Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large-scale observational and Mendelian randomization evidence
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Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction : large-scale observational and Mendelian randomization evidence. / Nielsen, Maria Booth; Çolak, Yunus; Benn, Marianne; Mason, Amy; Burgess, Stephen; Nordestgaard, Børge Grønne.
I: Cardiovascular Research, Bind 120, Nr. 1, 2024, s. 95-107.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction
T2 - large-scale observational and Mendelian randomization evidence
AU - Nielsen, Maria Booth
AU - Çolak, Yunus
AU - Benn, Marianne
AU - Mason, Amy
AU - Burgess, Stephen
AU - Nordestgaard, Børge Grønne
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2024
Y1 - 2024
N2 - AIMS: Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction.METHODS AND RESULTS: In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin.In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37-1.66) for heart failure, 1.63 (1.50-1.78) for atrial fibrillation, 1.21 (1.03-1.41) for aortic valve stenosis, and 1.03 (0.93-1.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65-1.29), 0.87 (0.68-1.12), 1.55 (0.87-2.76), and 0.93 (0.67-1.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89-1.09), 1.00 (0.92-1.08), 1.01 (0.79-1.28), and 0.99 (0.86-1.13) in two-sample Mendelian randomization analyses, respectively.CONCLUSION: Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.
AB - AIMS: Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction.METHODS AND RESULTS: In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin.In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37-1.66) for heart failure, 1.63 (1.50-1.78) for atrial fibrillation, 1.21 (1.03-1.41) for aortic valve stenosis, and 1.03 (0.93-1.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65-1.29), 0.87 (0.68-1.12), 1.55 (0.87-2.76), and 0.93 (0.67-1.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89-1.09), 1.00 (0.92-1.08), 1.01 (0.79-1.28), and 0.99 (0.86-1.13) in two-sample Mendelian randomization analyses, respectively.CONCLUSION: Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.
KW - Humans
KW - Adiponectin/genetics
KW - Aortic Valve Stenosis/epidemiology
KW - Atrial Fibrillation/diagnosis
KW - Genome-Wide Association Study
KW - Heart Failure/diagnosis
KW - Mendelian Randomization Analysis/methods
KW - Myocardial Infarction/diagnosis
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
U2 - 10.1093/cvr/cvad162
DO - 10.1093/cvr/cvad162
M3 - Journal article
C2 - 37897683
VL - 120
SP - 95
EP - 107
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 1
ER -
ID: 385010757