The obesity paradox in heart failure: Is etiology a key factor? Elisabet Zamora ⁎, Josep Lupón, Marta de Antonio, Agustín Urrutia, Ramon Coll, Crisanto Díez, Salvador Altimir, Antoni Bayés-Genís Unitat d' Insuficiència Cardíaca, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain abstract article info Article history: Received 30 June 2011 Received in revised form 4 November 2011 Accepted 24 November 2011 Available online 26 December 2011 Keywords: Heart failure Body mass index Etiology Mortality Ischemic heart disease Background: Obesity is paradoxically associated with survival in patients with heart failure (HF). Our objec- tive was to assess whether the relationship between body mass index (BMI) and long-term survival is asso- ciated with HF etiology (ischemic vs. non-ischemic) in a cohort of ambulatory HF patients. Methods: BMI and survival status after a median follow-up of 6.1 years (IQR 2.2–7.8) were available for 504 patients (73% men; median age 68 years [IQR 58–74]). Fifty-nine percent of patients had ischemic etiology. Median left ventricular ejection fraction (LVEF) was 30% (IQR 23–39.7%). Most patients were in NYHA func- tional class II (51%) or III (42%). Patients were divided into four groups according to BMI: low weight (BMI b 20.5 kg/m 2 ), normal weight (BMI 20.5 to b 25.5 kg/m 2 ), overweight (BMI 25.5 to b 30 kg/m 2 ), and obese (BMI ≥ 30 kg/m 2 ). Results: Mortality differed significantly across the BMI strata in non-ischemic patients (log-rank p b 0.0001) but not in ischemic patients. Using normal weight patients as a reference, hazard ratios for low weight, over- weight, and obese patients were 2.08 (1.16–3.75, p = 0.014), 0.88 (0.54–1.43, p = 0.60), and 0.49 (0.28–0.86, p = 0.01), respectively, for non-ischemic patients and 1.19 (0.48–2.97, p = 0.71), 0.88 (0.61–1.27, p = 0.48), and 0.96 (0.66–1.41, p = 0.85), respectively, for ischemic patients. After adjusting for age, sex, NYHA func- tional class, LVEF, co-morbidities, and treatment, BMI remained an independent predictor of survival in non-ischemic patients. Conclusion: Over long-term follow-up of ischemic and non-ischemic HF, the obesity paradox was only ob- served in patients with non-ischemic HF. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Obesity is considered an independent risk factor for heart failure (HF) [1,2] and is not only associated with coronary heart disease, but also with conditions such as arterial hypertension, insulin resis- tance, and metabolic syndrome, and different pathophysiological mechanisms have been suggested [3–7]. Obesity also leads to a poor prognosis in patients with heart disease [8]. However, a paradoxical relationship has been observed over the past few years between obe- sity and short and long-term survival in HF patients [9–11]. The role of HF etiology in this relationship has not been analyzed, but HF etiol- ogy has already shown an interaction with the prognostic value of other HF risk factors, such as atrial fibrillation [12] and left atrial di- ameter [13]. Our objective was to analyze the long-term relationship be- tween body mass index (BMI) and mortality and whether it is associated with ischemic or non-ischemic disease in ambulatory pa- tients with HF. 2. Materials and methods 2.1. Study population A total of 508 patients were consecutively admitted to an ambulatory multidisci- plinary HF unit between August 2001 and December 2004. We prospectively analyzed 504 of these patients, for whom BMI was recorded on the first visit and whose survival status was known at the end of follow-up on September 30, 2010. The criterion for ad- mission to the unit was diagnosis of HF according to the European Society of Cardiolo- gy guidelines. We also admitted patients with severely depressed ventricular function following acute myocardial infarction; 71% were referred from a Cardiology depart- ment, 16% from an Internal Medicine department, 6% from an Emergency Department or Short Stay Unit, and 7% from other clinical specialties (e.g., Oncology, Nephrology, Respiratory). Fifty-four percent of patients had at least one hospital admission due to HF in the previous year. Demographic, clinical, and echocardiographic data were recorded. BMI was ana- lyzed according to weight and height using the formula: weight in kilograms/ (height in meters) 2 . We then evaluated the relationship between BMI and survival throughout follow-up. Patients were classified according to BMI in four subgroups following the criteria defined by the World Health Organization (WHO Technical Re- port Series, no. 854, Geneva, 1999): low weight (BMI b 20.5 kg/m 2 ), normal weight (BMI 20.5 to b 25.5 kg/m 2 ), overweight (BMI 25.5 to b 30 kg/m 2 ), and obese (BMI ≥30 kg/m 2 ). Patients were considered to have HF of ischemic etiology when International Journal of Cardiology 166 (2013) 601–605 ⁎ Corresponding author at: Unitat d'Insuficiencia Cardíaca, Hospital Universitari Ger- mans Trias i Pujol, Carretera de Canyet s/n, 08916 Badalona, Spain. Tel.: + 34 93 497 89 96; fax: +34 93 487 87 72. E-mail address: e.zamora@telefonica.net (E. Zamora). 0167-5273/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2011.11.022 Contents lists available at SciVerse ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard