Tissue plasminogen activator antigen and coronary heart disease. Prospective study and meta-analysis.

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.