Risk of VBA Stroke and Chiropractic Care • Cassidy et al
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Methods Study Design
catherization, cervical spine surgery, cervical percuta- neous nerve blocks, radiation therapy and diagnostic cerebral angiography have been identified as possible risk factors. 17–21 The true incidence of vertebrobasilar dissection is un- known, since many cases are probably asymptomatic, or the dissection produces mild symptoms. 22 Confirming the diagnosis requires a high index of suspicion and good vascular imaging. The cases that are most likely to be diagnosed are those that result in stroke. 19,22 Ischemic stroke occurs when a thrombus develops intraluminally and embolizes to more distal arteries, or less commonly, when the dissection extends distally into the intracranial vertebral artery, obliterating branching vessels. 22 The best incidence estimate comes from Olmstead county, where vertebral artery dissection causing stroke affected 0.97 residents per 100,000 population between 1987 and 2003. 23 To date there have been two case-control studies of stroke following neck manipulation. Rothwell et al used Ontario health data to compare 582 cases of VBA stroke to 2328 age and sex-matched controls. 24 For those aged ! 45 years, cases were five times more likely than con- trols to have visited a chiropractor within 1 week of VBA stroke. Smith et al studied 51 patients with cervical ar- tery dissection and ischemic stroke or transient ischemic attack (TIA) and compared them to 100 control patients suffering from other strokes not caused by dissections. 25 Cases and controls came from two academic stroke cen- ters in the United States and were matched on age and sex. They found no significant association between neck manipulation and ischemic stroke or TIA. However, a subgroup analysis showed that the 25 cases with verte- bral artery dissection were six times more likely to have consulted a chiropractor within 30 days before their stroke than the controls. Finally, because patients with vertebrobasilar artery dissection commonly present with headache and neck pain, 23 it is possible that patients seek chiropractic care for these symptoms and that the subsequent VBA stroke occurs spontaneously, implying that the associ- ation between chiropractic care and VBA stroke is not causal. 23,26 Since patients also seek medical care for headache and neck pain, any association between pri- mary care physician (PCP) visits and VBA stroke could be attributed to seeking care for the symptoms of verte- bral artery dissection. The purpose of this study is to investigate the asso- ciation between chiropractic care and VBA stroke and compare it to the association between recent PCP care and VBA stroke using two epidemiological designs. Evidence that chiropractic care increases the risk of VBA stroke would be present if the measured associa- tion between chiropractic visits and VBA stroke ex- ceeds the association between PCP visits and VBA strokes.
We undertook population-based case-control and case- crossover studies. Both designs use the same cases. In the case- control design, we sampled independent control subjects from the same source population as the cases. In the case-crossover design, cases served as their own controls, by sampling control periods before the study exposures. 27 This design is most ap- propriate when a brief exposure ( e.g. , chiropractic care) causes a transient change in risk ( i.e. , hazard period) of a rare-onset disease ( e.g. , VBA stroke). It is well suited to our research ques- tions, since within person comparisons control for unmeasured risk factors by design, rather than by statistical modeling. 28–30 Thus the advantage over the case control design is better con- trol of confounding. Source Population The source population included all residents of Ontario (109,020,875 person-years of observation over 9 years) cov- ered by the publicly funded Ontario Health Insurance Plan (OHIP). Available utilization data included hospitalizations with diagnostic coding, and practitioner (physician and chiro- practic) utilization as documented by fee-for-service billings accompanied by diagnostic coding. We used two data sources: (1) the Discharge Abstract Database (DAD) from the Canadian Institute for Health Information, which captures hospital sep- arations and ICD codes, and (2) the OHIP Databases for ser- vices provided by physicians and chiropractors. These data- bases can be linked from April 1992 onward. Cases We included all incident vertebrobasilar occlusion and stenosis strokes (ICD-9433.0 and 433.2) resulting in an acute care hos- pital admission from April 1, 1993 to March 31, 2002. Codes were chosen in consultation with stroke experts and an epide- miologist who participated in a similar past study (SB). 24 Cases that had an acute care hospital admission for any type of stroke (ICD-9433.0, 433.2, 434, 436, 433.1, 433.3, 433.8, 433.9, 430, 431, 432, and 437.1), transient cerebral ischemia (ICD- 9435) or late effects of cerebrovascular diseases (ICD-9438) before their VBA stroke admission or since April 1, 1991 were excluded. Cases residing in long-term care facilities were also excluded. The index date was defined as the hospital admission date for the VBA stroke. Controls For the case-control study, four age and sex-matched controls were randomly selected from the Registered Persons Database, which contains a listing of all health card numbers for Ontario. Controls were excluded if they previously had a stroke or were residing in a long-term care facility. For the case crossover study, four control periods were ran- domly chosen from the year before the VBA stroke date, using a time-stratified approach. 31 The year was divided into disjoint strata with 2 week periods between the strata. For the 1 month hazard period, the disjoint strata were separated by 1 month periods and the five remaining control periods were used in the analyses. We randomly sampled disjoint strata because chiro- practic care is often delivered in episodes, and this strategy eliminates overlap bias and bias associated with time trends in the exposure. 32
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