Abstract
The article aims to describe the association between midlife body mass index (BMI) and cardiovascular disease (CVD)- and all-cause mortality, and to use early adulthood BMI as an instrumental variable for midlife BMI, in order to obtain an estimate less distorted by midlife confounders and reverse causality. Data from Norwegian health surveys (1974–2003) (midlife BMI, smoking, blood pressure, total cholesterol, heart rate), Military Conscription Records, National Tuberculosis Screenings (early adulthood BMI), National Educational Registry and Cause of Death Registry were linked. Participants with data on BMI in early adulthood and midlife were included (n = 148.886). Hazard Ratio (HR) for CVD mortality was higher in men with midlife obesity relative to normal weight (HR = 1.46(95% CI 1.25, 1.70). For all-cause mortality, HR was higher in those with obesity or underweight in midlife relative to normal weight (Men:HR = 1.19(95% CI 1.09, 1.29), HR = 2.49(95% CI 1.81, 3.43) Women:HR = 1.33(95% CI 1.13, 1.56), HR = 1.61(95% CI 1.22, 2.13)). In instrumental variable analyses, increased BMI became more strongly associated with CVD and all-cause mortality, and the increased risk of all-cause mortality among the underweight attenuated.
Highlights
A number of studies have reported a J-shaped or U-shaped association between Body Mass Index (BMI) and mortality from all-causes and several specific causes, including cardiovascular diseases (CVD)[1,2,3,4,5]
This approach could exclude deaths from illness caused by obesity, and attenuate the risk associated with high BMI8
The risk factors were more strongly associated with BMI in midlife than in early adulthood (Table 3)
Summary
A number of studies have reported a J-shaped or U-shaped association between Body Mass Index (BMI) and mortality from all-causes and several specific causes, including cardiovascular diseases (CVD)[1,2,3,4,5]. Most of the evidence on the risk associated with different levels of BMI comes from observational studies where measurements of BMI have been conducted in midlife This may cause biased estimates on the role of BMI because BMI may become increasingly related to a number of confounders through the life course. Illness causing low BMI can last for a longer period than the time excluded This approach could exclude deaths from illness caused by obesity, and attenuate the risk associated with high BMI8. Instrumental variable analysis is an approach that may ideally handle misclassification, confounding and reverse causality, and provide an alternative estimate of the association between BMI and mortality. An instrumental variable is ideally associated with the risk factor of interest, and only through that, to the outcome under study. There is no pathway from the instrumental variable to the outcome, except through the risk factor
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