In a large young population from Iran, we investigated the association between recreational opium consumption and the risk of premature CAD. We found that opium users were at an increased risk of CAD (OR 4.3, 95% CI 3.0–6.2) compared with non-users, even when other major cardiovascular risk factors were taken into account.
Very few studies have investigated the relationship between opium addiction and the risk of arterial thrombosis, with small sample size and with contrasting results, ranging from a protective to a harmful effect. Opium has been reported to be protective against the risk of ischaemic stroke, and not affecting the risk of ischaemic hearth disease in a previous study. However, Masoomi et al. suggested that opium use is associated with an increased risk of CAD in cases without cigarette smoking but not in addicted cases with cigarette smoking, by investigating a small population in Kerman, Iran (a case control study including 58 cases and 33 controls). Same conclusion was reported by Sadeghian et al., reporting unadjusted OR for the relationship between opium consumption and CAD in men of 4.5 (95% CI 1.5–13.4), very close to the ones found in our study. In a previous study by Khademi et al., opium consumption has been associated with an increased risk of overall death in men and women, for major causes of death, including death from cardiovascular disease, and for different subtypes of opium and various routs of use. The authors discussed whether this association was causal, or confounded by other shared risk factors, primarily the deleterious effects of smoking. Since smoking is the most used route of opium consumption (through smoking the absorption of morphine and codeine, the two sedative alkaloids that bind to the µ opioid receptor (MOR) in the brain, is quick across the lining of the lungs, and they achieve the target tissues within seconds), cigarette smoking is widespread among opium users. However, our results showed that the association between opium consumption and CAD decreased only slightly when smoking was taken into account (OR adjusted for smoking 2.9, 95% CI 2.0–4.3), and remained high even when other major cardiovascular risk factors were considered (fully adjusted OR 3.8, 95% CI 2.4–6.2). Our results from a large study confirm that opium addiction is a risk factor for CAD and suggest a causal relationship between the increased cardiovascular mortality found by Khademi et al., and opium consumption.
However, the biological mechanisms underlying this association are still to be clarified. Opium and its components might have a direct effect on the vessel wall, affecting atherosclerotic plaque formation and proliferation, according to what has been suggested in a preclinical study on rats. There is paucity of data with regard to the effects of opiates and opium on blood pressure. Acute or chronic exposure to morphine in rats significantly decreased the systolic, diastolic, and mean arterial blood pressures. In humans, however, although opium might temporarily reduce blood pressure by vasodilation, no differences has been found in long term diastolic and systolic blood pressure between opioid users and non-users[19, 20], even though an association with chronic kidney disease, which may affect the blood pressure, has been reported. In our analysis, adjustment for hypertension did not change the results. Moreover, we found no interaction between hypertension and opium use in our population. Since the relative risk of CAD for hypertensive subject who used opium was closed to the expected one by the sum of the relative risk of hypertension and opium use, it seems that the two risk factors act on non-interacting pathways. On the contrary, in our study, patients with dyslipidaemia who used opium had an excess risk of CAD compared with dyslipidaemic patients who did not use opium (OR for the combination 16.8, 95% CI 8.9–31.7), suggesting a positive biological interaction between high lipids levels and opium. There is little evidence that opium use is associated with increased lipid levels in humans. However, our observation is supported by animal models, in which opium consumption had worsening effects on atherosclerosis formation related with hypercholesterolemia, mainly affecting lipid profile. Finally, the effect of opium on serum glucose levels is controversial. Studies have indicated that opium consumption is related with either an unaltered or a reduced serum glucose levels.[22, 23] In our study, diabetic patients who used opium seemed to be at a relatively lower risk of CAD compared with diabetic patients who did not use opium, suggesting a protective effect of opium on the risk of CAD in diabetic patients. However, this analysis included few subjects, and therefore, should be considered very cautiously.
Strength and limitations
Our study has several limitations. First, the use of opium was self-reported in our study. The prevalence of recreational opium consumption in the Iranian population has been reported to be as high as 14% in the Golestan cohort, much higher than the prevalence we have found within our controls subjects (3.3%). Part of this difference is related to the case-control design of our study, to the different study populations, and to the definition of opium users, that in our study included only regular users. However, although it has previously been demonstrated in an Iranian population that a self-reported use of opium can be a reliable measurement of its real consumption, an underestimation of the real prevalence of opium users in both cases and controls may have occurred. This might partly explain the low prevalence of opium consumption within women, especially when compared with men (0.4% in control women compared with 7.3% in control men). In our analysis, the association between opium and CAD was stronger for men (OR 5.5, 95% CI 3.0–9.9) than for women (OR 2.6, 95% CI 0.5–12.6). Because the number of exposed women in the latter analyses is too small, we cannot argue that this difference is related to a specific sex effect, or merely to chance. Differential misclassification is less likely to have occurred. Since there is no perception that opium might cause myocardial infarction, it is unlikely that an underestimation of the exposure occurred differently between cases and controls. Second, due to lack of data, we were unable to perform additional analyses on dose related response and route of consumption. Those analyses might have helped in understanding the biological mechanisms underlying the association. Third, although we adjusted the analysis for several factors, we cannot exclude that residual confounding, such as for example physical activity, associated substance abuse, and medications, might have played a role in our results. Finally, despite our study is the largest on the relationship between opium and CAD, numbers in some sub-analyses were relatively small, leading to uncertainty and wide confidence intervals.