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(Circulation. 2007;115:2119-2127.)
© 2007 American Heart Association, Inc.

Epidemiology

Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke

The Edinburgh Artery Study

Ioanna Tzoulaki, PhD; Gordon D. Murray, PhD; Amanda J. Lee, PhD; Ann Rumley, PhD; Gordon D.O. Lowe, DSc; F. Gerald R. Fowkes, MBChB, PhD

From the Wolfson Unit for Prevention of Peripheral Vascular Diseases (I.T., G.D.M., F.G.R.F.), Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh; Department of General Practice and Primary Care (A.J.L.), University of Aberdeen, Foresterhill Health Centre, Westburn Road, Aberdeen; Division of Cardiovascular and Medical Sciences (A.R., G.D.O.L.), University of Glasgow, Royal Infirmary, Glasgow, UK.

Correspondence to Ioanna Tzoulaki, Wolfson Unit for Prevention of Peripheral Vascular Diseases, Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK. E-mail I.Tzoulaki{at}sms.ed.ac.uk

Received January 12, 2006; accepted January 31, 2007.

Background— The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability.

Methods and Results— We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein(a) (all P<0.01), as well as von Willebrand factor and plasma viscosity (both P<0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein(a)] provided some added discrimination.

Conclusions— Several "novel" risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.

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