Affiliations 

  • 1 Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada. Electronic address: [email protected]
  • 2 Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada
  • 3 Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Laboratory Medicine, McMaster University, Hamilton, ON, Canada
  • 4 Université Laval Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada
  • 5 Department of Medicine, University of Ottawa, Ottawa, ON, Canada
  • 6 Faculty of Health Sciences, and Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Vancouver, BC, Canada
  • 7 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
  • 8 Estudios Clinicos Latinoamerica ECLA, Rosario, Santa Fe, Argentina
  • 9 Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil
  • 10 Fundación Oftalmológica de Santander-FOSCAL, Floridablanca, Santander, Colombia
  • 11 Universidad de La Frontera, Temuco, Araucanía, Chile
  • 12 Post Graduate Institute of Medical Education and Research, School of Public Health, Chandigarh, India
  • 13 Eternal Heart Care Centre and Research Institute, Jawahar Circle, Jaipur, India
  • 14 Madras Diabetes Research Foundation, Chennai, India
  • 15 St John's Research Institute, St John's National Academy of Health Sciences, Koramangala, Bangalore, India
  • 16 Sree Chitra Tirunal Institute for Medical Sciences and Technology, Achutha Menon Centre for Health Science Studies, Thiruvananthapuram, India
  • 17 Department of Social Medicine, Medical University of Wroclaw, Wrocław, Poland
  • 18 Department of Community Health Sciences and Medicine, Aga Khan University, Karachi, Pakistan
  • 19 School of Life Sciences, Independent University, Dhaka, Bangladesh
  • 20 Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
  • 21 Institute of Community and Public Health, Birzeit University, Birzeit, occupied Palestinian territory
  • 22 Faculty of Medicine, Health and Wellbeing, Universiti Teknologi MARA, Shah Alam, Malaysia
  • 23 Department of Community Health, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur, Malaysia
  • 24 Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Goztepe, Istanbul, Turkey
  • 25 Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital/Östra, Göteborg, Sweden
  • 26 Dubai Medical University, Hatta Hospital, Dubai Health Authority, Dubai, United Arab Emirates
  • 27 Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa
  • 28 School of Public Health, Faculty of Community and Health, University of the Western Cape, Cape Town, South Africa
  • 29 Physiology Department, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe
  • 30 Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
Lancet Diabetes Endocrinol, 2017 10;5(10):774-787.
PMID: 28864143 DOI: 10.1016/S2213-8587(17)30283-8

Abstract

BACKGROUND: The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries.

METHODS: We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events.

FINDINGS: Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all ptrend<0·0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all ptrend<0·0001, apart from ApoB [ptrend=0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol.

INTERPRETATION: Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.

FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.