Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

Acute-Phase Blood Pressure Levels Correlate With a High Risk of Recurrent Strokes in Young-Onset Ischemic Stroke.

BACKGROUND AND PURPOSE: High blood pressure (BP) in acute stroke has been associated with a poor outcome; however, this has not been evaluated in young adults. METHODS: The relationship between BP and long-term outcome was assessed in 1004 consecutive young, first-ever ischemic stroke patients aged 15 to 49 years enrolled in the Helsinki Young Stroke Registry. BP parameters included systolic (SBP) and diastolic BP, pulse pressure, and mean arterial pressure at admission and 24 hours. The primary outcome measure was recurrent stroke in the long-term follow-up. Adjusted for demographics and preexisting comorbidities, Cox regression models were used to assess independent BP parameters associated with outcome. RESULTS: Of our patients (63% male), 393 patients (39%) had prestroke hypertension and 358 (36%) used antihypertensive treatment. The median follow-up period was 8.9 years (interquartile range 5.7-13.2). Patients with a recurrent stroke (n=142, 14%) had significantly higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure (P<0.001) and 24-h SBP, diastolic BP, and mean arterial pressure compared with patients without the recurrent stroke. Patients with SBP ≥160 mm Hg compared with those with SBP <160 mm Hg had significantly more recurrent strokes (hazard ratio 3.3 [95% confidence interval, 2.05-4.55]; P<0.001) occurring earlier (13.9 years [13.0-14.6] versus 16.2 [15.8-16.6]; P<0.001) within the follow-up period. In multivariable analyses, higher admission SBP, diastolic BP, pulse pressure, and mean arterial pressure were independently associated with the risk of recurrent stroke, while the 24-hour BP levels were not. CONCLUSIONS: In young ischemic stroke patients, high acute phase BP levels are independently associated with a high risk of recurrent strokes.

Etiologic subtypes of first and recurrent ischemic stroke in young patients using A-S-C-O and TOAST classification criteria: A retrospective follow-up study.

INTRODUCTION: Scarce data exist on the etiology of recurrent ischemic strokes (ISs) among young adults. We analyzed the etiology of first-ever and recurrent events and the differences between them. PATIENTS AND METHODS: Patients aged 15-49 years with a first-ever IS in 1994-2007 were included in the Helsinki Young Stroke Registry. In this retrospective cohort study, data on recurrent ISs were identified from Care Register for Health Care until the end of 2017 and Causes of Death Register and from patient records until the end of 2020. All first-ever and recurrent ISs were classified using Atherosclerosis-Small vessel disease-Cardioembolism-Other Cause (A-S-C-O) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classifications. RESULTS: A total of 970 patients were included (median age at index IS 46 years, interquartile range 43-48, 33% women), of which 155 (16.0%) patients had recurrent IS, with 8 (5.2%) fatal cases and 5 (3.2%) unverifiable cases. The median follow-up was 17.4 (IQR 13.9-21.7) years. Median time from the index event to the first recurrent event was 4.5 (interquartile range [IQR] 1.6-10.2) years. Recurrence was more often due to definite cardioembolism (10.7% vs 18.0%, p = 0.013), while the proportion of other definite A-S-C-O subgroups remained the same. With TOAST classification, the proportion of true cryptogenic ISs decreased (16.7% vs 6.7%, p = 0.003), while those with incomplete evaluation increased (9.3% vs 19.3%, p = 0.015). Other TOAST phenotypes remained the same. CONCLUSION: The proportion of definite cardioembolism increased at recurrence using the A-S-C-O classification and the number of cryptogenic ISs decreased using the TOAST classification, while cases with incomplete evaluation increased. Most etiologies remained the same.

24-hour ambulatory blood pressure and cryptogenic ischemic stroke in young adults.

BACKGROUND: In young patients, up to 40% of ischemic strokes remain cryptogenic despite modern-day diagnostic work-up. There are limited data on blood pressure (BP) behavior in these patients. Thus, we aimed to compare ambulatory blood pressure (ABP) profiles between young patients with a recent cryptogenic ischemic stroke (CIS) and stroke-free controls. PATIENTS AND METHODS: In this substudy of the international multicenter case-control study SECRETO (NCT01934725), 24-hour ambulatory blood pressure monitoring (ABPM) was performed in consecutive 18-49-year-old CIS patients and stroke-free controls. The inclusion criteria were met by 132 patients (median age, 41.9 years; 56.1% males) and 106 controls (41.9 years; 56.6% males). We assessed not only 24-hour, daytime, and nighttime ABP but also hypertension phenotypes and nocturnal dipping status. RESULTS: 24-hour and daytime ABP were higher among controls. After adjusting for relevant confounders, a non-dipping pattern of diastolic blood pressure (DBP) was associated with CIS in the entire sample (odds ratio, 3.85; 95% confidence interval, 1.20-12.42), in participants without antihypertensives (4.86; 1.07-22.02), and in participants without a patent foramen ovale (PFO) (7.37; 1.47-36.81). After excluding patients in the first tertile of the delay between the stroke and ABPM, a non-dipping pattern of DBP was not associated with CIS, but a non-dipping pattern of both systolic BP and DBP was (4.85; 1.37-17.10). In participants with a PFO and in those without hypertension by any definition, no associations between non-dipping patterns of BP and CIS emerged. CONCLUSIONS: Non-dipping patterns of BP were associated with CIS in the absence of a PFO but not in the absence of hypertension. This may reflect differing pathophysiology underlying CIS in patients with versus without a PFO. Due to limitations of the study, results regarding absolute ABP levels should be interpreted with caution.Key MessagesNocturnal non-dipping patterns of blood pressure were associated with cryptogenic ischemic stroke except in participants with a patent foramen ovale and in those without hypertension by any definition, which may indicate differing pathophysiology underlying cryptogenic ischemic stroke in patients with and without a patent foramen ovale.It might be reasonable to include ambulatory blood pressure monitoring in the diagnostic work-up for young patients with ischemic stroke to detect not only the absolute ambulatory blood pressure levels but also their blood pressure behavior.

Return to work after ischemic stroke in young adults: A registry-based follow-up study.

OBJECTIVE: We aimed to investigate the proportion of young patients not returning to work (NRTW) at 1 year after ischemic stroke (IS) and during follow-up, and clinical factors associated with NRTW. METHODS: Patients from the Helsinki Young Stroke Registry with an IS occurring in the years 1994-2007, who were at paid employment within 1 year before IS, and with NIH Stroke Scale score ≤15 points at hospital discharge, were included. Data on periods of payment came from the Finnish Centre for Pensions, and death data from Statistics Finland. Multivariate logistic regression analyses assessed factors associated with NRTW 1 year after IS, and lasagna plots visualized the proportion of patients returning to work over time. RESULTS: We included a total of 769 patients, of whom 289 (37.6%) were not working at 1 year, 323 (42.0%) at 2 years, and 361 (46.9%) at 5 years from IS. When adjusted for age, sex, socioeconomic status, and NIH Stroke Scale score at admission, factors associated with NRTW at 1 year after IS were large anterior strokes, strokes caused by large artery atherosclerosis, high-risk sources of cardioembolism, and rare causes other than dissection compared with undetermined cause, moderate to severe aphasia vs no aphasia, mild and moderate to severe limb paresis vs no paresis, and moderate to severe visual field deficit vs no deficit. CONCLUSIONS: NRTW is a frequent adverse outcome after IS in young adults with mild to moderate IS. Clinical variables available during acute hospitalization may allow prediction of NRTW.