In this preliminary prospective cohort study of early survivors of acute myocardial infarction, marijuana use, as measured at the time of hospitalization, was associated with three-fold higher mortality following infarction. There was a gradient in risk, with the highest risk of death among individuals who used marijuana most frequently, and the risk was entirely unchanged by multivariate adjustment.
Marijuana use has important cardiovascular effects that could pose risk for patients with coronary heart disease. Among the best-defined of these is an increase in resting heart rate that can be selectively blocked by pretreatment with a cannabinoid receptor antagonist.26
This effect may be related to the prolonged catecholamine release that marijuana can induce.27
Marijuana use can also increase supine blood pressure, although it leads to orthostatic hypotension, postural dizziness, and even syncope in some cases.28, 29
At the same time that marijuana increases heart rate and, therefore, myocardial oxygen demand, it may also limit oxygen uptake. Marijuana smoking leads to a dose-dependent increase in carbon monoxide exposure30
and even higher blood levels of carboxyhemoglobin than does cigarette smoking.12
These effects have a demonstrably detrimental impact on patients with known coronary heart disease, in whom marijuana use decreases exercise time to the onset of angina by 50%, twice as great an effect as use of a standard cigarette.31
Marijuana use could also lead to higher risk of death among patients by interfering with adherence to standard therapies. Although the relationship of marijuana use and adherence to therapy among patients with coronary heart disease has not been evaluated, it may interfere with adherence to other life-saving medication, such as antiretroviral therapy for human immunodeficiency virus infection.32
The effects of marijuana use on cognitive function could conceivably exacerbate this further.33
Over half of deaths among Onset Study participants who reported marijuana use were non-cardiovascular, a substantially higher proportion than in non-users. Despite the lack of specificity inherent in use of death certificates to assign accurate causes of death,34
our results suggest that patients with coronary heart disease who use marijuana may be at particular for risk for all causes of death, and not recurrent cardiovascular disease alone. In this regard, the possible effects of marijuana use on unintentional injury and upper airway malignancy may be particularly important.35, 36
Marijuana use also directly increases risk-taking behavior in some settings,37, 38
but our findings were not altered by adjustment for other markers of risky behavior that were available, including binge drinking and cocaine use, perhaps because marijuana use was less strongly related to risk-taking in this relatively older aged cohort.
Similar to our findings, Sidney and colleagues also found that marijuana use was associated with AIDS-related death in men.2
It seems likely that this, at least in part, reflects confounding by indication, in which marijuana is used for nausea or appetite stimulation. However, cannabinoids may also have direct immunosuppressive effects that could accelerate disease progression among susceptible individuals.14
Further studies to understand the degree to which marijuana use could influence post-infarct mortality via direct cardiovascular effects, cognitive changes that reduce adherence, non-cardiovascular effects of marijuana, or simply other confounding factors related to marijuana use are clearly needed.
The Onset Study has both strengths and limitations. An important and perhaps unique strength is its assessment of marijuana use in a population of early survivors of myocardial infarction; to our knowledge, no comparable cohort studies exist. All participants were interviewed in a standardized manner during hospitalization for enzymatically confirmed infarcts, and a relatively large body of information on clinical and sociodemographic variables was obtained.
On the other hand, these results should be viewed as hypothesis-generating only. The number of marijuana smokers was relatively small, follow-up was limited to approximately four years, and the confidence limits around our estimates – even when they exclude the null – were relatively wide. The cohort was assembled in the early 1990s, and the association of marijuana use with prognosis, while collected prospectively, was not a primary aim. Although further follow-up of this cohort is not possible, and could be of limited value without updated assessments of marijuana, our results do point to the urgent need for larger and longer studies of marijuana use in comparable populations.
As with any observational study, we cannot prove cause-and-effect relationships, although it is unclear how a randomized trial to test our findings could be performed. Our results were also consistently unchanged by adjustment for a wide variety of clinical characteristics, including alcohol intake and smoking. Nonetheless, there are apt to be unmeasured confounding clinical or lifestyle factors that may be responsible for our findings.
We asked participants to report their usual marijuana use over the year prior to the infarction that resulted in their hospitalization and did not have information on post-MI use, which is likely to have differed from that measured here. Assuming that some marijuana users cease use following hospitalization, we may have underestimated the true effect of post-infarction marijuana use on survival. On the other hand, by assessing marijuana exposure prior to infarction and prior to follow-up, we minimized the potential bias that could affect assessment of post-infarction marijuana use alone if sicker patients give up marijuana use more often than healthier patients following hospitalization. Future studies should also include repeated assessments of marijuana use to address this possibility.
In conclusion, marijuana use was associated with three-fold greater mortality following acute myocardial infarction in this exploratory study, with a graded increase in risk with more frequent use. Because marijuana use appears to be increasing among middle-aged and older adults, this finding may have growing importance in the future. Although marijuana use does not appear to be associated with mortality among the general population, our results suggest that it may carry particular risks for vulnerable populations with established cardiovascular disease.