Background To investigate the effect of body mass index (BMI) on heart rate variability (HRV) and inflammatory parameters in patients with heart failure. Methods We analyzed 55 consecutive patients (mean age, 63.5 +/- 12.8 years; male/female, 39/16) with symptomatic left ventricular systolic (ejection fraction <45%) heart failure. The participants were classified into three categories according to BMI: lean (BMI < 25 kg/m(2)), overweight (BMI = 25-29.9 kg/m(2)) and obese (BMI:? 30 kg/m(2)). The cause of heart failure was mainly ischemic heart disease (75%) with mean ejection fraction 30 +/- 7%. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein levels were measured, and time-domain HRV indices were determined on Holter electrocardiogram. The relationship between HRV indices and laboratory, inflammatory and echocardiographic parameters was investigated with correlation analysis. Results Age, sex, clinical characteristics (hypertension, diabetes mellitus, dyslipidemia, family history, smoking) were similar between groups. BMI was inversely correlated with NT-pro BNP levels (P = 0.001). HRV indices did not differ between groups. Correlation analysis demonstrated the relationship between HRV indices and fasting blood glucose (SDNN, SDANN, SDNNI, root mean square successive differences, VTI), C-reactive protein (SDANN, SDNNI, VTI), pulmonary artery pressure (SDNN, SDANN, VTI) levels. Conclusion In systolic heart failure patients a higher BMI is associated with decreased NT-proBNP levels. Although HRV indices were not different between groups, inflammatory parameters, fasting blood glucose and pulmonary artery pressure were correlated with them. J Cardiovasc Med 11:118-124 (C) 2010 Italian Federation of Cardiology.