of inflammation/coagulation significantly improved the net reclassification for ABI progression (p = 0.03), but was only marginally significant for incident PAD (p = 0.06).
  
  
  CONCLUSIONS
  P-selectin is significantly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of P-selectin with incident PAD and change in the ABI, as well as its potential predictive ability.
authors: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: cwassel@pitt.edu.
authors: Christina L
authors: CL
authors: Wassel
authors: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Cecilia
authors: C
authors: Berardi
authors: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors: James S
authors: JS
authors: Pankow
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Nicholas B
authors: NB
authors: Larson
authors: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Paul A
authors: PA
authors: Decker
authors: Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors: Naomi Q
authors: NQ
authors: Hanson
authors: Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA.
authors: Michael Y
authors: MY
authors: Tsai
authors: Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California - San Diego, La Jolla, CA, USA.
authors: Michael H
authors: MH
authors: Criqui
authors: Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California - San Diego, La Jolla, CA, USA.
authors: Matthew A
authors: MA
authors: Allison
authors: Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors: Suzette J
authors: SJ
authors: Bielinski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D050197:Atherosclerosis / Q000097:blood* / Q000208:ethnology*; D001777:Blood Coagulation; D015331:Cohort Studies; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D058729:Peripheral Arterial Disease / Q000097:blood*; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D019007:P-Selectin; C546937:SELP protein, human
keywords: Ankle brachial index; Incidence; Net reclassification improvement; P-selectin; Peripheral artery disease; Prediction