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Opioid use and cardiovascular risk – insights from a large population-based study

Comment by Dr. Martin Bahls, EAPC Young Community

Risk Factors and Prevention
Cardiovascular Pharmacotherapy

Opiates, like opium, morphine, and codeine, are natural alkaloid compounds harvested from the opium poppy plant. While an estimated 29.2 million people globally use opiates, 24.2 million use other opioids, mostly as illegal drugs. Opioid use is of large interest for cardiovascular disease (CVD) prevention since the years of life lost related to opioid use in the United States now exceed those attributable to high blood pressure. However, the reports about a potential association between opioid use and risk for CVD have been inconsistent and are mainly explored in prescription or medical claims data. In the present study Nalini et al. analysed data of the Golestan Cohort Study (GCS)[1]. Citizens of the Golestan Province (Iran) use opium and its related products recreationally and mostly without stigma allowing data to be obtained from the general population. Initial results of the GCS were published in 2012 and supported the notion that opioid use significantly increases the risk for CVD. In September of last year the European Journal of Preventive Cardiology (EJPC) published an updated analysis.

A total of 50,045 men and women aged 40–75 years, without a history of upper gastrointestinal cancers, from Gonbad City (n= 10,032) and 326 villages (n = 40,013) in the Golestan Province were enrolled into the study between 2004 and 2008. The GCS questionnaire included detailed queries about opiate use, i.e. age of starting and ending use, types of opiates, and routes of administration. Individuals were considered opiate users if they had ever used opiates at least once per week for a period of at least 6 months. An extensive number of potential confounders are also available in the GCS. For example, information was collected with regards to physical activity, presence of hypertension or type 2 diabetes mellitus, wealth status and nutritional information. The vital status of study participants was checked yearly to collect information about any admissions to hospitals or outpatient clinics. CVD deaths were defined as ICD-10 codes I00 – I99.

Of the 50,045 study participants 8,487 had a history of long-term opioid use. Long-term opiate users were more likely to have used tobacco and alcohol, be men, live in rural areas, and were poorer. During the 548,940 person-years of follow-up 3,079 study participants died due to CVD. The CVD mortality rate per 105 person-years follow-up was 1,005 in opiate users and 478 in non-users. Even in the adjusted model the hazards ratio for the association between opioid use and CVD was 1.63 (95% confidence interval 1.49–1.79). A number this high could mean that up to 11% of all CVD deaths are due to opioid use. Despite the cross-sectional study design, potential pathways or pathophysiological mechanisms that link opioids to CVD mortality include arrhythmia, adverse respiratory effects, inflammation, oxidative stress, microvascular coronary dysfunction, hypogonadism, and insulin resistance.

The findings from this elegant study further support the adverse cardiovascular effects of opioid use and also warrant future studies to explore preventive strategies. Also in a broader picture the results of this study are important. Considering the large number of opioid users in the United States and the potential impact for the US health care system once the now younger patients need to be treated for CVD.

Note: The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology


Martin Bahls commented on this article:

  1. Nalini, M., et al., Long-term opiate use and risk of cardiovascular mortality: results from the Golestan Cohort Study. European Journal of Preventive Cardiology, zwaa006, 
    10 September 2020