Background-The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart. Methods and Results-After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 g/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5Ϯ0.8 mm 3 /mm vessel (range 0.6 to 13.7 mm 3 /mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (PϽ0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (PϽ0.006 for both). There was a strong inverse correlation between the LAD plaque burden and release of active tPA (rϭϪ0.61, Pϭ0.003). Cigarette smoking was associated with impaired coronary release of active tPA (current smokers, 31Ϯ23 IU/min; ex-smokers, 50Ϯ33 IU/min; nonsmokers 202Ϯ73 IU/min; PϽ0.05). Conclusions-We found that both the coronary atheromatous plaque burden and smoking habit are associated with a reduced acute local fibrinolytic capacity of the heart. These important findings provide evidence of a direct link between endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the coronary circulation and may explain the greater efficacy of thrombolytic therapy for myocardial infarction in cigarette smokers.

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Non-invasive measures of carotid-radial pulse wave velocity correlate with the extent of coronary artery plaque volume and may be a useful non-invasive surrogate marker for the extent of coronary atherosclerosis. Our findings are consistent with the suggestion that central aortic stiffness may promote the development of coronary atherosclerosis and ischaemic heart disease.