Stimulant Drug Abuse Tied to Stroke Risk

DALLAS, April 3 -- Amphetamine and cocaine abuse appear to promote the risk of stroke among young adults, according to a large hospital database.

Amphetamine abuse quadrupled the risk of hemorrhagic stroke while cocaine more than doubled the risk of both hemorrhagic and ischemic stroke among those ages 18 to 44, said Robert W. Haley, M.D., of the University of Texas Southwestern Medical Center here, and colleagues.

Amphetamine abuse, though not cocaine abuse, was also associated with increased mortality after hemorrhagic stroke, they wrote in the April issue of Archives of General Psychiatry.

Although the abuse of neither drug rivaled hypertension or other traditional stroke risk factors, amphetamines accounted for 2.3% of hemorrhagic strokes treated in Texas hospitals among patients in the 18 to 44 age group, the researchers calculated, and cocaine was associated with 4.1% of hemorrhagic and 2.3% of ischemic strokes.

Previous case reports and animal studies have consistently suggested a link with stroke, but epidemiologic studies have had conflicting results.

"Evidence has been accumulating for two decades supporting a link between abuse of stimulant drugs and strokes in young people," they wrote.

So the researchers analyzed data from all hospitalizations in Texas, reported to the state's quality-of-care database. Small, rural hospitals, exempt from reporting, were not included. The sample included 3,148,165 hospital discharges for men and women ages 18 to 44.

Over the study period from 2000 to 2003, strokes gradually increased from 1,887 to 2,097 to 2,133 to 2,252 per year. Likewise, the rate of strokes increased among drug abusers, particularly amphetamine users (P=0.004).

Cocaine was second only to alcohol as the most frequently abused drug (about 3.5 and 1.9 cases per 100 discharges, respectively), while amphetamines came in fifth (about 0.4 per 100 discharges).

When the researchers examined data from the 812,247 discharges in 2003, which was the only year with accurate stratification by stroke type, they found 937 hemorrhagic and 998 ischemic strokes. In-hospital death occurred in 3,763 admissions (0.46%).

In multivariate analysis, the adjusted risk of stroke from amphetamines and cocaine use in 2003 were:

• Amphetamine abuse was associated with hemorrhagic stroke (odds ratio 4.95, 95% confidence interval 3.24 to 7.55).
• Cocaine abuse was associated with hemorrhagic stroke (OR 2.33, 95% CI 1.74 to 3.11).
• Cocaine abuse was associated with ischemic stroke (OR 2.03, 95% CI 1.48 to 2.79).
• Amphetamine abuse was associated with a higher risk of death after hemorrhagic stroke (OR 2.63, 95% CI 1.07 to 6.50).

The strength of the association between hemorrhagic stroke and amphetamines was greater than for cocaine (see above), tobacco (OR 1.85, 95% CI 1.55 to 2.21), cannabis (OR 1.36, 95% CI 0.90 to 2.06), or alcohol (OR 1.28, 95% CI 0.99 to 1.65).

However, more traditional risk factors for stroke remained the best predictors.

Cerebrovascular anomalies were by far the most predictive factor in hemorrhagic stroke (OR 70.84, 95% CI 36.61 to 137.06). Intercranial tumors (OR 10.98, 95% CI 6.57 to 18.30) and hypertension (OR 7.68, 95% CI 6.66 to 8.86) also elevated hemorrhagic stroke risk more than amphetamine abuse.

Likewise for ischemic stroke, the risk with cocaine abuse was less than for abnormalities of the cerebrovascular system, hypertension, coagulation defect, endocarditis, dissection, migraine, lipid disorders, and atherosclerosis.

In an analysis of in-hospital death for all strokes combined, amphetamine abuse (OR 3.92, 95% CI 1.79 to 8.59, P<0.001) was associated with a greater risk than coagulation defects (OR 3.06, 95% CI 1.89 to 4.95, P<0.001) or hypertension (OR 1.29, 95% CI 0.97 to 1.73, P=0.08).

Controlling for amphetamine and cocaine, "any illicit drug use" did not independently increase risk of hemorrhagic stroke (OR 1.42, 95% CI 0.93 to 2.18). Abuse of more than one drug did not add significantly to the risk prediction models.

Altogether, abuse of any drugs -- including amphetamines, cocaine, cannabis, and tobacco -- accounted for 14.4% of hemorrhagic strokes and 14.4% of ischemic strokes in young adults in Texas hospitals in 2003, the researchers said, "assuming that the associations are causal and unbiased."

The mechanism by which stimulant drugs produce strokes may be direct effects on cerebral circulation, such as increased blood pressure, vasculitis and cerebral vasospasm, they suggested.

The study was limited in that there were no data on time between last drug use and stroke, though the study excluded diagnoses of substance abuse in remission so all were active drug abusers.

Also, "misclassification of drug abuse history is an unavoidable hazard of studies of drug abuse," Dr. Haley and colleagues wrote. This source of bias was unlikely to have substantially affected the findings since the broadening of confidence intervals would be offset by the large sample size in the study.