Estimating the causal effect of BMI on mortality risk in people with heart disease, diabetes and cancer using Mendelian randomization. (1st May 2021)

• Record Type: Journal Article
• Authors: Jenkins, David A.; Wade, Kaitlin H.; Carslake, David; Bowden, Jack; Sattar, Naveed; Loos, Ruth J.F.; Timpson, Nicholas J.; Sperrin, Matthew; Rutter, Martin K.
• Is Part Of: International journal of cardiology. Volume 330(2021)
• Page Start: 214
• Page End: 220
• Publication Date: 2021-05-01
• Subjects: Obesity -- Mortality -- Coronary heart disease; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2021.02.027
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: Observational data have reported that being overweight or obese, compared to being normal weight, is associated with a lower risk for death - the " obesity paradox ". We used Mendelian randomization (MR) to estimate causal effects of body mass index (BMI) on mortality risks in people with coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) or malignancy in whom this paradox has been often reported. Methods: We studied 457, 746 White British UK Biobank participants including three subgroups with T2DM ( n = 19, 737), CHD ( n = 21, 925) or cancer ( n = 42, 612) at baseline and used multivariable-adjusted Cox models and MR approaches to describe relationships between BMI and mortality risk. Results: Observational Cox models showed J-shaped relationships between BMI and mortality risk including within disease subgroups in which the BMI values associated with minimum mortality risk were within overweight/obese ranges (26.5–32.5 kg/m 2 ). In all participants, MR analyses showed a positive linear causal effect of BMI on mortality risk (HR for mortality per unit higher BMI: 1.05; 95% CI: 1.03–1.08), also evident in people with CHD (HR: 1.08; 95% CI: 1.01–1.14). Point estimates for hazard ratios across all BMI values in participants with T2DM and cancer were consistent with overall positive linear effects but confidence intervals included the null. Conclusion: These data support the idea that population efforts to promote intentional weight loss towards the normal BMI range would reduce, not enhance, mortality risk in the general population including, importantly, individuals with CHD. Highlights: Observational studies sometimes report a lower risk of death for overweight or obese BMIs than normal range BMIs We used Mendelian randomization to estimate the causal effect of body mass index on mortality risk in disease subgroups. Mendelian randomization analyses showed a positive linear causal effect of BMI on mortality risk. The results indicate that preventing overweight and obesity at a population level would have major public health benefits.