Trisha O'Moore‐Sullivan

BACKGROUND: Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. METHODS AND RESULTS: Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity (em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV systolic and diastolic function and increased myocardial reflectivity compared with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB, and reduced em, whereas LV ejection fraction remained normal. Differences in regional or global strain, sm, and em were identified between the severely obese (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of reduced function by sm, em, and basal septal strain and increased reflectivity by cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35) groups (P<0.05). Although tissue Doppler measures were not associated with duration of obesity, they did correlate with fasting insulin levels and reduced exercise capacity. BMI was independently related to average LV strain (beta=0.40, P=0.02), sm (beta=-0.36, P=0.002), and em (beta=-0.41, P<0.001). CONCLUSIONS: Overweight subjects without overt heart disease have subclinical changes of LV structure and function even after adjustment for mean arterial pressure, age, gender, and LV mass.

OBJECTIVES: In non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is intricately linked with a number of metabolic alterations. We studied substrate utilisation in NAFLD during basal, insulin-stimulated and exercise conditions, and correlated these outcomes with disease severity. METHODS: 20 patients with NAFLD (mean ± SD body mass index (BMI) 34.1 ± 6.7 kg/m(2)) and 15 healthy controls (BMI 23.4 ± 2.7 kg/m(2)) were assessed. Respiratory quotient (RQ), whole-body fat (Fat ox) and carbohydrate (CHO ox) oxidation rates were determined by indirect calorimetry in three conditions: basal (resting and fasted), insulin-stimulated (hyperinsulinaemic-euglycaemic clamp) and exercise (cycling at an intensity to elicit maximal Fat ox). Severity of disease and steatosis were determined by liver histology, hepatic Fat ox from plasma β-hydroxybutyrate concentrations, aerobic fitness expressed as VO2 peak, and visceral adipose tissue (VAT) measured by computed tomography. RESULTS: Within the overweight/obese NAFLD cohort, basal RQ correlated positively with steatosis (r=0.57, p=0.01) and was higher (indicating smaller contribution of Fat ox to energy expenditure) in patients with NAFLD activity score (NAS) ≥ 5 vs <5 (p=0.008). Both results were independent of VAT, % body fat and BMI. Compared with the lean control group, patients with NAFLD had lower basal whole-body Fat ox (1.2 ± 0.3 vs 1.5 ± 0.4 mg/kg FFM/min, p=0.024) and lower basal hepatic Fat ox (ie, β-hydroxybutyrate, p=0.004). During exercise, they achieved lower maximal Fat ox (2.5 ± 1.4 vs. 5.8 ± 3.7 mg/kg FFM/min, p=0.002) and lower VO2 peak (p<0.001) than controls. Fat ox during exercise was not associated with disease severity (p=0.79). CONCLUSIONS: Overweight/obese patients with NAFLD had reduced hepatic Fat ox and reduced whole-body Fat ox under basal and exercise conditions. There was an inverse relationship between ability to oxidise fat in basal conditions and histological features of NAFLD including severity of steatosis and NAS.