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Obesity as a Causal Risk Factor for Aortic Valve Stenosis

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@article{3c73f3436aeb4e63a798e7446059ab03,
title = "Obesity as a Causal Risk Factor for Aortic Valve Stenosis",
abstract = "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.",
author = "Morten Kaltoft and Anne Langsted and Nordestgaard, {B{\o}rge Gr{\o}nne}",
note = "Copyright {\circledC} 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = "1",
day = "21",
doi = "10.1016/j.jacc.2019.10.050",
language = "English",
volume = "75",
pages = "163--176",
journal = "American College of Cardiology. Journal",
issn = "0735-1097",
publisher = "Elsevier Inc",
number = "2",

}

RIS

TY - JOUR

T1 - Obesity as a Causal Risk Factor for Aortic Valve Stenosis

AU - Kaltoft, Morten

AU - Langsted, Anne

AU - Nordestgaard, Børge Grønne

N1 - Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2020/1/21

Y1 - 2020/1/21

N2 - 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.

AB - 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.

U2 - 10.1016/j.jacc.2019.10.050

DO - 10.1016/j.jacc.2019.10.050

M3 - Journal article

VL - 75

SP - 163

EP - 176

JO - American College of Cardiology. Journal

JF - American College of Cardiology. Journal

SN - 0735-1097

IS - 2

ER -

ID: 59310799