Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. Twenty‐two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non‐invasively, during incremental pacing (from 60 to 110 beats min−1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non‐invasively from the brachial artery. There was a significant, inverse, linear relationship between AIx and heart rate (r=−0.76; P < 0.001). For a 10 beats min−1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r=−0.51; P < 0.001). Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure (P < 0.001), which was accounted for by the observed change in central pressure augmentation. These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.

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.