Obesity as a causal risk factor for deep venous thrombosis: a M endelian randomization study

J Klovaite, M Benn… - Journal of internal …, 2015 - Wiley Online Library
J Klovaite, M Benn, BG Nordestgaard
Journal of internal medicine, 2015Wiley Online Library
Objective To test the hypothesis that obesity is causally associated with deep venous
thrombosis (DVT). Design AM endelian randomization design. Setting The C openhagen G
eneral P opulation S tudy and the C openhagen C ity H eart S tudy combined. Subjects Body
mass index (BMI) measurements were available for 87 574 individuals of D anish descent
from the adult general population. All subjects completed questionnaires and were
genotyped for the FTO rs9939609 variant. Main outcome measure First events of DVT with …
Objective
To test the hypothesis that obesity is causally associated with deep venous thrombosis (DVT).
Design
A Mendelian randomization design.
Setting
The Copenhagen General Population Study and the Copenhagen City Heart Study combined.
Subjects
Body mass index (BMI) measurements were available for 87 574 individuals of Danish descent from the adult general population. All subjects completed questionnaires and were genotyped for the FTO rs9939609 variant.
Main outcome measure
First events of DVT with or without pulmonary embolism (PE).
Analysis
The results were assessed using Cox regression, instrumental variable analysis and Poisson regression.
Results
Observationally, the risk of DVT increased with increasing BMI (P‐trend < 0.0001). The multivariable‐adjusted hazard ratio [95% confidence interval (CI)] for DVT was 1.3 (1.1–1.6) in overweight, 1.8 (1.4–2.2) in moderately obese and 3.4 (2.6–4.6) in severely obese compared with normal‐weight individuals. For DVT complicated by PE, corresponding hazard ratios (95% CI) were 1.2 (0.8–1.8), 2.1 (1.3–3.5) and 5.1 (2.8–9.2). FTO AA versus TT genotype was associated with a 2.4% increase in BMI with hazard ratios (95% CI) of 1.09 (0.95–1.25) for DVT and 1.54 (1.12–2.10) for DVT complicated by PE. In instrumental variable analysis, the causal odds ratio (95% CI) for an increase in BMI of 1 kg m−2 was 1.13 (0.92–1.39) for DVT alone and 1.86 (1.14–3.02) for DVT complicated by PE. The absolute 10‐year risk of DVT in a high‐risk group (i.e. those aged >60 years and homozygous for Factor V Leiden) was 35% in obese individuals and 18% in normal‐weight individuals.
Conclusion
A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity‐specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.
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