Post-Transplantation Body Mass Index in Heart Transplant Recipients: Determinants and Consequences

Post-Transplantation Body Mass Index in Heart Transplant Recipients: Determinants and Consequences

Post-Transplantation Body Mass Index in Heart Transplant Recipients: Determinants and Consequences I. Milaniaka,b,*, P. Przybyłowskia,c, K. Wierzbicki...

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Post-Transplantation Body Mass Index in Heart Transplant Recipients: Determinants and Consequences I. Milaniaka,b,*, P. Przybyłowskia,c, K. Wierzbickia,c, and J. Sadowskia,c a Cardiovascular Surgery and Transplantology Department, John Paul II Hospital; bAndrzej Frycz Modrzewski Krakow University, Faculty of Health and Medical Science; and cCollegium Medicum UJ, Krakow, Poland

ABSTRACT Background. Heart transplantation (HTx) is an important treatment for end-stage chronic heart failure. After HTx, recipients frequently become obese. Gaining weight measured by body mass index (BMI) has been reported as a common phenomenon for patients before and after solid organ transplantation, becoming specifically significant for the long-term follow up after organ transplantation. In the long term following HTx, overweight and obesity may lead to increased risk of cardiovascular complications, developing metabolic syndromeea topic well documented in previous studies. Aim. The aims of this study were to calculate the BMI in patients after HTx with follow up in our center and to assess potential predictors for overweight and obesity as well as their consequences. Methods. A complete assessment of the BMI among all available heart transplant (HT) recipients (n ¼ 169) was performed. Data were retrieved from patients’ charts. Data were statistically analyzed. Results. The sample mean age was 55.12  13.34 years, mean years since transplantation being 10.70  5.26 years and the majority of study subjects were males (76.33%). Overall BMI was mean 26.33  3.79. Based on the World Health Organization (WHO) classification, 32.54% were normal, 46.74% were overweight, and 18.34% were obese. We did not observe a statistical difference between BMI before and after transplantation, between immunosuppressive protocol, and receipt of steroids. We observed an association between BMI and level of fasting glucose (r ¼ 0.35; P < .05) and difference between BMI and gender as well as the presence of cardiovascular diseases. Conclusions. Overweight and obesity after HTx are common and reflect a risk factor for cardiac allograft vasculopathy and other cardiovascular diseases as well as metabolic syndrome among HT recipients.

A

2012 report from the National Center for Health Statistics indicated that 35.7% of adults (about 78 million people) are obese, defined as a body mass index (BMI) of 30 [1]. According to guidelines from the International Society for Heart and Lung Transplantation, pretransplantation BMI >30 kg/m2 is associated with poor outcome after cardiac transplantation. For obese patients, it is reasonable to recommend weight loss to achieve a BMI of <30 kg/m2 before listing for cardiac transplantation (Level of Evidence: C) [2].

Clark et al found no significant relationship between BMI and survival, but they reported that patients with very low or high “percentage ideal body weight” had a worse outcome [3].

*Address correspondence to Irena Milaniak, PhD, MSN, CETC, MA, John Paul II Hospital, Cardiovascular Surgery and Transplantology Department, Pradnicka str 80, 31-202 Krakow, Poland. E-mail: [email protected]

0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.09.025

ª 2014 Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

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Transplantation Proceedings, 46, 2844e2847 (2014)

BMI IN HT RECIPIENTS

Despite many advances in surgical techniques, diagnostic approaches and immunosuppressive strategies, survival after heart transplantation (HTx) is limited by the development of cardiac allograft vasculopathy (CAV), which is the most important cause of death late after transplantation and by the adverse effects of immunosuppression [4,5]. Primary prevention of CAV in heart transplant (HT) recipients should include strict control of cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking, and obesity), as well as strategies for the prevention of cytomegalovirus (CMV) infection [6]. BMI at the time of transplantation is an important predictor of posttransplantation outcomes, including survival, perioperative morbidity, post-transplantation cardiovascular comorbidities, and long-term complications of transplantation [7]. After HTx patients frequently gain weight, often to obesity. This weight gain is certainly caused partly by an increase in appetite due to the use of prednisone in many immunosuppressive regimens. Excessive weight gain resulting in obesity is commonly seen after orthotopic HTx. Obesity increases the risk for the development of many significant health problems and the associated morbidity and mortality. The purposes of this study were to calculate the BMI in patients after HTx with follow up for overweight and obesity occurrence in our center and to assess the potential predictors for overweight and obesity as well as their consequences. METHODS Selection and Description of Participants The study group consisted of all available HT recipients (n ¼ 169). Medical data were retrieved retrospectively from patients’ charts. Demographical data included: age, gender, education, place of living. Clinical evaluation included a complete assessment of the BMI. BMI is the most widely used parameter for characterization of abnormalities of body weight. The recommended classification for BMI adopted by the Expert Panel on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults, and endorsed by the National Institutes of Health and the World Health Organization (WHO) is as follows: BMI <18.5 (underweight), 18.5e24.99 (normal weight), 25e29.99 (overweight), 30e34.99 (obesity class I), 35e39.99 (obesity class II), and 40 (obesity class III) [8]. Calculation of BMI ¼ weight [kg]/height [m2]. Clinical evaluation also included: time since transplantation; comorbidities; hypertension; CAV; diabetes, as well as level of fasting glucose and glycosylated hemoglobin; New York Heart Association (NYHA) class; ejection fraction; and level of total cholesterol.

Statistical Techniques Data was analyzed using Statistica PL software version V. 9. We examined descriptive statistics by mean values, standard deviation, and percentages. Comparisons between group (gender, BMI, years after transplantation, comorbidities, level of fasting glucose, and glycosylated hemoglobin) were performed using Mann Whitney U, Student, analysis of variance (ANOVA), and Kruskal-Wallis tests. To analyze the association between BMI and variable, the Pearson or Spearman correlation was performed. Multiple regression was

2845 used to test associations with BMI of fasting glucose, gender, and cardiovascular disease. Logistic regression analyses were used to assess odds ratio (OR) for BMI. The significance level was P < .05 and P < .01.

RESULTS

The study group consisted of 169 recipients. The majority of the group was male (76.33%). The sample mean age was 55.12  13.34 years. Mean years since transplantation was 10.70  5.26 years (Table 1). Comorbidity is a determinant factor of mortality as well as disability. It also influences several outcomes, such as functional status and quality of life. The analysis of recipient medical documentation has shown that the main post-transplantation complication was hypertension rather than kidney failure. Sixteen (9.47%) subjects had no somatic comorbidity, 116 (68.64%) had 1 or 2 comorbidities, and 36 (21.30%) had 3 or more comorbidities. The frequency of complications is shown in Table 2. The results of clinical evaluation have shown that most recipients were in the I and II NYHA scale (97.04%) with a good ejection fraction (56.94%). Laboratory tests have shown an increased level of fasting glucose (mean 6.08 mmol/L and glycosylated hemoglobin 6.18; Table 2). The majority of recipients received immunosuppressive therapy that consisted of tacrolimus and MMF (40.82%). Steroids were needed by 64 recipients and the average dose was 4.75 mg/d (standard deviation [SD], 1.08). The mean BMI for the whole group was 26.60 þ/ 3.94. The BMI of recipients at time of transplantation was 24.37 þ/ 3.43. There was no statistical difference between BMI before and after Htx. Post-transplantation BMI was normally distributed for both men (mean, 26.69; median, Table 1. Background Characteristics of the Sample of HT Recipients Characteristic

Age Gender (%) Male Female Years since transplantation Employment status (unemployed) (%) Employed (part time) Place of living (%) Town Village Family status (%) Single Married or living with partner Widow/widower or divorced Educational degree (%) Less than college College/university

Study sample (n ¼ 169)

Average, 55.45; SD, 13.83; median, 59; max, 83; min, 18 132 (78.10) 37 (21.89) Average, 10.76; median, 12; max, 20; min, 3 mo 168 (99.40) 26 (15.38) 106 (62.73) 63 (37.27) 22 (13.02) 126 (74.55) 21 (12.43) 34 (20.12) 134 (79.88)

Abbreviations: SD, standard deviation; max, maximum; min, minimum.

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MILANIAK, PRZYBYŁOWSKI, WIERZBICKI ET AL Table 2. Medical Evaluation Variable

NYHA scale n (%) I II III IV Ejection fraction Fasting glucose (mmol/L); norm, 3.40e5.60 Cholesterol (mmol/L); norm, 3.10e5.0 Glycosylated hemoglobin (HbA1c); norm, 4.8e5.9 Comorbidity Hypertension CAV Kidney failure Diabetes Cancer

N (%)

116 (68.64) 48 (28.40) 5 (2.96) 0 56.94; SD, 9.31 6.08; SD, 1.83 4.75; SD, 1.08 6.18; SD, 0.84 Frequency 135 18 60 28 16

(%) (79.88) (10.65) (35.50) (16.57) (9.46)

Abbreviation: CAV, cardiac allograft vasculopathy.

26.53; SD, 3.94) and women (mean, 25.01; median, 26; SD, 3.72). In this study 32.54% of the group had normal BMI and 65.08% of the group was overweight or obese (Fig 1). There was a statistical difference between BMI and gender (P ¼ .026). We did not observe a significant difference between immunosuppressive protocol, and receipt of steroids. We detected a significant association between BMI and level of fasting glucose (r ¼ 0.35; P < .05) and total cholesterol (r ¼ 0.27; P < .05). Obese patients in comparison with nonobese patients were characterized by a significantly higher level of fasting glucose (6.41 vs 5.57 mmol/L; P < .01) as well as the presence of cardiovascular diseases (P ¼ .0060). In multivariate analysis with forced entry BMI, fasting glucose, gender, and cardiovascular disease, a statistical interaction was found (R ¼ 0.378; R2 ¼ 0.143; adjusted R2 ¼ 0.097; F ¼ 3; 107; P ¼ .004). In a logistic regression, BMI predicted only cardiovascular disease (OR ¼ 2.18; 95% confidence interval [CI], 1.022e4.5 ¼ 657; P ¼ .044) and higher level of fasting glucose (OR ¼ 1.758; 95% CI, 0.866e3.341; P ¼ .040). The BMI was nonsignificant for

level of cholesterol (OR ¼ 1.786; 95% CI, .891e3.580; P ¼ .099). Neither gender nor years after HTx and age of recipients appeared as significant predictors of CAV on multivariate logistic regression (P > .05).

DISCUSSION

The results of our study indicate that the group of overweight and obese recipients prevails in our study population. In the previous study we found that patients who have undergone cardiac transplantation frequently put on weight [9,10]. Post-transplantation BMI was related to gender (men), but not to prednisone dose, immunosuppressive protocol, and pretransplantation BMI. Post-transplantation weight gain was significantly greater in male recipients than in females in the previous study [11]. Grady et al have shown that risk factors for increased BMI were as follows: increased BMI at transplantation, younger age, black race, nonischemic etiology of heart disease, status I at time of transplantation, and nonuse of MMF. They also found that patients who were underweight or obese at 1 year posttransplantation were at greater risk for rejection over time than patients who were of normal weight or overweight [12]. Among HT recipients, obesity is associated with increasing cardiovascular disease and diabetes [13]. CAV in the postecardiac transplantation population is partially attributed to the presence of traditional cardiovascular risk factors. In our study we confirmed that obese recipients were characterized by a significantly higher level of fasting glucose as well as presence of cardiovascular diseases. de Oliveira Carlos et al in their study showed that mean values of glucose, total cholesterol, low-density lipoprotein (LDL), and triglycerides were higher than those of normal weight/underweight patients [14]. Cristiano et al in their study found that BMI >25 kg/m2 was observed in more than 80% of the study population, with raised systolic blood pressure (BP) in 42% and diabetes in more than a quarter of subjects [15]. These findings point the way to a hypothesis that interventions specifically designed to prevent weight gain might influence outcome following HTx. Data from our experience show that health professionals should encourage healthy eating and exercise and continue to screen for obesity, hypertension, dyslipidemia, and diabetes.

REFERENCES

Fig 1. BMI (%) before and after HTx (P > .05).

[1] Ogden CL, Carroll MD, Kit BK. Prevalence of obesity in the United States, 2009-2010. NCHS Data Brief, No 82 2012. National Center for Health Statistics. [2] Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidatesd2006. J Heart Lung Transplant 2006;25(9):1024e41. [3] Clark AL, et al. Heart transplantation in heart failure: The prognostic importance of body mass index at time of surgery and subsequent weight changes. Eur J Heart Fail 2007;9:839e44.

BMI IN HT RECIPIENTS [4] Lund LH, Edwards LB, Kucheryavaya AY. The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Reportd2013; Focus Theme: Age. The Journal of Heart and Lung Transplantation 2013;32(10):951e64. [5] Pethig K, Klauss V, Heublein B. Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors. Heart 2000;84(5):494e8. [6] Costanzo MR, Dipchand A, Starling R. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant 2010;29(8): 914e56. [7] Kashem MA, Fitzpatrick JT, Nikolaidis L. BMI effects on heart transplant survival: single institution vs. national experience. J Heart Lung Transplant 2009;28:116. [8] Obesity preventing and managing the global epidemic. Report of WHO Consultation on Obesity. Geneva 3-5 June 1997 WHO/NUT/NCD. Geneva 1998, 276. [9] Grady KL, Costanzo-Nordin MR, Herold LS, et al. Obesity and hyperlipidemia after heart transplantation. J Heart Lung Transplant 1991;10:449e54.

2847 [10] Lake KD, Reutzel TJ, Pritzker MR, et al. The impact of steroid withdrawal on the development of lipid abnormalities and obesity in heart transplant recipients. J Heart Lung Transplant 1993;12:580e90. [11] Wiliams JJ, Lundh LH, Kunavarapu C, et al. Excessive weight gain in cardiac transplant recipients. J Heart Lung Transplant 2006;25(1):36e41. [12] Grady KL, Naftel D, Pamboukian SV, et al. Post-operative obesity and cachexia are risk factors for morbidity and mortality after heart transplant: multi-institutional study of post-operative weight change. J Heart Lung Transplant 2005;24(9):1424e30. [13] Russo MJ, Hong KN, Davies RR, et al. The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines? Ann Surg 2010;251(1):144e52. [14] de Oliveira Carlos DM, Clineu Queiroz França F, de Sousa Neto JD. Impact of weight variation on the metabolic stability of cardiac transplant patients in the state of Ceara. Arq Bras Cardiol 2008;90(4):268e73. [15] Cristiano HY, Lee GA, Bergin JP. Cardiovascular risk factors associated with cardiac allograft vasculopathy following cardiac transplantation: a longitudinal follow-up. Transplant J Australasia 2012;21(3):16.