Author + information
- Received October 3, 2019
- Revision received October 22, 2019
- Accepted October 23, 2019
- Published online January 13, 2020.
- Morten Kaltoft, MDa,b,c,
- Anne Langsted, MD, PhDa,b,c and
- Børge Grønne Nordestgaard, MD, DMSca,b,c,∗ (, )@HerlevGentofte@uni_copenhagen
- aDepartment of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
- bThe Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
- cFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- ↵∗Address for correspondence:
Dr. Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, 2730 Herlev, Denmark.
Background Causal risk factors for aortic valve stenosis are poorly understood, limiting the possibility of preventing the most common heart valve disease.
Objectives The hypothesis was tested that genetically based obesity measured by body mass index is causally associated with risk of aortic valve stenosis and replacement.
Methods The authors included 108,211 individuals from the Copenhagen General Population Study. Participants had measurements of body mass index, waist-hip ratio, and waist circumference, and information on 5 genetic variants associated with obesity. A Mendelian randomization design was used to investigate genetic and observational associations of obesity with incident aortic valve stenosis (n = 1,215) and replacement (n = 467) for a median follow-up time of 8.7 years.
Results Genetically increased body mass index was causally associated with increased risk of aortic valve stenosis. Compared with an unweighted allele score of 0 to 3, individuals with an allele score 7 to 10 had a mean increase in body mass index of 0.87 kg/m2, and the age and sex–adjusted hazard ratio for aortic valve stenosis was 1.3 (95% confidence interval [CI]: 1.0 to 1.7) for allele score 4, 1.4 (95% CI: 1.1 to 1.8) for allele score 5 to 6, and 1.6 (95% CI: 1.3 to 2.1) for allele score 7 to 10 (p for trend: 9 × 10−5). A 1-kg/m2 increase in body mass index was associated with causal risk ratios for aortic valve stenosis and replacement, respectively, of 1.52 (95% CI: 1.23 to 1.87) and 1.49 (95% CI: 1.07 to 2.08) genetically, and with corresponding hazard ratios of 1.06 (95% CI: 1.05 to 1.08) and 1.06 (95% CI: 1.03 to 1.08) observationally.
Conclusions Obesity from human genetics was causally associated with higher risk of aortic valve stenosis and replacement.
This work was supported by Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark, the Novo Nordisk Foundation grant NNF18OC0052893, Denmark, and Chief Physician Johan Boserup and Lise Boserup‘s Fund, Denmark. The Copenhagen General Population Study is supported by the Copenhagen County Foundation and Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 3, 2019.
- Revision received October 22, 2019.
- Accepted October 23, 2019.
- 2020 American College of Cardiology Foundation
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