Associations of C-reactive protein with depressive symptoms over time after mild to moderate ischemic stroke in the PROSCIS-B cohort

BACKGROUND AND PURPOSE: C-reactive protein serves as a marker of inflammation and is linked to depression in the general population. We aimed to assess whether elevated baseline levels of high-sensitivity C-reactive protein (hs-CRP) are associated with depressive symptoms over time in a prospective cohort of mild-to-moderate first-ever ischemic stroke patients. METHODS: Data were obtained from the Prospective Cohort with Incident Stroke Berlin (NCT01363856). Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) at three annual follow-up points. We assessed the association of elevated levels of hs-CRP with CES-D scores over time via linear mixed models. In a subgroup analysis, we explored an interaction effect with sex. RESULTS: We included 585 ischemic stroke patients with baseline data on CRP levels. The mean age was 67 (13 SD), 39% (n = 226) were female, and the median National Institutes of Health Stroke Scale (NIHSS) was 3 (IQR 1-4). Twenty percent of survivors showed evidence for depressive symptoms one year after stroke with CES-D = 16, 21% at year two, and 17% at year three. Higher log-transformed baseline hs-CRP levels were associated with higher CES-D Scores over time in the adjusted linear mixed model (ß = 1.28; (95% CI 0.22-2.34)). The subgroup analysis revealed an interaction effect of hs-CRP on depressive symptoms in women (ß = 2.33; (95% CI 0.71-3.95)). CONCLUSION: In our cohort with mild-to-moderate first-ever ischemic stroke patients, hs-CRP levels were associated with more depressive symptoms over time, with an interaction effect for the female sex

Low ankle-brachial index and cognitive function after stroke-the PROSpective with Incident Stroke Berlin (PROSCIS-B)

Introduction: Low ankle-brachial index (ABI) Clinical epidemiolog

Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study

OBJECTIVES: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The 'Berlin Beat of Running' study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. DESIGN: Prospective observational cohort study including healthy volunteers. SETTING AND PARTICIPANTS: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2-3 days prior, directly after and 1-2 days after the race. RESULTS: Overall, 108 athletes (median 48 years (IQR 45-53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. CONCLUSIONS: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. TRIAL REGISTRATION: ClinicalTrials.gov NCT01428778; Results

Combined oral triglyceride and glucose tolerance test after acute ischemic stroke to predict recurrent vascular events: the Berlin "Cream&Sugar" study

Background: Elevated triglyceride and glucose levels are associated with an increased cardiovascular disease risk including ischemic stroke. It is not known whether the response to a combined oral triglyceride and glucose challenge after ischemic stroke improves identification of patients with increased risk for recurrent vascular events. Methods: The prospective, observational Berlin "Cream&Sugar" study was conducted at 3 different university hospital sites of the Charite-Universitatsmedizin Berlin, Germany, between January 24, 2009 and July 31, 2017. Patients with first-ever ischemic stroke were recruited 3 to 7 days after stroke. An oral triglyceride tolerance test (OTTT) and consecutive blood tests before (t(0)) as well as 3 (t(1)), 4 (t(2)), and 5 hours (t(3)) after OTTT were performed in fasting patients. An oral glucose tolerance test was performed in all nondiabetic patients 3 hours after the start of OTTT. Outcomes of the study were recurrent fatal or nonfatal stroke as well as a composite vascular end point including stroke, transient ischemic attack, myocardial infarction, coronary revascularization, and cardiovascular death assessed 1 year after stroke. Cox regression models were used to estimate hazard ratios and corresponding 95% CIs between patients with high versus low levels of triglyceride and glucose levels. Results: Overall 755 patients were included; 523 patients completed OTTT and 1-year follow-up. Patients were largely minor strokes patients with a median National Institutes of Health Stroke Scale score of 1 (0-3). Comparing highest versus lowest quartiles of triglyceride levels, neither fasting (adjusted hazard ratio(t0), 1.24 [95% CI, 0.45-3.42]) nor postprandial triglyceride levels (adjusted hazard ratio(t3), 0.44 [95% CI, 0.16-1.25]) were associated with recurrent stroke. With regard to recurrent vascular events, results were similar for fasting triglycerides (adjusted hazard ratio(t0), 1.09 [95% CI, 0.49-2.43]), however, higher postprandial triglyceride levels were significantly associated with a lower risk for recurrent vascular events (adjusted hazard ratio(t3), 0.42 [95% CI, 0.18-0.95]). No associations were observed between fasting and post-oral glucose tolerance test blood glucose levels and recurrent vascular risk. All findings were irrespective of the diabetic status of patients. Conclusions: In this cohort of patients with first-ever, minor ischemic stroke, fasting triglyceride or glucose levels were not associated with recurrent stroke at one year after stroke. However, higher postprandial triglyceride levels were associated with a lower risk of recurrent vascular events which requires further validation in future studies. Overall, our results do not support the routine use of a combined OTTT/oral glucose tolerance test to improve risk prediction for recurrent stroke.Clinical epidemiolog

High-sensitivity cardiac troponin T and cognitive function in patients with ischemic stroke

Background and Purpose-Our study aim was to assess whether high-sensitivity cardiac troponin T (hs-cTnT), a specific biomarker for myocardial injury, is associated with cognitive function in patients after mild-to-moderate first-ever ischemic stroke.Methods-We used data from PROSCIS-B (Prospective Cohort With Incident Stroke Berlin). Cognitive function was assessed by Mini-Mental-State-Examination at baseline, and Telephone Interview for Cognitive Status-modified after 1 to 3 years of follow-up. Patients were categorized according to hs-cTnT quartiles. We performed generalized linear regression to calculate risk ratios of cognitive impairment (Mini-Mental-State-Examination <27; Telephone Interview for Cognitive Status-modified <32). Association of hs-cTnT with cognitive function over time was estimated using a linear mixed model.Results-We included 555 patients (mean age, 67 years, 62% male, median National Institutes of Health Stroke Scale 2 [interquartile range, 1-5], hs-cTnT above upper reference limit 40%, baseline cognitive impairment 28%). Baseline Mini-Mental-State-Examination score and rate of cognitive impairment were lower in patients in the highest versus lowest hs-cTnT quartile (median Mini-Mental-State-Examination 27 versus 29, and 15.3% versus 43.0%, adjusted risk ratio, 1.76 [95% CI, 1.07-2.90], respectively). If anything, cognition seemed to improve in all groups, yet Telephone Interview for Cognitive Status-modified scores were consistently lower in patients within the highest versus lowest hs-cTnT quartile (adjusted beta, -1.33 [95% CI, -2.65 to -0.02]), without difference in the rate of change over time.Conclusions-In patients with mild-to-moderate first-ever ischemic stroke without dementia, higher hs-cTnT was associated with higher prevalence of cognitive impairment at baseline and lower Telephone Interview for Cognitive Status-modified during 3-year follow-up.Registration-URL: ; Unique identifier: NCT01363856

Endothelial and leukocyte-derived microvesicles and cardiovascular risk after stroke PROSCIS-B

Objective To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up. Methods In the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured with flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. Results Five hundred seventy-one patients were recruited (median age 69 years, 39% female, median NIH Stroke Scale score 2, interquartile range 1-4), and 95 endpoints occurred. Patients with levels of EMV (adjusted hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2-4.9) or LMV (HR 3.1, 95% CI 1.4-6.8) in the highest quartile were more likely to experience an event than participants with lower levels with the lowest quartile used as the reference category. The association was less pronounced for PMV (HR 1.7, 95% CI 0.9-3.2) and absent for MMV (HR 1.1, 95% CI 0.6-1.8). Conclusion High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients. ClinicalTrials.gov Identifier NCT01363856. Classification of Evidence This study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke.Clinical epidemiolog

Depressive symptoms and anti-N-methyl-D-aspartate-receptor GluN1 antibody seropositivity in the PROSpective cohort with incident stroke

Background: Anti-NMDA-receptor GluN1 antibodies (NMDAR1-abs) are present in an autoimmune encephalitis with severe neuropsychiatric symptoms. We aimed to estimate the impact of serum NMDAR1-abs on depressive symptoms years after first-ever ischemic stroke (IS). Methods: Data were used from the PROSpective Cohort with Incident Stroke-Berlin (PROSCIS-B; NCT01363856). Serum NMDAR1-abs (IgM/IgA/IgG) were measured within 7 days after IS using cell-based assays. We defined seropositivity as titers ≥1:10, thereof low titers as ≤1:100 and high titers as >1:100. We used the Center for Epidemiological Studies–Depression (CES-D) scale to measure depressive symptoms at year one, two and three following IS. We calculated crude and confounder adjusted weighted generalized linear models to quantify the impact of NMDAR1-abs on CES-D assessed at three annual time-points. Results: NMDAR1-abs were measured in 583 PROSCIS-B IS patients (mean age = 67 [SD = 13]; 42%female; median NIHSS = 2 [IQR = 1–4]) of whom 76 (13%; IgM: n = 49/IgA: n = 43/IgG: n = 2) were seropositive, 55 (9%) with low and 21 (4%) with high titers. CES-D regarded over all follow-up time-points was higher in seropositive patients (β(crude) = 2.56 [95%CI = −0.34 to 5.45]; β(adjusted) = 2.26 [95%CI = −0.68 to 5.20]) and effects were highest in patients with high titer (low titers: β(crude) = 1.42 [95%CI = −1.79 to 4.62], β(adjusted) = 0.53 [95%CI = −2.47 to 3.54]; high titers: β(crude) = 5.85 [95%CI = 0.20 to 11.50]; β(adjusted) = 7.20 [95%CI = 0.98 to 13.43]). Conclusion: Patients with serum NMDAR1-abs (predominantly IgM&IgA) suffer more severe depressive symptoms after mild-to-moderate IS compared to NMDAR1-abs seronegative patients

Incidence of hemorrhagic stroke in Black Caribbean, Black African, and White Populations : The South London Stroke Register, 1995-2004

Background and Purpose—Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. Methods—First-ever stroke patients were drawn from a prospective community stroke register based in a multi-ethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression. Results—Between 1995 and 2004, 566 incident stroke patients were registered: 395 PICHs and 171 SAHs. For PICH, age and sex-adjusted IRRs were higher in BAs (IRR, 2.80; 95% CI, 2.00 to 3.91) than in BCs (IRR, 1.46; 95% CI, 1.07 to 1.99) and were particularly pronounced for patients age 0 to 64 years: IRR3.95 (95% CI, 2.65 to 5.87) in BAs and 2.38 (95% CI, 1.50 to 3.80) in BCs. For those 65 years, prestroke hypertension was more prevalent in BAs and BCs (P=0.049). For SAH, the IRR was higher in BCs (IRR; 1.62; 95% CI, 1.05 to 2.48) than in BAs (IRR, 0.80; 95% CI, 0.43 to 1.46). Conclusions—The higher incidence of PICH observed in BCs and BAs could be explained by prestroke hypertension being more common among young blacks. The different incidences of SAH in BCs and BAs suggest that the baseline risk of stroke for distinct black ethnic groups is not homogeneous.Peer reviewe

Predictors of survival after haemorrhagic stroke in a multi-ethnic population : The South London Stroke Register (SLSR)

Objectives: To identify the predictors of long-term survival after haemorrhagic stroke. Methods: Data were collected within the population-based South London Stroke Register covering a multiethnic source population of 271 817 inhabitants (2001) in South London. Death data were collected at post-stroke follow-up. The impact of patients’ demographic and clinical characteristics, ethnic origin, pre-stroke risk factors and acute treatment on long-term survival were investigated. Survival methods included Kaplan–Meier curves and Cox’s proportional hazards model. Results: Between January 1995 and December 2004, a total of 566 patients with first-ever haemorrhagic stroke (395 primary intracerebral haemorrhage; 171 subarachnoid haemorrhage) were registered. Mean age was 62.3 years; 365 (64.5%) were white, 132 (23.3%) were black and 69 (12.2%) were other or unknown ethnic origin; there were 1340 person-years of follow-up. After multivariable adjustment, age (p12). Treatment on a stroke unit reduced the long-term risk of death (HR 0.70; 95% CI 0.50 to 0.98). Black patients had a reduced risk of death (HR 0.62; 95% CI 0.42 to 0.92) compared with white patients. Conclusions: Age, diabetes, stroke severity and stroke unit care influenced the long-term risk of death after haemorrhagic stroke. An independent survival advantage was observed in black patients. These factors can be utilised for clinical predictions but the cause of the observations in black patients remains unclear.Peer reviewe