Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study

Author:

Nalini Mahdi12,Shakeri Ramin1,Poustchi Hossein34,Pourshams Akram14,Etemadi Arash15ORCID,Islami Farhad16ORCID,Khoshnia Masoud17,Gharavi Abdolsamad17,Roshandel Gholamreza71ORCID,Khademi Hooman1,Zahedi Mahdi8,Abedi-Ardekani Behnoush9,Vedanthan Rajesh10ORCID,Boffetta Paolo11,Dawsey Sanford M5,Pharaoh Paul D12ORCID,Sotoudeh Masoud1ORCID,Abnet Christian C5,Day Nicholas E12,Brennan Paul9,Kamangar Farin13ORCID,Malekzadeh Reza134

Affiliation:

1. Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran

2. Cardiovascular Research Center, Kermanshah University of Medical Sciences, Imam Ali Hospital, Shahid Beheshti Boulevard, Kermanshah, Iran

3. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran

4. Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Shariati Hospital, North Kargar Avenue, Tehran 14117-13135, Iran

5. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

6. Surveillance and Health Services Research, American Cancer Society, Atlanta, GA, USA

7. Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran

8. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran

9. Section of Genetics, International Agency for Research on Cancer, World Health Organization, Lyon, France

10. Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA

11. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

12. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom

13. Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University Portage Avenue Campus, Room 103, Baltimore, MD 21251, USA

Abstract

Abstract Aims Tens of millions of people worldwide use opiates but little is known about their potential role in causing cardiovascular diseases. We aimed to study the association of long-term opiate use with cardiovascular mortality and whether this association is independent of the known risk factors. Methods and results In the population-based Golestan Cohort Study—50 045 Iranian participants, 40–75 years, 58% women—we used Cox regression to estimate hazard ratios and 95% confidence intervals (HRs, 95% CIs) for the association of opiate use (at least once a week for a period of 6 months) with cardiovascular mortality, adjusting for potential confounders—i.e. age, sex, education, wealth, residential place, marital status, ethnicity, and tobacco and alcohol use. To show independent association, the models were further adjusted for hypertension, diabetes, waist and hip circumferences, physical activity, fruit/vegetable intake, aspirin and statin use, and history of cardiovascular diseases and cancers. In total, 8487 participants (72.2% men) were opiate users for a median (IQR) of 10 (4–20) years. During 548 940 person-years—median of 11.3 years, >99% success follow-up—3079 cardiovascular deaths occurred, with substantially higher rates in opiate users than non-users (1005 vs. 478 deaths/100 000 person-years). Opiate use was associated with increased cardiovascular mortality, with adjusted HR (95% CI) of 1.63 (1.49–1.79). Overall 10.9% of cardiovascular deaths were attributable to opiate use. The association was independent of the traditional cardiovascular risk factors. Conclusion Long-term opiate use was associated with an increased cardiovascular mortality independent of the traditional risk factors. Further research, particularly on mechanisms of action, is recommended.

Funder

Tehran University of Medical Sciences

Cancer Research UK

National Cancer Institute

National Institutes of Health

Intramural Research Program

International Agency for Research on Cancer

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Epidemiology

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