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Abstract

Introduction: Obesity is associated with increased morbidity and mortality in patients with acute sepsis. However, it is unknown if obesity at a stable phase of health is associated with risk of future sepsis events. Hypothesis: Obese individuals are at increased risk for future sepsis events. Methods: We conducted a population-based longitudinal cohort study using the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Using body measurements at the start of the study, we defined obesity using body mass index (BMI; <25.0=underweight, 25.0-29.9=normal, 30.0-39.9=obese,?40=morbidly obese) and waist circumference (WC; [male?102 cm or female?88 cm]= normal, [male>102 cm or female>88 cm]=obese). We identified incident sepsis events over an 8-year observation period, defining sepsis as hospitalization for a serious infection with the presence of?2 systemic inflammatory response syndrome criteria. Using Cox regression, we evaluated the association between obesity and the risk of subsequent sepsis events, adjusting for sociodemographic factors (age, sex, race, region, education, income), health behaviors (tobacco and alcohol use, exercise), chronic medical conditions (hypertension, diabetes, dyslipidemia, coronary artery disease, chronic kidney disease, chronic lung disease), statin use and high-sensitivity C-reactive protein. Results: Of the 30,329 subjects, mean BMI was 29.3 ± 6.2 kg/m2 and mean WC was 96.2 ± 15.7 cm. Over one-third (38.4%) were obese by BMI and almost one-half (48.8) were obese by WC. Over a mean observation period of 4.6 ± 1.6 years, there were 820 incident sepsis events. Risk of sepsis was associated with increased BMI (BMI<25.0, referent; BMI 25.0-29.9, adjusted HR 0.91 (95% CI 0.75-1.12); BMI 30.0-39.9, HR 1.08 (0.88-1.34); BMI?40, HR 1.46 (1.06-2.02)). Risk of sepsis was associated with increased WC (adjusted HR 1.34 (1.14-1.57)). In a model with both BMI and WC, sepsis risk was associated with increased WC (HR 1.47 (1.19-1.81)) but not BMI. Conclusions: Obesity at a stable phase of health is independently associated with future sepsis events. WC is a better predictor of future sepsis risk than BMI.