Bryan Hodson

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.

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.

Intrafamilial Aggregation and Heritability of Aortic Reflected (Backward) Waves Derived From Wave Separation Analysis

BACKGROUND Although aortic wave reflection may be inherited, the extent to which indexes of wave reflection derived from wave separation analysis (reflected (backward) wave index (RI) and pressure (Pb)) show intrafamilial aggregation and heritability is uncertain. We therefore aimed to determine the intrafamilial aggregation and heritability of RI and Pb and compare these with indexes of pressure augmentation. METHODS Aortic Pb, RI, augmented pressure (Pa), and augmentation index (AIx) were determined using radial applanation tonometry and SphygmoCor software in 1,152 participants of 315 families (111 father-mother, 705 parent-child, and 301 sibling-sibling pairs) from an urban developing community of black Africans. Heritability estimates were determined from Statistical Analysis for Genetic Epidemiology software. RESULTS With appropriate adjustments, significant correlations were noted between parent-child pairs for Pb and Pa (P < 0.05 for all), but not for RI (P = 0.50) or AIx (P = 0.90) and between sib-sib pairs for Pb and Pa (P < 0.05), but not for RI (P = 0.54) or AIx (P = 0.14). No correlations for indexes of wave reflection were noted between fathers and mothers (P > 0.57). After adjustments, Pb (h2 = 0.24±0.07) and Pa (h2 = 0.23±0.07) (P < 0.001 for both) but not RI (h2 = 0.04±0.06, P = 0.27) or AIx (h2 = 0.10±0.07, P = 0.07) showed significant heritability. CONCLUSIONS Aortic reflected (backward) waves derived from either wave separation (Pb) or pulse wave analysis (Pa) show a similar degree of intrafamilial aggregation and heritability, but the use of RI or AIx may underestimate reflected wave effects.

Impact of castration on changes in left ventricular diastolic pressure-volume relations induced by chronic adrenergic stimulation in rats.

Abstract: A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the &bgr;-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg−1·d−1), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure–volume (P-V) relationships. As compared with the saline vehicle–treated group, after 6 months of &bgr;-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V0 in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic &bgr;-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V0 in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.

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.

4D.03: INTRAFAMILIAL AGGREGATION AND HERITABILITY OF AORTIC REFLECTED (BACKWARD) WAVES DERIVED FROM WAVE-SEPARATION ANALYSIS.

Objective: Although aortic augmentation index (AIx) and pressure (Pa) are inherited, AIx and Pa are poor measures of reflected (backward) wave function. As wave reflection predicts outcomes beyond brachial BP, we aimed to determine the intra-familial aggregation and heritability of indices of aortic wave reflection derived from wave separation analysis (reflected [backward] wave index [RI] and pressure [Pb]) and compare these with the intra-familial aggregation and heritability of AIx and Pa. Design and method: Aortic Pb, RI, Pa and AIx were determined using radial applanation tonometry and SphygmoCor software in 1152 participants of 315 families (111 father-mother pairs, 705 parent-child pairs and 301 sibling-sibling pairs) with 24 families including three generations from an urban developing community of black African ancestry. Aortic Pb was determined using wave separation analysis where the aortic forward and backward waves were separated using a triangular aortic flow wave. Heritability estimates (h2) were determined from S.A.G.E software. Results: With adjustments for age, sex, pulse rate, mean arterial pressure, body weight, body height, regular smoking, regular alcohol intake and diabetes mellitus or an HbA1c > 6.1%, significant correlations were noted between parent-child pairs for Pb, RI and Pa (p < 0.05 for all), but not for AIx (p = 0.90) and between sibling-sibling pairs for Pb and Pa (p < 0.05), but not for RI (p = 0.06) or AIx (p = 0.14). No correlations for indices of wave reflection were noted between fathers and mothers (p > 0.57). After the aforementioned adjustments, Pb (h2 = 0.24 ± 0.07), RI (h2 = 0.26 ± 0.07) and Pa (h2 = 0.23 ± 0.07)(p < 0.001 for all) but not AIx (h2 = 0.10 ± 0.07, p = 0.07) showed significant heritability. Intra-familial correlations and heritability estimates for Pa remained significant despite further adjustments for either Pb (h2 = 0.13 ± 0.06, p < 0.05) or RI (h2 = 0.14 ± 0.06, p < 0.05). The intra-familial aggregation and heritability of aortic pulse pressure was accounted for by both Pb and forward wave pressures. Conclusions: Aortic reflected (backward) waves derived from wave separation analysis show intra-familial aggregation and heritability, but these effects are poorly characterized by measures of aortic pressure augmentation.