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Short Communication

Effect of Gastric Banding on Aminoterminal Pro-brain Natriuretic Peptide in the Morbidly Obese Ursula Hanusch-Enserer,* Katharina Maria Hermann,† Edmund Cauza,* Marita Spak,* Bruno Ma¨hr,‡ Attila Dunky,* Harald R. Rosen,§ Ursula Ko¨ller,† and Rudolf Prager¶

Abstract HANUSCH-ENSERER, URSULA, KATHARINA MARIA HERMANN, EDMUND CAUZA, MARITA ¨ HR, ATTILA DUNKY, HARALD R. SPAK, BRUNO MA ¨ LLER, AND RUDOLF PRAGER. ROSEN, URSULA KO Effect of gastric banding on aminoterminal pro-brain natriuretic peptide in the morbidly obese. Obes Res. 2003; 11:695-698. Objective: Aminoterminal pro-brain natriuretic peptide (NT-proBNP), like brain natriuretic peptide, might have diagnostic utility in detecting left ventricular hypertrophy and/or left ventricular dysfunction. The aim of the study was to investigate the relationship between morbid obesity and NT-proBNP and the effect of weight reduction on this parameter. Research Methods and Procedures: A total of 34 morbidly obese patients underwent laparoscopic adjustable gastric banding (LAGB). NT-proBNP levels were measured before and 12 months after the surgery. Results: Metabolic features and systolic and diastolic blood pressure were significantly decreased (p ⬍ 0.00001 for both) after a cumulative weight loss of 19.55 kg 1 year after LAGB. NT-proBNP concentration was significantly higher in morbidly obese patients before LAGB than in normalweight control subjects (341.15 ⫾ 127.78 fmol/mL vs. 161.68 ⫾ 75.78 fmol/mL; p ⬍ 0.00001). After bariatric surgery, NT-proBNP concentration decreased significantly from 341.15 ⫾ 127.78 fmol/mL to 204.87 ⫾ 59.84 fmol/mL

Received for review November 14, 2002. Accepted in final form April 15, 2003. *Department of Internal Medicine V, Division of Endocrinology and Metabolism, Wilhelminenspital, Vienna, Austria; †Department for Medical and Chemical Labdiagnostics, Hospital Lainz, Vienna, Austria; §Department of Surgery, Sozialmedizinisches Zentrum Ost, Vienna, Austria; ¶Ludwig Boltzmann Institute of Metabolism and Nutrition, Hospital Lainz, Vienna, Austria; ‡Department of Internal Medicine I, Kaiser Franz Josef Hospital, Vienna Austria. Address correspondence to Ursula Hanusch-Enserer, MD, V. Department of Internal Medicine, Wilhelminenspital, Montleartstrasse 37, 1160 Vienna, Austria. E-mail: [email protected] Copyright © 2003 NAASO

(p ⬍ 0.00,001) and remained statistically significantly elevated (204.88 ⫾ 59.84 fmol/mL vs. 161.68 ⫾ 75.78 fmol/ mL; p ⫽ 0.04) compared with normal-weight subjects. Discussion: This investigation demonstrates higher levels of NT-proBNP in morbidly obese subjects and a significant decrease during weight loss after laparoscopic adjustable gastric banding. In obesity, NT-proBNP might be useful as a routine screening method for identifying left ventricular hypertrophy and/or left ventricular dysfunction. Key words: morbid obesity, laparoscopic adjustable gastric banding (LAGB), hypertension, left ventricular hypertrophy, aminoterminal pro-brain natriuretic peptide (NT-proBNP)

Introduction In obesity, changes in the heart structure can be partially explained by the increase of total blood volume leading to volume overload, hypertension, left ventricular hypertrophy (LVH),1 and/or left ventricular dysfunction (LVD) (1). Although patients with LVH have improved survival rates when medicated in the early stages of the disease, diagnosis may be difficult. Obese patients present as asymptomatic or with different stages of dyspnea, and echocardiography is not being performed routinely. Aminoterminal pro-brain natriuretic peptide (NTproBNP), secreted from the left cardiac ventricle as a response to pressure overload and ventricular damage, correlates with echocardiographic results (2). Therefore, the introduction of a serum assay that provides accurate information on the cardiac status of a patient may be useful. In morbid obesity (BMI ⱖ 40 kg/m2 or ⱖ35 kg/m2 with comorbidities), weight-loss programs fail to achieve good long-term results (3). Because of the superiority of bariatric

1 Nonstandard abbreviations: LVH, left ventricular hypertrophy; LVD, left ventricular dysfunction; NT-proBNP, aminoterminal pro-brain natriuretic peptide; LAGB, laparoscopic adjustable gastric banding; BNP, brain natriuretic peptide; ANP, atrial natriuretic peptide.

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NT-proBNP Levels before and after Gastric Banding, Hanusch-Enserer et al.

surgery, including laparoscopic adjustable gastric banding (LAGB), for the reduction of comorbidities (4), we evaluated the effect of weight loss on NT-proBNP levels.

Research Methods and Procedures Patients Thirty-four patients were enrolled (5 men, 29 women; mean age, 40.65 ⫾ 9.86 years) when they were referred to our Outpatient Obesity Department for surgery (LAGB group). All patients fulfilled the criteria for surgical treatment according to the American Bariatric Surgery Association (5) and underwent LAGB (Lap-Band, BioEnterics, Carpinteria, CA). A healthy, nonobese (mean BMI 21.50 ⫾ 3.20 kg/m2), age- and sex-matched group of 34 participants was recruited from our hospital staff. All enrolled subjects were examined at the beginning of the study and the LAGB group again after a follow-up period of 12.13 ⫾ 4.7 months. Controls had been weight stable (⫾ 3 kg) for at least 3 months before the beginning of the study. During all visits, in addition to medical history, physical examination, electrocardiography, and routine blood checks were performed and dietary advice was given. The Institutional Review Board approved the study. Written informed consent was obtained from each participant. Methods Body weight was measured to the next 0.1 kg with light outdoor clothing and without shoes, height was rounded to the nearest 0.01 m, and BMI was calculated as the weight divided by the height in meters squared. Waist circumference, measured only in the obese subjects, was determined at the level of the umbilicus, and blood pressure was measured twice on the right arm using an appropriate size cuff and after a 5-minute rest during each visit. The mean of the two measurements was used to determine blood pressure. Among the normal-weight, healthy subjects, only those without a medical history of hypertension and with a systolic blood pressure of ⱕ130 mm Hg and a diastolic blood pressure of ⱕ85 mm Hg were included in the study. Secondary causes of hypertension were excluded through a comprehensive checkup. A 12-lead electrocardiogram was performed (by two staff members). No participant had clinical signs of acute or chronic heart disease or LVH in the electrocardiogram. NT-proBNP Levels Blood samples were gathered after a 12-hour fast and a 10-minute rest in a lying position. From ethylenediaminetetraacetic acid-plasma samples, NT-proBNP was determined by an enzyme-linked immunosorbent assay (Biomedica, Vienna, Austria), with inter- and intra-assay coefficients of variation being ⬍5%, respectively. 696


Statistical Analysis Data are presented as means ⫾ SD. Statistical analyses were performed with Origin 5.0 for Windows (MicroCal, Northampton, MA). Statistical comparison between groups was performed with paired Student’s t test. Statistical significance was considered as p ⬍ 0.05.

Results The cumulative weight loss in the LAGB group was 18.37 kg for the mean study period of 12 months. Subjects with LAGB weighed 127.3 ⫾ 18.41 kg before (range: 98.0 to 181.2 kg) and 107.75 ⫾ 17.45 kg (range: 65 to 143.5 kg) after surgery (p ⬍ 0.00001 for both), which resulted in a reduction of BMI from 43.22 ⫾ 3.42 kg/m2 (range: 38.8 to 61.3 kg/m2) to 37.08 ⫾ 5.86 kg/m2 (range: 25.22 to 49.65 kg/m2; p ⬍ 0.00001) and a percentage of excess weight loss of 31.81 ⫾ 18.51% (range: 6.25% to 98.89%). Changes in anthropometric and biochemical parameters are presented in Table 1. Systolic and diastolic blood pressure were lowered significantly by 17.64 ⫾ 3.74 mm Hg and 13.09 ⫾ 2.85 mm Hg, respectively, after LAGB (p ⫽ 0.00001 for both), but was still significantly higher after surgery when compared with controls (p ⬍ 0.00001 for both). Plasma NT-proBNP concentration was significantly higher before LAGB than in normal-weight subjects (341.15 ⫾ 127.78 fmol/mL vs. 161.68 ⫾ 75.78 fmol/mL; p ⬍ 0.00001). At 12 months post-LAGB, NT-proBNP concentration decreased significantly from 341.15 ⫾ 127.78 fmol/mL to 204.88 ⫾ 59.84 fmol/mL (p ⬍ 0.00001). The change in NT-proBNP concentration reached statistical significance comparing “poor” (percentage of excess weight loss ⬍25%) and “good” (p ⫽ 0.04) responders. Compared with normal-weight subjects, NT-proBNP levels still remained significantly elevated (204.88 ⫾ 59.84 fmol/mL vs. 161.68 ⫾ 75.78 fmol/mL; p ⫽ 0.04) in the LAGB group (Figure 1).

Discussion This study demonstrated elevated levels of NT-proBNP in morbidly obese patients and its decrease as an effect of significant weight reduction after LAGB. Recently, brain natriuretic peptide (BNP) and NT-proBNP have received major attention as cardiovascular markers because these peptides are secreted in cases of volume overload and increased ventricular wall tension (2,6,7). In addition to BNP, the co-secreted neurohormone NT-proBNP was identified as a discerning marker of LVH and/or early LVD. Because obesity and hypertension are accompanied by LVH and LVD, this novel parameter could serve as a screening method to enable early diagnosis, which might improve morbidity and mortality (8).


Table 1. Clinical characteristics and changes in body weight, BMI, blood pressure, and metabolic parameters in morbidly obese patients before and after LAGB in comparison with normal-weight control subjects Variables

LAGB group before surgery

LAGB group after surgery

n Sex (female/male) Age (years) Weight (kg) BMI (kg/m2) Waist (cm) NT-pro BNP (fmol/mL) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Total cholesterol (mg/dL) High-density lipoproteins (mg/dL) Low-density lipoproteins (mg/dL) Triglycerides (mg/dL) Fasting blood glucose (mg/dL) Hemoglobin A1c (%) Uric acid (mg/dL)

34 29/5 40.65 ⫾ 9.86 127.3 ⫾ 18.41 43.22 ⫾ 3.42 129.00 ⫾ 8.72 341.15 ⫾ 127.78 149.38 ⫾ 19.23 92.12 ⫾ 12.71 214.31 ⫾ 23.49 51.69 ⫾ 8.89 131.87 ⫾ 22.16 162.69 ⫾ 40.76 97.5 ⫾ 49.16 5.61 ⫾ 0.96 5.4 ⫾ 1.21

107.75 ⫾ 17.45* 37.08 ⫾ 5.86* 116.50 ⫾ 11.87† 204.88 ⫾ 59.84* 131.74 ⫾ 15.49* 79.03 ⫾ 9.6* 205.88 ⫾ 38.84 53.19 ⫾ 7.62 123.38 ⫾ 33.48 121.00 ⫾ 51.90§ 93.81 ⫾ 25.53§ 5.56 ⫾ 0.47 5.20 ⫾ 0.84

Controls 34 30/4 38.34 ⫾ 5.90 58.45 ⫾ 8.49* 21.5 ⫾ 3.20* 161.68 ⫾ 75.78* 119.71 ⫾ 8.70* 71.76 ⫾ 6.84* 184.76 ⫾ 38.00‡ 63.70 ⫾ 23.21* 101.42 ⫾ 33.24* 71.61 ⫾ 26.43* 83.15 ⫾ 17.15¶ 5.32 ⫾ 0.86

Values are presented as means ⫾ SD. * p ⬍ 0.00001 versus LAGB group before surgery. † p ⫽ 0.0009 versus LAGB group before surgery. ‡ p ⫽ 0.002 versus LAGB group before surgery. § p ⫽ 0.03 versus LAGB group before surgery. ¶ p ⫽ 0.01 versus LAGB group before surgery.

Results of the effect of significant weight loss on LVH in morbid obesity are limited. Preliminary results of the Swedish Obese Subject Study have confirmed the beneficial effect of bariatric surgery on obesity-associated comorbidities (4). Karason et al. (9) showed a surgically induced regression of LVH, and the magnitude of weight loss itself was confirmed to be a better predictor for changes of LVH (10). To date, only a few studies have investigated the response of natriuretic peptides to weight reduction. Atrial natriuretic peptide (ANP) concentration decreased dramatically after a 12-week diet (11), and Messaoudi et al. (12) found a reduction of ANP but not BNP after an 8-day diet and suggested that BNP, unlike ANP, is not responsive to an acute volume change. Furthermore, Minami et al. (13) proved a significant decrease of plasma BNP and ANP levels in obese subjects on a 3-week hypocaloric diet. Although a limitation of this study was the short study period and a moderate BMI (mean BMI ⫽ 29 kg/m2), the findings of Minami et al. demonstrated that the reduction in BNP concentration is largely reflected by the decrease in total blood volume after weight loss.

Because our morbidly obese subjects were still moderately overweight at the end of the study, NT-proBNP levels remained significantly higher compared with lean subjects. The surgically induced weight loss resulted in a noteworthy decrease of systolic (9.2%) and diastolic (10.1%) blood pressure and a reduction to almost normal range. The extent of weight loss might contribute to the reduction of NTproBNP because changes in NT-proBNP levels were significantly lower in the group of “poor responders” than in the group with greater weight loss. A limitation of the current study is the lack of echocardiography. Nevertheless many studies have confirmed NT-proBNP as a sensitive marker for LVH and/or asymptomatic LVD (2,6,7); therefore, our results support the hope for an easy and reliable method for predicting the presence or absence of cardiac dysfunction in morbidly obese patients. Recently, the value of 100 pg/mL for BNP was taken as the upper limit of the normal range for healthy individuals (14). A reference range is still undetermined for NT-proBNP and should be the aim of further investigations. OBESITY RESEARCH Vol. 11 No. 6 0724 2003

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Figure 1: NT-proBNP levels in 34 morbidly obese patients before and after LAGB (p ⬍ 0.0001). NT-proBNP levels still remained higher compared with normal-weight controls (p ⫽ 0.04).

Nevertheless, taking the highest value of NT-proBNP as a threshold (256 fmol/mL) in our control subjects, we discovered that, in the LAGB group, 27 of 34 patients (79.41%) before LAGB and 8 patients (23.52%) after LAGB had higher levels than this threshold value. Furthermore, 12 of 34 (35.29%) patients showed levels ⬎400 fmol/L before LAGB, and only 1 patient (2.94%) showed such a level after LAGB. Because the negative predictive value of NT-proBNP for LVH is very high, elevated NTproBNP levels might suggest the need for further cardiological examination and medical therapy with angiotensinconverting enzyme inhibitors, ␤-blockers, and diuretics as first-line treatments in the management of hypertension in obese patients (15). In summary, NT-proBNP concentrations in morbidly obese subjects are significantly increased before LAGB, with a significant decrease in NT-proBNP occurring after LAGB. NT-proBNP might be a useful routine screening method for identifying LVH and/or LVD, but further studies will be necessary for evaluating the clinical relevance of this marker.

Acknowledgments There was no outside funding/support for this study. We thank Martha M. Eibl, MD, for her assistance in preparing this manuscript. References 1. Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry. JAMA. 1991;266:231– 6.

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