Document Detail


Symptomatic peripheral arterial disease in women: nontraditional biomarkers of elevated risk.
MedLine Citation:
PMID:  18227386     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Most investigations of novel biomarkers for prediction of cardiovascular disease pertain to coronary artery disease. Few large-scale prospective studies have critically assessed plasma-based factors as predictors of peripheral arterial disease (PAD), and comparative data between individual biomarkers and lipid levels are sparse, especially among women. METHODS AND RESULTS: We evaluated the relationship between baseline levels of several novel biomarkers and confirmed incident symptomatic PAD (n=100) in a prospective cohort study (median follow-up, 12.3 years) involving 27,935 US female health professionals > or = 45 years of age without diagnosed vascular disease at baseline. Biomarkers assessed were high-sensitivity C-reactive protein, fibrinogen, soluble intercellular adhesion molecule-1 (sICAM-1), homocysteine, lipoprotein(a), hemoglobin A1c, creatinine, and conventional lipid levels. In univariate analyses, levels of high-sensitivity C-reactive protein, fibrinogen, sICAM-1, homocysteine, lipoprotein(a), creatinine clearance, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and the ratio of total cholesterol to HDL-C (TC:HDL-C) were significantly related to PAD (all P<0.05). However, after multivariable adjustment, risk associations were significant only for high-sensitivity C-reactive protein (adjusted hazard ratio [HR] extreme tertiles, 2.1; 95% confidence interval, 1.2 to 3.7), sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6), HDL-C (adjusted HR, 0.4; 95% confidence interval, 0.3 to 0.8), and TC:HDL-C (adjusted HR, 2.2; 95% confidence interval, 1.2 to 3.9). In a model simultaneously controlling for traditional risk factors plus these significant biomarkers, sICAM-1 remained independently predictive of PAD (adjusted HR in each tertile, 1.0 [reference], 2.3, and 3.5). CONCLUSIONS: Among a broad range of biomarkers of cardiovascular risk, only 4 factors, sICAM-1, high-sensitivity C-reactive protein, HDL-C, and TC:HDL-C, were significantly associated with incident symptomatic PAD in women. Findings pertaining to novel biomarkers provide clinical confirmation of a prominent role of endothelial activation and leukocyte recruitment in lower-extremity arterial disease.
Authors:
Aruna D Pradhan; Sanjay Shrivastava; Nancy R Cook; Nader Rifai; Mark A Creager; Paul M Ridker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-28
Journal Detail:
Title:  Circulation     Volume:  117     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-12     Completed Date:  2008-02-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  823-31     Citation Subset:  AIM; IM    
Affiliation:
Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Ave E, Boston, MA 02215-1204, USA. apradhan@partners.org
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MeSH Terms
Descriptor/Qualifier:
Biological Markers / blood*
C-Reactive Protein / analysis
Cholesterol, HDL / blood
Creatinine / metabolism
Female
Fibrinogen / analysis
Humans
Intercellular Adhesion Molecule-1 / blood*
Lipoprotein(a) / blood
Middle Aged
Multivariate Analysis
Peripheral Vascular Diseases / blood*
Prospective Studies
Risk Assessment / methods*
Grant Support
ID/Acronym/Agency:
CA47988/CA/NCI NIH HHS; HL-082740/HL/NHLBI NIH HHS; HL-43851/HL/NHLBI NIH HHS; HL-58755/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Cholesterol, HDL; 0/Lipoprotein(a); 126547-89-5/Intercellular Adhesion Molecule-1; 60-27-5/Creatinine; 9001-32-5/Fibrinogen; 9007-41-4/C-Reactive Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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