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Introduction. Nonmodifiable cardiovascular risk factors, like age and sex, are easily quantifiable. Due to immense technical progress in diagnostics and medical data storage, the aim of this study was to quantify, verify, and to compare parental cardiovascular events (CVE) as an additional nonmodifiable risk factor for young and middle-aged ischaemic stroke patients and controls. Methods. Information about parental CVE was first obtained by standardized questionnaires answered by 385 acute ischaemic stroke patients (15-60 years of age) and 260 controls. After consent to contact living and include deceased parents, patients and controls provided necessary personal identification of their parents. Thereafter, CVE were verified by standardized questionnaires answered by parents or medical records in case of deceased parents. Results. One hundred-and-nine (14.2%) of 770 patient parents vs. 128 (24.6%) of 520 control parents were not available for verification. Active participation was obtained for 229 (73.9%) of 310 patient parents vs.113 (58.2%) of 194 control parents. Medical record verification was obtained for 192 (54.7%) of 351 deceased patient parents, vs.103 (52.0%) of 198 deceased control parents. This study showed highest death rates of fathers (65.3% patient fathers and 57.6% control fathers) and highest numbers of CVE, especially myocardial infarction among patient fathers of patients aged 50-60 years. Discussion and Conclusion. Obtaining verified parental CVE as a nonmodifiable risk factor is still challenging, despite widely available digital medical information. To attain more accurate information on parental CVE, we recommend active involvement of family members in addition to medical record verification, especially for patients aged

Objectives: We studied the prevalence of vascular risk factors (RFs) among 385 ischaemic stroke patients ⩽60 years and 260 controls, and their association with atherosclerosis in seven vascular areas. Methods: History of cardiovascular events (CVE), hypertension, diabetes mellitus (DM), dyslipidaemia, pack-years of smoking (PYS), alcohol, and physical inactivity were noted. Blood pressure, body mass index (BMI), waist-hip ratio (WHR), lipid profile, epicardial adipose tissue (EAT), visceral abdominal adipose tissue (VAT), and subcutaneous abdominal adipose tissue were measured. Numeric staging of atherosclerosis was done by standardized examination of seven vascular areas by right and left carotid and femoral intima-media thickness, electrocardiogram, abdominal aorta plaques, and the ankle-arm index. All results were age and sex-adjusted. Poisson regression analysis was applied. Results: At age ⩽49 years at least one RF was present in 95.6% patients versus 90.0% controls. Compared to controls, male patients and middle-aged female patients showed no significant differences. Young female patients compared to young female controls had a higher burden of RFs (94.3% vs 88.6%, p = 0.049). Poisson regression analysis combined for patients and controls, adjusted for age and sex, showed numeric staging of atherosclerosis associated with age, prior CVE, hypertension, DM, dyslipidaemia, PYS, alcohol, BMI, WHR, EAT, VAT, and an increased number of risk factors. Adjusted for all risk factors, numeric staging of atherosclerosis was associated with increasing age, hypertension, DM, PYS, and BMI. Conclusion: Vascular risk factors are highly prevalent in young- and middle-aged patients and controls, and are predictors of established atherosclerosis at study inclusion. Focus on main modifiable vascular RFs in primary prevention, and early and aggressive secondary treatment of patients are necessary to reduce further progression of atherosclerosis.

Introduction: Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. Patients and methods: We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Results: Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1–10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5–14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0–17.4). Mild stroke (NIHSS Discussion and conclusions: Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Objectives: We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up. Methods: Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle–arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied. Results: Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients ( p = 0.044, p = 0.020, p = 0.023 and p Conclusion: Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.

Background and Purpose— The NOR-SASS (Norwegian Sonothrombolysis in Acute Stroke Study) aimed to assess effect and safety of contrast-enhanced ultrasound treatment in an unselected acute ischemic stroke population. Methods— Patients treated with intravenous thrombolysis within 4.5 hours after symptom onset were randomized 1:1 to either contrast-enhanced sonothrombolysis (CEST) or sham CEST. A visible arterial occlusion on baseline computed tomography angiography was not a prerequisite for inclusion. Pulse-wave 2 MHz ultrasound was given for 1 hour and contrast (SonoVue) as an infusion for ≈30 minutes. Magnetic resonance imaging and angiography were performed after 24 to 36 hours. Primary study end points were neurological improvement at 24 hours defined as National Institutes of Health Stroke Scale score 0 or reduction of ≥4 National Institutes of Health Stroke Scale points compared with baseline National Institutes of Health Stroke Scale and favorable functional outcome at 90 days defined as modified Rankin scale score 0 to 1. Results— A total of 183 patients were randomly assigned to either CEST (93 patient) or sham CEST (90 patients). The rates of symptomatic intracerebral hemorrhage, asymptomatic intracerebral hemorrhage, or mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days was similar in the 2 groups both in the intention-to-treat analysis and in the per-protocol analysis. Conclusions— CEST is safe among unselected ischemic stroke patients with or without a visible occlusion on computed tomography angiography and with varying grades of clinical severity. There was, however, statistically no significant clinical effect of sonothrombolysis in this prematurely stopped trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01949961.

Masked hypertension (MHT) is characterized by normal clinic blood pressure (BP), but elevated ambulatory BP has been associated with a higher prevalence of cardiovascular organ damage.We assessed the prevalence and characteristics of MHT in 298 ischemic stroke patients aged 15-60 years. High-normal office BP was considered present if systolic BP was 130-139 mmHg and/or diastolic BP was 85-89 mmHg. Arterial damage was defined as increased pulse wave velocity measured by applanation tonometry and/or mean common carotid intima-media thickness more than 0.9 mm measured by ultrasound.MHT was found in 12% of patients. In multivariable logistic regression analysis, MHT patients were characterized by higher BMI [odds ratio (OR) 1.09; 95% confidence interval (CI) 1.03-1.16], high-normal office BP (OR 2.30; 95% CI 1.26-4.21), and higher serum triglycerides (OR 1.32; 95% CI 1.01-1.47, all P0.05) in the total study population. Compared with normotensive patients, MHT was characterized by a higher prevalence of high-normal office BP (OR 2.05; 95% CI 1.08-3.90), obesity (OR 2.67; 95% CI 1.31-5.47), and arterial damage (OR 2.87; 95% CI 1.46-5.66, all P0.05). Compared with patients with sustained hypertension, MHT was associated with a lower prevalence of arterial damage (OR 0.48; 95% CI 0.23-0.99, P=0.05) despite a higher prevalence of high-normal office BP and comparable ambulatory BP values.Among young and middle-aged ischemic stroke patients, MHT was found in 12% and associated with high-normal office BP, obesity, and more prevalent arterial damage compared with normotensive patients, underscoring the importance of identification of MHT in these patients.

Abnormal night-time blood pressure (BP) reduction is associated with increased cardiovascular risk in hypertension. Little is known about the prevalence and covariates of night-time BP reduction in ischemic stroke patients. Clinic and ambulatory BP measurements were recorded in 268 stroke survivors aged 15-60 years. The degree of night-time dipping was calculated from the difference between day-time and night-time mean BP, and defined as non-dipping if

Objectives There is increasing knowledge about an association between migraine and ischaemic stroke. Cortical spreading depression (CSD) is the probable biological substrate of migrainous aura. To investigate the influence of CSD on the apparent stroke – migraine association, we hypothesized that magnetic resonance (MR) diffusion weighted images of acute ischaemic stroke patients would reveal an association between small cortical infarctions and migraine. Methods We included all patients admitted to the Bergen stroke unit between 2006 and 2012 with verified acute ischaemic stroke by MR imaging. Patients were grouped in a migraine and a no-migraine group. Baseline data and clinical characteristics were analysed between the groups. Imaging data were analysed with respect to infarct location and size. Multivariate analyses were performed to adjust for confounders and provide risk estimates for observed associations. Results A total of 1703 subjects were enrolled, 787 subjects were excluded due to uncertain or unobtainable migraine diagnosis, leaving 196 and 720 subjects in the migraine and no-migraine group, respectively. The migraine group was younger and included a higher proportion of females. There were more infarctions due to cardio-embolism (P = 0.015) and fewer due to small vessel disease (P = 0.018) in the migraine group. A higher rate of patients in the migraine group presented symptoms from the posterior circulation (P = 0.008). Migraine was associated with cortical infarctions (OR 1.8 CI: 1.3–2.5, P = 0.001). Migraine was also associated with small infarctions (OR 1.9 CI: 1.04–3.5, P = 0.038). Conclusions Migraine was associated with small cortical infarctions. This association may be due to cortical spreading depression.

Christopher Elnan Kvistad,Halvor Oygarden,Nicola Logallo,Lars Thomassen,Ulrike Waje-Andreassen,Gunnar Moen,Halvor Naess Department of Neurology, Haukeland University Hospital, Bergen, Norway Background: A hypertensive response after ischemic stroke is frequent, yet its pathophysiology is unknown. Mechanisms related to local ischemic damage, major vascular occlusion, and psychological stress due to acute illness have been proposed. We assessed the natural course of blood pressure (BP) within the first 24h in groups of ischemic stroke patients with different characteristics. We hypothesized that a consistent BP reduction, regardless of stroke location, time window from debut to admission and presence of persistent vascular occlusion, would favor a stress-related mechanism as an important cause of the hypertensive response after ischemic stroke. Methods: Ischemic stroke patients (n=1067) were prospectively registered, and BP was measured on admission and

Background and Purpose Positive family history (FH+) of cardiovascular disease (CVD) is a risk factor for own CVD. We aimed to analyze the effect of different types of FH (stroke, coronary heart disease (CHD), peripheral artery disease (PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic stroke patients. Methods First-degree FH of CVD was assessed in ischemic stroke patients ≤ 60y using a standardized interview. Carotid ultrasound was performed and far wall cIMT in three carotid artery segments was registered, representing the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative groups and stepwise backward regression analyses were performed to identify factors associated with increased cIMT. Results During the study period 382 patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH of CVD. Regression analyses adjusting for risk factors revealed age as the most important predictor of cIMT in all segments. The association between FH+ and cIMT was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+ was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not in patients ≥ 45y (p = 0.083). The association with ICA-IMT was present for a FH of stroke (p = 0.034), but not a FH+ of CHD or PAD. Conclusions FH of stroke is associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of cardiovascular FH is important to investigate heredity in young ischemic stroke patients. Trial Registration ClinicalTrials.gov NCT01597453

Background and purpose Family history (FH) is used as a marker for inherited risk. Using FH for this purpose requires the FH to reflect true disease in the family. The aim was to analyse the concordance between young and middle-aged ischaemic stroke patients' reported FH of cardiovascular disease (CVD) with their parents' own reports. Methods Ischaemic stroke patients aged 15–60 years and their eligible parents were interviewed using a standardized questionnaire. Information of own CVD and FH of CVD was registered. Concordance between patients and parents was tested by kappa statistics, sensitivity, specificity, predictive values and likelihood ratios. Regression analyses were performed to identify patient characteristics associated with non-concordance of replies. Results There was no difference in response rate between fathers and mothers (P = 0.355). Both parents responded in 57 cases. Concordance between patient and parent reports was good, with kappa values ranging from 0.57 to 0.7. The patient-reported FH yielded positive predictive values of 75% or above and negative predictive values of 90% or higher. The positive likelihood ratios (LR+) were 10 or higher and negative likelihood ratios (LR−) were generally 0.5 or lower. Interpretation regarding peripheral arterial disease was limited due to low parental prevalence. Higher age was associated with impaired concordance between patient and parent reports (odds ratio 1.05; 95% confidence interval 1.01–1.09; P = 0.020). Conclusions The FH provided by young and middle-aged stroke patients is in good concordance with parental reports. FH is an adequate proxy to assess inherited risk of CVD in young stroke patients.

Background Family history (FH) is a risk factor for cardiovascular disease, especially coronary artery disease (CAD). The impact on risk of stroke is less clear. This study investigated young and middle-aged ischemic stroke patients’ knowledge on FH of stroke, CAD, and peripheral artery disease (PAD) with a special regard to sex differences. Methods From September 2010 to February 2014, all ischemic stroke patients aged 15–60 years were prospectively included in the Norwegian Stroke in the Young Study (NOR-SYS). FH of stroke, CAD and PAD in offspring, siblings, parents, and grandparents was assessed using a standardized face-to-face interview. In addition to ‘yes’ and ‘no’, the optional reply ‘don’t know’ was included to improve accuracy. McNemar’s test was used to compare paired proportions, i.e. FH in male vs. female relatives. Multiple logistic regression analyses were used to test the influence of patient sex on FH reporting and to adjust for possible confounding factors. Results Altogether 257 patients were included. Mean age was 49.5 years and 68.1% were males. FH of cardiovascular disease was reported by 59% of patients. When asked about FH of stroke, 48 (18.7%) and 46 (17.9%) patients reported yes, whereas 17 (6.6%) and 9 (3.5%) reported ‘don’t know’ regarding father and mother respectively, similarly patients reported ‘don’t know’ regarding 117 (45.5%) paternal vs. 83 (32.4%) maternal grandmothers (p

Background Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients. Methods We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram. Results Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p

Background and Purpose— Diffusion-weighted imaging (DWI) is highly accurate in identifying and locating ischemic stroke injury. Few studies using DWI have investigated large subcortical infarctions (LSIs). We aimed to study clinical characteristics, cause, and outcome in patients with ischemic stroke with LSI diagnosed on DWI and compare these with those who had lacunar DWI lesions or DWI lesions located elsewhere. Methods— Patients with stroke admitted between February 2006 and July 2013 were prospectively registered in a stroke database and examined with DWI. Patients with DWI lesions classified as LSI (subcortical, ≥15 mm) were compared with those with lacunar lesions (subcortical, Results— A total of 1886 patients with ischemic stroke were included, of which 128 patients (6.8%) had LSI, 317 (16.8%) LI, and 544 (28.8%) CI. The no LSI group included 1758 patients. Occlusive pathology in the proximal middle cerebral artery was more frequent in patients with acute stroke with LSI. Lacunar syndrome was associated with LSI when compared with CI and no LSI. Unknown cause was frequent in the LSI group (60.4%) and independently associated with LSI in the LSI versus LI ( P P =0.002), and LSI versus no LSI population ( P P =0.002), CI ( P P =0.002). Conclusions— LSI is associated with distinct clinical characteristics, unknown cause, and unfavorable outcome, which separates this stroke entity from patients with lacunar subcortical DWI lesions or DWI lesions located elsewhere.

Background: Transient elevated blood pressure (BP) is frequent in patients presenting with acute ischemic stroke. The pathophysiology of this response is not clear and its effect on clinical outcome has shown contradictory results. Some studies have suggested that BP elevation may represent a protective response to enhance perfusion in ischemic brain tissue. In this study, we aimed to explore the association between elevated admission BP and stroke severity in the acute phase of ischemic stroke. If it is true that elevated BP represents a protective response in acute ischemia, we expected an inverse association between elevated BP and admission stroke severity, and a positive association between elevated BP and complete neurological recovery within 24 h and/or favorable short-term outcome. Methods: Patients with ischemic stroke with hospital admission Results: A total of 749 patients with ischemic stroke were included, of which 621 patients (82.9%) presented with elevated BP. Elevated BP was independently associated with mild stroke (odds ratio, OR: 2.12; 95% CI: 1.39-3.24; p < 0.001), whereas lack of elevated BP was independently associated with severe stroke (OR: 0.41; 95% CI: 0.25-0.68; p < 0.001). There was a nonsignificant association between elevated BP and CNR (OR: 2.11; 95% CI: 0.96-4.68; p = 0.063), yet no association between elevated BP and favorable short-term outcome (OR: 0.97; 95% CI: 0.59-1.59; p = 0.906) when adjusted for confounders. Conclusion: Our study showed an inverse association between elevated BP and stroke severity on admission, where elevated BP was associated with mild stroke and lack of elevated BP was associated with severe stroke. This could be explained by a protective effect of elevated BP in the acute phase of ischemic stroke, although the absence of association between elevated BP and favorable outcome argues against this hypothesis.

Objective:Lack of nightly blood pressure (BP) reduction is associated with increased cardiovascular risk. The aim of this study was to assess the association of nightly BP reduction with arterial stiffness in young and middle-aged ischemic stroke patients.Design and method:Clinic and ambulatory BP m

Christopher Elnan Kvistad,1 Halvor Øygarden,1 Lars Thomassen,1 Ulrike Waje-Andreassen,1 Halvor Naess1,21Department of Neurology, Haukeland University Hospital, Bergen, Norway; 2Centre for age-related medicine, Stavanger University Hospital, Stavanger, NorwayBackground: Low body temperature is considered neuroprotective in ischemic stroke, yet some studies suggest that low body temperature may also inhibit clot lysis and recanalization. We hypothesized that low body temperature was associated with persistent proximal middle cerebral artery (MCA) occlusion in patients with acute ischemic stroke presenting with symptoms of proximal MCA occlusion, suggesting a possible detrimental effect of low body temperature on recanalization.Methods: All patients with acute ischemic stroke admitted to our Stroke Unit between February 2006 and August 2012 were prospectively registered in a database. Computed tomography (CT) angiography was performed in patients admitted