LONG-TERM OUTCOME OF YOUNG ADULTS WITH ISCHEMIC STROKE

Ischemic stroke (IS) is one of the most common causes of death and disability worldwide. Around 10% of ISs affect young adults less than 50 years of age. Incidence of IS in young adults is approximately 10-20/100 000 people per year in the developed countries. Young patients typically have many years of active life ahead, and have families and work to take care of. Therefore, their long-term outcomes after IS are of paramount importance, but remain understudied. The aim of this thesis was to investigate the outcome of these young patients; regarding their cancer diagnoses and long-term risk of death, future cardiovascular events, and return to work, as well as to study factors, such as the etiology of index IS, that are associated with poor outcome. Also, we wanted to investigate whether the incidence of pregnancyand deliveryrelated complications before and after IS were different from stroke-free matched controls. Helsinki Young Stroke Registry (HYSR) includes 1008 consecutive firstever IS patients aged 15-49 years, treated 1994 to 2007 at the Department of Neurology, Helsinki University Hospital. We obtained outcome data for these patients from several national registries, including Hospital Discharge Registry (HDR) and Medical Birth Registry (MBR) from the National Institute of Health and Welfare (THL), Death Registry from Statistics Finland, and Earnings and Accrual registry from the Finnish Centre for Pensions. The unique personal identification number that exists for all people residing in Finland allowed the linkage of patients from HYSR to the follow-up data. The outcome events were verified from patient records whenever feasible. A total of 3.9% of young IS patients had cancer diagnosed before or during hospitalization for IS, with a median time of 4.9 years from cancer diagnosis to IS. Similarly, 3.8% of patients had cancer diagnosed after IS until the end of 2011, with a median time of 6.7 years from IS to cancer diagnosis. We found no cancers in the youngest patients aged <30 years at IS onset. The largest single groups of cancers were lung and respiratory tract cancers. Especially active cancer without any other cause of IS, melanoma, and lung/respiratory tract cancers were significantly associated with death, when adjusted for known confounders. Limiting to those young patients who survived over 30 days from the index event, a total of 152 (15.7%) patients died during a median follow-up of 10.1 years. We found a 35.7% cumulative 15-year risk for composite vascular events and a 11.1% risk for vascular death, accordingly. Adjusted for age and sex, patients whose index IS were caused by large-artery atherosclerosis (LAA), had the highest hazard ratio (HR) for recurrent strokes, 2.7, compared with patients with IS of undetermined etiology. Similarly, patients whose index strokes were caused by high-risk sources of cardioembolism (CEH) had the highest HR, 3.7, for any subsequent cardiovascular events. On the contrary, patients whose ISs were caused by vertebral artery dissection (VAD) had the lowest HR, 0.3, for future cardiovascular events, again adjusted for age and sex. Overall, the cumulative 15-year risks were 9 times greater for arterial (33.7%) than for venous events (3.9%). In addition, patients with a cardiovascular disease or hemorrhagic stroke diagnosed before the index event had 4 times higher long-term incidence rate for any cardiovascular event (113.0/1000 person-years) than patients without such history (28.1/1000 person-years). There were 207 singleton pregnancies for 124 mothers before IS and 68 pregnancies for 45 mothers after IS. A total of 17 mothers had pregnancies both before and after IS. No deaths occurred during pregnancy or puerperium. Mothers with a history of IS seemed to have had more assisted reproductive technologies (ART), induced abortions, miscarriages, and cesarean sections at first pregnancy after IS compared with matched controls in the descriptive analyses, without statistical testing applied. Mothers with an impending IS in the future had a slightly increased risk for pregnancyand delivery-related complications adjusted for socioeconomic status and maternal smoking, compared with matched control mothers, although only being borderline in statistical significance. Mothers who had experienced IS had more hospitalizations during subsequent pregnancies than their matched controls, with an adjusted incidence rate ratio of 1.85. When restricting to patients with mild to moderate IS and who were working within one year before IS, as many as 37.6% of patients were not working at one year, 42.0% at two years, the number increasing up to 46.9% at five years from IS. Large anterior strokes, strokes caused by LAA, CEH, and rare causes other than dissection, compared with undetermined etiology, moderate to severe aphasia compared with no aphasia, mild and moderate to severe limb paresis compared with no paresis, and moderate to severe visual field deficit compared with no deficit, were associated with a patient not working at one year after IS, when adjusted for age, sex, socioeconomic status, and National Institutes of Health Stroke Scale (NIHSS) score at admission. In conclusion, despite their young age, IS affected many life aspects, specifically the morbidity, mortality, and return to work, and as such has a major impact for the patient, also during the long-term follow-up. The worst prognosis regarding their long-term risk of vascular death, future cardiovascular events, and return to work seems to be for those individuals with an etiology of LAA and CEH underlying their index ISs.