Risk of Vertebrobasilar Stroke and Chiropractic Care: Results of a Population-based Case-control and Case-crossover Study
Cassidy JD, Boyle E, Côté P, He Y, Hogg-Johnson S, Silver FL, Bondy SJ
Centre of Research Expertise for Improved Disability Outcomes,
University Health Network Rehabilitation Solutions,
Toronto Western Hospital,
Toronto, ON, Canada.
STUDY DESIGN: Population-based, case-control and case-crossover study.
OBJECTIVE: To investigate associations between chiropractic visits and vertebrobasilar artery (VBA) stroke and to contrast this with primary care physician (PCP) visits and VBA stroke.
SUMMARY OF BACKGROUND DATA: Chiropractic care is popular for neck pain and headache, but may increase the risk for VBA dissection and stroke. Neck pain and headache are common symptoms of VBA dissection, which commonly precedes VBA stroke.
METHODS: Cases included eligible incident VBA strokes admitted to Ontario hospitals from April 1, 1993 to March 31, 2002. Four controls were age and gender matched to each case. Case and control exposures to chiropractors and PCPs were determined from health billing records in the year before the stroke date. In the case-crossover analysis, cases acted as their own controls.
RESULTS: There were 818 VBA strokes hospitalized in a population of more than 100 million person-years. In those aged <45 years, cases were about three times more likely to see a chiropractor or a PCP before their stroke than controls. Results were similar in the case control and case crossover analyses. There was no increased association between chiropractic visits and VBA stroke in those older than 45 years. Positive associations were found between PCP visits and VBA stroke in all age groups. Practitioner visits billed for headache and neck complaints were highly associated with subsequent VBA stroke.
CONCLUSION: VBA stroke is a very rare event in the population. The increased risks of VBA stroke associated with chiropractic and PCP visits is likely due to patients with headache and neck pain from VBA dissection seeking care before their stroke. We found no evidence of excess risk of VBA stroke associated chiropractic care compared to primary care.
From the FULL TEXT Article
Our study advances knowledge about the association between chiropractic care and VBA stroke in two respects. First, our case control results agree with past case control studies that found an association between chiropractic care and vertebral artery dissection and VBA stroke. [24, 25] Second, our case crossover results confirm these findings using a stronger research design with better control of confounding variables. The case-crossover design controls for time independent confounding factors, both known and unknown, which could affect the risk of VBA stroke. This is important since smoking, obesity, undiagnosed hypertension, some connective tissue disorders and other important risk factors for dissection and VBA stroke are unlikely to be recorded in administrative databases.
We also found strong associations between PCP visits and subsequent VBA stroke. A plausible explanation for this is that patients with head and neck pain due to vertebral artery dissection seek care for these symptoms, which precede more than 80% of VBA strokes.  Since it is unlikely that PCPs cause stroke while caring for these patients, we can assume that the observed association between recent PCP care and VBA stroke represents the background risk associated with patients seeking care for dissection-related symptoms leading to VBA stroke. Because the association between chiropractic visits and VBA stroke is not greater than the association between PCP visits and VBA stroke, there is no excess risk of VBA stroke from chiropractic care.
Our study has several strengths and limitations. The study base includes an entire population over a 9-year period representing 109,020,875 person-years of observation. Despite this, we found only 818 VBA strokes, which limited our ability to compute some estimates and bootstrap confidence intervals. In particular, our age stratified analyses are based on small numbers of exposed cases and controls (Table 2). Further stratification by diagnostic codes for headache and neck pain related visits imposed even greater difficulty with these estimates. However, there are few databases that can link incident VBA strokes with chiropractic and PCP visits in a large enough population to undertake a study of such a rare event.
A major limitation of using health administrative data are misclassification bias, and the possibility of bias in assignment of VBA-related diagnoses, which has previously been raised in this context.  Liu et al have shown that ICD-9 hospital discharge codes for stroke have a poor positive predictive value when compared to chart review.  Furthermore, not all VBA strokes are secondary to vertebral artery dissection and administrative databases do not provide the clinical detail to determine the specific cause. To investigate this bias, we did a sensitivity analysis using different positive predictive values for stroke diagnosis (ranging from 0.2 to 0.8). Assuming nondifferential misclassification of chiropractic and PCP cases, our analysis showed attenuation of the estimates towards the null with lower positive predictive values, but the conclusions did not change (i.e., associations remained positive and significant—data not shown). The reliability and validity of the codes to classify headache and cervical visits to chiropractors and PCPs is not known.
It is also possible that patients presenting to hospital with neurologic symptoms who have recently seen a chiropractor might be subjected to a more vigorous diagnostic workup focused on VBA stroke (i.e., differential misclassification).  In this case, the predictive values of the stroke codes would be greater for cases that had seen a chiropractor and our results would underestimate the association between PCP care and VBA stroke.
A major strength of our study is that exposures were measured independently of case definition and handled identically across cases and controls. However, there was some overlap between chiropractic care and PCP care. In the month before their stroke, only 16 (2.0%) of our cases had seen only a chiropractor, while 20 (2.4%) had seen both a chiropractor and PCP, and 417 (51.0%) had just seen only a PCP. We were not able to run a subgroup analysis on the small number of cases that just saw a chiropractor. However, subgroup analysis on the PCP cases (n = 782) that did not visit a chiropractors during the 1 month before their stroke did not change the conclusions (data not shown).
Our results should be interpreted cautiously and placed into clinical perspective. We have not ruled out neck manipulation as a potential cause of some VBA strokes. On the other hand, it is unlikely to be a major cause of these rare events. Our results suggest that the association between chiropractic care and VBA stroke found in previous studies is likely explained by presenting symptoms attributable to vertebral artery dissection. It might also be possible that chiropractic manipulation, or even simple range of motion examination by any practitioner, could result in a thromboembolic event in a patient with a pre-existing vertebral dissection. Unfortunately, there is no acceptable screening procedure to identify patients with neck pain at risk of VBA stroke.  These events are so rare and difficult to diagnose that future studies would need to be multicentered and have unbiased ascertainment of all potential exposures. Given our current state of knowledge, the decision of how to treat patients with neck pain and/or headache should be driven by effectiveness and patient preference. 
Our population-based case-control and case-crossover study shows an association between chiropractic visits and VBA strokes. However, we found a similar association between primary care physician visits and VBA stroke. This suggests that patients with undiagnosed vertebral artery dissection are seeking clinical care for headache and neck pain before having a VBA stroke.