Association of fibrinolytic parameters with early atherosclerosis: The ARIC study

Background: Thrombosis, provoked by a rupture of an atherosclerotic plaque, plays a crucial role in precipitating a coronary heart disease event. Its role at the early stage of atherosclerosis has, however, been unclear, but it has been hypothesized that thrombosis or defective fibrinolysis contributes to the progression of atherosclerotic lesions. Methods and Results: We studied the association of plasminogen activator inhibitor antigen (PAI-1), tissue-type plasminogen activator antigen (TPA), and D- dimer with early atherosclerosis in a cross-sectional case-control study involving 457 pairs chosen from the biracial cohort of the Atherosclerosis Risk in Communities (ARIC) Study. As examined by B-mode ultrasound, patients (cases) had intima-media thickness of carotid arteries above the 90th percentile and control subjects had thickness below the 75th percentile of the ARIC cohort. Persons with a history of heart disease, stroke, or claudication were excluded from the case-control selection. PAI-1, TPA, and D-dimer were higher in patients than in control subjects (P≤.001, Wilcoxon signed rank statistic). In conditional logistic regression analyses, the odds ratios of carotid atherosclerosis were, for PAI-1, for example, 1.22, 1.54, and 1.60 in the second, third, and fourth quartiles compared with the first quartile (P<.0001, test of linear trend, adjusting for age, systolic blood pressure, total cholesterol, acetylsalicylic acid use, and time of blood draw). Corresponding tests for D-dimer and TPA also showed an increasing trend (P<.0001). Conclusions: The findings support the hypothesis that thrombosis and fibrinolysis play a role at the early stage of the atherosclerotic process.