Prospective study of fibrinolytic factors and incident coronary heart disease - The Atherosclerosis Risk in Communities (ARIC) Study

The fibrinolytic system may play a role in the pathogenesis of coronary hea rt disease (CHD), but existing prospective studies have not consistently sh own an independent association between fibrinolytic factors and CHD. None h as reported an association between plasminogen and CHD incidence. In the pr ospective Atherosclerosis Risk in Communities (ARIC) Study of middle-aged a dults, we examined the association of incident CHD with several fibrinolyti c factors: tissue plasminogen activator antigen, plasminogen activator inhi bitor-1, plasminogen, and fibrin fragment D-dimer as well as a marker of co agulation activation (prothrombin fragment F1.2). We measured these in stor ed baseline plasma samples of 326 subjects who developed CHD and, for compa rison, a stratified random sample of the entire cohort (n=720). Tissue plas minogen activator and plasminogen activator inhibitor-1 antigen levels were associated positively with CHD incidence in analyses adjusted for age, rac e, and sex but were not associated with CHD after adjustment for other risk factors. Plasminogen and D-dimer levels were associated positively and ind ependently with CHD incidence; the multivariable-adjusted relative risks (9 5% CIs) for the highest versus lowest quintiles were 2.20 (1.2 to 4.2) for plasminogen and 4.21 (1.9 to 9.6) for D-dimer. F1.2 was not associated with CHD incidence. Our findings lend support for a link between fibrinolytic f actors and CHD incidence. A positive association between plasminogen and CH D is seemingly opposite the direction expected but may reflect a compensato ry response to impaired plasminogen activation in subjects prone to CHD.