Right heart overload contributes to cardiac natriuretic hormone elevation in patients with heart failure.

BACKGROUND: Atrial and brain natriuretic peptides (ANP and BNP) plasma concentration increases and holds a prognostic significance in patients with left ventricular dysfunction. We assessed the hypothesis that right ventricular (RV) overload might significantly contribute to plasma elevation of cardiac natriuretic hormones in patients with heart failure. METHODS: Forty-one patients with cardiomyopathy and depressed left ventricular (LV) function (ejection fraction, EF, <40%), underwent cardiac magnetic resonance imaging (MRI) and resting plasma determination of ANP and BNP. Nineteen healthy subjects were also studied as control group. Ventricular volumes and function were assessed by MRI. RESULTS: In the group of patients, LVEF was 22.6+/-1.2% (controls: 61.2+/-1.3%, P<0.001, mean+/-S.E.M.), while RVEF was 48.2+/-2.5% (controls: 66.7+/-1.6%, P<0.001); LV and RV end diastolic/systolic volumes, corrected by body surface area, were 143+/-7/114+/-7 ml/m2 (controls 70+/-3/27+/-2 ml/m2, both P<0.001) and 66+/-3/37+/-4 ml/m2 (controls: 63+/-4/21+/-2 ml/m2, P<0.01 only for end-systolic volume). BNP plasma value was on average 324+/-39 pg/ml (range: 23-1280, controls 10+/-2 pg/ml), ANP value was 144+/-17 pg/ml (range: 26-534, controls 15+/-1 pg/ml). BNP positively correlated with either end-diastolic or end-systolic RV volume in patients, less with LV systolic, and not with LV diastolic volume. Moreover, a significant negative correlation was observed between BNP and either LVEF or RVEF. Conversely, ANP showed a significant correlation only with end-systolic RV volume and with both RVEF and LVEF. When multivariate stepwise linear regression analysis was applied LVEF resulted the only independent predictor for ANP plasma values (R=0.591, P<0.001), while LVEF and RV end-diastolic volume for BNP (R=0.881, P<0.001, and R=0.881, P=0.035, respectively). CONCLUSIONS: Right heart overload contributes independently to plasma elevation of natriuretic peptides. RV involvement, which is known to independently worsen prognosis in patients with cardiomyopathy, might contribute to their established prognostic power, inducing compensatory secretion of plasma cardiac natriuretic hormones.

beta-cell function in obesity: effects of weight loss.

In nondiabetic subjects, obesity is associated with a modest expansion of beta-cell mass, possibly amounting-according to the best available estimates-to 10-30% for each 10 kg of weight excess. Whether age of onset and duration of obesity, recent changes in body weight, and body fat distribution have any effect on beta-cell mass in humans is unknown. Both fasting insulin secretion and the total insulin response to oral glucose have the following characteristics: 1) they increase with BMI in an approximately linear fashion, 2) both fat-free and fat mass are significant positive correlates, and 3) BMI exerts a positive effect separate from that of insulin resistance (i.e., obesity may be a state of primary insulin hypersecretion). The mechanisms are currently unknown, though chronic small increments in plasma glucose may play a role. In contrast, dynamic properties of beta-cell function, such as glucose sensitivity (i.e., dose-response function), rate sensitivity, and potentiation, do not appear to be substantially altered by the presence of obesity, body fat distribution, or insulin resistance as long as glucose tolerance is maintained. Weight loss, by diet or restrictive bariatric surgery, is associated with consensual decrements in insulin resistance and insulin hypersecretion. The latter, however, seems to be more persistent, suggesting that the postobese state may reproduce the primary insulin hypersecretion of the obese state. Malabsorptive bariatric surgery, in contrast, normalizes insulin sensitivity and abolishes insulin hypersecretion even before achievement of ideal body weight. Lipid-triggered messages from the gastrointestinal tract to the insulin target tissues and endocrine pancreas are the subject of intense investigation.