By Michael H. Crawford, MD
Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco
SYNOPSIS: An observational study of a huge cohort of patients admitted to California hospitals showed patients who used cocaine, methamphetamine, opiates, and cannabis were at a higher risk of developing atrial fibrillation vs. those with similar risk factors who did not use the substances.
SOURCE: Lin AL, Nah G, Tang JJ, et al. Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation. Eur Heart J 2022;Oct 18:ehac558. doi: 10.1093/eurheartj/ehac558. [Online ahead of print].
Modern treatment for atrial fibrillation (AF) focuses on rate control, rhythm control, and anticoagulation to prevent systemic embolism. Identifying modifiable risk factors for AF would significantly affect patient outcomes and healthcare costs.
In California, Lin et al interrogated the Office of Statewide Health Planning and Development databases for adult inpatient, emergency department, and ambulatory surgery patients between 2005 and 2015. The authors used ICD-9 codes to identify illicit substance use and AF. Researchers excluded patients with AF on their first encounter. Follow-up started with the first encounter and continued until AF occurred or the study ended. Investigators did not consider atrial flutter to be AF. Lin et al used negative controls to assess the validity of any associations between AF and illicit substances (appendicitis for acute conditions, and sarcoma and renal cell carcinoma for chronic conditions). After excluding patients with missing data, the study population consisted of 23,561,884 patients, of whom 98,271 used methamphetamine, 48,701 cocaine, 10,032 opiates, and 132,834 cannabis. AF developed in 998,747 patients during the study period.
After adjusting for potential confounders and mediators, each illicit substance was associated with AF: methamphetamines (HR, 1.86; 95%, CI 1.81-1.92), cocaine (HR, 1.61; 95% CI, 1.55-1.68), opiates (HR, 1.74; 95% CI, 1.62-1.87), and cannabis (HR, 1.35; 95% CI, 1.30-1.40). Also, none of the chronic negative controls exhibited an association with AF, but there was a weak association with cannabis use and appendicitis (HR, 1.2; 95% CI, 1.14-1.26). The authors concluded efforts to mitigate illicit substance use may be a new way to prevent AF.
COMMENTARY
In the Lin et al study, the HR for tobacco use was 1.32 and 1.99 for alcohol use. The associations observed with the four illicit substances were in this range. Other factors known to be associated with AF carried similar HRs: 1.99 for hypertension, 1.47 for obesity, and even 1.06 for age. Accordingly, the increase in the probability of developing AF over time was at least partially explained by the study population aging. This was especially the case for cannabis and methamphetamine use. Notably, all other racial or ethnic groups exhibited a weaker association with AF compared to white individuals (HR for Black patients, 0.70; HR for Hispanic patients, 0.65; and HR for Asian patients, 0.69).
Although these results augment our knowledge of the connections between substance use and AF beyond tobacco and alcohol, there were significant limitations to this study. It was observational, so there may be residual confounding and biases. The study population was of unprecedented size, but about half were white and about one-quarter were Hispanic. The study population was individuals admitted to hospitals, so their use of illicit substances may be more severe, and AF may have been more severe. ICD-9 codes were used to identify AF, which can be subject to classification errors. Also, the population risk of AF is low because of the relatively infrequent prevalence of substance abuse (all less than 1%). Finally, ICD-9 codes do not allow the determination of dose-response relationships.
Cocaine and methamphetamine stimulate the central nervous system (CNS), while opiates and cannabis usually depress the CNS. The mechanism of this association is less clear with the latter two agents. Autonomic aberrations are known to pose an acute risk of AF, so perhaps the effects of cannabis and opiates operate by altering the autonomic nervous system centrally. More work is needed to establish the mechanism for inciting AF by opiate and cannabis use. Our list of substances that could induce AF has grown to at least six: tobacco, alcohol, cocaine, methamphetamines, opiates, and cannabis. Efforts to eliminate or reduce the use of these substances, especially among those at high risk for developing AF because of other comorbidities, are warranted.
An observational study of a huge cohort of patients admitted to California hospitals showed patients who used cocaine, methamphetamine, opiates, and cannabis were at a higher risk of developing atrial fibrillation vs. those with similar risk factors who did not use the substances.
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