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Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality

List of authors.
  • David J.A. Jenkins, M.D., Ph.D.,
  • Mahshid Dehghan, Ph.D.,
  • Andrew Mente, Ph.D.,
  • Shrikant I. Bangdiwala, Ph.D.,
  • Sumathy Rangarajan, M.Sc.,
  • Kristie Srichaikul, M.D.,
  • Viswanathan Mohan, D.Sc.,
  • Alvaro Avezum, M.D.,
  • Rafael D¨ªaz, M.D.,
  • Annika Rosengren, M.D.,
  • Fernando Lanas, M.D.,
  • Patricio Lopez-Jaramillo, M.D.,
  • Wei Li, Ph.D.,
  • Aytekin Oguz, M.D.,
  • Rasha Khatib, Ph.D.,
  • Paul Poirier, M.D., Ph.D.,
  • Noushin Mohammadifard, Ph.D.,
  • Andrea Pepe, M.Sc.,
  • Khalid F. Alhabib, M.B., B.S.,
  • Jephat Chifamba, D.Phil.,
  • Afzal Hussein Yusufali, M.D.,
  • Romaina Iqbal, Ph.D.,
  • Karen Yeates, M.D.,
  • Khalid Yusoff, M.D.,
  • Noorhassim Ismail, M.D.,
  • Koon Teo, M.B., B.Ch.,
  • Sumathi Swaminathan, Ph.D.,
  • Xiaoyun Liu, Ph.D.,
  • Katarzyna Zato¨½ska, M.D.,
  • Rita Yusuf, Ph.D.,
  • and Salim Yusuf, D.Phil.
  • for the PURE Study Investigators*

Abstract

Background

Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.

Methods

This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.

Results

In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.

Conclusions

In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death. (Funded by the Population Health Research Institute and others.)

Funding and Disclosures

Supported by the Population Health Research Institute, Hamilton Health Sciences Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Strategy for Patient Oriented Research of the Canadian Institutes of Health Research through the Ontario Strategy for Patient-Oriented Research Support Unit, and the Ontario Ministry of Health and Long-Term Care; by unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, and GlaxoSmithKline; and by additional contributions from Novartis and King Pharma and from various national or local organizations in participating countries as follows: Argentina: Fundaci¨®n Estudios Cl¨ªnicos Latino America; Bangladesh: Independent University, Bangladesh, and Mitra and Associates; Brazil: Unilever Health Institute; Canada: Dairy Farmers of Canada, National Dairy Council of the United States, Public Health Agency of Canada, and Champlain Cardiovascular Disease Prevention Network; Chile: Universidad de La Frontera; China: National Center for Cardiovascular Diseases and ThinkTank Research Center for Health Development; Colombia: Colciencias; India: Indian Council of Medical Research; Malaysia: Ministry of Science, Technology, and Innovation of Malaysia, Ministry of Higher Education of Malaysia, Universiti Teknologi MARA, and Universiti Kebangsaan Malaysia; Palestinian territory: United Nations Relief and Works Agency for Palestine Refugees in the Near East and International Development Research Centre, Canada; Philippines: Philippine Council for Health Research and Development; Poland: Polish Ministry of Science and Higher Education and Wroclaw Medical University; Saudi Arabia: Saudi Heart Association, Dr. Mohammad Alfagih Hospital, Deanship of Scientific Research at King Saud University, Saleh Hamza Serafi Chair for Research of Coronary Heart Disease, and Umm al-Qura University; South Africa: North-West University, Netherlands Programme for Alternative Development, National Research Foundation, Medical Research Council of South Africa, South Africa Sugar Association, and Faculty of Community and Health Sciences; Sweden: Swedish government, Swedish Heart and Lung Foundation, Swedish Research Council, Swedish Council for Health, Working Life, and Welfare, King Gustaf V and Queen Victoria¡¯s Foundation of Freemasons, and AFA Insurance; Turkey: Metabolic Syndrome Society, AstraZeneca, and Sanofi-Aventis; and the United Arab Emirates: Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences and Dubai Health Authority. Dr. Jenkins receives salary support and discretionary funding from the Canada Research Chair endowment of the federal government of Canada. Dr. S. Yusuf is supported by the Marion W. Burke Chair in Cardiovascular Disease of the Heart and Stroke Foundation of Ontario.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on February 24, 2021, at NEJM.org.

We thank Ruchi Patel for her work in creating food-group categories and for computing carbohydrate values that were used for deriving the glycemic index and glycemic load; Meaghan Kavanagh and Brendan Gleason for their work in validating the seven-category glycemic index approach; Melanie Paquette and Sandhya Sahye-Pudaruth for assistance in the preparation of earlier versions of Figures 2 and S3; and Darshna Patel for helping to coordinate the manuscript preparation.

Author Affiliations

From the Departments of Nutritional Sciences and Medicine, Temerty Faculty of Medicine, University of Toronto (D.J.A.J.), and Li Ka Shing Knowledge Institute, St. Michael¡¯s Hospital Toronto (D.J.A.J., K.S.), Toronto, the Population Health Research Institute (M.D., S.I.B., K.T., S.Y.) and Department of Health Research Methods, Evidence, and Impact (A.M., S.I.B.), McMaster University, and McMaster University and Hamilton Health Sciences (S.R.), Hamilton, ON, Facult¨¦ de Pharmacie, Universit¨¦ Laval, Institut Universitaire de Cardiologie et de Pneumologie de Qu¨¦bec, Quebec, QC (P.P.), the Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa (A.P.), and the Department of Medicine, Queen¡¯s University, Kingston, ON (K. Yeates) ¡ª all in Canada; the Madras Diabetes Research Foundation, Chennai (V.M.), and St. John¡¯s Research Institute, St. John¡¯s National Academy of Health Sciences, Bangalore (S.S.) ¡ª both in India; the International Research Center, Hospital Alem?o Oswaldo Cruz, S?o Paulo (A.A.); Estudios Cl¨ªnicos Latino Am¨¦rica, Rosario, Santa Fe, Argentina (R.D.); the Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, and Sahlgrenska University Hospital, Gothenburg, Sweden (A.R.); Universidad de la Frontera, Temuco, Chile (F.L.); the Masira Research Institute, Medical School, Universidad de Santander, Bucaramanga, Colombia (P.L.-J.); the Medical Research and Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing (W.L., X.L.); the Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkey (A.O.); the Institute for Community and Public Health, Birzeit University, Birzeit, Palestine (R.K.); Advocate Research Institute, Advocate Health Care, Downers Grove, IL (R.K.); Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran (N.M.); the Department of Cardiac Sciences, King Fahad Cardiac Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia (K.F.A.); the Department of Physiology, University of Zimbabwe College of Health Sciences, Harare (J.C.); Hatta Hospital, Dubai Medical College, Dubai Health Authority, Dubai, United Arab Emirates (A.H.Y.); the Department of Community Health Sciences and Medicine, Aga Khan University, Pakistan (R.I.); Universiti Teknologi MARA, Sungai Buloh, and UCSI University, Selangor (K. Yusoff), and the Department of Community Health, University Kebangsaan Malaysia Medical Center, Kuala Lumpur (N.I.) ¡ª both in Malaysia; the Department of Social Medicine, Wroclaw Medical University, Wroclaw, Poland (K.Z.); and the School of Life Sciences, Independent University, Dhaka, Bangladesh (R.Y.).

Address reprint requests to Dr. Jenkins at the Department of Nutritional Sciences, Medical Sciences Bldg., 5th Fl., Rm. 5336B, 1 King¡¯s College Cir., Toronto, ON M5S 1A8, Canada, or at .

A complete list of investigators in the PURE study is provided in the Supplementary Appendix, available at NEJM.org.

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