Copyright © 2004 by the European Society of Cardiology.
Clinical research
Tissue plasminogen activator antigen and coronary heart disease
Prospective study and meta-analysis
a University Department of Medicine, Royal Infirmary, Glasgow, UK
b Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
c Department of Primary Care and Population Sciences, Royal Free and University College London Medical School, London, UK
d Department of Public Health Sciences, St George's Hospital Medical School, London, UK
* Correspondence to: Professor G. D. O. Lowe, Department of Medicine, Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, UK. Tel: +44 141 211 5412; Fax: +44 141 211 0414
E-mail address: gdl1j{at}clinmed.gla.ac.uk
Received 14 May 2003; revised 28 October 2003; accepted 6 November 2003
Abstract
Aims To determine whether circulating tissue plasminogen activator (t-PA) antigen concentrations are prospectively related to risk of coronary heart disease (CHD) in the general population
Methods and results We measured baseline concentrations of t-PA antigen in the stored serum samples of 606 CHD cases and 1227 controls ‘nested’ in a prospective cohort of 5661 men monitored for 16 years, and conducted a meta-analysis of previous relevant studies to place our findings in context. Tissue plasminogen activator antigen values were strongly correlated with several vascular risk factors, including serum lipids, body mass index, alcohol consumption, and markers of systemic inflammation. In a comparison of men in the top third compared with those in the bottom third of baseline t-PA antigen values, the odds ratio for CHD was 2.20 (95% confidence interval (CI) 1.70–2.85) after adjustment for age and town only, but this fell to 1.48 (1.09–2.01) after further adjustment. Analysis of t-PA as a continuous variable gave similar results. Similarly, when published information on all seven available prospective cohort studies in general populations (2119 cases and 8832 controls in total) was synthesized, the combined odds ratio was 2.18 (1.77–2.69) after adjustment for age and sex only, and this fell to 1.47 (1.19–1.81) after further adjustment.
Conclusion Although there is a statistically significant association between circulating concentrations of t-PA antigen and subsequent CHD, additional studies are needed to determine to what extent this is independent from more established risk factors.
Key Words: Coronary heart disease • Epidemiology • Fibrinolysis
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