INTERHEART study

INTERHEART study
Name	INTERHEART study
Type	Case–control study
Field	Cardiovascular epidemiology
Participants	15,152 cases and 14,820 controls
Countries	52
Published	2004
Journal	The Lancet

INTERHEART study

The INTERHEART study was a large multinational case–control investigation of risk factors for acute myocardial infarction involving investigators from many institutions. Its lead publication reported associations between myocardial infarction and modifiable exposures across diverse populations, influencing guidelines and global health initiatives. The study recruited participants from multiple continents and applied standardized protocols to evaluate behavioral, metabolic, and psychosocial contributors to risk.

Background and objectives

The project was conceived amid rising interest in non-communicable diseases where teams sought cross-population evidence, drawing contributors from institutions associated with World Health Organization, Centers for Disease Control and Prevention, National Institutes of Health, Imperial College London, McMaster University, University of Toronto, Harvard Medical School, University of Oxford, Johns Hopkins University, Karolinska Institutet, University of Melbourne, University of Cape Town, Peking University, All India Institute of Medical Sciences, Universidad Nacional Autónoma de México, Sao Paulo University, Cairo University, University of Nairobi, Addis Ababa University, Tehran University of Medical Sciences, St Bartholomew's Hospital, Royal Brompton Hospital, Royal Free Hospital, University College London, Trinity College Dublin, University of Glasgow, University of Edinburgh, Queen's University Belfast, University of Auckland, Seoul National University, National University of Singapore, University of Hong Kong, Osaka University, Kyoto University, Hokkaido University, Mayo Clinic, Cleveland Clinic, Mount Sinai Hospital, Beth Israel Deaconess Medical Center, Vanderbilt University Medical Center, Duke University School of Medicine, University of California, San Francisco, Stanford University School of Medicine, University of Washington School of Medicine, McGill University, Universite de Montreal, Institut Pasteur, Karachi Medical University, Bangabandhu Sheikh Mujib Medical University, University of Colombo, University of Kelaniya, Makerere University, University of Zambia, University of Zimbabwe, University of Ghana, Lagos University Teaching Hospital, Baylor College of Medicine, Albert Einstein College of Medicine, Weill Cornell Medicine, Columbia University Irving Medical Center, University of Pennsylvania, Yale School of Medicine and others. Its primary objective was to quantify the contribution of potentially modifiable risk factors to myocardial infarction worldwide and to assess consistency across regions and ethnicities.

Methods

Investigators used a standardized case–control design enrolling acute myocardial infarction cases and matched controls with data collection harmonized across centers including clinical assessment, questionnaires, and point-of-care assays. The protocol incorporated measurements and instruments linked to established institutions such as European Society of Cardiology, American Heart Association, British Heart Foundation, World Medical Association, International Committee of the Red Cross, Bill & Melinda Gates Foundation, Wellcome Trust, National Heart, Lung, and Blood Institute, Canadian Institutes of Health Research, Australian National Health and Medical Research Council, Swiss National Science Foundation and laboratory standards from Clinical Laboratory Improvement Amendments-aligned facilities. Data on cigarette smoking, diet, physical activity, lipid profiles, blood pressure, diabetes, abdominal obesity, psychosocial stress, and alcohol intake were collected using questionnaires and assays standardized against reference centers at Mayo Clinic, Karolinska Institutet, Imperial College London, Johns Hopkins University and Harvard Medical School. Statistical analysis employed multivariable logistic regression with sensitivity analyses influenced by methodologies discussed at meetings held in venues like Geneva, London, New York City, Toronto, Stockholm, and Sydney.

Key findings

The primary publication reported that nine modifiable risk factors together explained most attributable risk for first myocardial infarction across populations: current smoking, abnormal lipids, hypertension, diabetes, abdominal obesity, psychosocial factors, low fruit and vegetable intake, lack of regular physical activity, and alcohol consumption patterns. The study found consistent associations across regions including sites in North America, South America, Europe, Africa, Asia, Oceania, and the Middle East, with effect sizes robust in analyses adjusted using approaches from Cochrane Collaboration-style sensitivity checks. It emphasized population-attributable risks driven largely by abnormal lipids and smoking, with notable contributions from psychosocial stress and central adiposity. Secondary analyses highlighted interactions with age, sex, and region in ways that echoed findings from cohort studies at Framingham Heart Study, Atherosclerosis Risk in Communities study, Nurses' Health Study, Physicians' Health Study, Whitehall Study, and British Regional Heart Study.

Interpretation and impact

Authors and commentators linked the findings to public health strategies advocated by World Health Organization, United Nations, World Bank, Global Burden of Disease Study, Disease Control Priorities Project, GAVI, the Vaccine Alliance, UNAIDS, UNICEF, Pan American Health Organization, and national agencies such as Health Canada and Public Health England. The study influenced clinical guidelines from European Society of Cardiology, American College of Cardiology, American Heart Association, Canadian Cardiovascular Society, National Institute for Health and Care Excellence, and national ministries of health. Policymakers and NGOs used the evidence to prioritize tobacco control measures consistent with the Framework Convention on Tobacco Control and to promote primary prevention strategies in programs supported by Bill & Melinda Gates Foundation and Wellcome Trust.

Limitations and criticisms

Critiques cited the case–control design and potential selection and recall bias, concerns about residual confounding despite adjustment strategies promoted by Cochrane Collaboration and statistical approaches from Institute for Health Metrics and Evaluation. Others questioned generalizability to low-resource settings despite broad geographic coverage including sites in India, China, Brazil, South Africa, Egypt, Kenya, and Nigeria'. Methodological debates referenced comparative strengths of randomized trials such as ALLHAT and cohort evidence from Framingham Heart Study and meta-analyses in journals like The Lancet and BMJ.

Subsequent research and policy implications

Following the study, research agendas funded by entities such as National Institutes of Health, European Commission Horizon 2020, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council (United Kingdom), Canadian Institutes of Health Research and regional health institutes advanced longitudinal studies, intervention trials, and implementation science. Findings informed national non-communicable disease plans adopted by governments represented at United Nations General Assembly meetings and integrated into monitoring frameworks of Sustainable Development Goals and the Global Action Plan for the Prevention and Control of Noncommunicable Diseases 2013–2020.

Category:Cardiovascular epidemiology studies