Objectives As myocardial fibrosis might be an important contributor to the association of obesity with left ventricular (LV) dysfunction and heart failure, we investigated the effects of spironolactone on LV function and serological fibrosis markers (procollagen type III N-terminal propeptide (PIIINP) and procollagen type I C-terminal propeptide (PICP)) in patients with obesity and abnormal LV performance. Design A prospective, randomised, double-blind, placebo-controlled study. Setting A university hospital. Patients and intervention 113 patients (mean±SD age 58±8 years) with body mass index≥30, without any comorbidities, with impaired early diastolic mitral annular velocity, randomised to spironolactone 25 mg/day or placebo for 6 months. Main outcome measures Echocardiographically derived indices of LV systolic (strain and strain rate) and diastolic (E velocity, tissue e′ and E/e′ ratio) function, myocardial reflectivity (calibrated integrated backscatter (IB)), and serum PICP and PIIINP. Results In the spironolactone group, significant improvements in myocardial deformation, peak early diastolic velocity (Em), E/e′ and IB were noted with a simultaneous decrease in PICP and PIIINP. No corresponding alterations were found with placebo. Improvement in LV systolic function (increase in strain) was independently associated with baseline strain (β=−0.43, p<0.001), change in IB (β=0.26, p<0.02) and baseline PICP (β=0.24, p<0.04). Among the independent determinants of LV diastolic improvement were for increase in Em – baseline Em (β=−0.44, p<0.001) and baseline PICP (β=0.35, p<0.002), and for decrease in E/e′ – baseline E/e′ (β=−0.35, p<0.005) and change in PICP (β=0.25, p<0.04). Conclusions In patients with obesity without other comorbidities, aldosterone antagonism improves LV function and myocardial acoustic properties, and reduces circulating procollagen levels. Beneficial changes in cardiac performance are independently predicted by baseline LV dysfunction and baseline disturbances, as well as treatment-induced improvements in fibrosis markers. Clinical Trial Registration http://www.anzctr.org.au ACTRN12609000655246.

Background—: Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. Methods and Results—: One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m ² and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=−0.17, P <0.006), C-reactive protein (β=−0.20, P <0.002) and abdominal fat deposit (β=−0.20, P <0.003); for tissue S velocity, PICP (β=−0.21, P <0.002) and abdominal fat deposit (β=−0.43, P <0.0001); for tissue E velocity, abdominal fat deposit (β=−0.30, P <0.0001), PICP (β=−0.31, P <0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=−0.20, P <0.002); and for E/e′-PICP, IL-18 (both β=0.18, P <0.01) and HOMA IR (β=0.16, P <0.04). Conclusions—: In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Objective Apelin – a novel multifunction peptide implicated in regulation of the cardiovascular system, including blood pressure and cardiac function control – has been postulated to be involved in the pathophysiology of hypertension and hypertensive heart disease. We investigated the circulating apelin level and its relationship to left ventricular function in patients with essential hypertension. Methods We enrolled 232 hypertensive patients without concomitant diseases affecting cardiovascular functions and 76 healthy controls. Each patient underwent plasma apelin measurement and echocardiographic assessment of left ventricular systolic and diastolic function using myocardial velocities and deformation parameters, and myocardial reflectivity using calibrated integrated backscatter. Results Hypertensive patients demonstrated lower plasma apelin than the controls (265 ± 127 vs. 330 ± 159 pg/ml; P < 0.001). Patients with the lowest plasma apelin, that is, from the first tertile, exhibited more severe left ventricular systolic and diastolic function abnormalities than their peers from the other two tertiles. In multivariable regression analysis, apelin was, in addition to patient age, BMI, blood pressure, left ventricular mass index and calibrated integrated backscatter in the basal septum, an independent correlate of left ventricular systolic function parameters (β = 0.18; P < 0.001 for strain and β = 0.12; P < 0.03 for systolic strain rate) and diastolic function parameters (β = 0.13; P < 0.01 for early diastolic strain rate, β = 0.11; P < 0.04 for early diastolic myocardial velocity, and β = −0.11; P < 0.04 for the ratio of mitral inflow to mitral annular early diastolic velocity). Conclusion In patients with essential hypertension, circulating apelin levels are reduced, and lower plasma apelin is independently associated with more profound left ventricular systolic and diastolic function impairment.