The current study examined the relationship between amphetamine abuse/dependence and aortic dissection in patients aged 18-49 years in the NIS from 1995 to 2007. These findings suggest a strong and significant association between amphetamine abuse/dependence and aortic dissection. The strength of the relationship was greater for amphetamines than for cocaine (and the interaction effect between amphetamine and cocaine abuse/dependence was not significant). In this 18-49 year old cross-sectional study population, the hospitalization rate for aortic dissection increased, whereas for patients aged 50 years and older the hospitalization rate did not increase.
Our basic finding is consistent with prior mechanistic evidence for a relationship between aortic dissection and amphetamine abuse/dependence. Hypertension is a known trigger of aortic dissection22
and amphetamines are known to increase blood pressure.23, 24
Thus, it has been suggested by Swalwell et al. that perhaps the hypertensive effect of amphetamines is a cause of aortic dissection.10
An experiment by Hirst et al. demonstrated that intravenous injection of epinephrine (structurally and mechanistically related to amphetamines) in rabbits indeed led to aortic dissection.25
Vasculitis has been associated with aortic dissection, and in experiments and studies,22
methamphetamine has been shown lead to vasculitis.26-30
Cocaine, which is mechanistically similar to amphetamines, is linked to aortic dissection. Amphetamines and cocaine have similar hemodynamic effects; they both increase arterial blood pressure and heart rate, which is mediated through adrenergic receptors.31
Hsue et al. have reported in a chart review of acute aortic dissection from 1981 to 2001, 37% (14/38) of cases were associated with cocaine use.32
Daniel et al. also did a chart review from 1990 to 2006 and found that of 163 cases of acute aortic dissection, 9.8% were associated with cocaine use in the 24 hours prior to symptom onset.33
Singh et al. found that of 46 consecutive patients admitted with acute aortic dissection, 28% (13) were related to cocaine use.34
Divakaran et al. have published a case report of cocaine-associated aortic dissection.35
Possible mechanisms include cocaine-induced relaxation of aortic rings36
as well as cocaine-induced apoptosis of rat aortic vascular smooth muscle cells.37
This study has limitations. The population-based case control study (cross-sectional) design cannot rule out the possibility that other risk factors, measured or unmeasured, besides amphetamine abuse/dependence could have influenced the risk of aortic dissection. We did, however, include the obvious risk factors known to investigators. Race and sex were not entered into the multiple logistic regression model because analyses from the International Registry of Acute Aortic Dissection demonstrated they are not risk factors for aortic dissection.15
This study is also limited by the nature of administrative data and ICD-9-CM diagnoses. To our knowledge, the sensitivity and specificity for ICD-9-CM codes for amphetamine and cocaine abuse/dependence have not been established. We have previously discussed the impact of this.21
Westover AN, McBride S, Haley RW. Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry. 2007;64:495-502. Additionally, the sensitivity and specificity for ICD-9-CM codes for thoracic and thoracoabdominal aortic dissections have not been established. However, studies have used these codes in analyses.38-40
Additionally, Saad et al., in a study of consecutive autopsy cases, found 75% concordance between clinical and autopsy diagnoses for aortic dissection.41
In this de-identified administrative database, it is not possible to determine whether aortic dissection diagnoses are independent of each other. However, only analyzing aortic dissection diagnoses that were the primary discharge diagnosis somewhat mitigates the concern of readmission of aortic dissections.
Despite these limitations, this study has strengths. The large sample size of the NIS database allows for the study of relatively rare conditions, such as aortic dissection, with sufficient statistical power to test our hypothesis. The NIS, due to its geographic breadth, augments the external validity (generalizability) derived from a national representative population. Finally, our analytic approach properly accounted for the NIS sampling methodology (sampling weights and stratification) in the test of our hypothesis.