Abstract 1139: Plasminogen Activator Inhibitor (PAI-1) and Risk of Cardiovascular Disease: The Framingham Heart Study
Background: Although plasminogen activator inhibitor (PAI-1) plays a key regulatory role in fibrinolysis, it has not been clearly shown to predict cardiovascular disease (CVD) risk among individuals without prior CVD after accounting for other risk factors. We hypothesized that PAI-1 would be predictive of CVD.
Methods: Plasma PAI-1 antigen was measured in 3203 participants without prior CVD in the Framingham Heart Study offspring cohort, at a routine clinic visit between 1991–1995. Follow-up for occurrence of CVD events was an average of 10 years. We also repeated PAI-1 measurements 4 years after baseline, to determine the effect of serial changes in PAI-1 on subsequent CVD risk.
Results: PAI-1 antigen levels had a strong unadjusted linear relation with incident CVD (p<0.001). After adjustment for age, gender, systolic blood pressure, antihypertensive therapy, body mass index, diabetes mellitus, cigarette smoking, total cholesterol, HDL cholesterol and triglycerides, the relative risk of CVD for higher quartiles of PAI-1, as compared with subjects in the lowest quartile, were 1.4, 1.4, 1.8 (p=0.004). Individuals with the greatest increase in PAI-1 levels 4 years after baseline had the greatest subsequent CVD event rate. The adjusted relative risk for increasing quartiles of serial change in PAI-1, as compared with subjects in the lowest quartile (a mean decrease in PAI-1) were 0.9, 1.4, 1.4 (p=0.006).
Conclusion: Plasminogen activator inhibitor (PAI-1) levels are predictive of CVD after accounting for established risk factors. A serial increase in PAI-1 level leads to a further increase in subsequent events. These findings support the importance of fibrinolytic potential as a determinant of CVD risk.
This research has received full or partial funding support from the American Heart Association, National Center.