May Measurement Month 2021: an analysis of blood pressure screening results from South Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. In Sub-Saharan Africa, hypertension prevalence is higher and cardiovascular events occur at a younger age than in Europe or America. May Measurement Month (MMM) is a global campaign initiated by the International Society of Hypertension (ISH) aimed at raising awareness of high BP. In South Africa, the MMM campaign in 2017, 2018, and 2019 revealed that approximately one-third of adults had hypertension, only half of hypertensives were receiving antihypertensive therapy, and only a third of those with hypertension had controlled BP. These data highlight the need for continued BP screening and awareness campaigns in South Africa. From May to November 2021, a cross-sectional survey of volunteers aged ≥18 years was performed. Blood pressure measurements, definition of hypertension, and statistical analyses followed the MMM protocol. The screening sites targeted the general population mainly on university campuses and pharmacies in preference to hospitals and clinics, aiming to raise awareness and allow access to screening in those less likely to be aware of their BP status. Of the 2294 individuals (age 37.3 ± 16.9 years) screened, 30.8% had hypertension. Of those with hypertension, only 48.6% were aware and 43.5% were receiving treatment for hypertension. A large proportion (50.4%) of individuals receiving antihypertensive medication had uncontrolled BP (≥140/90 mmHg). In conclusion, the high prevalence of hypertension, despite the young adult age, and the high proportions of individuals unaware of their hypertension and with uncontrolled BP underscore the necessity for hypertension awareness campaigns and more rigorous management of hypertension.

Metformin Prevents Low-dose Isoproterenol-induced Cardiac Dilatation and Systolic Dysfunction in Male Sprague Dawley Rats.

ABSTRACT: Myocardial metabolic abnormalities are well-recognized alterations in chronic heart failure, effects that may contribute to progressive cardiac dysfunction. However, whether metabolic alterations in-part mediate their deleterious effects by modifying the chronic impact of excess low-dose sympathetic stimulation on cardiac chamber dilatation is uncertain. We therefore aimed to determine the effect of metformin administration on cardiac function and mitochondrial architectural changes in a rat model of chronic sympathetic-induced left ventricular (LV) remodeling and systolic dysfunction [daily subcutaneous isoproterenol (ISO) injection at a low dose of 0.02 mg/kg for 7 months]. Echocardiography was used to assess in vivo LV dimensions and function, and mitochondrial and myofibril arrangement was assessed using transmission electron microscopy. Seven months of low-dose ISO administration increased LV diastolic diameter (in mm) [control (CONT): 7.29 ± 0.19 vs. ISO: 8.76 ± 0.21; P = 0.001], an effect that was attenuated by metformin (ISO + MET: 7.63 ± 0.29 vs. ISO: P = 0.001) administration. Similarly, ISO increased LV end-systolic diameter (CONT: 4.43 ± 0.16 vs. ISO: 5.49 ± 0.16: P < 0.0001), an effect prevented by metformin (ISO + MET: 4.04 ± 0.25 vs. ISO: P < 0.0001). Moreover, chronic ISO administration reduced LV endocardial fractional shortening (P = 0.0001), midwall fractional shortening (P = 0.0001), and ejection fraction (P = 0.0001), effects similarly prevented by metformin administration. Furthermore, changes in mitochondrial arrangement and relative mitochondrial area (CONT: 37.7 ± 2.2 vs. ISO: 28.1 ± 2.9; P = 0.05) were produced by ISO administration, effects prevented by metformin. In conclusion, metformin offers cardiac protection against chronic sympathetic-induced LV dilatation and systolic dysfunction. These data support a role for myocardial metabolic changes in mediating LV dilatation and LV dysfunction produced by chronic neurohumoral activation in cardiac disease.

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

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<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Associations between circulating resistin concentrations and left ventricular mass are not accounted for by effects on aortic stiffness or renal dysfunction.

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.

May Measurement Month 2018: an analysis of blood pressure screening results in South Africa.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension (ISH) aimed at raising awareness of high BP and acting as a temporary solution to the lack of screening programmes worldwide. As part of MMM, screening in South Africa in 2017 revealed that 24.5% of adults (mean age = 31 years) have hypertension and only half of those with hypertension had controlled BP. These data highlight the need for continued screening and awareness campaigns. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2018. Blood pressure measurements, the definition of hypertension and statistical analyses followed the MMM protocol. The sites screened were general populations and university campuses in preference to hospitals and clinics, aiming to raise awareness and allow access to screening to those less likely to be aware of their BP. In total, 2965 individuals (age 40.5 ± 18.2 years) were screened. After multiple imputation for missing BP readings, 34.6% had hypertension, only 56.7% of those with hypertension were aware, 21.2% of those not receiving treatment for hypertension were hypertensive, and a large proportion (42.5%) of individuals receiving antihypertensive medication had uncontrolled BP. These results suggest that opportunistic screening campaigns can identify significant numbers with undiagnosed and uncontrolled hypertension. The high proportions of individuals with undiagnosed and treated uncontrolled hypertension highlight the need for hypertension awareness campaigns and more rigorous management of hypertension.

Limited Impact of ß-Adrenergic Receptor Activation on Left Ventricular Diastolic Function in Rat Models of Hypertensive Heart Disease.

BACKGROUND: Hypertension is a major cause of left ventricular (LV) diastolic dysfunction. Although ß-adrenergic receptor (ß-AR) blockers are often used to manage hypertension, the impact of ß-AR activation on LV lusitropic effects and hence filling pressures in the hypertensive heart with LV diastolic dysfunction is uncertain. METHODS: Using tissue Doppler imaging and Speckle tracking software, we assessed LV function in isoflurane anesthetised spontaneously hypertensive (SHR) and Dahl salt-sensitive (DSS) rats before and after ß-AR activation [isoproterenol (ISO) administration]. RESULTS: As compared to normotensive Wistar Kyoto control rats, or DSS rats not receiving NaCl in the drinking water, SHR and DSS rats receiving NaCl in the drinking water had a reduced myocardial relaxation as indexed by lateral wall e' (early diastolic tissue velocity at the level of the mitral annulus) and an increased LV filling pressure as indexed by E/e'. However, LV ejection fraction and deformation and motion were preserved in both SHR and DSS rats. The administration of ISO resulted in a marked increase in ejection fraction and decrease in LV filling volumes in all groups, and an increase in e' in SHR, but not DSS rats. However, after ISO administration, although E/e' decreased in DSS rats in association with a reduced filling volume, E/e' in SHR remained unchanged and SHR retained greater values than Wistar Kyoto control. CONCLUSIONS: The hypertensive heart is characterized by reductions in myocardial relaxation and increases in filling pressures, but ß-AR activation may fail to improve myocardial relaxation and when this occurs, it does not reduce LV filling pressures.

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.

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.

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.

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.

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.

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 systemic blood flow to untreated or inadequately controlled systolic--diastolic or isolated systolic hypertension in a community sample of African ancestry.

AIMS: Age-related increases in systemic blood flow [stroke volume (SV), cardiac output (CO), and aortic flow (Q)] contribute substantially to untreated or inadequately controlled (uncontrolled) blood pressure (BP) in Africa. We aimed to identify the haemodynamic determinants of uncontrolled systolic--diastolic (Syst--diast HT) versus uncontrolled isolated systolic (ISH) or diastolic (IDH) hypertension. METHODS: Using central arterial pressure and aortic outflow tract velocity and diameter measurements (echocardiography), the haemodynamic correlates of BP were determined in 725 community participants of African ancestry (19.6% uncontrolled Syst--diast HT, 9.2% uncontrolled ISH, 11.3% uncontrolled IDH). RESULTS: Independent of confounders, compared with those with a normotensive BP, those with uncontrolled Syst--diast HT had increases in SV, CO, Q, systemic vascular resistance (SVR) and aortic characteristic impedance (Zc) and decreases in total arterial compliance (TAC) (P < 0.05--P < 0.0001). In multivariate regression models, uncontrolled Syst--diast HT was as strongly associated with Q, SV or CO as with SVR (P = 0.04--P = 0.20), Zc (P = 0.74--P < 0.0005) and TAC (P = 0.43--P < 0.005). Independent of confounders, compared with normotensive individuals those with uncontrolled ISH had increases in SV, CO, Q and Zc but not SVR, and decreases in TAC (P < 0.05-P < 0.0001), and those with IDH only had increases in SVR (P < 0.0001). Uncontrolled ISH was more strongly associated with Q, SV and CO than with SVR (P < 0.0005), but less than with TAC (P < 0.05--P < 0.0005). CONCLUSION: In groups of African ancestry living in Africa, hypertension because of increases in either SBP or DBP is as strongly associated with increases in systemic flow (SV, Q) as with arterial and arteriolar effects (Zc, TAC, SVR).

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.

Impact of stroke work on the ability of left ventricular mass to account for pressure effects on function in a community with prevalent systemic flow-dependent hypertension.

AIMS: To determine whether the confounding influence of stroke work on left ventricular mass (LVM) limits the ability of LVM to detect hypertensive LV dysfunction in systemic flow-dependent hypertension. METHODS: In a community with prevalent systemic flow-dependent hypertension (n = 709), arterial haemodynamics, LVM and LV function were determined using central arterial pressure, aortic velocity and diameter measurements in the outflow tract, and echocardiography with tissue Doppler imaging. RESULTS: In multivariate models, stroke work showed markedly stronger relations with LVM index (LVMI) than blood pressure load [central arterial SBP (SBPc), backward wave pressure (Pb), 24-h SBP] (P < 0.0001 for comparisons). In contrast, although SBPc, Pb, and 24-h SBP were inversely associated with myocardial tissue shortening (s') and lengthening (e') velocity, stroke work was not. With adjustments for stroke work, positive relationships between SBPc, Pb, or 24-h SBP and LVMI were eliminated (P = 0.20 to P = 0.89), but strong relations between BP and s', e' or E/e' (P = 0.009 to P < 0.0001) remained. In mediation analysis, stroke work fully accounted for BP effects on LVMI, but explained none of the effects of BP on LV function. Hence LVMI accounted for little of the impact of BP load on LV function. Although LVMI beyond stroke work (inappropriate LVM) improved on relations between LVMI and s', it failed to improve on relations with e' or E/e' and contributed little beyond LVMI to the impact of BP on LV function. CONCLUSION: In systemic flow-dependent hypertension, the impact of stroke work markedly limits the ability of LVM to account for adverse effects of hypertension on LV function.

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.

Relations of aortic stiffness with arterial damage beyond brachial pressure are both dependent and independent of central arterial pulsatile load.

AIM: We aimed to determine whether the impact of aortic stiffness on atherosclerotic or small vessel end organ damage beyond brachial blood pressure depends in-part on stiffness-induced increases in central arterial pressures produced by an enhanced resistance to flow (characteristic impedance, Zc). METHODS: We studied 1021 participants, 287 with stroke or critical limb ischaemia, and 734 from a community sample with atherosclerotic or small vessel end organ measures. Central arterial haemodynamics were determined from arterial pressure (SphygmoCor) and velocity and diameter assessments in the outflow tract (echocardiography). RESULTS: Although Zc and carotid-femoral pulse wave velocity (PWV) were correlated (P < 0.0001), these relations were not independent of confounders (P = 0.90). Both Zc and hence central arterial pressures generated by the product of Zc and aortic flow (Q) (PQxZc), as well as PWV were independently associated with carotid intima-media thickness, estimated glomerular filtration rate (eGFR), endothelial activation markers [vascular cell adhesion molecule-1 (V-CAM-1)] and events. With further adjustments for brachial pulse pressure (PP) or SBP, PWV and PQxZc were both associated with eGFR and V-CAM-1. Relationships between PWV and eGFR or V-CAM-1 were independent of PQxZc (P < 0.05) and relationships between PQxZc and eGFR and V-CAM-1 were independent of PWV (P < 0.005). Similarly, with adjustments for confounders and brachial PP or SBP, across the full adult lifespan, both aortic PWV and PQxZc were increased in those with arterial events (P < 0.005). Relationships between PWV and events were again independent of PQxZc (P < 0.005) and between PQxZc and events were independent of PWV (P < 0.0001). CONCLUSION: Beyond brachial blood pressure, the impact of aortic stiffness on arterial damage involves effects that are both dependent (proximal aortic Zc and hence PQxZc) and independent (full aortic length indexed by PWV) of central arterial pulsatile load. Hence, PWV and brachial PP may be insufficient to account for all of the damage mediated by increases in aortic stiffness.

Impact of metabolic and inflammatory changes on glomerular function beyond conventional risk factors in an urban South Africa community with prevalent obesity.

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 ß-coefficient = -0.13 ± 0.03, p < 0.0001) and plasma resistin concentrations (ß-coefficient = -0.10 ± 0.02, p < 0.0001) were second only to age, and at least as strong as systolic blood pressure (ß -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.

Increased Aortic Characteristic Impedance Explains Relations Between Urinary Na+/K+ and Pulse or Systolic Blood Pressure.

Alterations in sodium (Na+) relative to potassium (K+) intake increase systolic blood pressure, effects in-part attributed to enhanced pulsatile loads (pulse pressure) beyond steady-state pressures (mean arterial pressure). Whether this effect is through reversible changes (increases in blood volume and hence aortic flow [Q] or wave reflection [Pb]), or potentially irreversible structural changes in the proximal aorta, is unknown. In 581 black South Africans, we determined 24-hour urinary Na+ and K+ excretion and aortic function from central aortic pressure (radial pulse wave analysis [SphygmoCor software]), velocity, and diameter measurements. Proximal aortic function was assessed from characteristic impedance (Zc). Beyond mean arterial pressure and additional confounders, urinary Na+/K+ was independently associated with Zc (P<0.005) but not peak aortic Q (P=0.30) or alternative aspects of Q or ejection volume. Although age was strongly associated with proximal aortic diameter, no independent relations between urinary Na+/K+ and aortic diameter were noted (P=0.17). Relations between urinary Na+/K+ and Zc translated into independent relations with early systolic compression wave pressures (QxZc [PQxZc]) and aortic forward wave pressures but not Pb. Moreover, neither reflected wave magnitude (P=0.92) nor aortic pulse wave velocity were independently associated with urinary Na+/K+. In product of coefficient mediation analysis, the independent relations between urinary Na+/K+ and peak aortic or brachial pulse pressure or systolic blood pressure were accounted for by Zc and PQxZc. In conclusion, abnormalities in Na+/K+ intake determine pulse pressure or systolic blood pressure beyond mean arterial pressure mainly through potentially irreversible impacts on proximal aortic impedance rather than readily modifiable increases in aortic flow (blood volume) or wave reflection.