N-Terminal Pro-B-Type Natriuretic Peptide in Overweight and Obese Patients With and Without Diabetes: An Analysis Based on Body Mass Index and Left Ventricular Geometry

Abstract

Background and ObjectivesSeveral recent studies have shown that there is an inverse relationship between plasma B-type natriuretic peptide (BNP) and body mass index (BMI) in subjects with and without heart failure. Obesity frequently coexists with diabetes, so it is important to consider the relationship between diabetes and natriuretic peptide levels. We evaluated the influence of diabetes on the correlation of BNP and BMI.Subjects and MethodsWe examined 933 patients with chest pain and/or dyspnea undergoing cardiac catheterization between Feb. 2006 and Nov. 2007 in the Maryknoll cardiac center who had creatinine levels <2.0 mg/dL and normal systolic heart function. BMI was checked, transthoracic echocardiography was performed, and aminoterminal pro-brain natriuretic peptide (NT-proBNP) was sampled at the start of each case.ResultsIn 733 non-diabetic patients, mean plasma NT-proBNP levels of non obese individuals (BMI <23 kg/m2), overweight individuals (23≤ BMI <25 kg/m2), and obese individuals (BMI ≥25 kg/m2) showed a significant negative correlation with increasing BMI (856.39±237.3 pg/mL, 601.69±159.6 pg/mL, 289.62±164.9 pg/mL, respectively, p<0.0001). However, in 200 diabetic patients, the correlation between BMI and NT-proBNP was not significant (r=-0.21, p=0.19), and NT-proBNP did not correlate with mitral E/Ea in obese diabetic patients (r=0.14, p=0.56). NT-proBNP was significantly correlated with mitral E/Ea in the non-obese (r=0.24, p=0.008) and non diabetic (r=0.32, p=0.003) groups. Left ventricular (LV) mass index was significantly correlated with NT-proBNP in all BMI groups (r=0.61, p<0.001), and patients with concentric cardiac hypertrophy showed the highest NT-proBNP levels.ConclusionThe present study demonstrates that obese patients have reduced concentrations of NT-proBNP compared to non obese patients despite having higher LV filling pressures. However, NT-proBNP is not suppressed in obese patients with diabetes. This suggests that factors other than cardiac status affect NT-proBNP concentrations.

The paradox of low BNP levels in obesity

“…A huge number of bioactive substances are increased in plasma of patients with obesity, such as noradrenaline, angiotensin II, vasopressin, endothelins, and some cytokines, which typically increase (rather than reduce) the production/secretion of CNH by cardiomyocytes (Table 1 and Fig. 2) [11][12][13][15][16][17]. Also insulin was reported in one study to increase ANP secretion and gene expression in cultured rat cardiomyocytes, while glucose has no effect [87].…”

“…In women, estrogens may promote a gynoid distribution of body fat [58] and also increase the BNP production/secretion by cardiomyocytes [11,46,64,65]. On the other hand, the results of the Dallas Heart Study [62, 63] suggested that androgens may regulate the cardiac endocrine function.…”

“…2) [13,15,16,[30][31][32]. Several studies indicate that BNP production/secretion may be differently regulated in the normal compared with the diseased ventricular myocardium [11,30,31,34]. Indeed, ventricular hypertrophy and especially the concomitant presence of mechanisms related to inflammation and fibrosis can stimulate BNP production in the diseased ventricular myocardium [34][35][36].…”

“…The existence of such a ''handicap'' was not definitively proven, although some experimental data suggest that ANP levels fail to rise appropriately in obese subjects after a saline load [3]. More recently, several studies have reported that circulating levels of BNP and its related peptide NT-proBNP are inversely related to body mass index (BMI) values in the general population [4,5], as well as in patients with heart failure (HF) [6][7][8][9][10][11]. These data seem to support the ''natriuretic handicap hypothesis'' indicating that the BNP levels are inappropriately low in obese subjects.…”

Theophylline and Cardiac Stress in Patients with Dyspnea: An Observational Study

“…To illustrate its magnitude, it is useful to compare the impact of theophylline use on NT-proBNP levels in regard to the effects of other covariates. Serum levels of NT-proBNP increase with age and are inversely associated with BMI [25,26] . If the analysis is restricted to our patients with asthma, COPD or respiratory muscle weakness, theophylline use has the same effect on the ln-transformed NTproBNP values as an 8-year decrease in age and a BMI increase of 11.…”