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Severe aortic stenosis induces abnormalities in central aortic pressure, with consequent impaired organ and tissue perfusion. Relief of aortic stenosis by transcatheter aortic valve replacement (TAVR) is associated with both a short- and long-term hypertensive response. Counterintuitively, patients who are long-term normotensive post-TAVR have a worsened prognosis compared with patients with hypertension, yet the underlying mechanisms are not understood. We investigated immediate changes in invasively measured left ventricular and central aortic pressure post-TAVR in patients with severe aortic stenosis using aortic reservoir pressure, wave intensity analysis, and indices of aortic function. Fifty-four patients (mean age 83.6±6.2 years, 50.0% female) undergoing TAVR were included. We performed reservoir pressure and wave intensity analysis on invasively acquired pressure waveforms from the ascending aorta and left ventricle immediately pre- and post-TAVR. Following TAVR, there were increases in systolic, diastolic, mean, and pulse aortic pressures (all P <0.05). Post-TAVR reservoir pressure was unchanged (54.5±12.4 versus 56.6±14.0 mm Hg, P =0.30) whereas excess pressure increased 47% (29.0±10.9 versus 42.6±15.5 mm Hg, P <0.001). Wave intensity analysis (arbitrary units, au) demonstrated increased forward compression wave (64.9±35.5 versus 124.4±58.9, ×10 3 au, P <0.001), backward compression wave (11.6±5.5 versus 14.4±6.9, ×10 3 au, P =0.01) and forward expansion wave energies (43.2±27.3 versus 82.8±53.1, ×10 3 au, P <0.001). Subendocardial viability ratio improved with aortic function effectively unchanged post-TAVR. Increased central aortic pressure following TAVR relates to increased transmitted power and energy to the proximal aorta with increased excess pressure but unchanged reservoir pressure. These changes provide a potential mechanism for the improved prognosis associated with relative hypertension post-TAVR.

Several morphological parameters based on the central aortic pressure waveform are proposed as cardiovascular risk markers, yet no study has definitively demonstrated the incremental value of any waveform parameter in addition to currently accepted biomarkers in elderly, hypertensive patients. The reservoir-wave concept combines elements of wave transmission and Windkessel models of arterial pressure generation, defining an excess pressure superimposed on a background reservoir pressure. The utility of pressure rate constants derived from reservoir-wave analysis in prediction of cardiovascular events is unknown. Carotid blood pressure waveforms were measured prerandomization in a subset of 838 patients in the Second Australian National Blood Pressure Study. Reservoir-wave analysis was performed and indices of arterial function, including the systolic and diastolic rate constants, were derived. Survival analysis was performed to determine the association between reservoir-wave parameters and cardiovascular events. The incremental utility of reservoir-wave parameters in addition to the Framingham Risk Score was assessed. Baseline values of the systolic rate constant were independently predictive of clinical outcome (hazard ratio, 0.33; 95% confidence interval, 0.13-0.82; P=0.016 for fatal and nonfatal stroke and myocardial infarction and hazard ratio, 0.38; 95% confidence interval, 0.20-0.74; P=0.004 for the composite end point, including all cardiovascular events). Addition of this parameter to the Framingham Risk Score was associated with an improvement in predictive accuracy for cardiovascular events as assessed by the integrated discrimination improvement and net reclassification improvement indices. This analysis demonstrates that baseline values of the systolic rate constant predict clinical outcomes in elderly patients with hypertension and incrementally improve prognostication of cardiovascular events., (© 2014 American Heart Association, Inc.)

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (P<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (-0.200, -0.181) and outflow tract (-0.238, -0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment naïve. Central pulse pressure (84+/-26 versus 75+/-28 mm Hg, P<0.001) was higher and aortic dimensions (transverse arch 2.56+/-0.31 versus 2.88+/-0.35 mm, P<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4+/-36.1 versus 22.1+/-21.3, P<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all P<0.001), and weight (P=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (P<0.001) even with inclusion of aortic dimensions (P=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all P<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.

The Second Australian National Blood Pressure Trial reported better prognosis for hypertensive subjects randomly assigned to an angiotensin-converting enzyme inhibitor (ACE-I) compared with a diuretic-based regimen despite no difference in brachial blood pressure control. A possible explanation is that there was a difference in central aortic pressures despite similar brachial pressure reductions. We examined this hypothesis in a subset of the Second Australian National Blood Pressure Trial cohort evaluated both before and after 4 years of treatment. The average age of the 479 subjects was 71.6+/-4.7 years (mean+/-SD), and 56% were women. Brachial systolic and pulse pressures after treatment were 145+/-1 (mean+/-SEM), 143+/-1, 72+/-1, and 70+/-1 mm Hg for diuretic and ACE-I groups, respectively. The respective changes from pretreatment values were -17+/-2, -16+/-2, -9+/-1, and -7+/-1 mm Hg. None of the differences between diuretic and ACE-I groups were significant. Central arterial pressure waveforms were acquired from carotid tonometry and calibrated from brachial pressures. Central systolic and pulse pressures posttreatment were 144+/-2, 144+/-2, 71+/-2, and 72+/-2 mm Hg for diuretic and ACE-I groups, respectively. The respective changes from pretreatment values were -15+/-2, -17+/-2, -6+/-2, and -8+/-2 mm Hg. None of the differences between diuretic and ACE-I groups were significant. The similarity of central and brachial pressures in this cohort of older hypertensive subjects is most likely because of the influences of age and hypertension in increasing arterial stiffness. There is no evidence that the better prognosis for patients randomly assigned to ACE-I in Second Australian National Blood Pressure Trial resulted from a disproportionate lowering of central blood pressure.

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study (untreated blood pressure 169/88+/-12/8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival (hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure > or =81 versus <81 mm Hg; P=0.01), no such relation was found for carotid augmentation index (HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance (HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.

The mechanisms relating pulse pressure to cardiovascular outcome may include surrogacy for coronary disease severity. Although pulse pressure is typically measured at the brachial artery, central pulse pressure and its principal determinant, large-artery stiffness, may relate more closely to disease severity. This study aimed to determine the relationships between large-artery stiffness and carotid and brachial blood pressures and coronary artery disease severity. One hundred fourteen male patients with coronary artery disease (age 60+/-8 years, mean+/-SD) and 57 age-matched healthy male controls (age 59+/-9 years) were recruited. Patients were classified into 2 groups based on the magnitude of their maximum coronary stenosis: moderate (50% to 89%) and severe (>/=90%). Large-artery stiffness was assessed as systemic arterial compliance and carotid-femoral pulse wave velocity. Mean pressure was not different between the 3 groups. Systemic compliance and carotid pulse pressure were significantly different between all 3 groups, with compliance lowest and pressure highest in the severe group (P<0.05). Pulse wave velocity was higher in patients with severe stenosis than in those with moderate stenosis (P<0.01) and those in the control group (P<0.001). Brachial pulse pressure was higher in patients than in controls (P<0.05), but there was no difference between the 2 disease groups. In separate multivariate analyses, carotid pressures and systemic arterial compliance were determinants of coronary artery disease severity, independent of age, smoking status, body mass index, mean arterial pressure, heart rate, cholesterol levels (total, LDL, and HDL), triglycerides, and beta-antagonist and lipid-lowering therapy (P<0.001), whereas brachial pressures and pulse wave velocity were not. In conclusion, central blood pressures and systemic arterial compliance are more sensitive markers of coronary artery disease severity than brachial pressures.

The present study characterized large-artery properties in patients with isolated systolic hypertension (ISH) and determined the efficacy of exercise training in modifying these properties. Twenty patients (10 male and 10 female) with stage I ISH and 20 age- and gender-matched control subjects were recruited, and large-artery properties were assessed noninvasively. Ten ISH patients (5 male and 5 female) were enrolled in a randomized crossover study comparing 8 weeks of moderate intensity cycling with 8 weeks of sedentary activity. Brachial and carotid systolic, diastolic, mean, and pulse pressures were higher in the ISH group than in the control group. Systemic arterial compliance (0.43+/-0.04 versus 0.29+/-0.02 arbitrary compliance units for the control versus ISH groups, respectively; P=0.01) was lower, and carotid-to-femoral pulse-wave velocity (9.67+/-0.36 versus 11.43+/-0.51 m. s(-1) for the control versus ISH groups, respectively; P=0.007), input impedance (2.39+/-0.19 versus 3.27+/-0.34 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.04), and characteristic impedance (1.67+/-0.17 versus 2.34+/-0.27 mm Hg. s. cm(-1) for the control versus ISH groups, respectively; P=0.05) were higher in the ISH group than in the control group. Training increased maximal oxygen consumption by 13+/-5% (P=0.04) and maximum workload by 8+/-4% (P=0.05); however, there was no effect on arterial mechanical properties, blood lipids, or left ventricular mass or function. These results suggest that the large-artery stiffening associated with ISH is resistant to modification through short-term aerobic training.

-In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima-media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (final sigma(C)) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to-wall thickness ratio (R/IMT) (where R=D/2) and final sigma(C) were increased in hypertensives. SI was correlated with IMT (r=0.56, P:<0.001); radius-to-wall thickness ratio was inversely correlated with central pulse pressure (r=-0.38, P:<0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace's law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness.

Aerobic exercise training increases arterial compliance and reduces systolic blood pressure, but the effects of muscular strength training on arterial mechanical properties are unknown. We compared blood pressure, whole body arterial compliance, aortic impedance, aortic stiffness (measured by beta-index and carotid pulse pressure divided by normalized systolic expansion [Ep]), pulse wave velocity, and left ventricular parameters in 19 muscular strength-trained athletes (mean+/-SD age, 26+/-4 years) and 19 sedentary controls (26+/-5 years). Subjects were healthy, non-steroid-using, nonsmoking males, and athletes had been engaged in a strength-training program with no aerobic component for a minimum of 12 months. There was no difference in maximum oxygen consumption between groups, but handgrip strength (mean+/-SEM, 44+/-2 versus 56+/-2 kg; P<0.01) and left ventricular mass (168+/-8 versus 190+/-8 g; P<0.05) were greater in athletes. Arterial stiffness was higher in athletes, as evidenced by lower whole body arterial compliance (0.40+/-0.04 versus 0.54+/-0.04 arbitrary compliance units; P=0.01), higher aortic characteristic impedance (1.55+/-0.13 versus 1.18+/-0.08 mm Hg. s. cm-1; P<0.05), beta-index (4.6+/-0.2 versus 3.8+/-0.4; P<0. 05), and ln Ep (10.86+/-0.06 versus 10.60+/-0.08; P<0.01). Femoral-dorsalis pedis pulse wave velocity was also higher in the athletes, but carotid-femoral pulse wave velocity was not different. Furthermore, both carotid (56+/-3 versus 44+/-2 mm Hg; P<0.001) and brachial (60+/-3 versus 50+/-2 mm Hg; P<0.01) pulse pressures were higher in the athletes, but mean arterial pressure and resting heart rate did not differ between groups. These data indicate that both the proximal aorta and the leg arteries are stiffer in strength-trained individuals and contribute to a higher cardiac afterload.

To elucidate the relationship between coronary artery disease (CAD), aortic stiffness, and left ventricular structure, we recruited 55 subjects (33 men; average age, 63+/-1 years) with previously unknown CAD from a healthy general population sample, as well as 55 control subjects matched for gender, age, and serum cholesterol level. We measured arterial blood pressure and the systolic expansion of the transverse aorta and left ventricular structure by echocardiography. Aortic stiffness was higher in CAD patients than in controls, with a brachial pulse pressure of 59+/-3 versus 52+/-2 mm Hg and stiffness indices of Ep=212+/-26 versus 123+/-13 kN/m2 and beat=16+/-2 versus 9+/-1 (all P<0.01). Mean arterial pressure was similar in both groups during the measurements (95+/-2 versus 93+/-2 mm Hg, P=NS). Most CAD patients (61%) were in the highest stiffness quartile defined by the normal control values (P<0.05 versus control). Left ventricular mass index was also higher in CAD patients than in matched controls (139+/-5 versus 123+/-4 g/m2, P<0.05). We conclude that aortic stiffness and left ventricular mass are increased in subjects newly diagnosed as having CAD. This might explain previously reported associations of an increased mortality, particularly from CAD, found among subjects with elevated pulse pressures.