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Background: Multimorbidity is common in patients with stroke and is associated with increased medium- to long-term mortality, but its value for clinical decision-making and case-mix adjustment will depend on other factors, such as age, stroke severity, etiological subtype, prior disability, and vascular risk factors. Aims: In the absence of previous studies, we related multimorbidity to long-term post-stroke mortality with stratification by these factors. Methods: In patients ascertained in a population-based stroke incidence study (Oxford Vascular Study; 2002–2017), we related pre-stroke multimorbidity (weighted/unweighted Charlson comorbidity index (CCI)) to all-cause/vascular/non-vascular mortality (1/5/10 years) using regression models adjusted/stratified by age, sex, predicted early outcome (THRIVE score), stroke severity (NIH stroke scale (NIHSS)), etiology (Trial of Org 10172 in Acute Stroke Treatment (TOAST)), premorbid disability (modified Rankin Scale (mRS)), and non-CCI risk factors (hypertension, hyperlipidemia, atrial fibrillation, smoking, deprivation, anxiety/depression). Results: Among 2454 stroke patients (M/SD age: 74.1/13.9 years; 48.9% male; M/SD NIHSS: 5.7/7.0), 1375/56.0% had ⩾ 1 CCI comorbidity and 685/27.9% had ⩾ 2. After age/sex adjustment, multimorbidity (unweighted CCI ⩾ 2 vs 0) predicted (all ps < 0.001) mortality at 1 year (aHR = 1.57, 95% CI = 1.38–1.78), 5 years (aHR = 1.73, 95% CI = 1.53–1.96), and 10 years (aHR = 1.79, 95% CI = 1.58–2.03). Although multimorbidity was independently associated with premorbid disability (mRS > 2: aOR = 2.76, 2.13–3.60) and non-CCI risk factors (hypertension: 1.56, 1.25–1.95; hyperlipidemia: 2.58, 2.03–3.28; atrial fibrillation: 2.31; 1.78–2.98; smoking: 1.37, 1.01–1.86), it predicted death after adjustment for all measured confounders (10-year-aHR = 1.56, 1.37–1.78, p < 0.001), driven mainly by non-vascular death (aHR = 1.89, 1.55–2.29). Predictive value for 10-year all-cause death was greatest in patients with lower expected early mortality: lower THRIVE score (pint < 0.001), age < 75 years (aHR = 2.27, 1.71–3.00), NIHSS < 5 (1.84, 1.53–2.21), and lacunar stroke (3.56, 2.14–5.91). Results were similar using the weighted CCI. Conclusion: Pre-stroke multimorbidity is highly prevalent and is an independent predictor of death after stroke, supporting its inclusion in case-mix adjustment models and in informing decision-making by patients, families, and carers. Prediction in younger patients and after minor stroke, particularly for non-vascular death, suggests potential clinical utility in targeting interventions that require survival for 5–10 years to achieve a favorable risk/benefit ratio. Data access statement: Data requests will be considered by the Oxford Vascular Study (OXVASC) Study Director (P.M.R.-peter.rothwell@ndcn.ox.ac.uk). [ABSTRACT FROM AUTHOR]

Background: Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality.Methods: Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors.Results: During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08–1.56, p = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06–1.96, p = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke.Conclusions: IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels.

Background: Intracranial arterial calcification (IAC) is highly prevalent in ischemic stroke patients. However, data on the association of IAC with stroke recurrence and mortality remains limited. We examined the effect of IAC on the long-term recurrence of stroke and the risk of post-stroke mortality. Methods: Using a prospective stroke registry, we recruited 694 patients (mean age 71.6 ± 12.4; male sex 50.3%) since December 2004. IAC was visualized using the computed tomography exam that was made at hospital admission and was quantified with the Agatston method. All patients were regularly followed up till July 2016. The impacts of IAC on stroke recurrence and mortality were assessed using Cox-regression models with adjustments for age, sex, and relevant cardiovascular risk factors. Results: During a median follow-up period of 8.8 years, 156 patients (22.5%) suffered a recurrent stroke and 84 died (12.1%). We found that a higher IAC Agatston score related to a higher risk of stroke recurrence (HR per 1-SD increase in IAC: 1.30; 95% CI, 1.08–1.56, p = 0.005) and a higher risk of post-stroke mortality (HR per 1-SD increase, 1.44; 95% CI, 1.06–1.96, p = 0.019). After investigating etiology-specific risks of stroke-recurrence, we found that a higher IAC Agatston score specifically associated with small-vessel occlusive stroke. Conclusions: IAC is a strong risk factor for recurrent stroke and post-stroke mortality. Among stroke subtypes, IAC relates to higher risk of stroke recurrence among patients with small-vessel disease, which indicates chronic calcification detected in large cerebral arteries may have potential effects on the cerebrovascular beds extending to small vessels. [ABSTRACT FROM AUTHOR]

• Meta-analysis on risk of stroke and post-stroke mortality in schizophrenia patients. • Schizophrenia (SZ) patients had 55% higher stroke risk relative to non-SZ controls. • SZ patients had elevated overall all-cause post-stroke mortality rate than controls. • Raised short-term (≤90 days) & longer-term (≥1y) post-stroke mortality rates in SZ. Sources of heterogeneity in risk of stroke and mortality risk following acute-stroke in schizophrenia are understudied. We systematically searched four electronic-databases until 1-November-2022, and conducted meta-analysis to synthesize estimates of stroke-risk and post-stroke mortality for schizophrenia patients relative to non-schizophrenia counterparts. Subgroup-analyses and meta-regression models stratified by sex, nature of sample (incident/prevalent), geographical region, study-period and time-frame following stroke were conducted when applicable. Fifteen and 5 studies were included for meta-analysis of stroke-risk (n =18,368,253; 129,095 schizophrenia patients) and all-cause post-stroke mortality (n =289,231; 4,477 schizophrenia patients), respectively. Schizophrenia patients exhibited elevated stroke-risk (relative-risk =1.55[95% CI:1.31–1.84]) relative to non-schizophrenia controls. Schizophrenia was associated with increased stroke-risk in both sexes, study-periods of 1990s and 2000s, and irrespective of nature of sample and geographical regions. Meta-regression revealed regional differences in relative-risk for stroke, but limited by small number of studies. After removal of an outlier study, meta-analysis demonstrated that schizophrenia was associated with increased overall (hazard-ratio=1.37[1.30–1.44]), short-term (≤90 days; 1.29[1.14–1.46]) and longer-term (≥1 year; 1.45[1.32–1.60]) post-stroke mortality rates. Raised post-stroke mortality rate for schizophrenia was observed irrespective of nature of sample, geographical regions and study-periods. Taken together, schizophrenia is associated with increased stroke-risk and post-stroke mortality. Multilevel-interventions are required to reduce these physical-health disparities. [ABSTRACT FROM AUTHOR]

Background: Several blood biomarkers have been identified as predictors for poor outcome after ischemic stroke. However, recent studies mainly focused on single or experimental biomarkers and considered rather short follow-up intervals limiting their value for daily clinical practice. We, therefore, aimed to compare various clinical routine blood biomarkers for their predictive value on post-stroke mortality over a 5-year follow-up period., Patients and Methods: This data analysis of a prospective single-center study included all consecutive ischemic stroke patients admitted to the stroke unit of our university hospital over a 1-year period. Various blood biomarkers of inflammation, heart failure, metabolic disorders, and coagulation were analyzed from standardized routine blood samples collected within 24 h of hospital admission. All patients underwent a thorough diagnostic workup and were followed for 5 years post-stroke., Results: Of 405 patients (mean age: 70.3 years), 72 deceased (17.8%) during the follow-up period. While various routine blood biomarkers were associated with post-stroke mortality in univariable analyses, only NT-proBNP remained an independent predictor (adjusted odds ratio 5.1; 95% CI 2.0-13.1; p  < 0.001) for death after stroke. NT-proBNP levels ⩾794 pg/mL ( n  = 169, 42%) had a sensitivity of 90% for post-stroke mortality with a negative predictive value of 97% and was additionally associated with cardioembolic stroke and heart failure (each p  ⩽ 0.05)., Conclusion: NT-proBNP represents the most relevant routine blood-based biomarker for the prediction of long-term mortality after ischemic stroke. Increased NT-proBNP levels indicate a vulnerable subgroup of stroke patients in which early and thorough cardiovascular assessment and consistent follow-ups could improve outcome after stroke.

Ischemic stroke is a complicated disease which is affected by environmental factors and genetic factors. In this field, various studies using whole-exome sequencing (WES) have focused on novel and linkage variants in diverse diseases. Thus, we have investigated the various novel variants, which focused on their linkages to each other, in ischemic stroke. Specifically, we analyzed the N-methylpurine DNA glycosylase (MPG) gene, which plays an initiating role in DNA repair, and the nitrogen permease regulator-like 3 (NPRL3) gene, which is involved in regulating the mammalian target of rapamycin pathway. We took blood samples of 519 ischemic stroke patients and 417 controls. Genetic polymorphisms were detected by polymerase chain reaction (PCR), real-time PCR, and restriction fragment length polymorphism (RFLP) analysis. We found that two NPRL3 polymorphisms (rs2541618 C>T and rs75187722 G>A), as well as the MPG rs2562162 C>T polymorphism, were significantly associated with ischemic stroke. In Cox proportional hazard regression models, the MPG rs2562162 was associated with the survival of small-vessel disease patients in ischemic stroke. Our study showed that NPRL3 and MPG polymorphisms are associated with ischemic stroke prevalence and ischemic stroke survival. Taken together, these findings suggest that NPRL3 and MPG genotypes may be useful clinical biomarkers for ischemic stroke development and prognosis. [ABSTRACT FROM AUTHOR]