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Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2

Caroline E Dale1, Ghazaleh Fatemifar2, Tom M Palmer2

  • 1From Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, United Kingdom (C.E.D., G.F., D.P.-M., A.D.H., J.P.C.); Department of Mathematics and Statistics, Lancaster University, United Kingdom (T.M.P.); UCLGenetics Institute, University College London, United Kingdom (J.W.); Applied Statistical Methods in Medical Research Group, Universidad Catolica de San Antonio de Murcia, Spain (D.P.-M.); Social Genetic & Developmental Psychiatry, King's College London, United Kingdom (D.Z.); Institute of Cardiovascular Science, University College London, United Kingdom (J.E.L.E., T.S., A.D.H., S.E.H.); MRC Unit for Lifelong Health & Ageing at UCL, London, United Kingdom (A.W., D.K.); Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (H.R.W., M.J.C., P.B.M.); NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (H.R.W., M.J.C., P.B.M.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, United Kingdom (S.M., J.F.P.); Department of Cardiology, Leiden University Medical Center, The Netherlands (S.T., W.J.); South Australian Health and Medical Research Institute, Adelaide (M.M., E.H.); EMBL Australia, Adelaide (M.M.); School of Social and Community Medicine, University of Bristol, United Kingdom (R.W.M., T.R.G., Y.B.-S., D.A.L., G.D.S.); Centre for Clinical Pharmacology, University College London, United Kingdom (R.S.); Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom (M.K.); Centre for Population Health Research, School of Health Sciences and Sansom Institute, University of South Australia, Adelaide (E.H., A.Z.); Population, Policy & Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom (E.H., C.P.); Department of Primary Care & Population Health, University College London, Royal Free Campus, United Kingdom (B.J.J.); MRC Integrative Epidemiology Unit, University of Bristol, United Kingdom (T.R.G., D.A.L., G.D.S.); Department of Women's Cancer, Institute for Women's Health, UCL, London, United Kingdom (A.G.-M., A.R., U.M.); Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands (R.d.M., D.O.M.-K.); Department of Internal Medicine, Section Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands (R.N., S.T.); Interuniversity Cardiology Institute Netherlands, Utrecht (W.J.); Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville (B.B.W.); Department of Public Health and Primary Care, Leiden University Medical Center, The Netherlands (D.O.M.-K.); BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, United Kingdom (N.S.); Department of Epidemiology and Public Health, University College London, United Kingdom (M.K.); Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom (F.D.); Department of Health Sciences, University of Leicester, United Kingdom (F.D.); Clinical Trial Service Unit & Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute Building, University of Oxford, United Kingdom (M.V.H.); Medical Research Council Population Health Research Unit at the University of Oxford, United Kingdom (M.V.H.); and National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospitals, United Kingdom (M.V.H.). jp.casas@ucl.ac.uk c.dale@ucl.ac.uk.

Circulation
|May 14, 2017
PubMed

Insights

Both general adiposity (body mass index [BMI]) and central adiposity (waist-to-hip ratio adjusted for BMI [WHRadjBMI]) causally impact cardiovascular disease and type 2 diabetes. Central adiposity may elevate stroke risk more significantly.

Area of Science:

  • Cardiovascular Disease Genetics
  • Metabolic Disease Research
  • Obesity Etiology

Background:

  • The distinct roles of general versus central adiposity in cardiometabolic disease development are not fully understood.
  • This study investigates the causal links between body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI) with cardiometabolic conditions.

Purpose of the Study:

  • To quantify and compare the causal effects of general adiposity (BMI) and central adiposity (WHRadjBMI) on cardiometabolic disease.
  • To elucidate the specific associations of these adiposity measures with coronary heart disease, stroke, and type 2 diabetes mellitus.

Main Methods:

  • Utilized Mendelian randomization analysis with 97 independent single-nucleotide polymorphisms for BMI and 49 for WHRadjBMI.
  • Integrated data from 14 prospective studies and large consortia for coronary heart disease (CHD), stroke, type 2 diabetes mellitus, and lipids.

Main Results:

  • Both WHRadjBMI and BMI showed significant causal associations with increased risk of coronary heart disease (CHD) and type 2 diabetes mellitus.
  • Central adiposity (WHRadjBMI) uniquely increased the risk of ischemic stroke.
  • Both measures were linked to adverse cardiometabolic traits, including elevated left ventricular hypertrophy, glycemic markers, interleukin-6, and lipids.

Conclusions:

  • General and central adiposity are causally linked to CHD and type 2 diabetes.
  • Central adiposity may play a more prominent role in stroke risk.
  • Future health burden assessments should incorporate both general and central adiposity measures.
Abstract

Keywords:
Mendelian randomization analysisadipositybody fat distributionbody mass indexcoronary artery diseasestrokewaist-hip ratio

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