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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.)

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 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.)

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.)