Helicobacter pylori and Cerebrovascular Disease
To the Editor:
We are currently conducting a Canada-wide study of inhospital adverse events after carotid endarterectomy, and as part of that research we have performed analyses exploring associations between a variety of clinical variables and adverse events—specifically, inhospital death or postoperative stroke. These analyses demonstrate an association between peptic ulcer disease (PUD) and adverse events after carotid endarterectomy. We had initially dismissed this association as being spurious, perhaps due to the inevitable type I errors that arise when multiple variables are considered in such analyses. However, the recent paper in Stroke by Ameriso and colleagues1 demonstrating Helicobacter pylori in human carotid plaques makes us wonder whether our finding is not, in fact, a “true” association.
We identified carotid endarterectomy cases across Canada by screening hospital discharge abstracts compiled by the Canadian Institute for Health Information for the presence of ICD-9-CM procedure code 50.12. The occurrence of inhospital death was determined from the “discharge alive” field in the discharge data, and postoperative stroke was identified by screening for diagnosis codes 997.0, 433, 434, 436, or 438 (for each of these, the associated ICD-9-CM diagnosis type indicator had to be coded as a “2,” indicating that the corresponding diagnosis is a complication rather than a preexisting diagnosis). We defined a number of clinical risk variables, including PUD, using a published ICD-9-CM coding algorithm for defining comorbidities.2
Bivariate analyses reveal that patients with PUD present as a diagnosis at time of admission were more likely to experience adverse events than were patients without PUD (10.3% versus 4.1%, P=0.022). After statistical adjustment to control for age, sex, urgency of admission, and a variety of other comorbidities (eg, diabetes and renal disease), the multivariate OR for adverse events associated with PUD was 2.12 (95% CI 0.95 to 4.76).
We congratulate Ameriso and colleagues for their interesting study. Their article leads us to believe that our finding of an association between PUD and adverse events after carotid endarterectomy may be meaningful and not just a “spurious” result. We await more research on this issue with interest.
We have read with great interest the letter by Ghali and colleagues. It provides a valuable example of the power wielded by a national epidemiological approach on a population database regarding the importance of detectable information.
The reported finding of an association between peptic ulcer disease and adverse events after carotid endarterectomy is interesting, and we agree that it may relate to our recent detection of Helicobacter pylori on carotid atherosclerotic plaques.
The medical literature has provided robust evidence of a potential link between infection/inflammation and vascular disease. Peptic ulcer disease, when associated with H pylori infection, may be considered an infectious process. Thus, the observation of Ghali and colleagues is provocative and demonstrates the need for further research in the area.
Several questions remain unanswered. Do patients with H pylori(+) peptic ulcer disease have an increased prevalence of carotid artery disease? Do patients with carotid artery disease have an increased prevalence of H pylori(+) peptic ulcer disease? Are there any meaningful clinical differences between H pylori(+) and H pylori(−) patients with carotid artery disease?
Our study demonstrated the presence of the microorganism in carotid lesions. However, we were unable to speculate on the role of H pylori in the initiation, progression, and/or complication of the atherosclerotic process. Neither were we able to explore the clinical or therapeutic implications of our findings.
The work of Ghali et al, together with research on the basic features of the relationship between infection and atherosclerosis, will undoubtedly expand the knowledge about this intriguing field.