Lack of evidence for obesity paradox in patients with cardiovascular diseases: A UK BioBank cohort study
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Background
Obesity paradox, a phenomenon that obesity seems to be associated with reduced risk of mortality in patients with established cardiovascular disease (CVD), has been controversial. We aimed to use Mendelian randomization to examine the causal relationship between obesity measures and CVD mortality in patients with known CVD in the UK BioBank study cohort.
Methods
A total of 58,278 participants with CVD were included. Polygenic risk scores (PRSs) for body mass index (BMI), body fat percentage (BF%), and waist to hip ration adjusted for BMI (WHRadjBMI) were used as instrumental variables. The following sensitivity analyses were performed: 1) using a representative variant rs1558902 in the fat mass and obesity associated gene as an instrumental variable, 2) by sex, and 3) by disease type.
Results
A total of 2203 patients died of CVD causes during a median follow-up period of 8.9 years. BMI in the overweight and class-I obesity range was associated with reduced mortality, with class-II or more severe obesity associated with increased mortality; however, there was a linear trend toward increased mortality with increasing BF% and WHRadjBMI. There was no clear indication that increased obesity-PRSs were associated with reduced risk of CVD mortality among individuals with known CVD. Sensitivity analyses using rs1558902 as an instrumental variable, by sex, and by disease type showed similar results.
Conclusion
Increased obesity does not show a protective effect in patients with CVD. Previously reported obesity paradox in observational studies may be a result of confounding or other biases, which needs further investigation.
