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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yusuf, Norton, Peterson, Mthembu, Libhaber, Tade, Bello, Bamaiyi, Mmopi, Dessein, Peters, Sareli and Woodiwiss.)

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.

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mthembu, Peterson, Norton, Sadiq, Kolkenbeck-Ruh, Naran, Yusuf, Tade, Bello, Bamaiyi, Libhaber, Dessein, Peters, Monareng, Abdool-Carrim, Cassimjee, Sareli, Modi and Woodiwiss.)

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 ± 0.07, P < 0.0001) than Zc (h2 = 0.44 ± 0.10, P < 0.0001)(P < 0.005 for comparisons) and TAC (h2 = 0.47 ± 0.08, P < 0.0001)(P < 0.005 for comparisons). Importantly, the heritability of Q was also greater than that for PP (h2 = 0.12 ± 0.09, P = 0.11) (P < 0.0001 for comparisons), or SBP (h2 = 0.13 ± 0.10, 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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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)., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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 <0.0001). Before 50 years of age, before when P Q×Zc positively correlates with age, Pb, but not systemic vascular resistance was independently associated with LV mass index ( P <0.002), E/e' ( P <0.002), and e' ( P <0.05). Moreover, in those over 50 years of age, when 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 <0.01), E/e' ( P <0.001), and e' ( P <0.001). The contribution of Pb to age-related decreases in LV diastolic function was as strong in those younger as compared with older than 50 years of age and poorly indexed by brachial BP. In conclusion, a striking age-related deterioration in LV diastolic function begins at an early adult age and Pb is the dominant hemodynamic factor that accounts for this relationship. Age-related increases in Pb in young adults contribute as much to functional abnormalities ultimately responsible for LV diastolic dysfunction in hypertension as at an older age, effects poorly indexed by brachial BP.

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 [LVM inappr ]) (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, LVM inappr , LV hypertrophy (LVH), PWV and eGFR. Furthermore, independent of confounders, LVMI, LVM inappr 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, LVM inappr or LVH. Moreover, in multivariate regression analysis neither PWV nor eGFR significantly modified the contribution of resistin to LVM inappr 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.

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 < 0.001-0.0001) and RWT (P < 0.05-0.001) were independently associated with E/A, e'/a', e' and E/e'. However, in product of coefficient mediation analysis, LVM and RWT failed to account for most BP-associated changes in diastolic function. Indeed, whilst a one SD increase in DBP or SBP (13 and 22 mmHg, respectively) translated into a 0.07, 0.13 and 0.53 decrease in E/A, e'/a', e' and a 0.73 increase in E/e', respectively, in mediation analysis LVMI accounted for only 0.0005, 0.0017, 0.05 and 0.08 of the impact of a one SD effect of LVMI on E/A, e'/a', e' and E/e', respectively. Similar contributions of RWT as for LVMI to BP-associated LV diastolic functional changes were noted and the contribution of LVMI or RWT to BP-related alterations in diastolic function was similar in those participants not receiving antihypertensive therapy., Conclusion: Although structural LV remodelling is independently associated with changes in LV diastolic function, LVMI and RWT account for only a minor proportion of the impact of BP on diastolic function. Thus, most BP-associated decreases in LV diastolic function are likely to be a transition process independent of LV hypertrophy or concentric remodelling.

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: 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., (© 2018 The Authors. Clinical Cardiology Published by Wiley Periodicals, Inc.)

Background: 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., Methods: 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., Results: 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., Conclusions: Independent of LVMI, a pro-inflammatory state rather than BP load is strongly associated with LV concentric remodelling., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Aims: To determine the extent to which the adverse effects of blood pressure (BP) are mediated by pulsatile haemodynamic changes across the normotensive as compared with the hypertensive adult brachial BP range, and whether aortic rather than brachial pulsatile changes best index these effects., Methods: In 1307 community participants, the contribution of pulsatile haemodynamics (applanation tonometry and SphygmoCor software) to variations in left ventricular mass index (LVMI) (echocardiography) (n = 920), carotid intima-media thickness (IMT) (n = 712) and estimated glomerular filtration rate (eGFR) (n = 1164) were assessed., Results: In normotensive participants (50.5%) independent of steady-state pressure (mean arterial pressure), significant relations between aortic backward wave pressure and LVMI (partial r = 0.16, P < 0.001) or IMT (partial r = 0.15, P < 0.005) and between aortic pulse wave velocity and eGFR (partial r = -0.18, P < 0.0001) were noted, effects which in hypertensive participants were observed for LVMI and eGFR, but not IMT. With adjustments for brachial pulse pressure (PP) or SBP and confounders, aortic backward wave pressure and aortic pulse wave velocity showed independent relations with LVMI, IMT or eGFR in normotensive participants, but only with LVMI or eGFR in hypertensive participants. In normotensive participants, as compared with brachial PP or SBP, aortic backward wave pressure showed a greater slope (β-coefficient) of the relation with LVMI (0.99 ± 0.24 versus 0.47 ± 0.10 and 0.41 ± 0.09 mmHg, P < 0.05) and IMT (0.0045 ± 0.0013 versus 0.0013 ± 0.0006 and 0.0013 ± 0.0005 mmHg, P < 0.05) and a stronger association with left ventricular hypertrophy [odds ratios (95% confidence interval), 1.125 (1.059-1.195) versus 1.054 (1.027-1.082) and 1.042 (1.020-1.066), P < 0.05]. However, in hypertensive participants, only the slope of the aortic backward wave pressure-LVMI relationship was greater than that of PP-LVMI and SBP-LVMI relations., Conclusion: Beyond brachial BP, pulsatile haemodynamics rather than steady-state pressures account for end-organ effects more consistently across the normotensive than the hypertensive BP range. Hence, targeting aortic pulsatile haemodynamic changes may best limit BP-related cardiovascular risk within the normotensive BP range.

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., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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 height 1.7 . 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., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

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., (© American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Whether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain., Methods: Echocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus [e'] [n=430], ratio of early-to-late transmitral blood flow velocity (E/A), and E/e' [n=430]) were determined in 737 randomly recruited participants of a community-based study (43% obese)., Results: Independent of LVMI and confounders, indexes of adiposity and the homeostasis model of insulin resistance (HOMA-IR) were independently associated with LV diastolic function (p<0.05). In addition, RWT was independently associated with LV diastolic function (p<0.002). Importantly, an independent interaction between HOMA-IR and RWT, but not between blood pressure or age and RWT, was related to LV diastolic function (p<0.05). This translated into an independent relationship between HOMA-IR and lateral e' (partial r=-0.17, p<0.02), septal e' (partial r=-0.14, p=0.05), E/A (partial r=-0.17, p<0.005) and E/e' (partial r=0.19, p<0.01) in those with RWT above, but a lack of relationship between HOMA-IR and LV diastolic function (p>0.59) in those with RWT below the median for the sample. Similarly, HOMA-IR was independently associated with LV diastolic dysfunction in those with RWT above (p<0.05) but not below (p>0.19) the median for the sample., Conclusions: The relationship between insulin resistance, but not alternative risk factors and LV diastolic function is markedly modified by the presence of a more concentrically remodeled LV., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Electrocardiographic (ECG) QRS voltages used to generate criteria for left ventricular hypertrophy (LVH) detection are considerably attenuated by obesity. This effect renders the utility of ECG criteria to detect LVH in obese individuals of African ancestry to be of limited value., Hypothesis: A novel approach to correcting QRS voltages for the attenuating effect of body mass index (BMI) will improve the ability of ECG criteria to detect LVH in a group of African descent., Methods: Left ventricular mass was determined from echocardiography in 661 randomly selected participants (43.0% obese) of black African ancestry in South Africa., Results: As compared with Cornell and Sokolow-Lyon voltage criteria, BMI best correlated with RaVL , Gubner-Ungerleider, and Lewis QRS complex voltages, but these relations were noted only in those with BMI <29 kg/m(2) . Correcting RaVL and Lewis voltages by the difference in the slope of BMI-voltage relations in those with BMI <29 kg/m(2) vs those with BMI ≥29 kg/m(2) showed the greatest performance for LVH detection (uncorrected RaVL : 0.695 ± 0.025, corrected RaVL : 0.733 ± 0.022; P < 0.0001), and also increased the sensitivity (uncorrected RaVL : 30.6%, corrected RaVL : 42.4%; P < 0.0005) with no significant change in specificity (uncorrected RaVL : 86.3%, corrected RaVL : 83.0%; P = 0.28)., Conclusions: We offer a novel approach to correcting ECG voltages for the attenuating effects of obesity in individuals of African ancestry, and this improves the performance and sensitivity for LVH detection., (© 2016 Wiley Periodicals, Inc.)

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 < .001) and sibling-sibling (r = 0.29; P < .005), but not in spouse (r = 0.13; P = .51) pairs. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.29; P < .005) pairs persisted with adjustments for SBPc. The relationships between parent-child (r = 0.22; P < .001) and sibling-sibling (r = 0.26; P < .01) pairs also persisted with adjustments for Pb. Independent of confounders including LVMI and RWT, E/e' showed significant heritability (h(2) ± standard error of the mean [SEM] = 0.51 ± 0.11; P < .0001) which similarly persisted with adjustments for SBPc (h(2) ± SEM = 0.50 ± 0.11; P < .0001) and Pb (h(2) ± SEM = 0.49 ± 0.11; P < .0001). In conclusion, in a group of African ancestry, independent of LV remodeling and aortic function, E/e' shows significant intrafamilial aggregation and robust heritability. Hence, genetic factors may play an important role in determining moderate-to-severe LV diastolic dysfunction independent of cardiac remodeling or aortic function in groups of black African ancestry., (Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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)., Results: Resistin concentrations were not independently associated with blood pressure (BP). However, resistin concentrations were associated with LVMI (partial r=0.12, p<0.0005), LVMinappr (partial r=0.18, p<0.0001) and LV hypertrophy (partial r=0.13, p<0.001) 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, p<0.002 in all and partial r=-0.15, p<0.0005 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., Conclusions: Resistin in-part explains variations in LVM, hypertrophy and myocardial systolic dysfunction, and these effects are independent of insulin resistance and general inflammatory changes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Whether left ventricular (LV) geometric remodeling, as indexed by relative wall thickness (RWT), aggregates in families and is inherited independent of LV mass (LVM) and additional confounders is uncertain., Methods: We determined whether RWT as assessed from 2D targeted M-mode echocardiography shows intrafamilial aggregation and heritability independent of LVM in 181 nuclear families (73 spouse pairs, 403 parent-child pairs, and 177 sibling-sibling pairs) with 16 families including 3 generations from an urban developing community of black Africans. Intrafamilial aggregation and heritability estimates (S.A.G.E. software) were assessed independent of confounders, including central aortic systolic blood pressure (SBPc) (radial applanation tonometry and SphygmoCor software)., Results: Independent of confounders including SBPc, LV RWT was correlated in parent-child (r = 0.32, P < 0.0001) and sibling-sibling (r = 0.29, P < 0.0001), but not in spouse (r = 0.11, P = 0.33) pairs. The relationships between parent-child (r = 0.28, P < 0.0001) and sibling-sibling (r = 0.24, P < 0.001) pairs persisted with further adjustments for LVM or LVM indexed to height(2.7) (LVMI). Similarly, independent of confounders, LV RWT showed significant heritability (h(2) ± SEM = 0.56 ± 0.09, P < 0.0001) and this persisted with further adjustments for LVM (h(2) ± SEM = 0.48 ± 0.09, P < 0.0001) or LVMI (h(2) ± SEM = 0.49 ± 0.09, P < 0.0001)., Conclusions: In a group of African ancestry, independent of LVM, LV geometric remodeling shows significant intrafamilial aggregation and heritability. Genetic factors may in-part determine the LV geometric remodeling process independent of the extent of cardiac hypertrophy., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: To determine whether blood pressure (BP) or an excess adiposity, both frequently observed comorbidities that independently relate to left ventricular diastolic dysfunction (LVDD), have a greater impact on LVDD at a community level., Methods: We assessed the relative independent impact of an excess adiposity versus BP on indices of LVDD as determined from the ratios of early-to-late transmitral blood flow velocity (E/A) and E/the mean of lateral and septal wall myocardial tissue lengthening at the level of the mitral annulus (e'; (E/e') in 417 randomly recruited participants of a community-based study with a high prevalence of excess adiposity (43% obese and 25% morbidly obese)., Results: In multivariate adjusted models, including adjustments for appropriate BP values (SBP for E/e' and DBP for E/A), waist circumference was independently associated with E/A (partial r = -0.12, P < 0.02) and E/e' (partial r = 0.15, P < 0.005). In contrast, BMI was independently associated with E/e' (partial r = 0.11, P < 0.05), but not E/A (partial r = -0.09, P = 0.08). In multivariate models, SBP had a greater impact on E/e' (standardized β-coefficient = 0.32 ± 0.05, P < 0.0001) than did waist circumference (standardized β-coefficient = 0.16 ± 0.05, P < 0.005; P < 0.05 for comparison), whereas DBP had a similar impact on E/A (standardized β-coefficient = -0.10 ± 0.03, P < 0.005) as did waist circumference (standardized β-coefficient = -0.10 ± 0.04, P < 0.05). Importantly, whereas SBP was the main factor independently associated with an increased E/e' (≥10) (P < 0.0005), waist circumference was not independently associated with either a decreased E/A (≤0.75) (P = 0.82) or an increased E/e' (≥10; P = 0.15)., Conclusion: In a community sample with a high prevalence of excess adiposity, BP exceeds obesity as the most important modifiable risk factor for LVDD. These data suggest that in communities with a high prevalence of obesity, if weight loss programmes fail to produce sustainable target body weights, rigorous BP management to lower than normal thresholds may be sufficient to prevent LVDD.

Background: Whether routine clinical parameters associated with left ventricular mass (LVM) enhance the performance of electrocardiographic (ECG) criteria for LV hypertrophy (LVH) detection and hence modify overall cardiovascular risk stratification is unknown., Methods: An approach to echocardiographic LVH detection was identified from ECG criteria and clinical variables [age, body mass index (BMI), systolic blood pressure (SBP) and estimated glomerular filtration rate] associated with LVM in 621 participants of African ancestry. Performance (area under the receiver operating curve) and classification accuracy for LVH detection and the impact on cardiovascular risk stratification were determined., Results: Compared to Cornell criteria alone, the combined use of Cornell criteria and clinical variables increased the performance (p < 0.001) and sensitivity (p < 0.05 to p < 0.0001) for LVH detection. The use of Cornell product together with additional clinical parameters as compared to Cornell product criteria alone increased the proportion of participants with pre-, grade I or grade II hypertension risk stratified as having a high added cardiovascular risk (56.3-67.9 %, p < 0.05)., Conclusions: In individuals of African ancestry, a combination of Cornell product criteria and age, BMI and SBP improves classification accuracy of Cornell criteria for LVH and increases those identified as having a high added as compared to lower cardiovascular risk scores.

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 < 0.002), but not SBP (partial r = -0.09, P = 0.18), was associated with E/A and the relationship between brachial DBP and E/A persisted with adjustments for brachial (P < 0.002) or aortic (P < 0.05) SBP. Although aortic SBP was independently associated with E/A, this relationship did not persist with adjustments for DBP (partial r = -0.05, P = 0.44). In contrast, both brachial (partial r = 0.34, P < 0.0001) and aortic (partial r = 0.34, P < 0.0001) SBP were independently associated with E/e', effects that persisted with adjustments for DBP (P < 0.0001), although independent relationships between DBP and E/e' did not persist with adjustments for brachial or aortic SBP (P = 0.17-0.57). In quartiles of DBP or SBP within normal-to-high normal ranges, multivariate adjusted E/A was decreased and E/e' increased as compared with those with optimal BP values (P < 0.05 to P < 0.005)., Conclusion: Both SBP and DBP are important determinants of separate components of left ventricular diastolic dysfunction and these effects are noted even within normotensive BP ranges. DBP may be as important as SBP in the transition to diastolic dysfunction.

Background: Whether independent relationships between white coat effects (office minus day (office-day blood pressure (BP))) and organ damage or arterial stiffness may be explained by associations with an attenuated nocturnal BP dipping, has not been determined., Methods: In 750 participants from a sample of African ancestry, office and 24-hour BP, carotid-femoral pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software) (n = 662), and left ventricular mass indexed to height(2.7) (LVMI) (echocardiography) (n = 463) were determined., Results: Office-day systolic BP (SBP) was correlated with day minus night (day-night) SBP, percentage night divided by day (night/day) SBP, and night SBP (P < 0.0005), and these relationships persisted with adjustments for confounders, including day SBP (P < 0.005). With adjustments for 24-hour SBP and additional confounders, office-day SBP was associated with LVMI (P < 0.01) and PWV (P < 0.0001). With adjustments for day SBP and additional confounders, day-night SBP, percentage night/day SBP, and night SBP were related to PWV (P < 0.05) but not to LVMI (P > 0.44). The relationships between office-day SBP and LVMI or PWV persisted with adjustments for either day-night or percentage night/day SBP (LVMI: P = 0.01; PWV: P < 0.0001) or night SBP (LVMI: P < 0.01; PWV: P = 0.0001), and in product of coefficient mediation analysis with appropriate adjustments, neither indexes of nocturnal BP dipping nor nocturnal BP per se contributed toward the impact of office-day BP on LVMI or PWV (P > 0.09)., Conclusions: In a group of African ancestry, although white coat effects are independently associated with an attenuated nocturnal decrease in SBP, neither decreased BP dipping nor nocturnal BP contribute toward the independent relationships between white coat effects and LVMI or arterial stiffness., (© American Journal of Hypertension, Ltd 2013. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: We determined the extent to which relationships between nurse-derived blood pressures (BPs) and cardiovascular damage may be attributed to isolated increases in in-office SBP independent of ambulatory BP., Methods: In 750 participants from a community sample, nurse-derived office BP, ambulatory BP, carotid-femoral pulse wave velocity (PWV; applanation tonometry and SphygmoCor software; n=662), and left ventricular mass indexed to height (LVMI; echocardiography; n=463) were determined., Results: Nurse-derived office BP was associated with organ changes independent of 24-h BP (LVMI; partial r=0.15, P<0.005, PWV; partial r=0.21, P<0.0001) and day BP. However, in both unadjusted (P<0.0001 for both) and multivariate adjusted models (including adjustments for 24-h BP; LVMI; partial r=0.14, P<0.01, PWV; partial r=0.21, P<0.0001), nurse office-day SBP (an index of isolated increases in in-office BP) was associated with target organ changes independent of ambulatory BP and additional confounders, with the highest quartile (≥15 mmHg) showing the most marked increases in LVMI (P<0.0005) and PWV (P<0.0001) as compared to the lowest quartile (<-5 mmHg). These relationships were reproduced in those with normotensive day BP values and the quantitative effect of nurse office-day BP on target organ changes was at least equivalent to that of ambulatory BP., Conclusion: Nurse-elicited isolated increases in in-office BP account for a significant proportion of the relationship between nurse-derived BP and target organ changes independent of ambulatory BP. Therefore, high quality nurse-derived BP measurements do not approximate the impact of BP effects per se on cardiovascular damage.

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 < 0.05 to P < 0.005 after multivariate adjustments)., Conclusion: In contrast to normal versus high-normal BP categories which do not clearly distinguish normotensives with from those without organ damage, noninvasively determined aortic BP measurements may refine the ability to detect those with a normal/high-normal BP at risk of BP-related cardiovascular damage.

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 < 0.0001; LVMinappr: partial r = -0.17, P < 0.0001) and normotensive (LVMI: partial r = -0.23, P < 0.0001; LVMinappr: partial r = -0.22, P < 0.0001) separate from hypertensive patients. Marked differences in LVMinappr were noted in the eGFR range below 132 compared to at least 132 ml/min per 1.73 m (P < 0.0005). When replacing clinic BP with either aortic SBP, 24-h BP, PWV, stroke work (for LVMI), left-ventricular end-diastolic diameter (LVEDD), or circumferential wall stress in the regression models, eGFR retained strong associations with LVMI (P = 0.01 to <0.0001) and LVMinappr (P < 0.005 to <0.0001) and these effects were replicated in normotensive separate from hypertensive patients., Conclusions: Strong relationships between eGFR and LVM occur at a community level irrespective of the presence of hypertension and independent of 24-h and aortic BP, PWV, LVEDD, stroke work and wall stress. Non-haemodynamic factors explain a considerable proportion of the relationship between early glomerular dysfunction and left-ventricular hypertrophy.

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<0.0001) but not in patients with an LVMI ≤51 g/m(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<0.0001) and EF increased (5.0±10.3%; P<0.05) after treatment, whereas in patients with an LVM(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<0.05), on-treatment decreases in LVM(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<0.0001). In conclusion, decreases in LVM(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.

The relative independent contribution of excess adiposity, as indexed by measures of central, general, or peripheral adiposity, toward abnormal cardiac diastolic chamber function at a community level is unclear. In 377 randomly selected participants >16 years old from a community sample with a high prevalence of excess adiposity ( approximately 25% overweight and approximately 43% obese), we assessed the independent contribution of the indexes of adiposity to the variation in early-to-late (atrial) transmitral velocity (E/A). After adjustments for a number of confounders, including age, gender, pulse rate, conventional diastolic (or systolic) blood pressure, antihypertensive treatment, left ventricular mass index, and the presence of diabetes mellitus or a hemoglobin A1c level >6.1%; waist circumference was an independent predictor of a reduced E/A (p = 0.0038). Body mass index (p = 0.07), waist-to-hip ratio (p = 0.23), and skinfold thickness (p = 0.37) were not independently associated with E/A, whereas waist circumference was independently associated with E/A, even after adjustments for other adiposity indexes, including body mass index (p <0.05 to 0.005). In contrast to the effects on diastolic function, the waist circumference did not correlate with the left ventricular ejection fraction (p = 0.23). The independent relation between the waist circumference and E/A (standardized beta coefficient -0.14 +/- 0.05, p = 0.0038) was second only to age (standardized beta coefficient -0.57 +/- 0.05, p <0.0001) and similar to blood pressure (standardized beta coefficient -0.11 +/- 0.04, p = 0.0075) in the magnitude of the independent effect on E/A. The inclusion of the relative wall thickness rather than the left ventricular mass index in the regression equation produced similar outcomes. The exclusion of the left ventricular mass index and relative wall thickness from the regression equations or the inclusion of carotid-femoral pulse wave velocity or 24-hour blood pressure as confounders failed to modify the relation between waist circumference and E/A. In conclusion, the waist circumference was second only to age in the impact on an independent association with E/A in a population sample with a high prevalence of excess adiposity. This effect was not accounted for by left ventricular hypertrophy or remodeling, the 24-hour blood pressure, or arterial stiffness.

Background: As it is uncertain whether excess adiposity promotes primarily concentric or eccentric left ventricular hypertrophy (LVH), we aimed to determine at a population level, the independent relationship between waist circumference (WC) and LV geometric changes and the potential hemodynamic mechanisms thereof., Methods: We assessed the relations between WC and LV end-diastolic diameter (EDD), LV mean wall thickness (MWT = posterior + septal wall thickness/2), LV relative wall thickness (RWT = MWT/EDD), LV mass index (LVMI), concentric LVH (LVMI > 51 g/m2.7 and RWT > 0.45), eccentric LVH (LVMI > 51 g/m2.7 and RWT < 0.45), or concentric LV remodeling (normal LVMI and RWT > 0.45), in 309 never treated for hypertension, randomly recruited adult participants with a high prevalence of excess adiposity ( approximately 25% overweight; 38% obese). Pulse-wave analysis was performed to determine central artery blood pressures (BPs). Two hundred and thirty-one participants had high-quality ambulatory BP monitoring., Results: Approximately 7% of participants had concentric LVH, approximately 16% concentric LV remodeling, and approximately 15% eccentric LVH. After adjustments for potential confounders including conventional systolic BP (SBP), WC was related to MWT (partial r = 0.23, P = 0.0001), RWT (partial r = 0.13, P = 0.03), concentric LVH (P < 0.04), concentric LV remodeling (P = 0.02), but not with EDD or eccentric LVH (P = 0.91). Similar outcomes were noted after adjustments for central or 24-h SBP, and for conventional, central, or 24-h pulse pressure. Separate analysis in normotensive subjects revealed similar outcomes., Conclusions: In a population sample with a high prevalence of obesity, excess adiposity promotes concentric, rather than eccentric LV geometric changes, effects which are independent of conventional, central artery or 24-h BP measured on a single occasion.

Background: Amino terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive marker of ventricular dysfunction. Exercise causes an increase in the secretion of NTproBNP, and with myocardial ischaemia the increase is more pronounced. This increase has been found to improve the diagnostic sensitivity of the stress ECG in diagnosing myocardial ischaemia in subjects with normal ventricular function., Objective: To assess whether the change in NT-proBNP can be used to diagnose effort-induced myocardial ischaemia in an unselected population., Methods: We enrolled a total of 51 consecutive patients, referred for exercise stress 99mTc-sestamibi SPECT MPI (single-photon emission computed tomography myocardial perfusion imaging) to diagnose inducible myocardial ischaemia. NT-proBNP was determined at rest and 30 minutes after cessation of exercise., Results: Of the 51 patients, 28 had normal perfusion scans, seven had scans with fixed perfusion defects (previous myocardial infarction with no inducible ischaemia) and 16 had reversible perfusion defects (inducible ischaemia). There was no correlation between ischaemia and resting NT-proBNP, post-stress NT-proBNP or the change in NTproBNP (delta-NT-proBNP)., Conclusion: In an unselected population the change in NTproBNP cannot be used to diagnose effort-induced myocardial ischaemia.

Background: In the treatment of hypertension in subjects of African origins, although hydrochlorothiazide (HCTZ) is not as effective as calcium channel blockers, indapamide is superior to HCTZ. In the present study we therefore compared the effects of slow release (SR) indapamide with the calcium channel blocker amlodipine, when used as initial therapy, on blood pressure (BP) and left ventricular mass (LVM) during 6 months of treatment in this group., Methods: Patients with a mean daytime ambulatory diastolic BP > or =90 mm Hg and < or =110 mm Hg (n = 125, aged 53 +/- 11 years, 68% women) were randomized to receive open-label 1.5 mg of indapamide SR or 5 mg of amlodipine. If daytime ambulatory diastolic BP at 1 month was >/=90 mm Hg, 4 mg of perindopril was added to indapamide SR or the dose of amlodipine was increased to 10 mg., Results: After 1 month of therapy, there was an equivalent decline in systolic and diastolic BP in both groups (P <.0001). In the indapamide-treated group (n = 62) the daytime BP decreased from 153 +/- 12/101 +/- 6 mm Hg to 138 +/- 15/92 +/- 10 mm Hg and for amlodipine (n = 58), it decreased from 152 +/- 13/99 +/- 5 mm Hg to 138 +/- 12/91 +/- 8 mm Hg. At 6 months daytime ambulatory BP decreased to 130 +/- 15/86 +/- 8 mm Hg and to 129 +/- 11/85 +/- 5 mm Hg for the indapamide SR (n = 42) and amlodipine (n = 44) treatment groups, respectively. Both groups showed equivalent regression of LVM index and relative wall thickness., Conclusions: These data suggest that in hypertensive patients of African ancestry initiating therapy with 1.5 mg of indapamide SR and then adding 4 mg of perindopril is equally as effective as amlodipine therapy at reducing BP, and modifying target organ damage.