Marijuana Use and Long-Term Mortality Among AMI Survivors
Background Smoking marijuana has been reported to increase risk of myocardial infarction (MI) immediately after use, but less is known about the long-term impact of marijuana use among patients with established coronary disease.
Methods The Determinants of MI Onset Study is a multicenter inception cohort study of myocardial infarction (MI) patients enrolled in 1989 to 1996 and followed up for mortality using the National Death Index. In an initial analysis of 1,935 MI survivors followed up for a median of 3.8 years, we found an increased mortality rate among marijuana users. The current article includes 3,886 Determinants of MI Onset Study patients followed up for up to 18 years. We used Cox proportional hazards models to calculate the hazard ratio and 95% CI for the association between marijuana use and mortality and a propensity score matched analysis to further control confounding.
Results Over up to 18 years of follow-up, 519 patients died, including 22 of the 109 reporting marijuana use in the year before their MI. There was no statistically significant association between marijuana use and mortality. Compared with nonusers, the mortality rate was 29% higher (95% CI 0.81–2.05, P = .28) among those reporting any marijuana use.
Conclusions Habitual marijuana use among patients presenting with acute MI was associated with an apparent increased mortality rate over the following 18 years that did not reach nominal statistical significance. Larger studies with repeated measures of marijuana use are needed to definitively establish whether there are adverse cardiovascular consequences of smoking marijuana among patients with established coronary heart disease.
Marijuana is the most commonly used illicit drug in the United States, and it is becoming increasingly popular over time. In 2009, it was estimated that 16.7 million (6.6%) people ages 12 years and older had used marijuana in the past month. Between 2002 and 2009, the rate of current illicit drug use increased from 2.7% to 6.2% among adults ages 50 to 59 years. Despite the common and increasing use, few studies have examined the long-term impact of marijuana use, a question that is of particular public health interest with the aging of the baby boomers who are now at risk for cardiovascular disease or who already are known to have coronary artery disease.
Cannabinoids are associated with both harmful and protective effects. The main active constituent of marijuana, tetrahydrocannabinol, is a mixed agonist for cannabinoid 1 and 2 receptors (CB1 and CB2). Activation of CB1 receptors may increase lipid resistance and promote chronic cardiovascular dysfunction in obesity and diabetes; on the other hand, activation of CB2 receptors may suppress the inflammatory response and, in turn, reduce atherosclerosis progression. In terms of short-term effects, marijuana can acutely lead to cardiac ischemia in susceptible individuals by causing a catecholamine release that, in turn, increases resting heart rate, ischemia, and arrhythmias. In addition, smoking marijuana decreases vascular resistance leading to orthostatic hypotension, limits oxygen uptake by increasing levels of carboxyhemoglobin, and may delay the treatment of chest pain because of the analgesic properties of tetrahydrocannabinol. Furthermore, marijuana use has been associated with a short-term increased risk of myocardial infarction in adults and children.
Little is known about the association between marijuana use and survival, particularly among those at highest cardiovascular risk, such as those who have survived a myocardial infarction (MI). We previously showed that the rate of MI is 4.8 times greater (95% CI 2.4–9.5) in the hour after marijuana use compared with other times. Regarding the risk from habitual marijuana use, several studies have reported that there is a relationship between heavy cannabinoid use and all-cause mortality, and some, but not all, studies have shown that there is a higher mortality rate associated with cannabinoid use in the general population. In a preliminary analysis of 1,913 Determinants of MI Onset Study (MIOS) participants including 52 people reporting marijuana use in the year before MI that were followed up for a median of 3.8 years, we found that compared with nonusers, using marijuana less than once per week was associated with a 2.5-fold (95% CI 0.9–7.3) higher rate of mortality, and the corresponding hazard ratio for using marijuana once or more per week was 4.2 (95% CI 1.2–4.3). It remains unclear whether marijuana use is associated with increased mortality among MI survivors over longer follow-up times. Therefore, we extended our previous analysis of the MIOS study to include a larger sample size (3,886 participants, including 109 marijuana users) with up to 18 years of follow-up. We hypothesized that compared with no use, self-reported marijuana use would be associated with a higher rate of all-cause mortality among patients who sustained an MI and that there would be a dose-response relationship with higher mortality rates for greater frequency of marijuana use.
Abstract and Introduction
Abstract
Background Smoking marijuana has been reported to increase risk of myocardial infarction (MI) immediately after use, but less is known about the long-term impact of marijuana use among patients with established coronary disease.
Methods The Determinants of MI Onset Study is a multicenter inception cohort study of myocardial infarction (MI) patients enrolled in 1989 to 1996 and followed up for mortality using the National Death Index. In an initial analysis of 1,935 MI survivors followed up for a median of 3.8 years, we found an increased mortality rate among marijuana users. The current article includes 3,886 Determinants of MI Onset Study patients followed up for up to 18 years. We used Cox proportional hazards models to calculate the hazard ratio and 95% CI for the association between marijuana use and mortality and a propensity score matched analysis to further control confounding.
Results Over up to 18 years of follow-up, 519 patients died, including 22 of the 109 reporting marijuana use in the year before their MI. There was no statistically significant association between marijuana use and mortality. Compared with nonusers, the mortality rate was 29% higher (95% CI 0.81–2.05, P = .28) among those reporting any marijuana use.
Conclusions Habitual marijuana use among patients presenting with acute MI was associated with an apparent increased mortality rate over the following 18 years that did not reach nominal statistical significance. Larger studies with repeated measures of marijuana use are needed to definitively establish whether there are adverse cardiovascular consequences of smoking marijuana among patients with established coronary heart disease.
Introduction
Marijuana is the most commonly used illicit drug in the United States, and it is becoming increasingly popular over time. In 2009, it was estimated that 16.7 million (6.6%) people ages 12 years and older had used marijuana in the past month. Between 2002 and 2009, the rate of current illicit drug use increased from 2.7% to 6.2% among adults ages 50 to 59 years. Despite the common and increasing use, few studies have examined the long-term impact of marijuana use, a question that is of particular public health interest with the aging of the baby boomers who are now at risk for cardiovascular disease or who already are known to have coronary artery disease.
Cannabinoids are associated with both harmful and protective effects. The main active constituent of marijuana, tetrahydrocannabinol, is a mixed agonist for cannabinoid 1 and 2 receptors (CB1 and CB2). Activation of CB1 receptors may increase lipid resistance and promote chronic cardiovascular dysfunction in obesity and diabetes; on the other hand, activation of CB2 receptors may suppress the inflammatory response and, in turn, reduce atherosclerosis progression. In terms of short-term effects, marijuana can acutely lead to cardiac ischemia in susceptible individuals by causing a catecholamine release that, in turn, increases resting heart rate, ischemia, and arrhythmias. In addition, smoking marijuana decreases vascular resistance leading to orthostatic hypotension, limits oxygen uptake by increasing levels of carboxyhemoglobin, and may delay the treatment of chest pain because of the analgesic properties of tetrahydrocannabinol. Furthermore, marijuana use has been associated with a short-term increased risk of myocardial infarction in adults and children.
Little is known about the association between marijuana use and survival, particularly among those at highest cardiovascular risk, such as those who have survived a myocardial infarction (MI). We previously showed that the rate of MI is 4.8 times greater (95% CI 2.4–9.5) in the hour after marijuana use compared with other times. Regarding the risk from habitual marijuana use, several studies have reported that there is a relationship between heavy cannabinoid use and all-cause mortality, and some, but not all, studies have shown that there is a higher mortality rate associated with cannabinoid use in the general population. In a preliminary analysis of 1,913 Determinants of MI Onset Study (MIOS) participants including 52 people reporting marijuana use in the year before MI that were followed up for a median of 3.8 years, we found that compared with nonusers, using marijuana less than once per week was associated with a 2.5-fold (95% CI 0.9–7.3) higher rate of mortality, and the corresponding hazard ratio for using marijuana once or more per week was 4.2 (95% CI 1.2–4.3). It remains unclear whether marijuana use is associated with increased mortality among MI survivors over longer follow-up times. Therefore, we extended our previous analysis of the MIOS study to include a larger sample size (3,886 participants, including 109 marijuana users) with up to 18 years of follow-up. We hypothesized that compared with no use, self-reported marijuana use would be associated with a higher rate of all-cause mortality among patients who sustained an MI and that there would be a dose-response relationship with higher mortality rates for greater frequency of marijuana use.