Andrew Raymond

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.

Independent Associations of Circulating Galectin-3 Concentrations With Aortic Pulse Wave Velocity and Wave Reflection in a Community Sample

Although the profibrotic inflammatory substance galectin-3 predicts outcomes in the general population, the mechanisms responsible for this effect are uncertain. We aimed to determine whether circulating galectin-3 concentrations are associated with carotid femoral (aortic) pulse wave velocity and aortic reflective wave index (applanation tonometry and SphygmoCor software) in 966 randomly selected participants from a community sample. Galectin-3 concentrations were not independently associated with office (n=966) or 24-hour (n=661) systolic (P=0.88–0.92) or diastolic (P=0.65–0.94) blood pressure. In contrast, with adjustments for age, sex (in all participants), office or 24-hour mean arterial pressure (or systolic blood pressure and pulse pressure), pulse rate, body mass index, regular smoking, regular alcohol intake, total cholesterol concentrations, diabetes mellitus or an glycohemoglobin >6.1%, treatment for hypertension, and estimated glomerular filtration rate, galectin-3 was independently associated with aortic pulse wave velocity in all participants (partial r=0.15, P<0.0001) and reflective wave index in men (partial r=0.13, P<0.02). In 745 participants who had never received antihypertensive therapy, galectin-3 concentrations were similarly independently associated with pulse wave velocity in all participants (partial=0.16, P<0.0001) and reflective wave index in men (partial r=0.15, P<0.02). The blood pressure–independent relations between galectin-3 concentrations and aortic hemodynamics persisted with further adjustments for C-reactive protein concentrations (pulse wave velocity in all participants: partial r=0.14, P<0.0001; reflective wave index in men: partial r=0.12, P<0.05). In conclusion, despite a lack of independent association with brachial blood pressure, the profibrotic inflammatory substance galectin-3 may contribute toward adverse outcomes through an effect on aortic stiffness, an effect that cannot be attributed to general inflammatory changes.

Relationship between average leucocyte telomere length and the presence or severity of idiopathic dilated cardiomyopathy in black Africans

A reduced average leucocyte telomere length is associated with ischaemic heart failure. Whether this relationship represents a cause or consequence of heart failure or is attributed to associated risk factors and coronary artery disease is uncertain. We evaluated if average leucocyte telomere length is associated with idiopathic dilated cardiomyopathy (IDC) or its severity.

Impact of Gender and Menopausal Status on Relationships Between Biological Aging, as Indexed by Telomere Length, and Aortic Stiffness

BACKGROUND Telomere length predicts cardiovascular disease (CVD) possibly through an impact of telomere attrition on aortic stiffness. Whether reduced biological aging and a lack of telomere length-aortic stiffness relationships in women contribute to the lower prevalence of CVD in women, prior to menopause, is uncertain. METHODS We evaluated the relationship between telomere length and carotid-femoral (aortic) pulse wave velocity (PWV) in 580 randomly recruited participants of Black African descent (age = 44 ± 19 years; women: n = 361; premenopausal: n = 195). PWV was determined using carotid and femoral applanation tonometry (SphygmoCor). Relative leukocyte telomere length (T/S) was measured using quantitative real-time polymerase chain reaction assays. RESULTS Men and women had similar T/S. T/S was inversely correlated with age (r = -0.14, P < 0.001) and this association was similar in all (r = -0.14, P < 0.01) and premenopausal (r = -0.17, P < 0.05) women as in men (r = -0.14, P < 0.05). An inverse relationship between T/S and PWV was noted both before (r = -0.20, P < 0.0001) and after (partial r = -0.14, P < 0.001) adjustments for confounders. No interaction between T/S and either sex or menopausal status was independently associated with PWV, and T/S was independently correlated with PWV in all (partial r = -0.14, P < 0.01) and premenopausal (partial r = -0.18, P < 0.05) women and in men (partial r = -0.15, P < 0.05). CONCLUSIONS Gender and premenopausal status do not affect age-related decreases in T/S and associations between T/S and PWV. In participants of African descent in whom telomere length did not differ by gender, the impact of gender prior to menopause on CVD is unlikely to be attributed to differences in the effect of biological aging on aortic stiffness.

Chronic kidney disease epidemiology collaboration-derived glomerular filtration rate performs better at detecting preclinical end-organ changes than alternative equations in black Africans.

Aim: To identify whether the more recently developed equation for estimated glomerular filtration rate (eGFR) [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] is more closely associated with end-organ changes than previous equations in a group of black African descent. Methods: In 1221 randomly recruited participants of black African ancestry in South Africa, we evaluated serum creatinine concentrations, echocardiographic left ventricular mass index (n = 833), carotid-femoral (aortic) pulse wave velocity (PWV) (n = 1053) and carotid intima–media thickness (n = 633). We calculated eGFR from the Jelliffe, five Cockcroft–Gault, Salazar–Corcoran, Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. Results: After multivariate adjustments, eGFR calculated from all formulae was inversely associated with left ventricular mass index (P < 0.0001) and PWV (P < 0.05 to <0.001), but not with carotid intima–media thickness (P > 0.08). However, although eGFR determined from all equations except Cockcroft–Gault lean body weight or adjusted body weight was independently associated with left ventricular hypertrophy (n = 390 of 833), CKD-EPI-derived eGFR, but not eGFR determined from alternative equations, was independently associated with an increased PWV (n = 88 of 1053). eGFR derived from the CKD-EPI and MDRD equations showed a better performance (area under the receiver operator characteristic curve) for the detection of left ventricular hypertrophy (P < 0.0005) than eGFR determined from alternative equations. Conclusions: In black Africans, eGFR derived from the CKD-EPI equation is better at detecting end-organ measures than eGFR derived from either the MDRD or alternative equations. To enhance risk prediction in black African communities, eGFR calculated from the CKD-EPI equation may be preferred to other equations.

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.

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.08: INDEPENDENT ASSOCIATIONS OF GALECTIN-3 CONCENTRATIONS WITH AORTIC PULSE WAVE VELOCITY AND WAVE REFLECTION IN A COMMUNITY SAMPLE.

Objective: Although the pro-fibrotic inflammatory substance galectin-3 predicts outcomes in the general population, the mechanisms responsible for this effect are uncertain. As galectin-3 expression contributes to aortic stiffness in preclinical studies, we aimed to determine whether circulating galectin-3 concentrations are associated with carotid femoral (aortic) pulse wave velocity (PWV) and aortic reflective wave index (RI) in a community sample. Design and method: Aortic PWV and RI were determined using applanation tonometry and SphygmoCor software in 966 randomly selected participants older than 16 years of age from a community sample of the South West Township (SOWETO) of Johannesburg. 661 participants had 24-hour ambulatory blood pressure (BP) monitoring that met with pre-specified quality control criteria. Results: Galectin-3 concentrations were not independently associated with office or 24-hour systolic (SBP) (p = 0.88–0.92), or diastolic (p = 0.65–0.94) BP. In contrast, with adjustments for age, sex, office or 24-hour mean arterial pressure (or SBP and pulse pressure), pulse rate, body mass index, regular smoking, regular alcohol intake, total cholesterol concentrations, diabetes mellitus or an HbA1c > 6.1%, treatment for hypertension and estimated glomerular filtration rate, galectin-3 was independently associated with aortic PWV (partial r = 0.15, p < 0.0001) and RI (partial r = 0.10, p < 0.005). In 745 participants that had never received antihypertensive therapy, galectin-3 concentrations were similarly independently associated with PWV (partial = 0.16, p < 0.0001), and RI (partial r = 0.11, p < 0.005). With adjustments for all confounders, markedly higher PWV and RI values were noted in the highest 3–4 octiles as compared to the lowest 3 octiles of galectin-3 concentrations. The BP-independent relations between galectin-3 concentrations and aortic haemodynamics persisted with further adjustments for C-reactive protein concentrations (PWV: partial r = 0.14, p < 0.0001, RI: partial r = 0.10, p = 0.002). Conclusions: Despite a lack of independent association with brachial BP, the pro-fibrotic inflammatory substance galectin-3 may contribute toward adverse outcomes through an impact on aortic stiffness and the magnitude of aortic reflected waves, effects that cannot be attributed to general inflammatory changes.

[OP.2B.04] CHRONIC KIDNEY DISEASE EPIDEMIOLOGY COLLABORATION-DERIVED GLOMERULAR FILTRATION RATE IS BETTER AT DETECTING PRE-CLINICAL END ORGAN CHANGES THAN OTHER EQUATIONS IN BLACK AFRICANS

Objective: The recent Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) is recommended for use in European populations. However, because the relationship between creatinine and GFR varies between ethnicities, the CKD-EPI equation may not perform as well in African as it does in Caucasian populations. We aimed to identify whether the CKD-EPI equation is more closely associated with end organ changes than previous equations in a group of black African descent. Design and method: In 1221 randomly recruited participants of black African ancestry in South Africa, we evaluated serum creatinine concentrations, echocardiographic left ventricular mass index (LVMI) (n = 833), carotid-femoral (aortic) pulse wave velocity (PWV) (n = 1053) and carotid intima-media thickness (IMT)(n = 633). We calculated eGFR from the Jelliffe, 5 Cockcroft-Gault, Salazar-Corcoran, (Modification of Diet in Renal Disease [MDRD] and CKD-EPI equations. Results: After multivariate adjustments, eGFR calculated from all formulae was inversely associated with LVMI (p < 0.0001), PWV (p < 0.05 to < 0.001), and IMT (p < 0.0001). However, while eGFR determined from all equations was independently associated with LV hypertrophy (LVH) and an increased IMT; CKD-EPI-derived eGFR, but not eGFR determined from alternative equations was independently associated with an increased PWV. Moreover, while eGFR derived from the CKD-EPI and MDRD equations showed a better performance (area under the receiver operator characteristic curve) for the detection of LV hypertrophy (LVH) (p < 0.0005) than eGFR determined from alternative equations, the MDRD equation showed a worse performance for the detection of an increased IMT (p < 0.05 for comparisons of the AUC) than eGFR calculated from alternative equations. Conclusions: In black Africans, eGFR derived from the CKD-EPI equation is better at detecting end-organ measures than eGFR derived from either the MDRD or alternative equations. To enhance risk prediction in black African communities eGFR calculated from the CKD-EPI equation may be preferred to other equations.