Aortic backward waves rather than stiffness account for independent associations between pulse pressure amplification and left ventricular mass in a young to middle-aged sample.

A decreased aortic-to-brachial pulse pressure (PP) amplification, which is independently associated with cardiovascular outcomes, may index several aortic functional changes. However, that aortic functional change most likely to account for this effect is uncertain. In 706 randomly selected community participants of African ancestry with a mean age of 44.4 ± 18.2 years, we assessed aortic function using radial applanation tonometry and SphygmoCor software (including forward [Pf] and backward [Pb] wave separation analysis assuming a triangular flow waveform) and left ventricular mass index (LVMI) (echocardiography). In multivariate models with the inclusion of brachial PP, 1/PP amplification (partial r = 0.12, P < .005), reflected wave pressures (partial r = 0.09, P < .05), and aortic pulse wave velocity (PWV; partial r = 0.09, P < .05) were independently associated with LVMI. Similarly, in multivariate models with the inclusion of brachial PP, 1/PP amplification (P < .005), the reflected wave pressure (P < .01), and aortic PWV (P < .01) were independently associated with LVH. With adjustments for reflected wave pressures, the brachial PP-independent relationships between 1/PP amplification and LVMI or LVH were abolished (P > .08 for both). However, adjustments for PWV failed to modify brachial PP-independent relations between 1/PP amplification and LVMI or LVH. Similar results were noted when brachial systolic blood pressure rather than PP was included in regression models and in sensitivity analysis conducted in participants not receiving antihypertensive therapy. In conclusion, the independent relations between the reciprocal of aortic-to-brachial PP amplification and LVMI or LVH in a largely young to middle-aged sample are accounted for by variations in backward wave pressures rather than aortic stiffness.

Enhanced Aortic Reflected Wave Magnitude Accounts for the Impact of Female Gender on Aortic Pressure Augmentation in a Group of African Ancestry.

BACKGROUND: Aortic reflected wave magnitude (RM) may not account for sex-specific differences in aortic pressure augmentation in Caucasians. However, aortic reflected waves are greater in groups of African descent than other ethnic groups. We determined whether RM or alternative factors explain the impact of sex on aortic augmented pressure (Pa) in participants of African ancestry. METHODS: We assessed aortic function (radial applanation tonometry, SphygmoCor) in 1,197 randomly recruited community participants of African ancestry (age ≥ 16 years). Aortic forward (Pf) and backward (Pb) wave separation was performed assuming an aortic triangular flow wave validated against aortic velocity measurements. RESULTS: Across the adult lifespan, women had greater multivariate-adjusted augmentation index (AIx) and Pa. This was associated with multivariate-adjusted age-related increases in Pb, RM (Pb/Pf), and time to the peak of Pf and decreases in backward wave foot time; but not increases in Pf. With adjustors, Pa was associated with female gender (ß-coefficient = 3.81 ± 0.34), a relationship which was markedly attenuated by adjustments for RM (ß-coefficient = 1.78 ± 0.31, P < 0.0001 vs. without adjustments for RM), and Pb (ß-coefficient = 2.05 ± 0.19, P < 0.0001 vs. without adjustments for Pb), but not by adjustments for Pf, time to the peak of Pf, or backward wave foot time. Similarly, AIx was associated with female gender, a relationship which was markedly attenuated by adjustments for RM, Pb, and backward wave foot time, but not alternative factors. CONCLUSIONS: In contrast to reports in alternative populations, the relationship between aortic pressure augmentation and female gender in participants of African descent is accounted for mainly by increases in RM.

Time to the peak of the aortic forward wave determines the impact of aortic backward wave and pulse pressure on left ventricular mass.

AIM: To determine the degree to which an extended time to the peak of the aortic forward wave or early wave reflection time enhance associations between aortic backward wave pressure and hence central aortic pulse pressure (PPc) and left ventricular mass index (LVMI). METHODS: In 701 adult participants from a community sample either receiving no antihypertensive therapy or receiving low-dose thiazide diuretic monotherapy for at least a year (the major therapy employed), we assessed aortic haemodynamics (SphygmoCor software and wave separation analysis; AtCor Medical, West Ryder, New South Wales, Australia) and LVMI (echocardiography). RESULTS: An interaction between time to the peak of the aortic forward wave and aortic backward wave pressure was independently associated with aortic augmented pressure (P < 0.01), PPc (P < 0.005), LVMI (P < 0.01), and LV hypertrophy (LVH; P = 0.01). The time to the peak of the aortic forward wave-aortic backward wave pressure interaction translated into a stepwise increase in the independent association between aortic backward wave pressure and aortic augmented pressure or PPc across quartiles of time to the peak of the aortic forward wave (P < 0.05 to < 0.0001 for comparison of slopes of relations). Furthermore, the time to the peak of the aortic forward wave-aortic backward wave pressure interaction translated into an increase in the independent association between PPc or aortic backward wave pressure and LVMI (P < 0.05 to < 0.001 for comparison of slopes and strength of relations) or LVH (P < 0.05 for comparisons of odds ratios), but not between forward wave pressures and LVMI or LVH across quartiles of time to the peak of the aortic forward wave. A markedly better ability of aortic backward wave pressure and PPc, but not forward wave pressures to detect LVH was noted in the highest as compared with the first three quartiles of time to the peak of the aortic forward wave (P < 0.05). In contrast, reflection time failed to influence the impact of aortic backward wave pressure or PPc on LVMI. CONCLUSIONS: Time to the peak of the aortic forward wave, but not early wave reflection markedly influences the impact of aortic backward wave pressure and hence aortic pulse pressure on LVMI and LVH in adults.

Aortic Pulse Pressure Amplification Imputed From Simple Clinical Measures Adds to the Ability of Brachial Pressure to Predict Survival.

BACKGROUND: Although aortic-to-brachial pulse pressure amplification (PPamp) may offer prognostic information beyond brachial blood pressure (BP), this approach is limited in resource-limited settings. We aimed to derive an equation to impute central aortic PP (PPc) from simple clinical measures and assess whether imputed PPamp adds to the ability of brachial BP to predict mortality. METHODS: An imputation equation for PPc, incorporating brachial PP, age, mean arterial pressure, and pulse rate, was identified from multivariate modeling of the factors associated with radial applanation tonometry-derived (measured) PPc in 1,179 community participants and validated in a clinical sample of 351 patients. We applied the equation to ambulatory awake BP and pulse rate values in a separate group of 4,796 patients referred for ambulatory monitoring and evaluated the impact on all-cause mortality. RESULTS: Imputed PPc values closely approximated measured PPc (r (2) = 0.96, mean difference ± (2 × SD) = 1.4±6.2mm Hg). In adjusted Cox proportional models including adjustments for awake brachial PP during 47,111 person-years of follow-up, where 648 patients died, hazards ratio for all-cause mortality per SD of awake PPamp was 0.79 (95% confidence interval (CI): 0.68-0.93, P < 0.005). The hazards ratio for brachial PP with (1.49, CI = 1.36-1.64, P < 0.0001) or without (1.46, CI = 1.35-1.59, P < 0.0001) PPamp in the model was similar. Awake PPamp also predicted survival independent of awake brachial systolic BP (P < 0.0001). CONCLUSIONS: PPc imputed from simple clinical assessments closely approximates measured PPc. PPamp derived from imputed PPc adds to the ability of brachial BP to predict survival. In resource-limited settings, an imputation equation may be employed to approximate aortic BP and enhance risk prediction.

Brachial Pressure Control Fails to Account for Most Distending Pressure-Independent, Age-Related Aortic Hemodynamic Changes in Adults.

BACKGROUND: Although several characteristics of aortic function, which are largely determined by age, predict outcomes beyond brachial blood pressure (BP), the extent to which brachial BP control accounts for age-related variations in aortic function is uncertain. We aimed to determine the extent to which brachial BP control in the general population (systolic/diastolic BP < 140/90 mm Hg) accounts for age-related aortic hemodynamic changes across the adult lifespan. METHODS: Central aortic pulse pressure (PPc), backward wave pressure (Pb), pulse wave velocity (PWV), and PP amplification (PPamp) (applanation tonometry and SphygmoCor software) were determined in 1,185 participants from a community sample (age >16 years; 36.4% uncontrolled BP). RESULTS: With adjustments for distending pressure (mean arterial pressure, MAP), no increases in PPc, Pb, or PWV and decreases in PPamp were noted in those with an uncontrolled brachial BP younger than 50 years. In those older than 50 years with an uncontrolled brachial BP, MAP-adjusted aortic hemodynamic variables were only modestly different to those with a controlled brachial BP (PPc, 46±14 vs. 42±15 mm Hg, P < 0.02, Pb, 23±8 vs. 21±8 mm Hg, PWV, 8.42±3.21 vs. 8.19±3.37 m/second, PPamp, 1.21±0.17 vs. 1.21±0.14). Nonetheless, with adjustments for MAP, marked age-related increases in PPc, Pb, and PWV and decreases in PPamp were noted in those with uncontrolled and controlled brachial BP across the adult lifespan (P < 0.0001). CONCLUSION: Brachial BP control in the general population fails to account for most distending pressure-independent, age-related changes in aortic hemodynamics across the adult lifespan.

Reflected rather than forward wave pressures account for brachial pressure-independent relations between aortic pressure and end-organ changes in an African community.

AIMS: To determine whether brachial blood pressure (BP)-independent relations between aortic pressure and cardiovascular damage are better explained by reflected (backward) (Pb) or forward (Pf) wave pressure effects. METHODS: In 1174 participants from a community of African ancestry, we assessed central aortic pulse pressure (PPc), Pb, and Pf (radial applanation tonometry, SphygmoCor) as well as left ventricular mass index (LVMI) (n = 786), aortic pulse wave velocity (PWV) (n = 1019), carotid intima-media thickness (IMT) (n = 578), transmitral early-to-late left ventricular diastolic velocity (E/A) (n = 779) and estimated glomerular filtration rate (eGFR) (n = 1174). RESULTS: Independent of mean arterial pressure and confounders, PPc, and both Pb and Pf were associated with end-organ measures or damage (P < 0.05 to P < 0.0001). With adjustments for brachial PP and confounders, Pb remained directly associated with LVMI (partial r = 0.09, P < 0.01), PWV (partial r = 0.28, P < 0.0001), and IMT (partial r = 0.28, P < 0.0001), and inversely associated with E/A (partial r = -0.31, P < 0.0001) and eGFR (partial r = -0.14, P < 0.0001). Similar relations were noted with the presence of end-organ damage (P < 0.05 to P < 0.0001). In contrast, with adjustments for brachial PP and confounders, Pf no longer retained direct relations with LVMI, PWV, and IMT or inverse relations with E/A and eGFR. Adjustments for Pb, but not Pf, diminished brachial PP-independent relationships between PPc and end-organ measures. Independent relations between Pb, but not Pf and end-organ measures, were largely attributed to Pb accounting for most of the variation in brachial-to-aortic PP amplification. CONCLUSIONS: In communities of African ancestry, brachial BP-independent relations between aortic pressure and end-organ changes are largely attributed to an impact of reflected rather than forward wave pressures.

Indexes of aortic pressure augmentation markedly underestimate the contribution of reflected waves toward variations in aortic pressure and left ventricular mass.

Although indexes of wave reflection enhance risk prediction, the extent to which measures of aortic systolic pressure augmentation (augmented pressures [Pa] or augmentation index) underestimate the effects of reflected waves on cardiovascular risk is uncertain. In participants from a community sample (age >16), we compared the relative contribution of reflected (backward wave pressures and the reflected wave index [RI]) versus augmented (Pa and augmentation index) pressure wave indexes to variations in central aortic pulse pressure (PPc; n=1185), and left ventricular mass index (LVMI; n=793). Aortic hemodynamics and LVMI were determined using radial applanation tonometry (SphygmoCor) and echocardiography. Independent of confounders, RI and backward wave pressures contributed more than forward wave pressures, whereas Pa and augmentation index contributed less than incident wave pressure to variations in PPc (P<0.0001 for comparison of partial r values). In those <50 years of age, while backward wave pressures (partial r=0.28, P<0.0001) contributed more than forward wave pressures (partial r=0.15, P<0.001; P<0.05 for comparison of r values), Pa (partial r=0.13, P<0.005) contributed to a similar extent as incident wave pressure (partial r=0.22, P<0.0001) to variations in LVMI. Furthermore, in those ≥50 years of age, backward wave pressures (partial r=0.21, P<0.0001), but not forward wave pressures (P=0.98), while incident wave pressure (partial r=0.23, P<0.0001), but not Pa (P=0.80) were associated with LVMI. Pa and augmentation index underestimated the effect of wave reflection on PPc and LVMI in both men and women. Thus, as compared with relations between indexes of aortic pressure augmentation and PPc or LVMI, strikingly better relations are noted between aortic wave reflection and PPc or LVMI.