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AIMS Whether renal mechanisms of hypertension primarily translate into increases in systemic vascular resistance (SVR) in all populations is uncertain. We determined whether renal mechanisms associate with either increases in SVR (and impedance to flow) or systemic flow in a community of African ancestry. METHOD In a South African community sampled across the full adult age range (n = 546), we assessed stroke volume (SV), peak aortic flow (Q), SVR, characteristic impedance (Zc) and total arterial compliance (TAC) from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. Renal changes were determined from creatinine clearance (glomerular filtration rate, GFR) and fractional Na+ excretion (FeNa+) (derived from 24-h urine collections). RESULTS Independent of confounders (including MAP and pressures generated by the product of Q and Zc), SV (and hence cardiac output) (P

Although hypertension in groups of African ancestry is volume-dependent, the relative impact of systemic flow (stroke volume, peak aortic flow [Q]) versus vascular mechanisms (systemic vascular resistance, aortic characteristic impedance [Zc], total arterial compliance) components of arterial load has not been evaluated across the adult age range. In participants of African ancestry (n=824, age=16–99 years, 68.3% female), using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the hemodynamic correlates of age-related increases in blood pressure. Strong independent positive relations between age and stroke volume or peak aortic Q were noted ( P P P P P P

The relative contribution of loading conditions at different ages across the full adult lifespan to decreases in left ventricular (LV) diastolic function is unclear. Using central arterial pressure and aortic velocity and diameter measurements in the outflow tract, we determined the contribution of systemic vascular resistance, compression wave pressures (characteristic impedance [Zc]×aortic flow [Q], [P Q×Zc ]) and backward wave pressures (Pb) to LV diastolic function (echocardiography) in a community sample across the full adult lifespan (n=605). Starting from early adulthood, stepwise age-related increases in LV filling pressures (E/e’) and decreases in myocardial relaxation (e’) were noted ( P Q×Zc positively correlates with age, Pb, but not systemic vascular resistance was independently associated with LV mass index ( P P P Q×Zc positively correlates with age, again Pb, but neither P QxZc nor systemic vascular resistance was independently associated with LV mass index ( P P P

OBJECTIVES To determine the extent to which metabolic and inflammatory changes are associated with renal damage beyond conventional risk factors in a community sample with a high prevalence of obesity in urban South Africa. METHODS This was a cross-sectional, community-based study in 1 010 (n = 872 without diabetes mellitus, DM) randomly selected participants over 16 years of age in an urban, developing community (Soweto, Johannesburg) with a high prevalence of obesity (41.8%). We assessed estimated glomerular filtration rate (eGFR), conventional risk factors including adiposity indices, and metabolic changes and plasma resistin concentrations (ELISA) and the homeostasis model of insulin resistance (HOMA-IR). Relationships independent of haemodynamic loads were confirmed using ambulatory blood pressure and central arterial haemodynamics. RESULTS In multivariate regression models conducted in those without DM, HOMA-IR (standardised β-coefficient = -0.13 ± 0.03, p < 0.0001) and plasma resistin concentrations (β-coefficient = -0.10 ± 0.02, p < 0.0001) were second only to age, and at least as strong as systolic blood pressure (β -coefficient = -0.04 ± 0.03, p = 0.19) in the impact on eGFR, while alternative conventional risk factors including adiposity indices and the metabolic syndrome features contributed little to eGFR. Similar results were obtained in relationships with chronic kidney disease (CKD) and in the whole group including those with DM. Adjustments for ambulatory blood pressure or central arterial loads did not influence these relationships. CONCLUSIONS The impact on glomerular function of insulin resistance and inflammatory changes is well beyond modifiable conventional risk factors, including the metabolic syndrome. Targeting conventional risk factors alone is likely to result in a marked residual risk of renal damage produced by insulin resistance and inflammation.

Background Although, in-part through an impact on left ventricular mass (LVM), resistin (an adipokine) may contribute to heart failure, whether this is explained by the adverse effects of resistin on aortic stiffness and renal function is unknown. Methods Relationships between circulating resistin concentrations and LVM index (LVMI), and LVM beyond that predicted by stroke work (inappropriate LVM [LVMinappr]) (echocardiography) were determined in 647 randomly selected community participants, and in regression analysis, the extent to which these relations could be explained by aortic pulse wave velocity (PWV) or estimated glomerular filtration rate (eGFR) was evaluated. Results Independent of confounders, resistin concentrations were independently associated with LVMI, LVMinappr, LV hypertrophy (LVH), PWV and eGFR. Furthermore, independent of confounders, LVMI, LVMinappr and LVH were independently associated with PWV and eGFR. However, adjustments for either PWV or eGFR failed to modify the relationships between resistin concentrations and LVMI, LVMinappr or LVH. Moreover, in multivariate regression analysis neither PWV nor eGFR significantly modified the contribution of resistin to LVMinappr or LVMI. Conclusions Independent relationships between circulating concentrations of the adipocytokine resistin and LVM are not explained by the impact of resistin on ventricular-vascular coupling or renal dysfunction. Resistin’s effects on LVM are therefore likely to be through direct actions on the myocardium.

Through both backward (Pb) and forward (Pf) wave effects, a lower heart rate (HR) associates with increased central (PPc), beyond brachial pulse pressure (PP). However, the relative contribution to Pf of aortic flow (Q) versus re-reflection of Pb, has not been determined. Using central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we constructed central pressure waveforms that account for the relative contribution of Q versus re-reflection to Pf. We thus evaluated the mechanisms of HR-PPc relations in a community sample (n=824) and the impact of age thereon. Inverse HR-PPc ( P P =0.064) relations were noted. The slope of HR-PPc relation was increased in older adults ( P P P P P P

AIMS Although the development of left ventricular (LV) dysfunction in hypertension has traditionally been viewed as a transition process from a phase of structural LV remodelling to dysfunction, the extent to which LV mass (LVM) and remodelling account for blood pressure (BP)-associated alterations in LV diastolic function is uncertain. In product of coefficient mediation analysis, we aimed to determine the extent to which LVM index (LVMI) or relative wall thickness (RWT) account for relations between BP and LV diastolic function. METHODS In 709 randomly selected participants from a community sample with a high prevalence of hypertension (49.6%), we determined BP and LVMI, RWT and several indices of diastolic function from transmitral blood flow and myocardial tissue Doppler (E/A, e'/a', e' and E/e') and left atrial volume using standard echocardiographic techniques. RESULTS With adjustments for confounders, LVMI (P

Background Although obesity‐associated metabolic abnormalities (insulin resistance‐IR) may not play as marked a role in determining left ventricular (LV) diastolic dysfunction (DD) as hypertension, the impact of combinations of these risk factors on DD is unknown. Hypothesis We hypothesized that IR influences the impact of hypertension on DD. Methods In 704 randomly selected participants from a community sample with a high prevalence of hypertension (50.6%) and obesity (46.5%), we determined adiposity indices, IR from the homeostasis model (HOMA‐IR) and LV diastolic function using standard echocardiographic techniques. Results HOMA‐IR was independently associated with lateral wall e' and E/e' (P < 0.05 to P < 0.005) as well as a diagnosis of DD (P < 0.02). Importantly, however, an enhanced relationship between HOMA‐IR and E/e' in hypertensives (n = 356, partial r = 0.15, P < 0.005) as compared to normotensives (n = 348, partial r = 0.02 P = 0.75) was noted. Consequently, as compared to normotensives, with adjustments for confounders, hypertension was independently associated with DD only in those with the highest tertile of HOMA‐IR (odds ratio = 2.65, 95% confidence interval = 1.29‐5.42, P < 0.01), while in those with the lowest tertile of HOMA‐IR, hypertension failed to show a higher prevalence of DD (P = 0.22). Conclusions Insulin resistance enhances the impact of hypertension on LV DD. Thus, DD is more likely to occur with the combination of hypertension and IR.

A reason for concentric left ventricular (LV) remodelling predicting cardiovascular outcomes independent of conventional risk factors and LV mass (LVM) has not been provided. We hypothesized that independent of LVM, concentric LV remodelling is associated with inflammatory changes rather than a pressure load on the LV.In 764 randomly selected community participants, we assessed relations between several inflammatory markers (ELISA) and LV relative wall thickness (RWT) (echocardiography), LV mass index (LVMI), and indexes of diastolic function.No independent relations were noted between circulating concentrations of inflammatory markers and LVM index (LVMI) (p 0.13 for all). However, independent of confounders including LVMI and blood pressure (BP), circulating tumour necrosis factor-α (TNF-α) (partial r = 0.14, p 0.0005) and to a lesser degree interleukin-6 (partial r = -0.09, p 0.02) were associated with RWT. The impact (standardized β-coefficient) of TNF-α on RWT (0.12 ± 0.03, p 0.0005) was at least as strong as age (0.13 ± 0.05, p 0.005), and second only to LVMI (0.27 ± 0.04, p 0.0001), whilst neither office, 24-hour, central aortic BP, nor aortic stiffness were associated with RWT independent of LVMI. With adjustments, as compared to participants with a normal LVMI and geometry (12.7 ± 0.8), circulating TNF-α concentrations (pg/ml) were increased as much in participants with concentric LV remodelling (16.8 ± 1.5, p 0.05) as in those with concentric LV hypertrophy (LVH) (17.0 ± 1.3, p 0.005), whilst eccentric LVH (13.7 ± 0.9) was not. No independent relations between inflammatory markers and LV diastolic function (trans-mitral and tissue Doppler) were noted.Independent of LVMI, a pro-inflammatory state rather than BP load is strongly associated with LV concentric remodelling.

Objective: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P P P P P Conclusions: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Alterations in sodium (Na

BACKGROUND The contribution of steady-state pressures and the forward (Pf) and backward (reflected) (Pb) wave pressure components of pulse pressure to risk prediction have produced contrasting results. We hypothesized that the independent contribution of steady-state pressures (mean arterial pressure [MAP]), Pf and Pb, to cardiovascular damage is organ specific and age dependent. METHODS In 1,384 black South Africans from a community sample, we identified independent relations between MAP, Pf, or Pb (applanation tonometry and SphygmoCor software) and left ventricular mass index (LVMI) (n = 997) (echocardiography), carotid intima-media thickness (IMT) (n = 804) (B-mode ultrasound), or aortic pulse wave velocity (PWV) (n = 1,217). RESULTS Independent of risk factors, relations between Pf and IMT were noted in those over 50 years (P < 0.02), whereas in those less than 50 years, MAP (P < 0.005) was independently associated with IMT. Pb failed to show independent relations with IMT at any age (P > 0.37) In contrast, independent relations between Pb and LVMI were noted in those less than (P < 0.0001), and greater than (P < 0.02) 50 years, whereas MAP was not independently associated with LVMI at any age (P > 0.07) and Pf tended to show significant relations only in the elderly (P = 0.05). Moreover, although MAP (P < 0.005) and Pb (P < 0.01) showed independent relations with PWV at any age, Pf failed to show independent relations (P > 0.10). CONCLUSION Independent of confounders, steady-state and aortic Pf and Pb show associations with end-organ measures that are organ specific and age dependent.

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.

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

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 0.08). 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

BACKGROUND Whether the impact of backward wave pressures (Pbs) on left ventricular (LV) diastolic dysfunction (DD) antedates the effects of aortic stiffness is uncertain. We compared the relative contribution of various aortic hemodynamic parameters to preclinical DD in a predominantly young-to-middle-aged community-based sample. METHODS In 524 randomly selected participants of African ancestry (mean age = 46.8±18.4 years), we assessed central aortic pulse pressure (PPc), forward wave pressure (Pf), Pb, augmented pressure (Pa), the time-to-wave reflection (Rt), and aortic pulse wave velocity (PWV) using applanation tonometry (SphygmoCor software). LV mass index (LVMI), early to late transmitral velocity (E/A), and E/velocity of myocardial tissue lengthening (E/e') were determined using echocardiography. RESULTS Independent of age, sex, mean arterial pressure, body mass index, diabetes mellitus and/or HbA1c > 6.1%, regular smoking, regular alcohol intake, treatment for hypertension, pulse rate, and LVMI; PPc (P < 0.002), Pb (P < 0.0005), Pa (P < 0.002), and Pf (P < 0.02), but not Rt or PWV were independently associated with E/e' (but not with E/A). With adjustments for confounders, PPc (P < 0.005), Pb (P < 0.002), and Pa (P < 0.001), but not Pf, Rt, or PWV were independently associated with E/e' ≥ 12 (moderate-to-severe DD, n = 69). The independent relations between PPc and E/e' or moderate-to-severe DD were not affected by adjustments for PWV, Pf, or Rt, but were abolished with adjustments for Pb. CONCLUSIONS In a predominantly young-to-middle-aged community sample, the impact of Pbs on LV DD antedates the effects of aortic stiffness, the time-to-wave reflection, or Pfs.

AIMS The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity. METHODS Plasma resistin, adiponectin, and C-reactive protein concentrations (ELISA); carotid-femoral (aortic) PWV and the aortic reflected wave index (applanation tonometry and SphygmoCor software) were determined in 683 randomly selected participants of African ancestry from SOWETO, South Africa who had never received antihypertensive therapy. RESULTS Resistin concentrations were not independently associated with office or 24-h (n = 492) blood pressure (BP). In a stepwise regression model with BMI included in the model, age (P

BACKGROUND Blunted nocturnal blood pressure (BP) dipping (nondipping) predicts cardiovascular morbidity and mortality, and is associated with heart failure (HF) independent of office BP. Whether nondipping is independently associated with cardiac systolic function prior to the development of HF is uncertain. METHODS We assessed whether nocturnal BP dipping pattern and nocturnal BP were associated with indexes of cardiac systolic function [endocardial fractional shortening (endFS), midwall FS (mFS), ejection fraction (EF)] independent of left ventricular mass index (LVMI) and relative wall thickness (RWT) in 491 randomly selected community participants not receiving antihypertensive therapy. Nocturnal BP and dipping pattern were determined from 24-hour BP monitoring where nighttime was defined from fixed-clock time intervals. BP dipping was defined as night-to-day BP ratio. Pulse wave velocity (PWV) was determined using SphygmoCor, and total peripheral resistance (TPR) was calculated from echocardiographic data. RESULTS On bivariate analyses, nocturnal BP and BP dipping but not day BP were correlated with indexes of cardiac systolic function (P < 0.005). After adjustments for potential confounders including age, LVMI (or RWT) and 24 hour (or day) BP, endFS (P < 0.01), mFS (P < 0.05), and EF (P < 0.01) were associated with nocturnal BP and BP dipping. These relationships survived further adjustments for PWV, and the homeostasis model of insulin resistance. The decreased mFS in reverse dippers was in-part explained by an increased TPR. CONCLUSIONS In an untreated community sample, blunted nocturnal BP dipping is independently and inversely associated with cardiac systolic function. Hence, nondipping is related to a reduced cardiac systolic function prior to the development of HF.

BACKGROUND Through the impact of conventional risk factors on arteries, several changes in aortic function contribute to cardiovascular events. It is nevertheless uncertain whether these effects are accurately reflected by changes in central aortic pulse pressure (PPc). We, therefore, aimed to determine the extent to which relations between modifiable risk factors and aortic function translate into increases in PPc. METHODS In 1,232 black South Africans from the South West Township (SOWETO) of Johannesburg, we determined risk factors and aortic function from carotid-femoral pulse wave velocity (PWV), aortic PPc, forward wave pressures (Pf), and reflected (backward) wave pressures (Pb) (applanation tonometry and SphygmoCor software). RESULTS With adjustments for alternative risk factors and distending pressure (mean arterial pressure (MAP)), diabetes mellitus (treatment or HbA1c > 6.5%, n = 151) was associated with an increased PWV (7.10 ± 2.09 vs. 6.17 ± 2.00 m/s, P < 0.0001), and Pf (26 ± 8 vs. 24 ± 8 mm Hg, P < 0.005), but neither brachial PP (46 ± 14 vs. 45 ± 13, P = 0.19), PPc (36 ± 12 vs. 35 ± 11 mm Hg, P = 0.48), nor Pb (17 ± 6 vs. 17 ± 6 mm Hg, P = 0.83). Moreover, independent of alternative risk factors and MAP, uncontrolled hypertension (office blood pressure > 140/90 mm Hg, n = 433) was associated with an increased Pf (26 ± 12 vs. 24 ± 10 mm Hg, P < 0.01), but not with changes in brachial PP (45 ± 19 vs. 44 ± 17, P = 0.75), PPc (35 ± 16 vs. 35 ± 15 mm Hg, P = 0.93), or Pb (18 ± 8 vs. 17 ± 8 mm Hg, P = 0.46). CONCLUSIONS Neither brachial nor aortic PP are adequate indexes of relations between the modifiable conventional risk factors, uncontrolled hypertension or diabetes mellitus, and risk-related aortic functional changes.

Although the adipokine resistin may play a role in heart failure, the mechanisms of this effect are uncertain. Relations with left ventricular mass (LVM) and function are uncertain.In 739 randomly selected participants from a community sample (43.6% obese), we assessed relations between circulating resistin concentrations and LVM index (LVMI), LVM beyond that predicted by stroke work (inappropriate LVMI [LVMinappr]) and systolic and diastolic LV function (echocardiography).Resistin concentrations were not independently associated with blood pressure (BP). However, resistin concentrations were associated with LVMI (partial r=0.12, p0.0005), LVMinappr (partial r=0.18, p0.0001) and LV hypertrophy (partial r=0.13, p0.001) independent of BP, BMI, the homeostasis model of insulin resistance and additional confounders. Independent relations between resistin concentrations and LVMI and LVMinappr persisted with further adjustments for C-reactive protein concentrations. Resistin concentration (partial r=-0.12, p0.002 in all and partial r=-0.15, p0.0005 in untreated) was the only factor independently associated with LV midwall fractional shortening and these relations were enhanced at incremental concentrations of CRP. Resistin was not independently associated with transmitral and myocardial tissue Doppler indices of LV diastolic function.Resistin in-part explains variations in LVM, hypertrophy and myocardial systolic dysfunction, and these effects are independent of insulin resistance and general inflammatory changes.

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.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.With appropriate adjustments, significant correlations were noted between parent-child pairs for Pb and Pa (P0.05 for all), but not for RI (P = 0.50) or AIx (P = 0.90) and between sib-sib pairs for Pb and Pa (P0.05), 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 (P0.57). After adjustments, Pb (h2 = 0.24±0.07) and Pa (h2 = 0.23±0.07) (P0.001 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.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.

Reports on the contribution of aortic forward (Pf) and backward (Pb) wave pressures to age-related increases in central aortic pulse pressure (PPc) have been confounded by the use of participants receiving antihypertensive therapy. We assessed the relative contribution of Pf and Pb to age-related increases in PPc (radial applanation tonometry and SphygmoCor software using an assumed triangular wave for wave separation analysis) in 892 community participants not receiving antihypertensive therapy. We validated our results using aortic flow waves (echocardiography) for wave separation analysis in 254 of these participants. In multivariate regression models in those aged50 years, adjustments for both Pb and a Pf-independent measure of reflected wave function (RM = Pb/Pf), but not Pf abolished the impact of age on PPc. However, in those aged50 years, adjustments for Pf (β-coefficient: 0.25 ± 0.06 vs. 0.74 ± 0.08; P .0001) and Pb (0.04 ± 0.04 vs. 0.74 ± 0.08; P .0001), but not RM markedly decreased the relationship between age and PPc. On product of coefficient mediation analysis, whether assessed in men or in women, in those participants aged50 years, independent of several confounders and mean arterial pressure, Pb (P .005), but not Pf contributed to age-related increases in PPc. In contrast, in those participants aged ≥50 years, independent of several confounders and mean arterial pressure, Pb (P .005) and Pf (P .01) contributed to age-related increases in PPc, and Pb effects were markedly diminished by adjustments for Pf (0.26 ± 0.002 vs. 0.52 ± 0.003 mm Hg per year, P .0001 for comparison). In conclusion, independent of the effects of antihypertensive therapy, aortic backward waves contribute to age-related increases in aortic PPc across the adult lifespan, but at an older age, this effect may be attributed in part to the impact of forward on backward wave pressures.

Aims 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. Methods and results We compared average leucocyte telomere length in 223 patients with heart failure due to IDC and 227 healthy controls of black African ancestry. We also evaluated the relationship between average leucocyte telomere length and left ventricular ejection fraction (LVEF). LVEF was determined using echocardiography and radionuclide multiple-gated acquisition (MUGA) scan in patients with IDC. Relative leucocyte telomere length (T/S) was measured using a quantitative real-time polymerase chain reaction assay. Log T/S was negatively correlated with age in patients with IDC (P = 0.0007) and in controls (P = 0.030), and with alcohol consumption (P = 0.032) and regular smoking (P = 0.021) in patients with IDC. Log T/S did not differ between IDC and control groups either before (P = 0.11) or after (IDC = 0.071 ± 0.187, control = 0.071 ± 0.187, P = 0.99) adjustments for confounders. Log T/S was not associated with echocardiographic (P = 0.47) or MUGA (P = 0.99) LVEF or LV end-diastolic diameter (LVEDD) (P = 0.34) in patients with IDC. With adjustments for age, sex, alcohol consumption, and smoking, log T/S was similarly not associated with echocardiographic (P = 0.60) or MUGA (P = 0.91) LVEF or LVEDD (P = 0.53) in patients with IDC. Conclusions Average relative leucocyte telomere length is not associated with IDC or its severity in groups of black African ancestry.

Aortic pulse wave velocity (PWV) and backward waves, as determined from wave separation analysis, predict cardiovascular events beyond brachial blood pressure. However, the extent to which these aortic hemodynamic variables contribute independent of each other is uncertain. In 749 randomly selected participants of African ancestry, we therefore assessed the extent to which relationships between aortic PWV or backward wave pressures (Pb) (and hence central aortic pulse pressure [PPc]) and left ventricular mass index (LVMI) occur independent of each other. Aortic PWV, PPc, forward wave pressure (Pf), and Pb were determined using radial applanation tonometry and SphygmoCor software and LVMI using echocardiography; 44.5% of participants had an increased left ventricular mass indexed to height1.7. With adjustments for age, brachial systolic blood pressure or PP, and additional confounders, PPc and Pb, but not Pf, were independently related to LVMI and left ventricular hypertrophy (LVH) in both men and women. However, PWV was independently associated with LVMI in women (partial r = 0.16, P < .001), but not in men (partial r = 0.03), and PWV was independently associated with LVH in women (P < .05), but not in men (P = .07). With PWV and Pb included in the same multivariate regression models, PWV (partial r = 0.14, P < .005) and Pb (partial r = 0.10, P < .05) contributed to a similar extent to variations in LVMI in women. In addition, with PWV and Pb included in the same multivariate regression models, PWV (P < .05) and Pb (P < .02) contributed to LVH in women. In conclusion, aortic PWV and Pb (and hence pulse pressure) although both associated with LVMI and LVH produce effects which are independent of each other.

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.

Although in cross-sectional studies left ventricular mass (LVM), which exceeds that predicted by workload (inappropriate LVM [LVM inappr ]) but not absolute LVM or LVM index (LVMI), is inversely related to LV ejection fraction (EF), whether on-treatment decreases in LVM inappr (%observed/predicted LVM) account for increases in EF beyond LVM or LVMI is unclear. Echocardiography was performed in 168 mild-to-moderate hypertensives treated for 4 months. Although in patients with an LVMI >51 g/m 2.7 (n=112; change in LVMI, −13.7±14.0 g/m 2.7 ; P 2.7 (n=56; change in LVMI, 1.3±9.3 g/m 2.7 ) LVMI decreased with treatment, treatment failed to increase EF in either group (1.2±10.8% and 2.7±10.7%, respectively). In contrast, in patients with inappropriate LV hypertrophy (LVM inappr >150%; n=33) LVM inappr decreased (−32±27%; P P inappr ≤150% (n=135), neither LVM inappr (−0.5±23%) nor EF (0.9±10.3%) changed with therapy. With adjustments for circumferential LV wall stress and other confounders, whereas on-treatment decreases in LVM or LVMI were weakly related to an attenuated EF (partial r =0.17; P inappr were strongly related to increases in EF even after further adjustments for LVM or LVMI (partial r =−0.63 [CI, −0.71 to −0.52]; P inappr are strongly related to on-treatment increases in EF beyond changes in LVM and LVMI. LV hypertrophy can, therefore, be viewed as a compensatory change that preserves EF, but when in excess of that predicted by stroke work, it can be viewed as a pathophysiological process accounting for a reduced EF.

Objectives One year of antihypertensive therapy may normalise left ventricular (LV) structure in 51% of hypertensive patients of European descent. Whether similar effects can be achieved in patients of African descent, who have a high prevalence of concentric LV hypertrophy (LVH) and remodelling, is unknown. Methods In 103 hypertensive patients in the Baragwanath Hypertension study we evaluated the prevalence of residual LV structural changes (echocardiography) after four and 13 months of stepwise antihypertensive therapy. Results After 13 months of therapy, 24-hour blood pressure control was achieved in 47% of patients. At baseline, 51.5% of patients had concentric LVH, 19% eccentric LVH and 12% concentric LV remodelling. Despite changes in LV mass index (p < 0.01) and relative wall thickness (p < 0.05) with treatment, the proportion of patients with a normal LV mass or geometry increased only from 17.5 to 25% (p > 0.05), while 26% remained with concentric LVH (p < 0.001 compared to baseline), 25% with eccentric LVH and 23% with concentric LV remodelling (p < 0.05 compared to baseline). Residual structural changes were associated with 24-hour pulse pressure (p = 0.02), but not with 24-hour systolic or diastolic blood pressure or clinic blood pressure. Conclusions Even after a year of antihypertensive therapy, a high proportion (74%) of hypertensives of African ancestry retained residual LV structural changes, an effect that was associated with 24-hour pulse pressure but not systolic or diastolic blood pressures or clinic blood pressure in this ethnic group.

In high-Na + , low-K + diets, which suppress renin release in salt-sensitive groups, the mechanisms maintaining increases in renin-angiotensin-aldosterone system activation downstream from renin and renin-angiotensin-aldosterone system–induced effects on blood pressure (BP) are uncertain. Whether circulating angiotensinogen concentrations (AGT) or its determinants may contribute to maintaining serum aldosterone concentrations (aldosterone) and increases in BP on high-Na + , low-K + diets was evaluated in 579 participants of a community sample of African ancestry. Plasma renin concentrations were inversely related to BP ( P + /K + , P + /K + was independently associated with aldosterone ( P P + /K + at or more than the median for the sample, AGT was positively associated with aldosterone ( P P + /K + less than the median for the sample. Standardized β-coefficients (slopes) of AGT-aldosterone and AGT-SBP relationships were greater in participants with urinary Na + /K + at or more than the median (AGT-aldosterone=0.30±0.06, AGT-SBP=0.16±0.05) compared with those with urinary Na + /K + less than the median (AGT-aldosterone=−0.04±0.06; AGT-SBP=−0.03±0.05; P + /K + at or more than the median for the sample was equivalent to the relationship between body mass index and BP. In conclusion, in participants of African ancestry, in the presence of high-Na + , low-K + diets, which suppress renin release, renin-angiotensin-aldosterone system activation and its impact on BP are maintained in part by AGT.

Objectives As the impact of mild smoking on blood pressure (BP) is uncertain, we assessed the relationship between predominantly mild current smoking and out-of-office BP and the effect of angiotensin-converting enzyme (ACE) genotype on this relationship in a community sample of black African ancestry. Methods In 689 participants randomly recruited from an urban, developing community of black African descent, we assessed smoking habits, out-of-office (24-h), and in-office conventional and central (applanation tonometry) BP, and ACE insertion (I)/deletion (D) variant genotype. Results A total of 14.5% (n = 100) were current smokers, the majority being mild (72%, 7.4 ± 4.6 cigarettes/day). Despite current smokers having only modest increases in in-office (P

AIM To determine whether high-quality nurse-recorded auscultatory blood pressure (BP) values obtained at a single visit predict cardiovascular target organ changes as closely as ambulatory BP measurements. METHODS In a randomly selected population sample (n = 458, 21% receiving antihypertensive treatment; approximately 40% hypertensive), we compared high-quality single visit nurse-recorded auscultatory BP values to same-day 24-h ambulatory BP in their ability to predict multiple target organ changes [left ventricular mass index (LVMI), left ventricle (LV) mean wall thickness (MWT), early-to-late transmitral velocity ratios (E/A), (echocardiography); log of urinary albumin-to-creatinine ratios (log ACR) (24-h urine samples); large artery dysfunction [carotid-femoral pulse wave velocity (PWV) and central augmentation index (Alc) (applanation tonometry)]. RESULTS Nurse-recorded systolic BP (SBP) measurements obtained at a single visit were as closely associated with LVMI (r = 0.44), LV MWT (r = 0.44), E/A (r = -0.55), log ACR (r = 0.20), PWV (r = 0.62) and AIc (r = 0.41) (P < 0.0001 for all relations) as was 24-h SBP (LVMI; r = 0.33, LV MWT; r = 0.37, E/A; r = -0.35, log ACR; r = 0.24, PWV; r = 0.41, and AIc; r = 0.18, P < 0.001 for all relations) and either day or night SBP. On multivariate regression analysis with both nurse-recorded SBP and 24-h SBP in the same model, nurse-recorded SBP was independently associated with LVMI (P = 0.006), LV MWT (P = 0.03), E/A (P < 0.02), PWV (P < 0.0001) and AIc (P = 0.0002), and 24-h SBP was independently and positively associated with log ACR (P < 0.005), and PWV (P = 0.01). CONCLUSION One or more, high-quality single visit nurse-recorded auscultatory BP measurements may be equally as effective as ambulatory BP in predicting target organ damage in a population sample of African ancestry.

AIM: The relationship between waist circumference (WC) and conventional blood pressure (BP) is independent of other clinical indices of adiposity. As ambulatory BP may offer more prognostic information than conventional BP, we aimed to identify whether indices of central adiposity are associated with ambulatory BP independent of other indices of adiposity. METHODS: The relationship between indices of adiposity [WC, waist-to-hip ratio, body mass index (BMI) or skin-fold thickness] and ambulatory or conventional BP was determined in 300 randomly selected individuals of African descent living in an urban developing community in South Africa. Relationships were determined with multiple indices of adiposity in the same regression model and after adjusting for age, gender, alcohol and tobacco intake, the presence or absence of diabetes mellitus or inappropriate blood glucose control [haemoglobin A1c (HbA1c)], antihypertensive therapy and menopausal status. RESULTS: Sixty-five per cent of participants were overweight or obese. With respect to the relationships between indices of adiposity, BMI and WC showed the strongest correlation (r=0.84, P

Although several indexes of left ventricular (LV) diastolic function show heritability, the genetic influence on the tissue Doppler index, E/e' (early transmitral velocity/velocity of myocardial tissue lengthening), an index of LV filling pressures in those of black African descent is currently unknown. Furthermore, whether any genetic influences on E/e' are through an impact of LV remodeling or aortic function is unknown. Intrafamilial aggregation and heritability (SAGE software) of E/e' (echocardiography) were assessed in 129 nuclear families (29 spouse pairs, 216 parent-child pairs, and 113 sibling-sibling pairs) from an urban developing community of black Africans, independent of LV mass index (LVMI), LV relative wall thickness (RWT), central aortic systolic pressure (SBPc), and backward wave pressures (Pb) (applanation tonometry, SphygmoCor software). Independent of confounders including LVMI and RWT, E/e' was correlated in parent-child (r = 0.23; P

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.

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

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 BP140/90 mm Hg) accounts for age-related aortic hemodynamic changes across the adult lifespan.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 (age16 years; 36.4% uncontrolled BP).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, P0.02, 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 (P0.0001).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.

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 r =0.13, P P r =0.15, P r =0.14, P r =0.12, P

We have reported previously that despite treatment with angiotensin-converting enzyme inhibitors and beta blockers, the outcome of patients with peripartum cardiomyopathy (PPC) remains unfavorable. Similar to other etiologies of left ventricular dysfunction, we found elevated levels of tumor necrosis factor-alpha (TNF-alpha) in this group of patients. In the present study we sought to evaluate the effects of pentoxifylline, a drug known to inhibit the production of TNF-alpha, on clinical status, left ventricular function, and circulating plasma levels of TNF-alpha, in patients with PPC. We followed prospectively 59 consecutive women with PPC. The first 29 patients (group 1) were treated with diuretics, digoxin, enalapril and carvedilol. The next 30 consecutive patients (group 2) received pentoxifylline 400 mg TID in addition to the previous therapy. Clinical evaluation, echocardiograms and TNF-alpha determinations were performed at baseline and after 6 months of treatment. Patients in the pentoxifylline group were older and had a higher E/A ratio. Nine patients died (eight in group 1, P = 0.009 between groups). A combined end-point of poor outcome defined as either death, failure to improve the left ventricular ejection fraction >10 absolute points or functional class III or IV at latest follow-up, occurred in 52% of patients in group 1 and 27% of patients in group 2 (P = 0.03). Treatment with pentoxifylline (P = 0.04) was the only independent predictor of outcome. In conclusion, the results of this study suggest that the addition of pentoxifylline to conventional treatment, improves outcome in patients with peripartum cardiomyopathy.

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 r values). In those r =0.28, P r =0.15, P P r values), Pa (partial r =0.13, P r =0.22, P r =0.21, P P =0.98), while incident wave pressure (partial r =0.23, P 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.

Although the circulating renin–angiotensin system (RAS) is suppressed in salt-sensitive populations, the role of the intrarenal RAS in blood pressure (BP) control in these groups independent of the circulating RAS is uncertain. We evaluated the relationship between 24-hour urinary angiotensinogen excretion and either office (mean of 5 measurements; n=425) or 24-hour ambulatory (n=340) BP independent of the circulating RAS in a community-based sample of African descent that had never received antihypertensive drug therapy. Circulating RAS activity was determined from plasma renin and angiotensinogen and serum aldosterone concentrations. Urinary angiotensinogen to creatinine ratio (angiotensinogen/creat) was correlated with plasma angiotensinogen concentrations ( P r =0.16; P r =0.07; P =0.14) was not independently associated with office systolic BP. Urinary angiotensinogen/creat was also associated with 24-hour systolic BP (partial r =0.11; P + /K + , or 24-hour urinary Na + excretion rates ( P P P =0.01) systolic BP. In conclusion, independent of the systemic RAS, including plasma angiotensinogen concentrations, urinary angiotensinogen excretion is associated with BP in a salt-sensitive, low-renin group of African descent. These data lend further support for a role of the RAS in BP control in salt-sensitive groups of African ancestry.

AIMS To determine whether SBP or DBP is best associated with different components of left ventricular diastolic dysfunction. METHODS In 241 randomly selected participants, echocardiographic left ventricular diastolic function was assessed from early-to-atrial (E/A) transmitral velocity and E/e' where e' represents myocardial tissue lengthening velocity in early diastole as measured at the mitral annulus. Relationships between diastolic function and blood pressure (BP) were assessed from brachial and central aortic (radial applanation tonometry and SphygmoCor software) measurements. RESULTS Independent of confounders, brachial DBP (partial r = -0.21, P

Echocardiographic quantification of the severity of anterior mitral leaflet retraction aids prediction of severe mitral regurgitation after balloon valvuloplasty.

AIM To evaluate whether the relationship between early glomerular dysfunction and left-ventricular mass (LVM) occurs in a community sample and whether this relationship depends on haemodynamic factors. METHODS In 621 randomly selected participants from a community sample (332 were normotensive), estimated glomerular filtration rate (eGFR), LVM and dimensions were determined using echocardiography, and aortic blood pressure (BP) assessed from applanation tonometry and SphygmoCor software. Aortic pulse wave velocity (PWV) and high-quality 24-h BP values were available from 554 and 437 participants, respectively. RESULTS With adjustments for confounders (including clinic SBP), eGFR was associated with LVM index (LVMI) and LVM in excess of that predicted from stroke work (inappropriate LVM, LVMinappr) in all participants (LVMI: partial r = -0.18, P

AIMS We sought to determine whether within normal/high-normal blood pressure (BP) ranges (120-139/80-89 mmHg), aortic BP may further refine BP-related cardiovascular risk assessment, as determined from target organ changes. METHODS In 1169 participants from a community sample of African ancestry, 319 (27%) of whom had a normal/high-normal BP, aortic BP was determined using radial applanation tonometry and SphygmoCor software, and target organ changes assessed from carotid-femoral pulse wave velocity (PWV) (n = 1025), estimated glomerular filtration rate (eGFR) (n = 944), and left ventricular mass indexed to height (LVMI) (n = 690). RESULTS Normal versus high-normal BP categories failed to differentiate between those participants with a BP above optimal values with versus without multivariate-adjusted target organ changes. However, in those with a normal/high-normal BP with aortic SBP values that were less than 95% confidence interval of healthy participants with optimal BP values (45% of those with a normal/high-normal BP), no unadjusted or multivariate adjusted target organ changes were noted. In contrast, those with a normal/high-normal BP with aortic SBP values that exceeded optimal thresholds, demonstrated unadjusted and multivariate adjusted increases in PWV and LVMI and decreases in eGFR (P

AIM We determined whether left ventricular hypertrophy (LVH) which exceeds that predicted from workload [inappropriate LV mass (LVM(inappr))] is associated with reduced left ventricle (LV) systolic chamber function independent of and more closely than absolute or indexed left ventricular mass (LVM). METHODS In 626 randomly selected adult participants from a community sample of black Africans, using echocardiography we assessed absolute LVM, LVM indexed to height(2.7) (LVMI), LVM(inappr), LV wall stress, ejection fraction, and midwall fractional shortening (FSmid). LVM(inappr) was determined as percentage of observed/predicted LVM. Predicted LVM was calculated from a previously validated formula that incorporates stroke work. LVMI(inappr) more than 150% was considered to be inappropriate LVH. This threshold was identified from the upper 95% confidence interval for LVMI(inappr) determined in 140 healthy participants. RESULTS A total of 21.7% of participants had LVH (LVMI > 51 g/m(2.7)) and 18.5% had inappropriate LVH. With adjustments for LV stress and other confounders there was a strong inverse relationship between LVM(inappr) and ejection fraction (partial r = -0.41, P

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height 1.7 (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height 1.7 (partial r =0.18; P r =0.40; P 1.7 : partial r =0.17, P r =0.37, P r =−0.21 to 0.05). Twenty-four–hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.

The importance of concomitant low-dose hydrochlorothiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic parameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 +/- 17 versus 102 +/- 23 g/m2, and 24-hour ambulatory BP measured 120 +/- 8/75 +/- 6 versus 155 +/- 12/100 +/- 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 +/- 15/100 +/- 7 mm Hg to 148 +/- 19/96 +/- 11 mm Hg after treatment (p < 0.05 for systolic BP); systolic BP load (70% to 59%, p < 0.05), and diastolic BP load (67% to 60%, p = NS) decreased. Baseline BP decreased from 157 +/- 9/101 +/- 6 to 132 +/- 13/86 +/- 8 mm Hg (p < 0.0001); systolic BP load (64% to 29%, p < 0.0001), and diastolic BP load (64% to 33%, p < 0.0001) decreased in group 2. Exercise systolic BP was attenuated (p = 0.007, group 2; p = NS, group 1) and duration increased (p = NS) only in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty consecutive patients with chronic rheumatic atrial fibrillation (AF) ≥3 months after successful mitral valve surgery and left atrial diameter ≤60 mm were treated with oral amiodarone. Protocol included high loading dosages of amiodarone for 4 weeks, and if conversion to sinus rhythm (SR) was not achieved then electrical cardioversion was performed. Patients converted to SR were maintained on low-dose amiodarone for another 4 weeks when treatment was discontinued. Overall, 23 patients (77%) converted to SR after 4 weeks of therapy: 12 (40%) taking amiodarone alone and 11 (37%) with the addition of electrical cardioversion. The duration of AF >48 months was an adverse factor in the ability to restore SR. Sixteen patients (70%) remained in SR at a mean follow-up of 17 months. The duration of AF ≤48 months alone or in combination with left atrial diameter ≤48 mm were the best predictors for long term maintenance of SR. Thus, short-term amiodarone with or without electrical cardioversion is effective and safe in the treatment of chronic rheumatic AF after mitral valve surgery. The duration of AF and left atrial size can be used to identify patients with successful outcome.

The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double-balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p0.001), but was significant (or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score8; group I) and pliable (scoreor = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives. This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. Background. Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. Methods. Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). Results. Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax]and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. Conclusions. Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.

Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis.