Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis.

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections.

INTRODUCTION: Stroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. METHODS: This cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. RESULTS: 77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. CONCLUSION: Almost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.

Stroke as the index presentation of traditional cardiovascular risk factors and Human Immunodeficiency Virus in a South African population.

OBJECTIVES: We sought to identify what proportion of each cardiovascular risk factor and Human Immunodeficiency Virus (HIV) was first diagnosed at the time of stroke, compared to those that were diagnosed prior to the event, and to explore if this had any impact on the severity of stroke. METHODS: Adult patients presenting with a new stroke to a quaternary hospital in Johannesburg between 2014 and 2017 were prospectively recruited. Patients were investigated for undiagnosed traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidaemia, atrial fibrillation, obesity and smoking), as well as HIV infection. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: 346 patients were included. Stroke was the index presentation for at least one risk factor in 199 (57.5 %) patients. Dyslipidaemia was newly diagnosed in 76.0 % of all dyslipidaemics (95 out of 125). Newly-diagnosed dyslipidaemia was associated with a more severe neurological deficit (Median NIHSS of 12 (8-16) vs 7 (4-12), p=0.0007) and younger age on presentation (53 (44-63) years vs 62 (51-71) years, p=0.02) as compared to previously-diagnosed dyslipidaemia. CONCLUSIONS: More than half of patients had previously undiagnosed modifiable risk factors at the time of their stroke. Dyslipidaemia was undiagnosed in a very high proportion, and this was associated with a higher stroke severity and younger age of presentation.

High prevalence but lack of awareness of hypertension in South Africa, particularly among men and young adults.

Cardiovascular disease (CVD) is a leading cause of death in South Africa (SA) and high blood pressure (BP) is the primary risk factor. However, hypertension prevalence is high, BP control is poor and CV events occur at a younger age than in Europe or America. Increasing screening, raising awareness and improving management of hypertension are critical to prevent CVD in SA. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high BP. As part of the MMM campaign, in SA (2017, 2018, 2019 and 2021), BP measurements and a cross-sectional survey of volunteers aged ≥ 18years were performed. Of 11,320 individuals (age 36.6 ± 16.8years) screened, 29.7% had hypertension (systolic BP/diastolic BP ≥ 140/90 mmHg or antihypertensive medication use) and the prevalence was higher (p < 0.0001) in men (35.6%) than in women (26.3%). Of those with hypertension, only 54.3% were aware and 46.8% were receiving antihypertensive medication, and 53.7% of these had controlled BP. In men with hypertension, awareness (45.2%, treatment (38.2%) and controlled BP on antihypertensive medication (45.2%) were lower (p < 0.0001) than in women (awareness: 60.8%; treatment: 53.5%; controlled BP: 58.3%). In young participants (age < 40years), 15.6% had hypertension, 18.6% of these were on treatment but 76.0% were not aware, and only 57.7% had controlled BP. The high prevalence of hypertension, but low levels of awareness, treatment, and BP control in SA, especially in young adults and men, highlight the need for systematic BP screening programmes and improvements in education and management of hypertension.

Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

Associations of Traditionally Determined Left Ventricular Mass Indices and Hemodynamic and Non-Hemodynamic Components of Cardiac Remodeling with Diastolic and Systolic Function in Patients with Chronic Kidney Disease.

We aimed to evaluate the extent to which different left ventricular mass parameters are associated with left ventricular function in chronic kidney disease (CKD) patients. We compared the associations between traditionally determined left ventricular mass indices (LVMIs) and hemodynamic (predicted LVMIs) and non-hemodynamic remodeling parameters with left ventricular function in patients with CKD; non-hemodynamic remodeling was represented by inappropriate left ventricular mass and inappropriate excess LVMIs (traditionally determined LVMIs-predicted LVMIs). Non-hemodynamic left ventricular remodeling parameters were strongly associated with impaired left ventricular systolic function (p < 0.001), whereas hemodynamic left ventricular remodeling was also related strongly (p < 0.001) but directly to left ventricular systolic function. Independent of one another, hemodynamic and non-hemodynamic left ventricular remodeling had associations in opposite directions to left ventricular systolic function and was associated directly with traditionally determined left ventricular mas indices (p < 0.001 for all relationships). Non-hemodynamic cardiac remodeling parameters discriminated more effectively than traditionally determined LVMIs between patients with and without reduced ejection fraction (p < 0.04 for comparison). Left ventricular mass parameters were unrelated to impaired diastolic function in patients with CKD. Traditionally determined LVMIs are less strongly associated with impaired systolic function than non-hemodynamic remodeling parameters (p < 0.04-0.01 for comparisons) because they represent both adaptive or compensatory and non-hemodynamic cardiac remodeling.

Role of atrial natriuretic peptide in the dissociation between flow relations with ventricular mass and function in a community with volume-dependent hypertension.

Background: Whether differential effects of volume load on left ventricular mass (LVM) and function occur in sustained volume-dependent primary hypertension, and the impact of atrial natriuretic peptide (ANP) on these effects, is unknown. Methods: From aortic pressure, velocity and diameter measurements and echocardiography, we determined in an African community (n = 772), the impact of systemic flow-induced increases in central pulse pressure (PPc) and circulating ANP (ELISA) on LVM and indexes of function. Results: Stroke volume (SV), but not aortic flow (Q), was associated with LVM and mean wall thickness (MWT) beyond stroke work and confounders (p < 0.0001). Adjustments for SV markedly decreased the relationships between PPc and LVMI or MWT. However, neither SV, nor Q were independently associated with either myocardial s', e', or E/e' (p > 0.14) and adjustments for neither SV nor Q modified relationships between PPc and s', e' or E/e' (p < 0.005 to <0.0001). SV was nevertheless strongly and independently associated with ANP (p < 0.0001) and ANP was similarly strikingly associated with s' (p < 0.0001) and e' (p < 0.0005), but not E/e', independent of confounders and several determinants of afterload. Importantly, ANP concentrations were inversely rather than positively associated with LV diastolic dysfunction (DD) (p < 0.005) and lower rather than higher ANP concentrations contributed markedly to the ability to detect DD in those with, but not without LV hypertrophy. Conclusion: In populations with sustained volume-dependent hypertension, flow (SV)-related increases in PP have a major impact on LV structure, but not on function, an effect attributed to parallel striking beneficial actions of ANP on myocardial function.

Attenuated Relationships Between Indexes of Volume Overload and Atrial Natriuretic Peptide in Uncontrolled, Sustained Volume-Dependent Primary Hypertension.

BACKGROUND: Whether systolic blood pressure (SBP) control in sustained volume-dependent primary hypertension is associated with blunted ANP (atrial natriuretic peptide) relationships with indexes of volume load is unknown. METHODS: Systemic hemodynamics (central pressure, echocardiographic aortic velocity and diameter measurements in the outflow tract), circulating ANP concentrations (ELISA assays) and glomerular and tubular function (24-hour urine collections [n=519]) were determined in a community of African ancestry (n=772). RESULTS: As compared with those with a controlled SBP, those with an uncontrolled SBP (n=198) showed lower ANP concentrations (P<0.005) despite higher stroke volume and cardiac output (P<0.0001) and renal differences consistent with enhanced fluid retention. In those with a controlled SBP, fractional Na+ excretion (FeNa+; P<0.0005) and creatinine clearance (glomerular filtration rate; P<0.005) were inversely associated with ANP concentrations independent of confounders. Moreover, in those with a controlled SBP, stroke volume and cardiac output (P<0.0001) were independently and positively associated with ANP concentrations. In addition, in those with a controlled SBP, ANP concentrations were independently and inversely associated with systemic vascular resistance (SVR; P<0.0001) and aortic characteristic impedance (Zc; P<0.005). By contrast, in those with uncontrolled SBP, no relationships between either stroke volume (P>0.25), cardiac output (P>0.29), FeNa+ (P>0.77), or glomerular filtration rate (P>0.47) and ANP concentrations were noted. Furthermore, in those with an uncontrolled SBP, no relationships between ANP concentrations and SVR or Zc were observed (P>0.34). CONCLUSIONS: In a population where primary hypertension is strongly volume-dependent, those with an uncontrolled SBP have an attenuated relationship between ANP and both renal and hemodynamic indexes of volume overload and the vascular effects of ANP.

Evaluation of aortic wall strength in human immunodeficiency virus associated thoracic ascending aortic aneurysm: a pilot study.

Background: Human immunodeficiency virus (HIV) associated aortopathy is associated with considerable morbidity and mortality. The pathophysiology of aortic wall strength in HIV thoracic aortic aneurysm has not been studied. Methods: The patients with HIV associated thoracic ascending aortic aneurysm (TAAA) were enrolled in the study and underwent surgery as part of their routine management. We compared collagen quantity in aneurysmal and non-aneurysmal aortic tissue in TAAA with regards to hydroxyproline concentration as a surrogate measure for collagen content and sent aneurysmal aorta for routine clinical histological assessment. This data was analysed to identify potential relations between aortic aneurysm formation and the collagen content of the aortic wall. Results: The study included 12 patients with HIV aortopathy (9 females, median age 49 years). In total 33 tissue samples were investigated (14 aneurysmal, 13 non-aneurysmal aortic tissue and 6 aortic leaflets). There was no difference in hydroxyproline concentration of aneurysmal aortic tissue and seemingly normal tissue [19.40 (15.19-22.98) vs. 20.85 (15.55-25.83) µg/mg; P=0.82]. No difference was noted in hydroxyproline concentration among aneurysmal, seemingly normal aortic tissue and aortic valve leaflets [19.40 (15.19-22.98) vs. 20.85 (15.55-25.83) vs. 19.09 (13.94-22.00) µg/mg; P=0.86]. Histology showed fragmentation of elastin fibres in 50% of the cases. Conclusions: No difference in collagen concentration in the aneurysmal and non-aneurysmal aortic tissue was noted. However, most of the aneurysmal tissue had fragmentation of elastin fibres.

Uric Acid, Ferritin, Albumin, Parathyroid Hormone and Gamma-Glutamyl Transferase Concentrations are Associated with Uremic Cardiomyopathy Characteristics in Non-Dialysis and Dialysis Chronic Kidney Disease Patients.

Introduction: Circulating uric acid, ferritin, albumin, intact parathyroid hormone and gamma-glutamyl transferase each participate in biochemical reactions that reduce or/and enhance oxidative stress, which is considered the final common pathway through which pathophysiological mechanisms cause uremic cardiomyopathy. We hypothesized that the respective biomarkers may be involved in the development of uremic cardiomyopathy characteristics and can be useful in their identification among chronic kidney disease patients. Methods: We assessed traditional and non-traditional cardiovascular risk factors including biomarker concentrations and determined central systolic blood pressure using SphygmoCor software and cardiac structure and function by echocardiography in 109 (64 non-dialysis and 45 dialysis) patients. Associations were evaluated in multivariate regression models and receiver operator characteristic (ROC) curve analysis. Results: Each biomarker concentration was associated with left ventricular mass beyond stroke work and/or inappropriate left ventricular mass in all, non-dialysis and/or dialysis patients. Ferritin, albumin and gamma-glutamyl transferase levels were additionally associated with E/e' in all, non-dialysis and/or dialysis patients. Dialysis status influenced the relationship of uric acid concentrations with inappropriate left ventricular mass and those of gamma-glutamyl transferase levels with left ventricular mass and inappropriate left ventricular mass. In stratified analysis, low uric acid levels were related to inappropriate left ventricular mass in dialysis but not non-dialysis patients (interaction p=0.001) whereas gamma-glutamyl transferase concentrations were associated with left ventricular mass and inappropriate left ventricular mass in non-dialysis but not dialysis patients (interaction p=0.020 to 0.036). In ROC curve analysis, uric acid (area under the curve (AUC)=0.877), ferritin (AUC=0.703) and albumin (AUC=0.728) concentrations effectively discriminated between dialysis patients with and without inappropriate left ventricular hypertrophy, left ventricular hypertrophy, and increased E/e,' respectively. Conclusion: Uric acid, ferritin, albumin, parathyroid hormone and gamma-glutamyl transferase were associated with uremic cardiomyopathy characteristics and could be useful in their identification. Our findings merit validation in future longitudinal studies.

Proximal aortic stiffness modifies the relationship between heart rate and backward wave and hence central arterial pulse pressure.

Aims: A lower heart rate (HR) increases central blood pressure through enhanced backward wave pressures (Pb). We aimed to determine whether these relationships are modified by increases in aortic stiffness. Methods: Using non-invasive central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we assessed the impact of aortic stiffness on relationships between HR and arterial wave morphology in 603 community participants < 60 years of age, 221 ≥ 60 years, and in 287 participants with arterial events [stroke and critical limb ischemia (CLI)]. Results: As compared to community participants < 60 years, those ≥ 60 years or with events had increased multivariate adjusted proximal aortic characteristic impedance (Zc) and carotid femoral pulse wave velocity (PWV) (p < 0.05 to < 0.0001). Community participants ≥ 60 years and those with events also had a greater slope of the inverse relationship between HR and Pb (p < 0.001 for comparison). While in community participants < 60 years, no interaction between indexes of aortic stiffness and HR occurred, in those ≥ 60 years (p < 0.02) and in those with arterial events (p = 0.001), beyond aortic root diameter, an interaction between Zc and HR, but not between PWV and HR independently associated with Pb. This translated into stepwise increases in the slope of HR-Pb relationships at incremental tertiles of Zc. Although HR was inversely associated with the systemic reflection coefficient in community participants ≥ 60 years (p < 0.0001), adjustments for the reflection coefficient failed to modify HR-Pb relations. Conclusion: Beyond the impact on systemic wave reflection, increases in proximal aortic stiffness enhance the adverse effects of HR on Pb and hence central BP.

Contribution of Increases in Late Systolic Ejection Volume to the Impact of Heart Rate on Central Arterial Pulse Pressure in a Community Sample.

BACKGROUND: A lower heart rate (HR) increases left ventricular (LV) ejection volume. Whether this contributes to the adverse effects of HR on central pulse pressure (PPc) through reservoir volume effects is uncertain. METHODS: Using noninvasive central pressure, aortic velocity, and diameter measurements in the outflow tract (echocardiography), we assessed the role of LV ejection volume as a determinant of HR relations with PPc in 824 community participants. RESULTS: A lower HR was independently associated with both stroke volume (SV) (P < 0.001) and a shift in ejection volume from early (until the first systolic shoulder) to late (from first systolic shoulder to peak PP) systole (P < 0.05 to P < 0.005). Adjustments for LV end diastolic volume markedly diminished HR relations with SV and indexes of the shift in ejection volume to late systole. A lower HR was also independently associated with increases in forward traveling pressure waves (Pf) and PPc (P < 0.0001). However, adjustments for neither SV, nor indexes of a shift in ejection volume to late systole modified HR-Pf or PPc relations. This was despite relationships between indexes of a shift in ejection volume to late systole and both Pf and PPc (P < 0.0001). In contrast, adjustments for the increases in re-reflected and backward traveling wave pressures with a lower HR, eliminated HR-Pf and PPc relations. CONCLUSIONS: In contrast to current thought, a lower HR is not associated with increases in PPc through an impact of increases in late systolic ejection volume on aortic reservoir volume, but rather through increases in backward wave pressures.

Aortic Stiffness and Pulsatile Pressures as Potential Mediators of Chronic Kidney Disease Induced Impaired Diastolic Function.

PURPOSE: We assessed whether aortic stiffness and pulsatile pressures can mediate chronic kidney disease (CKD)-associated impaired diastolic function. PARTICIPANTS AND METHODS: In 276 black Africans including 46 CKD (19 non-dialysis; 27 dialysis) and 230 control subjects, pulse wave velocity (PWV) estimated aortic stiffness and pulsatile pressures (forward and backward wave pressure, central systolic blood pressure (CSBP) and pulse pressure (CPP)) were determined by applanation tonometry; e' as an index of left ventricular active relaxation and E/e' as a measure of left ventricular filling pressure or passive relaxation were evaluated by echocardiography. RESULTS: In age, sex, traditional cardiovascular risk factor and mean arterial pressure (MAP) adjusted regression models, CKD was inversely associated with e' (p = 0.03) and directly with E/e' (p < 0.01). The CKD-e' relationship was attenuated and no longer significant (p = 0.31) upon additional adjustment for aortic PWV but not pulsatile pressures (p = 0.03-0.05). In product of coefficient mediation analysis, PWV accounted for 47.6% of the CKD-e' association. CSBP (22.9%) and CPP (18.6%) but not PWV (11.3%) accounted for a significant and relevant proportion of the CKD-E/e' relationship. However, CKD remained strongly associated with E/e' independent of aortic function measures (p < 0.01). Treatable covariates that were or tended to be consistently associated with diastolic function included MAP (p < 0.01) and diabetes (p = 0.02-0.07) for the CKD-e' and CKD-E/e' relations, respectively. CONCLUSION: Aortic stiffness rather than pulsatile pressures mediates CKD-related impaired left ventricular active relaxation. By contrast, aortic pulsatile pressures (and not stiffness) contribute to CKD-related left ventricular filling pressures but do not fully account for the respective association.

The International Database of Central Arterial Properties for Risk Stratification: Research Objectives and Baseline Characteristics of Participants.

OBJECTIVE: To address to what extent central hemodynamic measurements, improve risk stratification, and determine outcome-based diagnostic thresholds, we constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a participant-level meta-analysis. The purpose of this article was to describe the characteristics of IDCARS participants and to highlight research perspectives. METHODS: Longitudinal or cross-sectional cohort studies with central blood pressure measured with the SphygmoCor devices and software were included. RESULTS: The database included 10,930 subjects (54.8% women; median age 46.0 years) from 13 studies in Europe, Africa, Asia, and South America. The prevalence of office hypertension was 4,446 (40.1%), of which 2,713 (61.0%) were treated, and of diabetes mellitus was 629 (5.8%). The peripheral and central systolic/diastolic blood pressure averaged 129.5/78.7 mm Hg and 118.2/79.7 mm Hg, respectively. Mean aortic pulse wave velocity was 7.3 m per seconds. Among 6,871 participants enrolled in 9 longitudinal studies, the median follow-up was 4.2 years (5th-95th percentile interval, 1.3-12.2 years). During 38,957 person-years of follow-up, 339 participants experienced a composite cardiovascular event and 212 died, 67 of cardiovascular disease. CONCLUSIONS: IDCARS will provide a unique opportunity to investigate hypotheses on central hemodynamic measurements that could not reliably be studied in individual studies. The results of these analyses might inform guidelines and be of help to clinicians involved in the management of patients with suspected or established hypertension.

Marked intrafamilial aggregation and heritability of aortic flow in a community with prevalent volume-dependent hypertension in Africa.

AIMS: Although peak aortic flow (Q) is now recognized as a major determinant of hypertension in Africa, current therapy has no proven ability to target this change. The mechanisms of this effect, therefore, require elucidation. We compared the intrafamilial aggregation and heritability of Q to that of the vascular determinants of pulse pressure (PP) and SBP in Africa. METHODS: The intrafamilial aggregation and heritability of Q and aortic characteristic impedance (Zc) or total arterial compliance (TAC) was determined in 669 participants of 194 families (69 father-mother, 385 parent-child, 157 sibling-sibling pairs) in a community in Africa with prevalent flow-dependent primary hypertension. Haemodynamics were determined from velocity and diameter measurements in the outflow tract (echocardiography) and central arterial pressures. RESULTS: No mother-father correlations were noted for either Q or Zc. However, with adjustments for confounders, parent-child (P < 0.0001) and sibling-sibling (P < 0.0001) correlations were noted for Q. Parent-child and/or sibling-sibling correlations were also noted for Zc or TAC but were weaker for Zc and mother-father correlations were noted for TAC. Moreover, Q showed markedly stronger multivariate adjusted heritability estimates (h2 = 0.82 ±â€Š0.07, P < 0.0001) than Zc (h2 = 0.44 ±â€Š0.10, P < 0.0001)(P < 0.005 for comparisons) and TAC (h2 = 0.47 ±â€Š0.08, P < 0.0001)(P < 0.005 for comparisons). Importantly, the heritability of Q was also greater than that for PP (h2 = 0.12 ±â€Š0.09, P = 0.11) (P < 0.0001 for comparisons), or SBP (h2 = 0.13 ±â€Š0.10, P = 0.08) (P < 0.0001 for comparisons). CONCLUSION: Of the haemodynamic determinants of SBP, peak aortic flow is the most strongly inherited in Africa. Peak aortic flow, therefore, represents an important target for identifying novel therapeutic approaches to controlling SBP in Africa.

Increased Backward Wave Pressures Rather than Flow Explain Age-Dependent Heart Rate Effects on Central, But not Peripheral Arterial Pressure.

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<0.0001), but not HR-brachial PP (P=0.064) relations were noted. The slope of HR-PPc relation was increased in older adults (P<0.005). HR was inversely associated with ventricular filling time, ejection duration, stroke volume, and peak Pf (P<0.001 to P<0.0001). However, an increased Q and hence pressures generated by the product of aortic characteristic impedance and Q did not account for Pf effects. Age-dependent HR-PPc and Pf relations were both accounted for by enhanced Pb (P<0.0001) with an increased Pf mediated by increments in wave re-reflection (P<0.0001). The lack of impact of ejection duration on PPc was explained by an increased time to peak Pb (P<0.0001). In conclusion, increases in PPc and Pf at a decreased HR are accounted for by an enhanced Pb rather than by a prolonged ejection or filling duration and hence flow (Q). These effects at a young-to-middle age are of little clinical significance, but at an older age, are of clinical importance.

Independent relationships between renal mechanisms and systemic flow, but not resistance to flow in primary hypertension in Africa.

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 < 0.0001) and Q (P < 0.01), but not SVR, Zc or TAC (P = 0.09-0.20) were independently associated with decreases in both GFR (index of nephron number) and FeNa+. Through an interactive effect (P < 0.0001), the impact of GFR on SV or Q was strongly determined by FeNa+ and vice versa. The relationship between the GFR-FeNa+ interaction and either SV or Q was noted in those above or below 50 years of age, although neither GFR, FeNa+ nor the interaction were independently associated with SVR, Zc or TAC at any age. CONCLUSION: Across the full adult lifespan, in groups of African ancestry, renal mechanisms of hypertension translate into increases in systemic flow rather than into resistance or impedance to flow.

Hemodynamic and Functional Correlates of Concentric vs. Eccentric LVH in a Community-Based Sample With Prevalent Volume-Dependent Hypertension.

BACKGROUND: Whether in volume-dependent primary hypertension, concentric left ventricular (LV) remodeling beyond hypertrophy (LVH) represents the impact of a pressure rather than a volume overload, is unclear. METHODS: Using central arterial pressure, and aortic velocity and diameter measurements in the outflow tract (echocardiography), we determined the factors that associate with concentric LVH or remodeling in a community of African ancestry (n = 709) with prevalent volume-dependent primary hypertension. RESULTS: Both left ventricular mass index (LVMI) and relative wall thickness (RWT) were positively and independently associated with end diastolic volume (EDV), stroke volume (SV), and peak aortic flow (Q) (P < 0.05 to <0.0001). However, neither LVMI nor RWT were positively and independently associated with systemic vascular resistance (SVR), or aortic characteristic impedance (Zc) or inversely associated with total arterial compliance (TAC). Consequently, both concentric (P < 0.0001) and eccentric (P < 0.0001) LVH were associated with similar increases in EDV, SV, and either office brachial, central arterial, or 24-hour blood pressures (BP), but neither increases in SVR or Zc nor decreases in TAC. LV RWT, but not LVMI was nevertheless independently and inversely associated with myocardial systolic function (midwall shortening and s') (P < 0.05 to <0.005) and decreases in LV systolic function were noted in concentric (P < 0.05), but not eccentric LVH. CONCLUSIONS: In volume-dependent primary hypertension, concentric LVH is determined as much by volume-dependent increases in systemic flow and an enhanced BP as eccentric LVH. Concentric remodeling nevertheless reflects decreases in systolic function beyond LVH.

Association of Post Transplantation Anaemia and Persistent Secondary Hyperparathyroidism with Diastolic Function in Stable Kidney Transplant Recipients.

INTRODUCTION: We hypothesized that post transplantation anaemia and persistent secondary hyperparathyroidism are potential determinants of diastolic function in stable kidney transplant recipients. METHODS: We assessed traditional and non-traditional cardiovascular risk factors and determined carotid artery intima-media thickness and plaque by ultrasound, arterial function by applanation tonometry using SphygmoCor software and diastolic function by echocardiography in 43 kidney transplant recipients with a transplant duration of ≥6 months, no acute rejection and a glomerular filtration rate of ≥15 mL/min/1.73m2. RESULTS: Mean (SD; range) transplant duration was 12.3 (8.0; 0.5-33.8) years. Post transplantation anaemia and persistent secondary hyperparathyroidism were identified in 27.9% and 30.8% of the patients, respectively; 67.5% of the participants were overweight or obese. In established confounder adjusted analysis, haemoglobin (partial R=-0.394, p=0.01) and parathyroid hormone concentrations (partial R=0.382, p=0.02) were associated with E/e'. In multivariable analysis, haemoglobin (partial R=-0.278, p=0.01) and parathyroid levels (partial R=0.324, p=0.04) were independently associated with E/e'. Waist-height ratio (partial R=-0.526, p=0.001 and partial R=-0.355, p=0.03), waist circumference (partial R=-0.433, p=0.008 and partial R=-0.393, p=0.02) and body mass index (partial R=-0.332, p=0.04 and partial R=-0.489, p=0.002) were associated with both e' and E/A, respectively, in established confounder adjusted analysis. The haemoglobin-E/e' (partial R=-0.422, p=0.02), parathyroid hormone-E/e' (partial R=0.434, p=0.03), waist-height ratio-e' (partial R=-0.497, p=0.007) and body mass index-E/A (partial R=-0.386, p=0.04) relationships remained consistent after additional adjustment for left ventricular mass index and cardiac preload and afterload measures. CONCLUSION: Haemoglobin and parathyroid hormone concentrations as well as adiposity measures are independently associated with diastolic function in kidney transplant recipients. Whether adequate management of post transplantation anaemia, persistent secondary hyperparathyroidism and excess adiposity can prevent the development of heart failure with preserved ejection fraction in kidney transplant recipients merits further investigation.