University of Oulu

Michael V. Holmes, Iona Y. Millwood, Christiana Kartsonaki, Michael R. Hill, Derrick A. Bennett, Ruth Boxall, Yu Guo, Xin Xu, Zheng Bian, Ruying Hu, Robin G. Walters, Junshi Chen, Mika Ala-Korpela, Sarah Parish, Robert J. Clarke, Richard Peto, Rory Collins, Liming Li, Zhengming Chen, Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke, Journal of the American College of Cardiology, Volume 71, Issue 6, 2018, Pages 620-632, ISSN 0735-1097,

Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke

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Author: Holmes, Michael V.1,2,3; Millwood, Iona Y.1,2; Kartsonaki, Christiana1,2;
Organizations: 1Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
2Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
3National Institute for Health Research Oxford Biomedical Research Centre, Oxford University Hospital, Oxford, United Kingdom
4Chinese Academy of Medical Sciences, Beijing, China
5Liuyang CDC, Changsha, China
6NCDs Prevention and Control Department, Zhejiang CDC, Hangzhou, China
7National Center for Food Safety Risk Assessment, Beijing, China
8Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
9Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom
10Population Health Science, Bristol Medical School, University of Bristol, Bristol, United Kingdom
11NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
12Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
13Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, the Alfred Hospital, Monash University, Melbourne, Victoria, Australia
14Department of Global Health, School of Public Health, Peking University, Beijing, China
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Elsevier, 2018
Publish Date: 2019-07-02


Background: Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.

Objectives: This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).

Methods: In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.

Results: Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.

Conclusions: Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non–lipid-related metabolites associated with all 3 diseases.

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Series: Journal of the American College of Cardiology
ISSN: 0735-1097
ISSN-E: 1558-3597
ISSN-L: 0735-1097
Volume: 71
Issue: 6
Pages: 620 - 632
DOI: 10.1016/j.jacc.2017.12.006
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
Funding: The China Kadoorie Biobank baseline survey and first re-survey was supported by the Kadoorie Charitable Foundation in Hong Kong. Long-term follow-up has been supported by the UK Wellcome Trust (202922/Z/16/Z, 088158/Z/09/Z, 104085/Z/14/Z), National Key Research and Development Program of China (2016YFC0900500, 2016YFC0900501, 2016YFC0900504), Chinese Ministry of Science and Technology (2011BAI09B01), and National Natural Science Foundation of China (Grant Nos. 81390540, 81390541, 81390544). NMR metabolomics was supported by the BHF Centre of Research Excellence, Oxford (RE/13/1/30181). The British Heart Foundation, UK Medical Research Council, and Cancer Research UK provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at the University of Oxford. Dr. Ala-Korpela was supported by the Sigrid Juselius Foundation, Finland; and works in a unit that is supported by the University of Bristol and UK Medical Research Council (MC_UU_12013/1). Dr. Holmes was supported by the National Institute for Health Research Oxford Biomedical Research Centre. Dr. Collins has received grants for independent research from Abbott/Solvay/Maylan, AstraZeneca, Bayer Germany, British Heart Foundation, Cancer Research UK, Medical Research Council, The Medicines Company, Merck, and Wellcome Trust. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Drs. Holmes, Millwood, and Kartsonaki contributed equally to this work and are jointfirst authors.
Copyright information: © 2018 The Authors. Published by Elsevier on behalf of the American College of CardiologyFoundation. This is an open access article under the CC BY license (