Dataset Information

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

ABSTRACT: Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular outcomes were examined in up to 22,193 individuals with 3062 incident cardiovascular events from nine prospective follow-up studies within the ENGAGE consortium. We used random-effects meta-analysis in an MR framework to provide causal estimates of the effect of adiposity on cardiovascular outcomes.There was a strong association between BMI and incident CHD (HR = 1.20 per SD-increase of BMI, 95% CI, 1.12-1.28, P = 1.9.10(-7)), heart failure (HR = 1.47, 95% CI, 1.35-1.60, P = 9.10(-19)) and ischaemic stroke (HR = 1.15, 95% CI, 1.06-1.24, P = 0.0008) in observational analyses. The genetic score was robustly associated with BMI (? = 0.030 SD-increase of BMI per additional allele, 95% CI, 0.028-0.033, P = 3.10(-107)). Analyses indicated a causal effect of adiposity on development of heart failure (HR = 1.93 per SD-increase of BMI, 95% CI, 1.12-3.30, P = 0.017) and ischaemic stroke (HR = 1.83, 95% CI, 1.05-3.20, P = 0.034). Additional cross-sectional analyses using both ENGAGE and CARDIoGRAMplusC4D data showed a causal effect of adiposity on CHD.Using MR methods, we provide support for the hypothesis that adiposity causes CHD, heart failure and, previously not demonstrated, ischaemic stroke.

SUBMITTER: Hagg S

PROVIDER: S-EPMC4553708 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

Hägg Sara S Fall Tove T Ploner Alexander A Mägi Reedik R Fischer Krista K Draisma Harmen H M HH Kals Mart M de Vries Paul S PS Dehghan Abbas A Willems Sara M SM Sarin Antti-Pekka AP Kristiansson Kati K Nuotio Marja-Liisa ML Havulinna Aki S AS de Bruijn Renée F A G RF Ikram M Arfan MA Kuningas Maris M Stricker Bruno H BH Franco Oscar H OH Benyamin Beben B Gieger Christian C Hall Alistair S AS Huikari Ville V Jula Antti A Järvelin Marjo-Riitta MR Kaakinen Marika M Kaprio Jaakko J Kobl Michael M Mangino Massimo M Nelson Christopher P CP Palotie Aarno A Samani Nilesh J NJ Spector Tim D TD Strachan David P DP Tobin Martin D MD Whitfield John B JB Uitterlinden André G AG Salomaa Veikko V Syvänen Ann-Christine AC Kuulasmaa Kari K Magnusson Patrik K PK Esko Tõnu T Hofman Albert A de Geus Eco J C EJ Lind Lars L Giedraitis Vilmantas V Perola Markus M Evans Alun A Ferrières Jean J Virtamo Jarmo J Kee Frank F Tregouet David-Alexandre DA Arveiler Dominique D Amouyel Philippe P Gianfagna Francesco F Brambilla Paolo P Ripatti Samuli S van Duijn Cornelia M CM Metspalu Andres A Prokopenko Inga I McCarthy Mark I MI Pedersen Nancy L NL Ingelsson Erik E

International journal of epidemiology 20150401 2

<h4>Background</h4>Adiposity, as indicated by body mass index (BMI), has been associated with risk of cardiovascular diseases in epidemiological studies. We aimed to investigate if these associations are causal, using Mendelian randomization (MR) methods.<h4>Methods</h4>The associations of BMI with cardiovascular outcomes [coronary heart disease (CHD), heart failure and ischaemic stroke], and associations of a genetic score (32 BMI single nucleotide polymorphisms) with BMI and cardiovascular out ...[more]

PMID: 26016847

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Project description:A greater risk of cardiovascular disease is associated with low educational attainment and high adiposity. Despite the correlation between low educational attainment and high adiposity, whether educational attainment modifies the risk of CVD caused by high adiposity remains poorly understood. We investigated the effect of adiposity (body mass index [BMI] and waist-to-hip ratio adjusted for BMI [WHRadjBMI]) on incident CVD among individuals with varying education levels, using associational and one-sample Mendelian randomization (MR) survival analyses. Data were collected from 2006 to 2021, and sample sizes were 254,281 (27,511 CVD cases) for BMI and 253,968 (27,458 CVD cases) for WHRadjBMI. In the associational model, a standard deviation (SD) higher BMI was associated with 19.81 (95% CI: 18.55-21.06) additional cases of incident CVD per 10,000 person-years for individuals with a secondary education, versus 32.96 (95% CI: 28.75-37.17) for those without. When university degree served as the education variable, education group differences attenuated, with 18.26 (95% CI: 16.37-20.15) cases from a one SD higher BMI for those with a university degree versus 23.18 [95% CI: 21.56-24.72] for those without. For the MR model, an SD higher BMI resulted in 11.75 (95% CI: -0.84-24.38) and 29.79 (95% CI: 17.20-42.44) additional cases of incident CVD per 10,000 person-years for individuals with versus without a university degree. WHRadjBMI exhibited no effect differences by education. While the associational model showed evidence of educational attainment modifying the relationship between adiposity and incident CVD, it does not modify the association between adiposity and incident CVD in the MR models. This suggests either less education does not cause greater risk of incident CVD from high adiposity, or MR models cannot detect the effect difference. The associational point estimates exist within the MR models' confidence intervals in all BMI analyses, so we cannot rule out the effect sizes in the associational models.

Dataset Information

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

Publications

Adiposity as a cause of cardiovascular disease: a Mendelian randomization study.

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