Published Online
on April 2, 2007

A more recent version of this article appeared on April 24, 2007

This Article Full Text (PDF) CME: Take the course for this article: Circulation: April 24, 2007, Volume 115, Number 16 Data Supplement All Versions of this Article: 115/16/2119    most recent CIRCULATIONAHA.106.635029v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tzoulaki, I. Articles by Fowkes, F. G. R. Search for Related Content PubMed PubMed Citation Articles by Tzoulaki, I. Articles by Fowkes, F. G. R. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Heart Attack Stroke Related Collections Risk Factors Epidemiology Coagulation and fibronolysis

Submitted on January 12, 2006
Accepted on January 31, 2007

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, and 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.

^* To whom correspondence should be addressed. E-mail: I.Tzoulaki{at}sms.ed.ac.uk.

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.

Key words: coagulation • epidemiology • fibrinolysis • follow-up studies • inflammation • myocardial infarction • stroke

This article has been cited by other articles:

				A. M. Kucharska-Newton, D. J. Couper, J. S. Pankow, R. J. Prineas, T. D. Rea, N. Sotoodehnia, A. Chakravarti, A. R. Folsom, D. S. Siscovick, and W. D. Rosamond Hemostasis, Inflammation, and Fatal and Nonfatal Coronary Heart Disease: Long-Term Follow-Up of the Atherosclerosis Risk in Communities (ARIC) Cohort Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 2182 - 2190. [Abstract] [Full Text] [PDF]

				J. E. Sharman, J. Brown, D. J. Holland, G. Macdonald, K. Kostner, and T. H. Marwick Influence of Altered Blood Rheology on Ventricular-Vascular Response to Exercise Hypertension, November 1, 2009; 54(5): 1092 - 1098. [Abstract] [Full Text] [PDF]

				D. I. Buckley, R. Fu, M. Freeman, K. Rogers, and M. Helfand C-Reactive Protein as a Risk Factor for Coronary Heart Disease: A Systematic Review and Meta-analyses for the U.S. Preventive Services Task Force Ann Intern Med, October 6, 2009; 151(7): 483 - 495. [Abstract] [Full Text] [PDF]

				M. Helfand, D. I. Buckley, M. Freeman, R. Fu, K. Rogers, C. Fleming, and L. L. Humphrey Emerging Risk Factors for Coronary Heart Disease: A Summary of Systematic Reviews Conducted for the U.S. Preventive Services Task Force Ann Intern Med, October 6, 2009; 151(7): 496 - 507. [Abstract] [Full Text] [PDF]

				A. Rohatgi, A. W. Owens, A. Khera, C. R. Ayers, K. Banks, S. R. Das, J. D. Berry, D. K. McGuire, and J. A. de Lemos Differential Associations Between Soluble Cellular Adhesion Molecules and Atherosclerosis in the Dallas Heart Study: A Distinct Role for Soluble Endothelial Cell-Selective Adhesion Molecule Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1684 - 1690. [Abstract] [Full Text] [PDF]

				R. E. Marioni, M. C. Stewart, G. D. Murray, I. J. Deary, F. G. R. Fowkes, G. D. O. Lowe, A. Rumley, and J. F. Price Peripheral Levels of Fibrinogen, C-Reactive Protein, and Plasma Viscosity Predict Future Cognitive Decline in Individuals Without Dementia Psychosom Med, October 1, 2009; 71(8): 901 - 906. [Abstract] [Full Text] [PDF]

				G. Ortiz-Munoz, X. Houard, J.-L. Martin-Ventura, B. Y. Ishida, S. Loyau, P. Rossignol, J.-A. Moreno, J. P. Kane, R. J. Chalkley, A. L. Burlingame, et al. HDL antielastase activity prevents smooth muscle cell anoikis, a potential new antiatherogenic property FASEB J, September 1, 2009; 23(9): 3129 - 3139. [Abstract] [Full Text] [PDF]

				C. Kleinschnitz, S. F. De Meyer, T. Schwarz, M. Austinat, K. Vanhoorelbeke, B. Nieswandt, H. Deckmyn, and G. Stoll Deficiency of von Willebrand factor protects mice from ischemic stroke Blood, April 9, 2009; 113(15): 3600 - 3603. [Abstract] [Full Text] [PDF]

				D. S. Frankel, J. B. Meigs, J. M. Massaro, P. W.F. Wilson, C. J. O'Donnell, R. B. D'Agostino, and G. H. Tofler Von Willebrand Factor, Type 2 Diabetes Mellitus, and Risk of Cardiovascular Disease: The Framingham Offspring Study Circulation, December 9, 2008; 118(24): 2533 - 2539. [Abstract] [Full Text] [PDF]

				C. Weikert, N. Stefan, M. B. Schulze, T. Pischon, K. Berger, H.-G. Joost, H.-U. Haring, H. Boeing, and A. Fritsche Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke Circulation, December 9, 2008; 118(24): 2555 - 2562. [Abstract] [Full Text] [PDF]

				P. Welsh, G. D.O. Lowe, J. Chalmers, D. J. Campbell, A. Rumley, B. C. Neal, S. W. MacMahon, and M. Woodward Associations of Proinflammatory Cytokines With the Risk of Recurrent Stroke Stroke, August 1, 2008; 39(8): 2226 - 2230. [Abstract] [Full Text] [PDF]

				J. Sanz, P. R. Moreno, and V. Fuster The year in atherothrombosis. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 944 - 955. [Full Text] [PDF]