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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 51-58

Does opium have benefit for coronary artery disease? A systematic review


1 Cardiovascular Disease Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine; Department of Community Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
2 Cardiovascular Disease Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Science, Rasht, Iran
3 Department of Community Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

Date of Web Publication22-May-2018

Correspondence Address:
Dr. Bijan Shad
Department of Cardiology, Guilan Cardiovascular Disease Research Center, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_12_17

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  Abstract 


Opium is a plant with euphoria effect. People from some parts of the world traditionally use opium for cardioprotective effects. We did a systematic review to assess the effect of opium on coronary artery disease (CAD). A systematic database search was conducted in PubMed, Web of Science, Google Scholar, Cochrane library, Scopus, and SID from their onset up to June 2016. The quality of the studies was assessed with a standardized scoring system. Articles assessing the effect of opium consumption as orally or smoked were included in this review. Outcome was defined as age on CAD disease, risk of CAD, and morbidity from CAD. Poor methodological studies, animal studies, and studies on cardiovascular risk factors or serum markers were excluded from the review. Three case–control, three cohort, and eight cross-sectional studies were included in this systematic review. The age at the occurrence of myocardial infarction, coronary bypass surgery, and percutaneous intervention in opium users was signifi cantly lower than that of nonusers. Odds ratio of opium consumption for CAD ranged from 1.3 to 3.8 in different studies. Hazard ratio of opium consumption for ischemic heart disease was 1.90 (1.57–2.29) with modification by sex, ethnicity, education level, marital status, residential place, and cigarette smoking. We concluded, in spite of the traditional belief, that the current evidence did not support the protective effect of opium on CAD. Future well-designed studies concerning probable confounders in Iran and other similar parts of world are required.

Keywords: Coronary artery disease, mortality, opium, smoking


How to cite this article:
Hasandokht T, Salari A, Pour SS, Tirani HD, Shad B, Rajabi E. Does opium have benefit for coronary artery disease? A systematic review. Res Cardiovasc Med 2018;7:51-8

How to cite this URL:
Hasandokht T, Salari A, Pour SS, Tirani HD, Shad B, Rajabi E. Does opium have benefit for coronary artery disease? A systematic review. Res Cardiovasc Med [serial online] 2018 [cited 2018 Oct 16];7:51-8. Available from: http://www.rcvmonline.com/text.asp?2018/7/2/51/232972




  Introduction Top


Papaver somniferum is a kind of plant which has euphoria effect called opium. Opium is used for medical or recreational purposes in many parts of the word including the Middle East region and in many Asian countries.[1],[2] Tragic reports in 2014 indicated that >20 million people used opium in different forms such as inhalation (vapor, sikh– sang) or oral.[3] Near to 19% of patients with a history of myocardial infarction reported opium consumption.[4] Previous studies suggested several health effects of opium such as analgesic, hypnagogic, anticough, and antidiarrheal effects.[5] Studies showed that patients with chronic disease such as diabetes, hypertension, and ischemic heart disease more use opium than the general population due to traditional medicinal effect of opium on cardiovascular risk factors.[6] It is worth mentioning that, such belief was common among some health-care workers, especially older physicians. Finding this answer can help physicians to give a correct consultation to patients. Many studies were conducted about the relationship between opium consumption and coronary artery disease (CAD). Till now, to our knowledge, no systematic review of these studies has been published. However, in 2016, a perspective article mentioned about the hazardous effects of opium consumption on cardiovascular risk factors.[7] The purpose of this systematic review is to assess the effect of opium consumption on CAD.


  Methods Top


Data sources

We searched the following electronic database including PubMed, Web of Science, Google Scholar, Cochrane library, Scopus, and SID in English and Persian languages from their onset up to June 2016 for studies reporting the relationship between opium use and CAD. We defined PICO frame of our review as P: Opium user, C: Nonopium user, O: CAD risk, age on cardiac event. Two independent authors (TH and AS) searched database with the terms (“opium” [tiab] OR “Papaver” [tiab]) AND (“cardiovascular disease” [tiab] OR “Coronary Artery Disease” [tiab] OR “myocardial infarction” [tiab] OR “coronary artery bypass surgery” [tiab] OR “percutaneous coronary intervention” [tiab]). Studies about synthetic opioids such as morphine and fentanyl did not enter into our review. All reference lists of relevant articles were reviewed to identify further reports that could be included in the systematic review. In addition, relevant congress and dissertation research projects registry were searched for identifying unpublished literature such as Proquest and Iranian Registry of Clinical Trials.

Study selection

After excluding the repeated studies, an initial screen of titles and abstracts was independently conducted by two reviewers (BSH and ER) based on inclusion criteria. A high degree of agreement in the selected literature was reported (kappa coefficient: 0.82). Then, the full articles of the remaining studies were reviewed for further evaluation. This review included observational studies determining the relationship between opium consumption and incidence, disease severity, re-admission, re-vascularization, and mortality from CAD. We included studies reporting opium consumption as orally or smoking. Outcome was defined as age on CAD disease, risk of CAD, severity of CAD and mortality from CAD. We excluded article if it falls under the following criteria: (1) reporting the effect of passive opium, (2) poor methodological quality score, (3) reporting opium effect of cardiovascular risk factors such as hypertension, diabetes, hyperlipidemia, and serum marker, and (4) studying the effect of opium on animals. Quality assessment of selected studies was conducted by two independent (TH and AS) reviewers by the scoring guideline which is used in previous studies [Table 1].[8],[9] Every question of scoring system was defined as positive (1), negative (0), or unclear (?), with a highest potential grade of 100%. If there is any disagreement, a third reviewer (SS) made a final decision. A score higher than mean (50%) was defined as of high quality. Details of quality score related to each included study are summarized in [Table 2].
Table 1: Details of methodological quality scoring criteria

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Table 2: Details of quality score of the selected articles

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Data extraction

Two independent authors (TH and BSh) extracted data using predetermined forms. Data extraction table included first author name, publication year, study location, study design, sample size, frequency of opium consumption, as well as the relationship/association between opium and cardiovascular disease and variables for which the results were controlled by statistical adjustments [Table 3].
Table 3: Information of the included studies in present review

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  Results Top


The search to find relative papers located 412 possible references (including duplication between databases). After title screening, we excluded several studies which investigated the opium epidemiology, association between opium and cancer, arrhythmia, or other nonrelevant issues. Furthermore, after abstract screening, some studies were nonrelevant and excluded as follows: 11 studies due to assessing the relation between opium and cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia,[6],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32] two animal studies,[33],[34] five narrative review articles,[35],[36],[37],[38],[39] one qualitative study,[40] two studies on serum marker,[41],[42] and nine on poor methodological quality studies [Figure 1].[43],[44],[45],[46],[47],[48],[49],[50],[51]
Figure 1: PRISMA flow diagram of various stages of selecting articles for present systematic review

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In total, we included 14 studies in this systematic review [Table 2]. Of these, one study was case–control, 11 were cross-sectional, and two were cohort studies. One included study related to the US population and other reviewed studies were conducted in Iran. The total number of patients in reviewed studies was 59,020, and sample size ranged from 91 in a cross-sectional study to 50,045 in a cohort study. The mean age of CAD patients in opium users and nonusers was 53.3 (10.1) and 66.3 (10.4) years, respectively. Several probable confounders, such as age, sex, and cigarette smoking, were adjusted in some studies.

Four studies investigated the relationship between opium and mortality, angiographic findings, functional class, and the need for revascularization in patients with acute myocardial infarction (AMI).[4],[52],[53],[54] Five studies examined the opium prevalence, CAD severity, and mortality in patients who underwent coronary angiography (CAG).[12],[13],[14],[16],[55] Two studies assessed the prevalence of opium consumption, in-hospital mortality, rehospitalizations, and postoperative complications in coronary artery bypass graft (CABG) surgery patients.[15],[21] One cross-sectional study with 125 patients in two groups assessed the relationship between opium addiction and microvascular angina.[10] One cross-sectional study assessed the severity of coronary disease in two groups of patients with and without opium or opiate consumption history.[19] And, in a large cohort study with median 4.7-year follow-up per participant, the association of opium consumption with risk of mortality from circulatory disease was investigated.[17]

Frequency of opium user

Prevalence of the opium consumption in patients with AMI ranged from 17% in Isfahan,[54] central area of Iran, to 51% in Kerman, south part of Iran, in 2013.[53] Opium user rate in CAG reports was about 50% (15.7%–44%).[12],[13],[14],[16],[55] Seventeen percent of the Golestan cohort population reported opium usage.[17] Moreover, approximately 20% of the CABG patients were opium users.[15],[21] Furthermore, opioid consumption rate in microvascular coronary dysfunction (MCD) patients was more prevalent than individuals without MCD (23.2% vs. 7.2%, P < 0.001, respectively).[10]

Age at cardiac event

In four cross-sectional studies with totally sample size of 1745, opioid consumption decreased the age at AMI: three [4],[53],[54] significantly and one [52] nonsignificantly. In one cross-sectional study with follow-up component,[15] the age of 782 CABG patients in opium users was significantly lower than nonusers (48.0 ± 8.3 vs. 54.4 ± 10.2, P = 0.004, respectively). In another study conducted on 600 CABG and cardiac valve surgery patients, the age at the surgery was similar in opium users and nonusers.[21] In a recent study conducted in patients undergoing percutaneous coronary intervention (PCI), the age at PCI in opium user was lower than nonusers.[12] In four studies conducted on CAD patients who underwent CAG, there was no report about age in opium users and nonusers [Table 2].[13],[14],[16],[44]

Risk of coronary artery disease

In three cross-sectional [13],[16],[55] and one case–control [14] study with 3735 CAD patients, opium use was a significant risk factor for CAD. Odds ratio (OR) of opium consumption for CAD ranged from 1.3 in Sadeghian study [13] to 3.8 in Masoomi study.[16] Opium consumption was an independent risk factor for CAD in nonsmokers after adjusting for conventional risk factors (OR = 38, 95% confidence interval [CI] = 2.7–53.17).[14] A large cohort study reported the hazard ratio of opium consumption for ischemic heart disease as 1.90 (1.57–2.29) with modification by sex, ethnicity, education level, marital status, residential place, and cigarette smoking.[17] Furthermore, another case–control study reported opium addiction was an important effective factor of MCD (adjusted OR = 3.575, 95% CI = 1.418–9.016, P = 0.006) based on multivariable logistic regression analysis.[10] On the other hand, multiple logistic regression analysis in Marmor's study [19] indicated a significant protective effect of opium or opiate against moderate or severe CAD (OR = 0.8, 95% CI = 0.23–01.98 and OR = 0.32, 95% CI = 0.10–0.92, respectively).

Complication after cardiac event

In a cross-sectional study,[4] in-hospital mortality after AMI was 18.6% in those patients with a history of opium consumption versus 6.2% in those without (P = 0.02). However, in three studies conducted in AMI patients, in-hospital mortality was similar with regard to opium consumption.[52],[53],[54] Also, in-hospital mortality after CABG in two studies was not different between opium users and nonusers.[15],[21]

Re-admission frequency,[52] revascularization rate,[52] Intensive Care Unit (ICU) re-admission,[15] postoperative complications including respiratory, neurological, infective, and renal complications, and ICU time and hospital stay [15],[21] were not lower in opium users compared to nonusers.

Among 782 CABG patients in Safaii et al's. study, opium was an effective factor (P < 0.0001) of readmission due to cardiac event.[15] The study by Sharafi et al.[12] found that opium was not a significant factor on the incidence of the major adverse cardiac event (11 [3.1%] vs. 53 [4.4%]; P = 0.286), in patients undergoing PCI. There were no difference in angiographic findings [16],[52] and ejection fraction [16],[52],[54] between opium users and nonusers in three of the twelve included studies.


  Discussion Top


The present systematic review suggests that opium usage cannot delay the age of onset of CAD and decrease the risk of CAD. As well as, in-hospital mortality in opium users was not lower than nonusers. The results of most included studies were adjusted for some effective variables such as age, smoking, and diabetes on CAD. Almost all studies were conducted in Iran with approximately 8% opium users.[11],[22] Valuable data from large Golestan prospective cohort study showed the increased risk of death from circulatory disease associated with opium consumption.[17] According to Ghazavi's study,[20] serum inflammatory markers such as high-sensitivity C-reactive protein (CRP) and some complementary factors and nitric oxide in opium smokers were greater than nonusers. Hence, opium could have harmful effect on the cardiovascular system. However, the results of a cadaver study showed that the long-term exposure to opium or opiate is associated with decreased severity of CAD.[19] The finding of Marmor's study was related to both opium and opiate consumption, whereas, in other reviewed article, only opium usage effect on cardiovascular disease was studied. It is worth nothing that valuable evidence indicated that the second cause of death in opium user was CAD after accident.[18] According to a study on 5900 individuals, using opium could not reduce the odds of diabetes, hypertension, and hypercholesterolemia.[28] Although blood pressure decreases shortly after opium consumption due to vasodilatation, this is an acute reaction. Furthermore, a few hours before the time of next dose of opium consumption, the blood pressure and heart rate elevate. According to Asgary et al's. study,[20] some risk factors for premature atherosclerosis such as HbA1c, high-density lipoprotein-cholesterol, Lpa, apo-B, factor VII, fibrinogen, apo-A, and CRP in opium users were higher than that in nonusers.

Our findings are parallel with that of a recent review which suggested that several types of cancers such as esophagus, stomach, larynx, lung, and urinary bladder was associated with opium usage.[56] In addition to the adverse cardiac effect of opium, Shirani et al., suggested opium as a risk factor for carotid stenosis.[50] Moreover, Masoudkabir et al., in a prospective article reported that opium not only has no cardioprotective effects, but it might have adverse effect.[7]

Some issues must be considered: (1) Traditionally, most opium users smoked tobacco. Hence, the cigarette smoking should be considered as a confounding factor. The results of some included studies in this review were adjusted for smoking, but opium remain risk factor for CAD, (2) There are different ways of opium consumption like inhalation (vapor, sikh– sang), oral, and intravenous with various absorption and blood level of its main sub extract, i.e., morphine. Hence, different cardiovascular effects might be expected. However, in large Golestan cohort study,[17] this adverse cardiac effect of opium was present for various forms of opium and for various methods of consumption, (3) In spite of pure opiates such as heroin, opium is a combination of various materials that may produce different effects. People believe opium (Taryak) in past years was more effective and pure than these days. Therefore, we cannot investigate the health related of opium itself, (4) There are difference in amount of opium consumption and duration of usage among opium user. Some individuals take orally opium in seed bead size or lentil once or twice a day. These probable confounding factors should be considered in designing of the study, in analyzing or interpretation the results, and (5) majority of studies were conducted in Iran except one study from the US. The high prevalence of opium in Iran allows us conducting epidemiological study. These studies conducted in the different parts of Iran with various races and climate. Although, some of them were poor quality, but the result of favorable studies did not support the cardioprotective effect of opium.


  Conclusion Top


The results of this systematic review did not support the protective effect of opium use on CAD. Future well-designed studies concerning probable confounders in Iran and other similar parts of world are required.

Acknowledgment

The authors would like to thank to research chancellor of Guilan University of Medical Sciences

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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