1. In this prospective study of the original and offspring Framingham cohort, maximum body mass index (BMI) over the course of a 24-year weight history was associated with increased risk of all-cause mortality. Greater levels of obesity were linked with higher-risk of mortality.
2. Individuals who were previously overweight or obese but were normal weight at time of baseline assessment were observed to have a higher mortality rate than those who were never overweight.
Evidence Rating Level: 2 (Good)
Study Rundown: Obesity is a well-established risk factor for cardiovascular and metabolic diseases, however prior meta-analyses have found a paradoxical reduced mortality in people who are overweight. Many of these prior studies have been criticized for being subject to reverse causality bias where weight at the baseline assessment may reflect systemic conditions that affect weight status and mortality. The current study sought to evaluate the impact of maximum BMI evaluated over a prolonged weight history period on all-cause mortality in order to minimize reverse causality bias. Using data from the original and offspring Framingham cohort studies, a 24-year weight history was obtained prior to analysis of mortality. The study found that maximum BMI was linked to increased mortality, with greater obesity conferring a higher risk. The study also found increased mortality amongst those who were normal weight but previously overweight or obese compared to those that were always normal weight.
The main strengths of the study include its long follow-up periods and repeated weight measurements over a prolonged weight history period. The main limitations to this study include the limited numbers of low-weight participants, and homogenous population of Caucasian participants hindering generalizability.
In-Depth [prospective cohort]: This study is a prospective cohort study including the Framingham Heart Study and its offspring cohort. The baseline examination marked the beginning of survival analysis and included 24 years of weight history. Participants who died or were lost to follow-up prior to the baseline examination were excluded, as were those bellow 20-years of age at enrollment, had fewer than 3 weight records, or who were underweight.
A total of 6197 participants were included in the study, with a mean follow-up of 17 years from the baseline examination and 3478 total deaths during the study period. Using the maximum BMI over the weight record period, 77% of participants were classified as overweight or obese. Those who were overweight did not demonstrate increased mortality (BMI of 25 to <30; hazard ratio [HR], 1.08; 95%CI, 0.99-1.18), but those who were BMI of 30 to <35 (HR 1.27; 95%CI, 1.14-1.41) and BMI of 35 to <40 (HR, 1.93; 95%CI, 1.68-2.20) did have an increased mortality. Those who were normal weight at baseline but previously overweight (47.48 per 1000 person-years), or obese (66.67 per 1000 person-years) had higher mortality rates than those that were always normal weight (27.93 per 1000 person-years)
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