Improvement of left ventricular function by lifestyle intervention in obesity: contributions of weight loss and reduced insulin resistance.

AIMS/HYPOTHESIS: Weight excess and insulin resistance mediate the link between obesity and left ventricular dysfunction. We investigated the effect and mechanisms of lifestyle modification on left ventricular function changes in obese patients. METHODS: Reduction of body weight and insulin resistance was sought using a behavioural intervention programme including dietary restrictions and exercise training in 261 patients (age 45 +/- 13 years) with BMI >or=30 kg/m(2), no history of cardiac disease and a normal stress echocardiogram. Each patient underwent echocardiographic measurement of myocardial deformation and velocity at baseline and at 6 month follow-up. RESULTS: Improvements in left ventricular systolic and diastolic function were demonstrated only in patients with significant reduction of weight and/or insulin resistance. Left ventricular improvement was less frequent in patients with diabetes than in those without (52% vs 82% for strain, 50% vs 81% for strain rate and 59% vs 80% for peak early diastolic myocardial velocity). The independent predictors of improved left ventricular systolic function (increase in strain) were: weight reduction (beta = 0.14, p < 0.05), decrease in the HOMA insulin resistance index (beta = 0.20, p < 0.005) and absence of diabetes (beta = 0.18, p < 0.02). A decrease in HbA(1c) also predicted improvement of left ventricular diastolic function (beta = 0.26, p < 0.001). There was a parallel increment in exercise capacity with intervention and increase in strain was independently correlated with increase in VO(2) (beta = 0.13, p < 0.04). CONCLUSIONS/INTERPRETATION: Effective lifestyle modifications in obese patients improve left ventricular systolic and diastolic function, but appear less effective with co-existing diabetes. The reversal of left ventricular function abnormalities is associated with reduction of both weight and insulin resistance, and is accompanied by an increase in cardiorespiratory fitness.

Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function.

BACKGROUND: Myocardial fibrosis is one of the mechanisms underlying left ventricular (LV) dysfunction in obese patients and may result from dysregulation of extracellular matrix (ECM) turnover. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) represent a regulatory system playing a crucial role in ECM metabolism. OBJECTIVES: We sought to assess plasma levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in obese young women and to evaluate the association between MMP/TIMP system components and LV function in this population. DESIGN: Prospective, cross-sectional study. SETTING: University hospital. PATIENTS: Seventy-one women aged < 35 years with body mass index > 30 kg m(-2) and 30 healthy slim female controls. MAIN OUTCOME MEASURES: Plasma MMP-2, MMP-9, TIMP-1 and TIMP-2 measurements and echocardiographic studies, including LV strain/strain rate evaluation. RESULTS: We demonstrated increased levels of MMP-9 and TIMP-1 and decreased MMP-2 in the obese population. LV dysfunction shown in patients with obesity was characterized by significantly lower values of strain/strain rate parameters. Plasma MMP-2 correlated positively and TIMP-1 negatively with systolic strain (r = 0.39, P < 0.001 and r = -0.40, P < 0.001, respectively), peak systolic strain rate (r = 0.38, P < 0.001 and r = -0.27, P < 0.03, respectively) and peak early diastolic strain rate (r = 0.40, P < 0.001 and r = -0.24, P < 0.05, respectively). Plasma MMP-2, fasting insulin and body mass index proved the only independent determinants of strain/strain rate parameters of LV systolic and diastolic performance in obese subjects. CONCLUSIONS: In premenopausal obese women (1) plasma MMP/TIMP profile is altered, (2) abnormalities of LV function are related to the changes in the MMP/TIMP system that might promote attenuated ECM degradation, mainly to the downregulation of MMP-2.