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

Abstract

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.

Keywords: Young stroke; cardiovascular disease; prognosis; risk factors.

Figure 1.

Cumulative risks of ischaemic events: (a) any ischaemic event; (b) cerebral ischaemia; (c) other arterial events.

Figure 2.

Annual risk of ischaemic events. Data points represent mean annual risks for the periods 2 to 5 years, 6 to 10 years, 11 to 15 years, 16 to 20 years and 21 to 25 years.

Figure 3.

Cumulative risk of any ischaemic event stratified by TOAST subtype. Patients with large artery (61.4%, 95%CI: 51.1–71.8%) or cardio-embolic stroke (62.7%, 95%CI: 38.6–86.7%) had a higher cumulative risk of any ischaemic event compared to undetermined cause (33.8%, 95%CI: 24.3–43.2%) (log rank p < 0.001 and p = 0.001 respectively).