Abstract-The aortic pulse wave contour in isolated systolic hypertension often shows a prominent reflection peak, which combines with the incident wave arising from cardiac ejection so as to widen pulse pressure. We investigated the effects of an extended-release nitrate preparation and of 2 angiotensin II (AII) inhibitors (an AII receptor antagonist and an ACE inhibitor) on the aortic pulse wave contour and systemic blood pressure in hypertensive subjects with high augmentation index caused by exaggerated pulse wave reflection. Two double-blind, randomized, placebo-controlled crossover studies were carried out in a total of 16 elderly patients with systolic hypertension resistant to conventional antihypertensive therapy. In 1 study, pharmacodynamic responses to single doses of placebo, isosorbide mononitrate, eprosartan, and captopril were determined; in the other, single-dose isosorbide mononitrate and placebo were compared in subjects treated with AII inhibitors at baseline. Blood pressure was measured by sphygmomanometry and pulse wave components by applanation tonometry at the radial artery. All 3 agents were shown to decrease brachial systolic blood pressure, aortic systolic blood pressure, and aortic pulse pressure. Qualitative effects on the aortic pulse wave contour differed: augmentation index was not significantly altered by either captopril or eprosartan but was decreased (PϽ0.0001) by Ϸ50% of the placebo value with isosorbide mononitrate in both study groups. We propose that isosorbide mononitrate corrected the magnified wave reflection in systolic hypertension of these elderly patients by an effect that was distinct from that exercised by either acute or chronic AII inhibition. Key Words: angiotensin antagonist Ⅲ antihypertensive therapy Ⅲ elderly Ⅲ hypertension, arterial Ⅲ isosorbide mononitrate Ⅲ pulse wave I solated systolic hypertension (ISH) and associated widening of pulse pressure have been identified as important risk factors for cardiovascular disease in the elderly 1-4 and may persist despite the use of conventional antihypertensive drugs. 5-7 A hierarchy of clinical responses to such therapy has been reported: Calcium antagonists produced the most significant antihypertensive effect, followed by diuretics, ACE inhibitors, and ␤-blockers. 5 A place for nitrates in this hierarchy has been surmised for more than a decade 8,9 but has not been clearly established. 10 The high pulse pressure of ISH is usually associated with the presence in the aortic pulse wave of a prominent reflection peak, long known to be nitrate-sensitive, 11 which combines with the tail of the incident peak arising from cardiac ejection to increase pulse pressure. 12,13 We showed in a previous study that the amplitude of this wave reflection, measured by applanation tonometry, could be decreased by the use of isosorbide mononitrate (ISMN) given as an adjunct to conventional combined antihypertensive therapy. 12 This effect was associated with sustained lowering of systolic blood pressure during continued once-daily admi...

Tan et al Heart Rate Dependency of Large Artery Stiffness 237 Hemodynamic MeasurementsBrachial BP, central aortic BP, and cfPWV were determined by cuffbased pulse wave analysis (SphygmoCor XCEL, AtCor, Sydney, Australia). Brachial BP was obtained by oscillometric method with a brachial cuff positioned on the right arm, and central aortic waveform was derived from the brachial BP volume displacement waveform using a validated transfer function. 16 For measurement of cfPWV, the carotid and femoral pulse waveforms were obtained by tonometry on the skin above the right carotid artery and by a cuff placed on the right upper thigh, respectively. 17,18 Subtraction method for path length was used to calculate cfPWV, whereby the path length was calculated as the distance between the sternal notch and the carotid site subtracted from the distance between the sternal notch and top of the thigh cuff. 17 In a subset of the study's cohort (n=45), beat-to-beat stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were determined from the finger arterial pressure waveform using the Modelflow method (Finometer PRO, Finapres Medical Systems, Amsterdam, The Netherlands). 19 Study ProtocolSubjects were advised to refrain from caffeine and fatty meals 4 hours before their study appointment, but to continue with their prescribed medications. There were no current tobacco users in the cohort. After 10 minutes of seated rest, seated brachial BP was measured in duplicate (SphygmoCor XCEL). After a further 10 minutes of supine rest, finger arterial pressure waveform was measured from the left middle finger (Finometer PRO) to obtain SV, CO, and TPR. Brachial and central aortic BP and cfPWV were then obtained (SphygmoCor XCEL). Subjects were then paced in a randomized sequence at 60, 70, 80, 90, and 100 bpm using their prescribed pacemaker settings, with BP and cfPWV measurements repeated at each pacing step after 3 minutes of stabilization. ECG was also acquired continuously for the duration of the study for monitoring of HR (PowerLab acquisition system, LabChart software, ADInstruments, Dunedin, New Zealand), and SV, CO, and TPR from the Finometer PRO device were also recorded via PowerLab and LabChart. The average duration for study protocol completion was 60 minutes. Data AnalysisFor pulse wave analysis, brachial and central aortic BP waveforms were averaged >5 s, and cfPWV was averaged >10 s. Observations with measured HR differing from the paced rate by >5 bpm were excluded from the analysis, and the lowest pace rates of 60 and 70 bpm were not achievable in some subjects because of a higher unpaced resting HR. A linear mixed model with maximum likelihood was used to determine the effects of HR on each measured variable, with paced HR modeled as the fixed effect and the random effect modeled as the intercept for each individual (Equation 1).where Yij denotes the outcome measure at a particular paced HR for one individual, ε ij , the residual of variances, and u j , the random effect becase of individual subjec...

3 Technical Efficacy: Stage 1 Stage 1 J. Magn. Reson. Imaging 2018.

No abstract