The ARIC study was a community-based prospective cohort study designed to investigate the causes of atherosclerosis. The study recruited 15,792 adults aged 45 years to 64 years at baseline who resided in four US communities. The first examinations of participants (visit 1) took place during 1987 to 1989, followed by three visits at 3-year intervals. The follow-up rates for the first, second, and third intervals were 91%, 82%, and 74%, respectively. At each visit, participants responded to an interviewer-administered questionnaire and underwent an extensive physical examination [21]. The current study was restricted to patients with incident HF through December 31, 2009. Among 2,169 patients with incident HF, 1,861 cases were excluded because HF developed after the fourth examination, meaning that no data were available after the development of disease. Therefore, the present study included 308 patients with data available both before and after the incidence of HF. The study sample had a 0% prevalence of HF at baseline. This study was approved by the institutional review board of the Shahid Beheshti University of Medical Sciences.

Incident HF was defined as death or hospitalization with an International Classification of Diseases, 9th revision (ICD-9) code for HF (i.e., any variation of 410) given the absence of prevalent HF at visit 1. HF cases were determined through annual telephone interviews regarding their experiences of hospitalization, reviewing hospital discharge lists, and a survey of the national death index and death certificate files. The latter two methods were performed through community-wide surveillance of the communities involved in the ARIC study. The response rate for telephone interviews was 93% to 96%. Mortality outcomes were evaluated in the same way.

For this study, demographic variables including sex, race (black or white), and education level (basic or no formal education, intermediate, and advanced education) were determined at visit 1. The data before and after the development of HF were considered to define pre-morbid and post-morbid variables. Premorbid variables were based the measurement of covariates ≥3 months before incident HF and post-morbid variables were defined as measurements of covariates ≥3 months after incident HF. On this basis, pre-morbid and post-morbid values for comorbidities including a history of cancer, coronary heart disease, stroke and chronic lung disease, as well as covariates including smoking and drinking status, diabetes mellitus, hypertension, and total serum cholesterol were obtained. Similarly, pre-morbid and post-morbid obesity were defined using BMI measurements from study visits occurring ≥3 months prior and ≥3 months after the date of incident HF, respectively. Due to the small sample of available patients, we categorized BMI into non-obese (BMI <30 kg/m²) and obese (BMI ≥30 kg/m²). Weight change was defined as percentage change in BMI and calculated as the change in BMI value divided by the original (pre-HF) values of BMI multiplied by 100. Weight change was then categorized based on a priori cutpoint [10]. A weight change of ≤-6% was classified as weight loss, a change of -6% to 6% was classified as stable weight, and a change of ≥6% was classified as weight gain. Smoking status was defined as positive if the subjects ever smoked or smoked cigarettes at the time of the study. Drinking status was considered as positive if subjects regularly drank at the time of the study or had ever consumed alcoholic beverages. Hypertension was defined as a systolic blood pressure ≥90 mmHg, a diastolic blood pressure ≥140 mmHg, or the use of medication for high blood pressure in the previous two weeks. Diabetes mellitus was defined as a non-fasting blood glucose ≥200 mg/dL, a fasting blood glucose level ≥126 mg/dL, or the use of diabetes medication in the previous two weeks. Fasting blood glucose and total serum cholesterol were measured after overnight fasting. Cholesterol level was categorized using the common cutpoint of ≥240 mg/dL.

Baseline data were described as mean (standard deviation, SD) or frequency (percentage) and compared using the t-test or the chi-square test. The pre-morbid and post-morbid measurements of risk factors were compared using the paired t-test or the McNemar test. Correlations between pre-morbid and post-morbid covariates were evaluated using the Spearman test. In the multivariate adjusted model, pre-morbid covariates were dropped if they were highly correlated with post-morbid covariate values (r≥0.80). The endpoint of interest was time to all-cause mortality after incident HF. A Cox proportional hazard model with age as the underlying time scale was used to examine the effect of pre-morbid and post-morbid obesity and other covariates on survival. The proportionality assumption was assessed using a graphical approach and testing the slope of Schoenfeld residuals. The Cox model used the date of birth as the origin of the time scale. In order to calculate weight change as a confounder, we used each participant’s weight before the potential onset of disease as their original weight. Weight change naturally occurs before post-morbid obesity, so it was not an intermediate variable between the exposure of interest and outcome. All statistical analyses were performed using Stata version 13.0 (StataCorp, College Station, TX, USA).