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Published in: BMC Cardiovascular Disorders 1/2020

Open Access 01-12-2020 | Research article

Higher BMI is linked to an increased risk of heart attacks in European adults: a Mendelian randomisation study

Authors: Benjamin Adams, Lauren Jacocks, Hui Guo

Published in: BMC Cardiovascular Disorders | Issue 1/2020

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Abstract

Background

BMI has been implicated as a risk factor for heart disease as a whole in multiple studies. Heart attack is one of the common complications of this disease. The aim of this study is to explore if elevated level of BMI causes an increase in the risk of heart attacks.

Methods

We used two Mendelian randomisation (MR) methods: inverse variance weighted estimation and robust adjusted profile score (RAPS) on the basis of summary data of adulthood BMI from Genetic Investigation of Anthropometric Traits consortium and heart attack data from the UK Biobank. BMI associated single nucleotide polymorphisms (SNPs) were used as instrumental variables.

Results

Seventy-two independent SNPs were associated with BMI (P < 5 × 10− 8). Using these SNPs as instruments, BMI was found to be causally associated with heart attacks in inverse variance weighted MR analysis. The risk of heart attacks increased by 0.8% per 1-SD (or 4.5 kg/m2) increase in BMI (OR = 1.008 with 95% CI (1.003, 1.012), P = 0.001). RAPS provided concordant results (OR = 1.007 with 95% CI (1.002, 1.012), P = 0.004).

Conclusions

This current study is the first to use MR to investigate causal relationship between BMI and heart attacks. Our findings suggest that high level of BMI may cause increased risk of heart attacks.
Literature
2.
go back to reference Atlantis E, Baker M. Obesity effects on depression: systematic review of epidemiological studies. Int J Obes. 2008;32:881–91.CrossRef Atlantis E, Baker M. Obesity effects on depression: systematic review of epidemiological studies. Int J Obes. 2008;32:881–91.CrossRef
3.
go back to reference Zhang X, Lv WQ, Qiu B, Zhang LJ, Qin J, Tang FJ, et al. Assessing causal estimates of the association of obesity-related traits with coronary artery disease using a Mendelian randomization approach. Sci Rep. 2018;8:7146.CrossRef Zhang X, Lv WQ, Qiu B, Zhang LJ, Qin J, Tang FJ, et al. Assessing causal estimates of the association of obesity-related traits with coronary artery disease using a Mendelian randomization approach. Sci Rep. 2018;8:7146.CrossRef
4.
go back to reference Buitrago F, Calvo JI, Redondo-López V, Canón-Barroso L, Rodríguez-Pérez L, Hinojosa-Díaz JF. Cardiovascular events in patients with obesity: an observational study. Br J Gen Pract. 2010;60:584–9.CrossRef Buitrago F, Calvo JI, Redondo-López V, Canón-Barroso L, Rodríguez-Pérez L, Hinojosa-Díaz JF. Cardiovascular events in patients with obesity: an observational study. Br J Gen Pract. 2010;60:584–9.CrossRef
5.
go back to reference Tsai F, Coyle WJ. The microbiome and obesity: is obesity linked to our gut flora? Curr Gastroenterol Rep. 2009;11:307–13.CrossRef Tsai F, Coyle WJ. The microbiome and obesity: is obesity linked to our gut flora? Curr Gastroenterol Rep. 2009;11:307–13.CrossRef
6.
go back to reference Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS One. 2015;10:e0133494.CrossRef Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS One. 2015;10:e0133494.CrossRef
8.
go back to reference Mittendorfer B, Peterson LR. Cardiovascular consequences of obesity and targets for treatment. Drug Discov Today Ther Strateg. 2008;5:53–61.CrossRef Mittendorfer B, Peterson LR. Cardiovascular consequences of obesity and targets for treatment. Drug Discov Today Ther Strateg. 2008;5:53–61.CrossRef
9.
go back to reference Shahar E. The association of body mass index with health outcomes: causal, inconsistent, or confounded? Am J Epidemiol. 2009;170:957–8.CrossRef Shahar E. The association of body mass index with health outcomes: causal, inconsistent, or confounded? Am J Epidemiol. 2009;170:957–8.CrossRef
10.
go back to reference Greenberg JA. Correcting biases in estimates of mortality attributable to obesity. Obesity. 2006;14:2071–9.CrossRef Greenberg JA. Correcting biases in estimates of mortality attributable to obesity. Obesity. 2006;14:2071–9.CrossRef
12.
go back to reference Stallones RA. The association between tobacco smoking and coronary heart disease. Int J Epidemiol. 2015;44:735–43.CrossRef Stallones RA. The association between tobacco smoking and coronary heart disease. Int J Epidemiol. 2015;44:735–43.CrossRef
13.
go back to reference Mukamal K, Lazo M. Alcohol and cardiovascular disease. BMJ. 2017;356:j1340.CrossRef Mukamal K, Lazo M. Alcohol and cardiovascular disease. BMJ. 2017;356:j1340.CrossRef
14.
go back to reference Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40:597–608.CrossRef Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40:597–608.CrossRef
15.
go back to reference Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206.CrossRef Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197–206.CrossRef
17.
go back to reference Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.CrossRef Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.CrossRef
20.
go back to reference Bowden J, Smith GD, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression. Int J Epidemiol. 2015. Bowden J, Smith GD, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression. Int J Epidemiol. 2015.
21.
go back to reference Zhao Q, Wang J, Hemani G, Bowden J, Small DS. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score; 2018. Zhao Q, Wang J, Hemani G, Bowden J, Small DS. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score; 2018.
22.
go back to reference Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.CrossRef Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658–65.CrossRef
23.
go back to reference Hemani G, Bowden J, Davey SG. Evaluating the potential role of pleiotropy in Mendelian randomization studies. Hum Mol Genet. 2018:R195–208.CrossRef Hemani G, Bowden J, Davey SG. Evaluating the potential role of pleiotropy in Mendelian randomization studies. Hum Mol Genet. 2018:R195–208.CrossRef
26.
go back to reference Lyall DM, Harris SE, Bastin ME, Muñoz Maniega S, Murray C, Lutz MW, et al. Alzheimer’s disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936. Neurobiol Aging. 2014;35:1513.e25–33.CrossRef Lyall DM, Harris SE, Bastin ME, Muñoz Maniega S, Murray C, Lutz MW, et al. Alzheimer’s disease susceptibility genes APOE and TOMM40, and brain white matter integrity in the Lothian Birth Cohort 1936. Neurobiol Aging. 2014;35:1513.e25–33.CrossRef
27.
go back to reference Larsson SC, Bäck M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK biobank: a Mendelian randomization study. Eur Heart J. 2020;41:221–6.CrossRef Larsson SC, Bäck M, Rees JMB, Mason AM, Burgess S. Body mass index and body composition in relation to 14 cardiovascular conditions in UK biobank: a Mendelian randomization study. Eur Heart J. 2020;41:221–6.CrossRef
28.
go back to reference He L, Culminskaya I, Loika Y, Arbeev KG, Bagley O, Duan M, et al. Causal effects of cardiovascular risk factors on onset of major age-related diseases: a time-to-event Mendelian randomization study. Exp Gerontol. 2018;107:74–86.CrossRef He L, Culminskaya I, Loika Y, Arbeev KG, Bagley O, Duan M, et al. Causal effects of cardiovascular risk factors on onset of major age-related diseases: a time-to-event Mendelian randomization study. Exp Gerontol. 2018;107:74–86.CrossRef
29.
go back to reference Hägg S, Fall T, Ploner A, Mägi R, Fischer K, Draisma HHM, et al. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study. Int J Epidemiol. 2015;44:578–86.CrossRef Hägg S, Fall T, Ploner A, Mägi R, Fischer K, Draisma HHM, et al. Adiposity as a cause of cardiovascular disease: a Mendelian randomization study. Int J Epidemiol. 2015;44:578–86.CrossRef
30.
go back to reference Lyall DM, Celis-Morales C, Ward J, Iliodromiti S, Anderson JJ, Gill JMR, et al. Association of body mass index with cardiometabolic disease in the UK biobank: a mendelian randomization study. JAMA Cardiol. 2017;2:882–9.CrossRef Lyall DM, Celis-Morales C, Ward J, Iliodromiti S, Anderson JJ, Gill JMR, et al. Association of body mass index with cardiometabolic disease in the UK biobank: a mendelian randomization study. JAMA Cardiol. 2017;2:882–9.CrossRef
31.
go back to reference Dale CE, Fatemifar G, Palmer TM, White J, Prieto-Merino D, Zabaneh D, et al. Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis. Circulation. 2017;135:2373–88.CrossRef Dale CE, Fatemifar G, Palmer TM, White J, Prieto-Merino D, Zabaneh D, et al. Causal associations of adiposity and body fat distribution with coronary heart disease, stroke subtypes, and type 2 diabetes mellitus: a Mendelian randomization analysis. Circulation. 2017;135:2373–88.CrossRef
32.
go back to reference Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. J Am Med Assoc. 2003;289:1799–804.CrossRef Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. J Am Med Assoc. 2003;289:1799–804.CrossRef
33.
go back to reference Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart. 2017;103:10–8.CrossRef Chapman AR, Adamson PD, Mills NL. Assessment and classification of patients with myocardial injury and infarction in clinical practice. Heart. 2017;103:10–8.CrossRef
Metadata
Title
Higher BMI is linked to an increased risk of heart attacks in European adults: a Mendelian randomisation study
Authors
Benjamin Adams
Lauren Jacocks
Hui Guo
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2020
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-020-01542-w

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