Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants.

OBJECTIVE: To evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke. DESIGN: Prospective population based cohort study. SETTING: UK Biobank Study, UK. PARTICIPANTS: 306 473 men and women, aged 40-73 years, recruited between 2006 and 2010. MAIN OUTCOME MEASURE: Hazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10-5 to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise. RESULTS: During a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10-8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10-13. The association with lifestyle was independent of genetic risk stratums. CONCLUSION: In this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

Risk factors and mechanisms of stroke in young adults: The FUTURE study.

Incidence of ischemic stroke and transient ischemic attack in young adults is rising. However, etiology remains unknown in 30-40% of these patients when current classification systems designed for the elderly are used. Our aim was to identify risk factors according to a pediatric approach, which might lead to both better identification of risk factors and provide a stepping stone for the understanding of disease mechanism, particularly in patients currently classified as "unknown etiology". Risk factors of 656 young stroke patients (aged 18-50) of the FUTURE study were categorized according to the "International Pediatric Stroke Study" (IPSS), with stratification on gender, age and stroke of "unknown etiology". Categorization of risk factors into ≥1 IPSS category was possible in 94% of young stroke patients. Chronic systemic conditions were more present in patients aged <35 compared to patients ≥35 (32.6% vs. 15.6%, p < 0.05). Among 226 patients classified as "stroke of unknown etiology" using TOAST, we found risk factors in 199 patients (88%) with the IPSS approach. We identified multiple risk factors linked to other mechanisms of stroke in the young than in the elderly . This can be a valuable starting point to develop an etiologic classification system specifically designed for young stroke patients.

The very long-term risk and predictors of recurrent ischaemic events after a stroke at a young age: The FUTURE study.

INTRODUCTION: Patients who suffer a stroke at a young age, remain at a substantial risk of developing recurrent vascular events and information on very long-term prognosis and its risk factors is indispensable. Our aim is to investigate this very long-term risk and associated risk factors up to 35 years after stroke. PATIENTS AND METHODS: Prospective cohort study among 656 patients with a first-ever ischaemic stroke or transient ischaemic stroke (TIA), aged 18-50, who visited our hospital (1980-2010). Outcomes assessed at follow-up (2014-2015) included TIA or ischaemic stroke and other arterial events, whichever occurred first. Kaplan-Meier analysis quantified cumulative risks. A prediction model was constructed to assess risk factors independently associated with any ischaemic event using Cox proportional hazard analyses followed by bootstrap validation procedure to avoid overestimation. RESULTS: Mean follow-up was 12.4 (SD 8.2) years (8105 person-years). Twenty-five years cumulative risk was 45.4% (95%CI: 39.4-51.5) for any ischaemic event, 30.1% (95%CI: 24.8-35.4) for cerebral ischaemia and 27.0% (95%CI: 21.1-33.0) for other arterial events. Risk factors retained in the prediction model were smoking (HR 1.35, 95%CI: 1.04-1.74), poor kidney function (HR 2.10, 95%CI: 1.32-3.35), history of peripheral arterial disease (HR 2.10, 95%CI: 1.08-3.76) and cardiac disease (HR 1.84, 95%CI: 1.06-3.18) (C-statistic 0.59 (95%CI: 0.55-0.64)). DISCUSSION AND CONCLUSION: Young stroke patients remain at a substantial risk for recurrent events; almost 1 of 2 develops a recurrent ischaemic event and 1 of 3 develops a recurrent stroke or TIA during 25 years of follow-up. Risk factors independently associated with recurrent events were poor kidney function, smoking, history of peripheral arterial disease and cardiac disease.

Clinical characteristics and outcome of intracerebral hemorrhage in young adults.

Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young adults are scarce. Our aim was to identify clinical determinants of prognosis after ICH in adults aged 18-50. We investigated 98 consecutive patients with an ICH, aged 18-50 years, admitted to our hospital between 1980 and 2010. Collected ICH characteristics included presenting symptoms, etiology, location, severity and Glasgow Coma Scale (GCS). Outcomes were case-fatality (death within 30 days), poor functional outcome (modified Rankin Scale >2), long-term mortality and recurrent ICH. We assessed discriminatory power of factors associated with case-fatality [area under receiver operating curve (AUC)]. Case-fatality was 20.4 % (n = 20) and well predicted by the GCS (AUC 0.83). Among 30-day survivors, a poor functional outcome at discharge was present in 51.3 %. During a mean follow-up of 11.3 years mortality was only increased in patients aged 40-50 years [standardized mortality ratio 4.8 (95 % CI 2.3-8.6)], but not in patients aged 18-40 years. Recurrent ICH occurred in 6 patients [10-year cumulative incidence 12.2 % (95 % CI 1.5-22.9 %)], all with the index ICH attributable to structural vascular malformations. Prognosis after ICH in young adults is poor, mainly due to high case-fatality, that is well predicted by the GCS. An exception is 30-day survivors <40 years, who have a similar risk of dying as the general population. Recurrence risk is especially present in patients with structural vascular malformations, whereas risk seems to be very low in other patients.