Stroke Risk and Outcomes in Patients With Traumatic Brain Injury: 2 Nationwide Studies Chien-Chang Liao, PhD, MPH; Yi-Chun Chou, MD; Chun-Chieh Yeh, MD; Chaur-Jong Hu, MD; Wen-Ta Chiu, MD, PhD; and Ta-Liang Chen, MD, PhD Abstract Objective: To investigate whether patients with traumatic brain injury (TBI) have an increased risk of stroke or poststroke mortality. Participants and Methods: Using Taiwan’s National Health Insurance Research Database, we conducted a retrospective cohort study of 30,165 patients with new TBI and 120,660 persons without TBI between January 1, 2000, and December 31, 2004. The risk of stroke was compared between 2 cohorts through December 31, 2008. To investigate the association between in-hospital mortality after stroke and history of TBI, we conducted a case- control study of 7751 patients with newly diagnosed stroke between January 1, 2005, and December 31, 2008. Results: The TBI cohort had an increased stroke risk (hazard ratio [HR], 1.98; 95% CI, 1.86-2.11). Among patients with stroke, those with a history of TBI had a higher risk of poststroke mortality compared with those without TBI (odds ratio, 1.57; 95% CI, 1.13-2.19). In the TBI cohort, factors associated with stroke were history of TBI hospitalization (HR, 3.14; 95% CI, 2.77-3.56), emergency care for TBI (HR, 3.37; 95% CI, 2.88-3.95), brain hemorrhage (HR, 2.69; 95% CI, 2.43-2.99), skull fracture (HR, 3.00; 95% CI, 2.42- 3.71), low income (HR, 2.65; 95% CI, 2.16-3.25), and high medical expenditure for TBI care (HR, 2.26; 95% CI, 2.09-2.43). The severity of TBI was also correlated with poststroke mortality. Conclusions: Traumatic brain injury was associated with risk of stroke and poststroke mortality. The rela- tionship between TBI and poststroke mortality does not seem to transcend all age groups. This research shows the importance of prevention, early recognition, and treatment of stroke in this vulnerable population. ª 2014 Mayo Foundation for Medical Education and Research n Mayo Clin Proc. 2014;89(2):163-172 S troke is the second leading cause of death worldwide and the leading cause of acquired disability in adults in most regions. 1-3 Cardiac disease, hypertension, dia- betes, smoking, alcohol intake, unhealthy diet, abdominal obesity, lack of exercise, psychoso- cial stress, and depression are risk factors associ- ated with 90% of stroke risk. 3 Previous studies identified several risk or protective factors for stroke and poststroke complications. 4-8 Never- theless, other potential risk factors associated with stroke prevalence need further validation. Traumatic brain injury (TBI) is a common trauma in the United States; it affects an esti- mated 1.7 million patients annually (1.365 million emergency care visits, 275,000 hospi- talizations, and 52,000 deaths). 9 The socioeco- nomic effects of disability after TBI are potentially long term or lifelong. 10-18 A lot is known about the epidemiologic features, natu- ral history, and risk factors of TBI. 9,19-22 How- ever, the high TBI fatality rate and post-TBI complications are still serious concerns. 23 The health effects after TBI include neuro- logic disorders, cognitive impairment, psychiat- ric illness, poor social functioning, and other adverse outcomes (such as brain tumor and mortality). 15-18 A previous study investigated the increased risk of stroke in individuals who survived TBI. 24 However, whether severity of TBI is associated with stroke is still unknown. Another recent study was limited by focusing on ischemic stroke. 25 No information was available on the association between TBI and poststroke mortality in patients with stroke. We evaluated the association between TBI and a new-onset stroke event in a case-control study and conduct- ed a nested case-control study to identify whether TBI contributes to poststroke mortality. PARTICIPANTS AND METHODS Source of Data The Department of Health of Taiwan in 1995 integrated 13 insurance systems into a univer- sal coverage health care program that covered For editorial comment, see page 142 From the Department of Anesthesiology (C.-C.L., T.-L.C.) and the Health Policy Research Center (C.-C.L., T.-L.C.), Taipei Medical University Hospi- tal, Taipei, Taiwan; School of Medicine (C.-C.L., C.J.H., T.-L.C.), Department of Neurology, Shuang Ho Hospital (C.-J.H.), and Graduate Institute of Injury Prevention and Control (W.-T.C.), Taipei Medical University, Taipei, Taiwan; Department of Physical Medicine and Rehabilita- tion, China Medical University Hospital, Taichung, Taiwan (Y.-C.C.); and School of Medicine, Graduate Institute of Clin- ical Medical Science, China Medical University, Tai- chung, Taiwan (C.-C.Y.). Mayo Clin Proc. n February 2014;89(2):163-172 n http://dx.doi.org/10.1016/j.mayocp.2013.09.019 www.mayoclinicproceedings.org n ª 2014 Mayo Foundation for Medical Education and Research 163 ORIGINAL ARTICLE