Moekanyi J. Sibiya

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.

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.

Gender-specific contribution of aortic augmentation index to variations in left ventricular mass index in a community sample of African ancestry

Although indices of aortic augmentation derived from radial applanation tonometry are independently associated with adverse cardiovascular effects, whether these relationships are influenced by gender is uncertain. We compared the brachial blood pressure-independent contribution of augmentation index (AIx) to variations in left ventricular mass index (LVMI) in a community sample of 808 participants, 283 of whom were men. Aortic haemodynamics were determined using radial applanation tonometry and SphygmoCor software and LVMI from echocardiography. In men, both AIx derived from aortic augmentation pressure/central aortic pulse pressure (AP/PPc; partial r=0.17, β-coefficient±s.e.m.=0.55±0.20, P<0.01) and AIx derived from the second peak/first peak (P2/P1) of the aortic pulse wave (partial r=0.21, β-coefficient±s.e.m.=0.42±0.12, P<0.0005) were associated with LVM indexed to body surface area (LVMI–BSA). In contrast, in women, neither AIx derived from AP/PPc (partial r=−0.08, β-coefficient±s.e.m.=−0.20±0.11, P=0.08) nor AIx derived from P2/P1 (partial r=−0.06, β-coefficient±s.e.m.=−0.07±0.05, P=0.17) were associated with LVMI–BSA. Both the strength of the correlations (P<0.001 and P<0.0005 with z-statistics) and the slope of the AIx–LVMI relationships (P=0.001 and P<0.0005) were greater in men as compared with women. The lack of relationship between AIx and LVMI was noted in both premenopausal (n=285; AP/PPc vs. LVMI–BSA, partial r=0.01, P=0.95, P2/P1 vs. LVMI–BSA, partial r=0.02, P=0.77), and postmenopausal (n=240; AP/PPc vs. LVMI–BSA, partial r=−0.06, P=0.37, P2/P1 vs. LVMI–BSA, partial r=−0.03, P=0.64) women. Similar differences were noted in the relationships between AIx and LVM indexed to height2.7 in men and women. In conclusion, radial applanation tonometry-derived AIx may account for less of the variation in end-organ changes in women as compared with men.

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.

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.

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 (β-coefficient = 3.81 ± 0.34), a relationship which was markedly attenuated by adjustments for RM (β-coefficient = 1.78 ± 0.31, P < 0.0001 vs. without adjustments for RM), and Pb (β-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.

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.

[OP.5B.02] PULSE PRESSURE AMPLIFICATION AND AORTIC REFLECTED WAVE MAGNITUDE BUT NOT AORTIC PRESSURES OR AUGMENTATION INDICES ADD TO BRACHIAL PULSE PRESSURE ASSOCIATIONS WITH END-ORGAN CHANGES

Objective: Although several indices of aortic pressure are associated with cardiovascular damage independent of brachial blood pressure (BP), those indices which enhance associations beyond brachial BP are uncertain. We aimed to identify those aortic pressure indices that best enhance brachial BP relations with end-organ measures. Design and method: Aortic function was determined using radial applanation tonometry and SphygmoCor software in 1197 community participants. End-organ measures included left ventricular mass index (LVMI) (n = 812), carotid intima-media thickness (n = 622) and estimated glomerular filtration rate (n = 1178). Results: Central aortic pulse pressure (PPc), aortic-to-brachial PP amplification (PPamp), aortic backward wave pressure (Pb), and the aortic reflection magnitude (RM = Pb/forward wave pressure), but neither aortic augmented pressures (Pa), nor index (AIx) were associated with all end-organ measures independent of brachial PP. In multivariate models with the inclusion of PPc or Pb, relations between brachial PP and end-organ measures or the presence of LV hypertrophy or chronic kidney disease were eliminated. In contrast, with the inclusion of brachial PP and PPamp or RM in multivariate models, brachial PP-end-organ relations were retained, whilst PPamp (p < 0.0005) and RM (p < 0.01 to < 0.0001) added significantly to the models. Relations between PPamp or RM and end-organ changes remained unchanged with further adjustments for aortic pulse wave velocity. Conclusions: PPamp and RM, but not PPc, Pb, Pa, or AIx independently associate with and add to brachial PP associations with end-organ measures. Thus, PP amplification and the reflection magnitude, but not aortic pressures or augmentation indices may enhance risk prediction beyond brachial BP.

1079 THE IMPACT OF CIRCULATING CHOLESTEROL CONCENTRATIONS ON CAROTID INTIMA MEDIA THICKNESS IN AN URBAN, DEVELOPING COMMUNITY OF AFRICAN ANCESTRY

Background: Cholesterol is an important determinant of atherogenesis1,2. However, populations of African ancestry have low total and LDL cholesterol concentrations (anti-atherogenic), but elevated triglyceride concentration and low HDL concentration (pro-atherogenic)3,4. The role of circulating lipids in atheroma formation in groups of African descent is uncertain. Therefore, in the current study I evaluated whether circulating lipids are independently associated with carotid intima media thickness (C-IMT), a surrogate marker of atheroma, in an urban developing community of African ancestry in SOWETO South Africa. Methodology430 participants were randomly selected. C-IMT was determined from Doppler images of the carotid artery using a SonoSite (SonoCalcTM IMT) version 3.4 device. Results: In Bivariate analysis total cholesterol, total:HDL cholesterol ratio, LDL cholesterol and triglyceride concentrations were strongly associated with C-IMT (r = 0.24 to r = 0.26, p-values < 0.0001); but was not associated with HDL cholesterol concentration (r = -0.08, p-value = 0.108). However, in multivariate models which included adjustments for age, conventional systolic blood pressure, diabetes mellitus, smoking, treatment for hypertension, regular alcohol intake,heart rate andpostmenopausal status (confirmed with follicle stimulating hormone measurement); none of the lipid variables were markedly associated with C-IMT (TCHOL cholesterol p = 0.884; LDL p = 0.682; TRGL p = 0.832; HDL p = 0.371; total:HDL cholesterol ratio p = 684). In multivariate regression analysis only age (p < 0.0001) and gender (p < 0.05) were independently associated with C-IMT. In conclusion: The current study shows that in urban developing community of African ancestrythere is noindependent relationship between circulating lipid concentrations and C-IMT thus no atheroma formation. However, age and gender independently predicted C-IMT in this population. ReferencesPignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation1986;74:1399-1406.Sharma K, Blaha MJ, Blumenthal RS, Musunuru K.Clinical and research applications of carotid intima-media thickness. AM J Cardiol 2009;103:1316-1320.Omran AR. The epidemiologic transition. A theory of the epidemiology ofpopulation change. Milbank Q 2005;83(4):731-757.Goedecke JH, Utzschneider K, Faulenbach MV, Rizzo M, Berneis K et al. Ethnic differences in serum lipoproteins and their determinants in South African women. J. Metabol 2010;59:1341-1350.