title: Associations of candidate biomarkers of vascular disease with the ankle-brachial index and peripheral arterial disease.
abstract: BACKGROUND
  The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs).
  
  
  METHODS
  Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use.
  
  
  RESULTS
  After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers - myeloperoxidase, NT-proBNP, and D-dimer - were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs.
  
  
  CONCLUSIONS
  A multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.
authors: Division of Cardiovascular Diseases and the Gonda Vascular Center, Mayo Clinic, Rochester, MN, USA.
authors: Zi
authors: Z
authors: Ye
authors: Zeenat
authors: Z
authors: Ali
authors: George G
authors: GG
authors: Klee
authors: Thomas H
authors: TH
authors: Mosley
authors: Iftikhar J
authors: IJ
authors: Kullo
mesh_terms: D001741:Black or African American; D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D058729:Peripheral Arterial Disease / Q000503:physiopathology*; D012307:Risk Factors; D044465:White People
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D017270:Lipoprotein(a); D053244:Osteoprotegerin; D010446:Peptide Fragments; C506030:TNFRSF11B protein, human; C036309:fibrin fragment D; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein