Ischemic stroke and atherosclerosis at a young age. The Norwegian Stroke in the Young Study

Abstract

Stroke risk and incidence increase exponentially with age. In Europe about one in three strokes occurs before the age of 65 years, with severe socioeconomic consequences on individual and society level. Despite improved diagnostic techniques and increasing knowledge, in 30-50% of young stroke patients the cause of stroke remains undetermined. However, due to the lack of one consistent definition for “young stroke”, published data are inhomogeneous regarding patient age, stroke types included and variables studied. It has been claimed that young stroke patients have a favorable prognosis, including usually good recovery from neurological deficits, low recurrence risk, a fair social prognosis, and favorable long-term outcome. Newer follow-up investigations documented, however, high rates of stroke recurrence, vascular co-morbidity and mortality. Further, increased rates of psychological disorders, reduced health-related quality of life and impared social activity are frequent long-term consequences. The underlying cause of stroke is related to differing risk of recurrent cardiovascular events, being highest in patients with largeartery atherosclerosis and cardioembolism. Hence, there is a need for systematic investigation and data collection from well-defined young stroke populations aiming to reveal the true cause of stroke, leading to right treatment of underlying conditions, and to optimal and aggressive secondary prevention. In the studies included in this thesis, we aimed to compare stroke characteristics in young ischemic stroke patients to older patient populations, and to controls free of cardiovascular disease. Data were obtained from 1217 ischemic stroke patients admitted to Haukeland University Hospital between 2006 and 2009 (the Bergen NORSTROKE study), and from 150 patients aged 15-60 years and 84 controls included in the Norwegian Stroke in the Young Study (NOR-SYS) between 2010 and 2012. Patients <50 years represented 8% of the NORSTROKE population. Undetermined cause of stroke was the most frequent subtype of stroke classified according to TOAST criteria in NORSTROKE and NOR-SYS. Of determined causes, non-arrhythmic cardioembolism, small artery occlusion and cervical artery dissection were the most frequent diagnoses among younger patients, while cardioembolism due to arrhythmia was the most frequent cause of stroke among older patients. Risk factor burden increased with age, and patients of all investigated age and sex subgroups had a higher risk factor burden than controls. Of the risk factors investigated, hypertension, dyslipidemia, smoking, overweight and family history of cardiovascular disease were most frequent. Carotid Intima-media thickness (cIMT), a surrogate marker of atherosclerosis, was measured by ultrasonography in the NOR-SYS population, and performed in the common carotid artery (CCA), the bifurcation (BIF) and the internal carotid artery (ICA). Increased cIMT was associated with age and prevalent vascular risk factors. The overall cIMT difference between patients and controls was 12% in CCA, 17% in BIF and 29% in ICA. Mean cIMT was higher compared to controls in patients with large-artery atherosclerosis, small artery occlusion, and stroke of undetermined cause. Our data add new information to our knowledge about young stroke patients concerning etiology, risk factors, and the prevalence of clinical and subclinical carotid artery disease. They support the conclusions drawn in previous studies regarding the varying impact of different risk factors on cIMT development dependent on age and sex. We find ICA to be the carotid segment distinctly associated with incident stroke, related to a family history of cardiovascular disease among young patients, and related to an increasing risk factor burden with increasing age. We further find that small artery occlusion and stroke of undetermined etiology represent stroke subtypes which hide a considerable number of patients suffering from atherosclerotic arterial disease in our cohort. Young stroke patients require extensive investigation with the purpose to detect and treat prevalent vascular disease and risk factors aggressively, to slow the progression of atherosclerotic disease, and to prevent future vascular events and subsequent disability, cognitive decline and death.