Acute ischaemic stroke in the absence of established vascular risk factors: Patient characteristics, stroke mechanism and long-term outcome.

Some acute ischaemic stroke (AIS) patients do not display established vascular risk factors (EVRFs). The aim was to assess their clinical characteristics, stroke subtype etiological classification and long-term outcome. All consecutive AIS patients from the Acute Stroke Registry of Lausanne (2003-2018) were retrospectively analyzed with complete assessment of the following EVRFs: hypertension, diabetes, major cardioembolic sources, dyslipidemia, smoking, obesity, alcohol abuse, previous stroke/transient ischaemic attack and depression/psychosis. Patients without EVRFs were compared to patients with one or more EVRFs using appropriate statistical models. Of 4889 included patients, 103 (2.1%) had no EVRFs. In multiple regression analysis, patients without EVRFs were significantly younger (odds ratio [OR] 0.13; 95% confidence interval [CI] 0.08-0.20) and had more multiterritorial strokes (OR 3.38; 95% CI 1.26-9.05). Strokes were more often related to patent foramen ovale (PFO) (OR 3.02; 95% CI 1.44-6.32) and less to atherosclerosis, cardioembolism or small vessel disease. In patients <55 years old, PFO (OR 2.76; 95% CI 1.50-5.08) and contraceptive use in females (OR 2.75; 95% CI 1.40-5.41) were more frequent, whereas sleep apnea syndrome (OR 0.09; 95% CI 0.01-0.63) was less. In patients ≥55 years, female sex (OR 2.84; 95% CI 1.43-5.65) and active cancer (OR 3.27; 95% CI 1.34-7.94) were more prevalent. At 12 months, patients without EVRFs had worse adjusted functional outcome (Rankin shift OR <sub>adj</sub> 0.63; 95% CI 0.42-0.95) and higher rate of recurrence and death (adjusted hazard ratio 2.11; 95% CI 1.19-3.74). In a consecutive cohort of AIS patients, only 2% showed no EVRFs. PFO and contraceptive use exhibited a strong association with the absence of EVRFs in younger patients and female sex and active cancer in elderly patients. Our findings highlight the importance of searching for previously unknown risk factors and/or unusual stroke mechanisms in patients without EVRFs