Search

Background: Pulse pressure (PP) depends on heart function and arterial wall elasticity, which is closely related to the incidence of ischemic stroke. However, the association of PP fluctuation during hospitalization with adverse outcomes after ischemic stroke remains unclear., Methods: The present study included 3,971 patients with ischemic stroke. The primary outcome was the composite outcome of death or vascular events within 3 months after ischemic stroke. PP fluctuation was reflected by successive variation of PP (PP-SV)., Results: The cumulative incidence rates of the primary outcome were the highest in the patients in the highest quartiles of PP-SV (P < 0.05). The multivariable-adjusted hazard ratios (95% confidence intervals) of the primary outcome in the highest quartiles were 1.86 (1.03-3.38) for death or vascular events, and 2.15 (1.06-4.37) for vascular events (all Ptrend < 0.05). Multivariable-adjusted restricted cubic spline analyses showed linear associations of PP-SV during hospitalization with the primary outcome (P for linearity <0.05)., Conclusions: Large PP fluctuation during hospitalization was associated with increased risks of adverse outcomes within 3 months after ischemic stroke, which provided valuable new insight for blood pressure management in the acute phase of ischemic stroke. Controlling PP fluctuation may be contributing to improving prognosis after ischemic stroke., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background We examined whether the relationship between baseline platelet count and clinical outcomes is modulated by HS-CRP (high-sensitivity C-reactive protein) in patients with ischemic stroke. Methods and Results A total of 3267 patients with ischemic stroke were included in the analysis. The primary outcome was a combination of death and major disability at 1 year after ischemic stroke. Secondary outcomes included major disability, death, vascular events, composite outcome of vascular events or death, and an ordered 7-level categorical score of the modified Rankin Scale at 1 year. Multivariate logistic regression and Cox proportional hazards regression models were used to assess the association between the baseline platelet count and clinical outcomes stratified by HS-CRP levels when appropriate. There was an interaction effect of platelet count and HS-CRP on the adverse clinical outcomes after ischemic stroke (all P interaction <0.05). Conclusions The HS-CRP levels had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke. Elevated platelet count was significantly associated with adverse clinical outcomes in patients with ischemic stroke with high HS-CRP levels, but not in those with low HS-CRP levels. These findings suggest that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.P trend <0.05). Conclusions The HS-CRP levels had a modifying effect on the association between platelet count and clinical outcomes in patients with ischemic stroke. Elevated platelet count was significantly associated with adverse clinical outcomes in patients with ischemic stroke with high HS-CRP levels, but not in those with low HS-CRP levels. These findings suggest that strategies for anti-inflammatory and antiplatelet therapy should be developed according to the results of both platelet and HS-CRP testing.

Background and Aims: l-Carnitine was suggested to prevent the progression of atherosclerosis, myocardial and neurologic injury, and exhibited cardioprotective effects. However, epidemiological data on circulating l-carnitine and risks of cardiovascular events in the setting of stroke is rare. We aimed to explore the relationships between plasma l-carnitine and cardiovascular events and stroke recurrence after ischemic stroke in a nested case-control study., Methods and Results: A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 matched controls (free of recurrent cardiovascular events) were included. Study outcomes included cardiovascular events and recurrent stroke after ischemic stroke. Plasma l-carnitine concentrations were measured by ultra-high-performance LC-MS/MS. Conditional logistic regression models were used to estimate odds ratios (ORs) of stroke outcomes. Plasma l-carnitine was inversely associated with cardiovascular events (OR = 0.69, 95% CI: 0.57-0.84 per SD) and recurrent stroke (OR = 0.72, 95% CI: 0.58-0.88 per SD) after adjusting for established risk confounders. Compared with the lowest tertile of l-carnitine, adjusted ORs of cardiovascular events and recurrent stroke for participants in the highest tertiles were 0.35 (95% CI: 0.21-0.57) and 0.36 (95% CI: 0.21-0.62), respectively. In addition, l-carnitine provided incremental predictive ability beyond established risk factors, shown by increase in C statistics, net reclassification improvement and integrated discrimination improvement., Conclusions: Higher l-carnitine levels were associated with lower risks of cardiovascular events and recurrent stroke after ischemic stroke. Our findings provided evidence supporting plasma l-carnitine as a potential prognostic marker in risk discrimination and stratification in patients with ischemic stroke., Trial Registration: Clinicaltrials.gov as NCT01840072. URL: https://www., Clinicaltrials: gov., Competing Interests: Declaration of competing interest The authors declare no financial interests or potential conflicts of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Thrombomodulin has been suggested to be implicated in ischemic stroke because of its anticoagulant, anti-inflammatory, and cytoprotective properties. We aimed to investigate the associations of plasma thrombomodulin levels with clinical outcomes after ischemic stroke in a multicenter prognostic cohort study., Methods: Our multicenter prognostic cohort study included 3,532 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥3) at 3 months after ischemic stroke. Secondary outcomes included major disability (mRS score 3-5), vascular events, and the ordered 7-level categorical score of the mRS., Results: During 3 months of follow-up, 867 participants experienced the primary outcome. After multivariate adjustment, the adjusted odds ratios or hazard ratios associated with the highest quartile of plasma thrombomodulin were 0.75 (95% CI 0.59-0.97; p trend = 0.029) for the primary outcome, 0.73 (95% CI 0.56-0.94; p trend = 0.028) for major disability, and 0.80 (95% CI 0.42-1.51; p trend = 0.232) for vascular events. In addition, a significantly better shift in the distribution of the mRS score was observed with higher thrombomodulin quartiles ( p trend = 0.005). A multivariable-adjusted spline regression model showed a linear relationship between plasma thrombomodulin and the risk of primary outcome ( p for linearity = 0.027). Subgroup analyses further confirmed these associations., Discussion: Increased plasma thrombomodulin levels at baseline were associated with decreased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting a protective role of thrombomodulin in the development of ischemic stroke. Further studies from various populations are needed to replicate our findings., (© 2022 American Academy of Neurology.)

Background: Previous researches have suggested that soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays a pivotal role in central nervous system pathologies and the development of neurodegenerative disorders. This study aimed to prospectively investigate the association between plasma sTREM2 levels and post-stroke cognitive impairment (PSCI)., Methods: A sample of 599 consecutive acute ischemic stroke patients with sTREM2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were eventually included in this analysis. Cognitive impairment was defined as a score of <25 for Mini-Mental State Examination, measured at 3-month follow up. Binary logistic regression was used to estimate the odds ratios (ORs) of plasma sTREM2 levels on the risk of PSCI., Results: Of the 599 participants (mean age, 60.0 ± 10.4 years; male, 70.5%), 228 (38.1%) patients were diagnosed as PSCI. The risk of PSCI elevated significantly with higher plasma sTREM2 levels (p for trend <0.01). After adjusting for several confounding factors, the ORs for the highest quartile of sTREM2 compared with the lowest quartile was 2.06 (95% confidence interval, 1.20-3.53) for PSCI. Moreover, the addition of sTREM2 to the conventional model with established risk factors significantly improved risk discrimination (C-statistics increased from 0.668 to 0.691, p = 0.02) and reclassification (net reclassification improvement: 32.2%, p < 0.001; integrated discrimination improvement: 1.3%, p = 0.01) for PSCI., Limitations: Results might be subject to selective bias and potential confounding., Conclusions: The present study demonstrated that elevated level of plasma sTREM2 may be associated with PSCI, and sTREM2 has potential value in predicting PSCI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Choline pathway nutrients, including choline and betaine, are reported to exert antidepressant effects. However, there is little population-based evidence on the relationships between circulating choline and betaine and poststroke depression (PSD). We aimed to prospectively explore the associations between plasma choline and betaine and depression after ischemic stroke., Methods: This study was based on the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 612 participants with plasma choline and betaine concentrations were included in the analysis. The study outcome was depression 3 months after ischemic stroke. Logistic regression models were performed to estimate the relationships between plasma choline and betaine and the risk of PSD. Risk reclassification and calibration of models with choline or betaine were analyzed., Results: Patients with PSD had lower choline and betaine levels than those without PSD (p < 0.05). Compared with tertile 1, the multivariable-adjusted odds ratios (95% CIs) for tertile 3 of choline and betaine were 0.54 (0.35-0.83) and 0.59 (0.38-0.92), respectively. Per 1 SD increase in choline or betaine was associated with a 25% (95% CI 9%-37%) or an 19% (95% CI 3%-32%) decreased risk of PSD, respectively. Furthermore, the addition of choline or betaine to the established risk factors model improved the risk reclassification for PSD, as shown by an increase in the net reclassification index and integrated discrimination improvement (all p < 0.05)., Conclusions: Patients with elevated levels of choline and betaine had a lower risk of depression after acute ischemic stroke, suggesting the protective significance of choline pathway nutrients for PSD., (© 2021 European Academy of Neurology.)

Background: L-carnitine has been shown to exert neuroprotective effects on cerebral ischemia, mainly by improving mitochondrial function and reducing inflammation. L-carnitine supplementation has also been promoted to enhance cognitive function. However, the relationship between L-carnitine and cognitive impairment after ischemic stroke has seldom been studied., Objective: We aimed to evaluate the association between plasma L-carnitine and poststroke cognitive impairment., Methods: The study sample population was drawn from the China Antihypertensive Trial in Acute Ischemic Stroke. Plasma L-carnitine were measured at baseline in 617 patients with ischemic stroke using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3-month follow-up after ischemic stroke., Results: Plasma L-carnitine were inversely associated with cognitive impairment at 3 months after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartiles of L-carnitine was 0.60 (0.37, 0.98; p for trend = 0.04). Each 1-SD increase in log-transformed L-carnitine concentration was significantly associated with a 15% (95% CI: 1%, 29%) reduction in the risk of cognitive impairment after stroke. The addition of L-carnitine to the model including conventional risk factors significantly improved the risk reclassification for cognitive impairment (net reclassification improvement: 17.9%, integrated discrimination improvement: 0.8%; both p < 0.05). Furthermore, joint effects of L-carnitine and inflammation markers were observed, and patients with higher L-carnitine and a lower inflammatory status simultaneously had the lowest risk of poststroke cognitive impairment., Conclusion: The present study provided prospective evidence on the inverse association between plasma L-carnitine and cognitive impairment after ischemic stroke.

Background: Soluble suppression of tumorigenesis-2 (sST2) was reported to be associated with cognitive performance and risk of incident stroke. However, the impact of sST2 on cognitive function after ischemic stroke is unclear. We aimed to assess the association of sST2 and cognitive impairment at 3 months in acute ischemic stroke patients., Methods: Baseline plasma sST2 levels were measured in 619 ischemic stroke patients (mean age: 60.0 ± 10.5 years) from 7 participating hospitals of the China Antihypertensive Trial in Acute Ischemic Stroke. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status. Cognitive impairment was defined as a MoCA score < 23 or MMSE score < 27. The association between sST2 and cognitive impairment was evaluated by logistic regression analysis., Results: 325 (52.5%) or 323 (52.2%) participants developed cognitive impairment according to MoCA or MMSE. After adjustment for age, sex, education, and other covariates, the odds ratio for the highest vs lowest quartile of sST2 was 2.38 (95% CI, 1.42-4.00) and 1.82 (95% CI 1.09-3.03) risk of cognitive impairment defined by MoCA and MMSE score, respectively. Incorporation sST2 into a model containing conventional risk factors significantly improved reclassification., Conclusions: Elevated plasma sST2 levels were significantly associated with post-stroke cognitive impairment.

Background and Purpose: Soluble suppression of tumorigenicity 2 (sST2) might be related to stroke and depression, but the association of sST2 with poststroke depression (PSD) is unclear. The study aimed to prospectively assess the association between plasma sST2 levels and PSD., Methods: A total of 635 acute ischemic stroke patients with sST2 measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Rating Scale for Depression to assess depression at 3 months, and PSD was defined as a score of ≥8. Logistic regression analysis was performed to estimate the risk of PSD associated with sST2, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to assess the predictive value of sST2., Results: Two hundred fifty (39.4%) patients developed depression at 3 months after ischemic stroke. Patients with PSD had higher sST2 levels than patients without PSD (172.7 vs. 153.8 pg/ml; p = 0.003). After adjustment for age, sex, education, National Institutes of Health Stroke Scale score, and other covariates, the odds ratio for the highest quartile of sST2 compared with the lowest quartile was 1.84 (95% confidence interval, 1.10-3.08) for PSD. Adding sST2 to a conventional model notably improved risk prediction for PSD (category-free NRI = 19.34%, 95% confidence interval = 4.39%-34.28%, p = 0.017; IDI = 1.20%, 95% confidence interval = 0.25%-2.15%, p = 0.014)., Conclusions: Increased plasma sST2 levels in the acute phase of ischemic stroke were significantly associated with the increased risk of PSD, independently of conventional risk factors., (© 2020 European Academy of Neurology.)

Background and Purpose: Choline metabolism was suggested to play pathophysiological roles in nervous system and atherosclerosis development. However, little is known about the impacts of choline pathway nutrients and metabolites on poststroke cognitive impairment. We aimed to prospectively investigate the relationships between circulating choline, betaine, and trimethylamine N-oxide with cognitive impairment among acute ischemic stroke patients., Methods: We derived data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Plasma choline, betaine, and trimethylamine N-oxide concentrations at baseline were measured in 617 participants. Cognitive impairment was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Reclassification and calibration of models with choline-related biomarkers were evaluated., Results: Plasma choline and betaine were inversely associated with cognitive impairment. Compared with the lowest tertile, adjusted odds ratios of Mini-Mental State Examination-defined cognitive impairment for participants in the highest tertiles of choline and betaine were 0.59 (95% CI, 0.39-0.90) and 0.60 (95% CI, 0.39-0.92), respectively. In addition, both choline and betaine offered incremental predictive ability over the basic model with established risk factors, shown by increase in net reclassification improvement and integrated discrimination improvement. There were similar significant relationships between choline and betaine with cognitive impairment as defined by the Montreal Cognitive Assessment. However, plasma trimethylamine N-oxide was only associated with cognitive impairment evaluated using the Mini-Mental State Examination; the adjusted odds ratio was 1.33 (95% CI, 1.04-1.72) for each 1-SD increment of trimethylamine N-oxide., Conclusions: Patients with higher choline and betaine levels had lower risk of cognitive impairment after ischemic stroke, supporting promising prognostic roles of choline pathway nutrients for poststroke cognitive impairment.

Background: To assess the potential incremental utility of multiple biomarkers reflecting several pathological pathways for the risk prediction of depression after stroke., Methods: We used data from the China Antihypertensive Trial in Acute Ischemic Stroke, and a panel of 13 circulating biomarkers were measured. The study outcome was depression (24-item Hamilton Depression Rating Scale score≥8) at 3 months after ischemic stroke. Logistic regression models were performed to evaluate the risk of depression associated with multiple biomarkers. Discrimination and risk reclassification for depression were analyzed., Results: Among 631 included ischemic stroke patients, elevated growth differentiation factor-15, anticardiolipin antibodies, antiphosphatidylserine antibodies and matrix metalloproteinase-9 were individually associated with increased risks of depression after stroke. The multiple biomarker analysis showed a clear gradient in the risk of depression with increasing numbers of elevated biomarkers, and multivariate adjusted odds ratio (95% confidence interval) of patients with 4 elevated biomarkers was 6.52 (2.24-18.95) compared with those without elevation in any of 4 biomarkers. The simultaneous inclusion of all 4 biomarkers to the conventional model significantly improved discrimination (C statistic increased from 0.702 to 0.748, P=0.004) and risk reclassification (net reclassification improvement 45.0%; integrated discrimination improvement 6.2%; both P<0.001) for depression after stroke., Limitations: We selected biomarkers that had previously been reported to be promising predictors of depression after stroke, while other novel biomarkers not tested might have additional predictive value., Conclusions: Simultaneously adding multiple biomarkers from several pathophysiological pathways to traditional risk factors provided substantial incremental utility of the risk stratification for depression after stroke., (Copyright © 2020. Published by Elsevier B.V.)

The expression of tissue inhibitor metalloproteinase-1 (TIMP-1) significantly increased after acute cerebral ischaemia and involved in neurodegeneration. The purpose was to prospectively investigate the relationship between serum TIMP-1 with post-stroke cognitive impairment. Our participants were from an ancillary study of China Antihypertensive Trial in Acute Ischemic Stroke. 598 ischaemic stroke patients from seven participating hospitals were included. Cognitive impairment was evaluated using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months. 316 (52.84%) or 384 (64.21%) participants had cognitive impairment according to MMSE or MoCA, respectively. Compared with the first quartile of TIMP-1, the multivariate-adjusted odds ratios (95% confidence intervals) for the highest quartile were 1.80 (1.09-2.97) for cognitive impairment defined by MMSE and 2.55 (1.49-4.35) by MoCA. Multiple-adjusted spline regression models showed linear associations between TIMP-1 concentrations and cognitive impairment (P value for linearity < 0.01). The addition of TIMP-1 to models including conventional factors improved reclassification for cognitive impairment, as shown by net reclassification index or integrated discrimination improvement (P < 0.05). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had highest risk of cognitive impairment. Higher serum TIMP-1 levels were associated with increased risk of cognitive impairment after acute ischaemic stroke, independently of established risk factors., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background Choline and betaine have been suggested to play a pivotal role in neurotransmitter synthesis, cell membrane integrity, and methyl-group metabolism, exerting neuroprotective effects in patients with various neurological disorders. However, population-based evidence on choline and betaine with subsequent cardiovascular events after stroke is rare. Objectives We aimed to prospectively investigate the relationships of circulating choline and betaine with cardiovascular events and recurrent stroke in patients with ischemic stroke. Methods We performed a nested case-control study within the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 controls (free of recurrent cardiovascular events) matched for age (±1 y), sex, and treatment group were included. The primary endpoint was a composite of cardiovascular events after ischemic stroke. Plasma choline and betaine were measured at baseline by ultra-high-performance LC-MS/MS. Conditional logistic regression models were applied, and discrimination, reclassification, and calibration of models with choline pathway metabolites were evaluated. Results Plasma choline and betaine were inversely associated with cardiovascular events and recurrent stroke after ischemic stroke. Specifically, in fully adjusted models, each additional SD of choline and betaine was associated with 35% (95% CI: 20%–48%) and 30% (95% CI: 14%–43%) decreased risks of subsequent cardiovascular events, respectively, and 34% (95% CI: 16%–48%) and 29% (95% CI: 12%–43%) decreased risks of recurrent stroke, respectively. In addition, both choline and betaine offered substantial risk discrimination and reclassification improvement for cardiovascular events and recurrent stroke beyond traditional risk factors, as evidenced by an increase in C statistics, the net reclassification index, and integrated discrimination improvement. Conclusions Plasma choline pathway metabolites, including choline and betaine, were associated with decreased risks of cardiovascular events and recurrent stroke and provided incremental value in risk discrimination and stratification in patients with ischemic stroke. This nested case-control study was based on the China Antihypertensive Trial in Acute Ischemic Stroke, which is registered at clinicaltrials.gov as NCT01840072. [ABSTRACT FROM AUTHOR]

Background: The effect of serum rheumatoid factor (RF) on poststroke cognitive impairment remains unknown. We aimed to investigate the association of serum RF in the acute phase with cognitive impairment at 3 months after ischemic stroke onset.Methods: Our study was based on a random sample from the China Antihypertensive Trial in Acute Ischemic Stroke, a total of 582 patients from 7 of 26 participating sites of the trial with serum RF levels were included in this analysis. Cognitive impairment was defined as Mini-Mental State Examination less than 27 or Montreal Cognitive Assessment less than 25.Results: According to Mini-Mental State Examination score, the multivariate-adjusted odds ratio and 95% confidence interval of cognitive impairment for the highest tertile of serum RF was 1.79 (1.08-2.99) compared with the lowest tertile. Each standard deviation increase of log-transformed RF was associated with 33% (95% confidence interval: 7%-66%) increased risk of cognitive impairment, and a linear association between serum RF and risk of poststroke cognitive impairment was observed (P for linearity < .01). Adding log-transformed RF to a model containing conventional risk factors improved the predictive power for poststroke cognitive impairment (net reclassification improvement: 26.21%, P < .01; integrated discrimination index: 1.24%, P = .02). Similar significant findings were observed when cognitive function was defined by Montreal Cognitive Assessment score.Conclusions: Elevated serum RF levels in the acute phase were independently associated with 3-month cognitive impairment among ischemic stroke patients. Further studies are needed to replicate our findings and to clarify the potential mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND Optimal blood pressure (BP) levels during acute ischemic stroke have not been established. We studied associations between systolic BP trajectories during acute phase and subsequent clinical outcomes among patients with ischemic stroke. METHODS A total of 4,036 patients with acute ischemic stroke and elevated BP from the China Antihypertensive Trial in Acute Ischemic Stroke trial were included in this analysis. Three BPs were measured every 2 hours in day 1, every 4 hours during days 2 and 3, and every 8 hours thereafter until hospital discharge or death. Clinical outcomes were assessed at 3, 12, and 24 months. Latent variable mixture modeling was used to identify subgroups that share a similar underlying trajectory of systolic BP during the first 7 days after stroke onset. Logistic regression and Cox proportional hazards models were used to examine the associations between systolic BP trajectories and clinical outcomes during follow-up. RESULTS We identified 5 systolic BP trajectories of high, high-to-moderate-low, moderate-high, moderate-low, and low. Compared to participants in high trajectory, multiple-adjusted odds ratios (95% confidence interval) of all-cause mortality at 3 months for individuals in high-to-moderate-low, moderate-high, moderate-low, and low were 0.34 (0.15–0.77), 0.58 (0.32–1.04), 0.29 (0.15–0.56), and 0.56 (0.26–1.19), respectively. Likewise, the corresponding hazard ratios for all-cause mortality in 24 months were 0.66 (0.44–1.00), 0.74 (0.53–1.05), 0.45 (0.32–0.66), and 0.61 (0.40–0.93), respectively. Similar associations were observed for recurrent stroke and cardiovascular disease, and in both the intervention and control groups. CONCLUSIONS Patients with moderate-low systolic BP during acute ischemic stroke had a lower risk of adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid activity was reported to be increased in depressive patients, while the impact of antiphospholipid antibodies (aPLs) on post-stroke depression (PSD) is unclear. We aimed to investigate the associations of aPLs, including antiphosphatidylserine (aPS) and anticardiolipin (aCL) antibodies with depression after acute ischemic stroke.Methods: aPS and aCL were measured in 497 ischemic stroke patients recruited from 7 of 26 participating hospitals of China Antihypertensive Trial in Acute Ischemic Stroke. 24-item Hamilton Depression Rating Scale was used to evaluate PSD status at 3 months after stroke.Results: Compared with aPS-negative or aCL-negative, the adjusted odds ratios (ORs) [95% confidence intervals (CIs)] associated with aPS-positive or aCL-positive were 1.77 (1.07-2.92) or 2.06 (1.11-3.80) for risk of PSD. On continuous analyses, per 1-SD increment of aPS and aCL were associated with 29% (OR 1.29, 95% CI 1.06-1.58) and 30% (OR 1.30, 95% CI 1.06-1.60) increased risks for PSD, respectively. Adding aPLs to conventional risk factors models significantly improved risk reclassification for PSD (net reclassification improvement index = 21.87%, P = 0.016 for aPS; net reclassification improvement index = 32.24%, P = 0.0004 for aCL).Limitations: aPLs levels were tested only at baseline without serial measurements, and we were unable to detect the association between aPLs changes and PSD.Conclusions: Higher aPS and aCL levels in the acute phase of ischemic stroke were associated with increased risk of 3-month PSD, suggesting that aPLs may play an important role in post-stroke depression prediction. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the ability of multiple novel biomarkers representing several pathophysiological pathways to improve risk prediction of post-stroke cognitive impairment. We conducted a prospective multicenter study in 638 ischemic stroke patients with elevated blood pressure based on a random subsample from China Antihypertensive Trial in Acute Ischemic Stroke and measured 12 circulating biomarkers in these participants. Cognitive impairment was assessed at 3 months after stroke with definitions of Mini-Mental State Examination (MMSE) score <27 or Montreal Cognitive Assessment (MoCA) score <25. According to MMSE score, 1 SD increase of rheumatoid factor (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.02–1.46), matrix metalloproteinase-9 (OR 1.47, 95% CI 1.22–1.77) and total homocysteine (OR 1.22, 95% CI 1.01–1.49) after log transformation was significantly associated with the risk of post-stroke cognitive impairment. The ORs associated with their simultaneously high levels were 4.89 (95% CI, 2.31–10.35; p trend <0.001) and 3.09 (95% CI, 1.60–5.98; p trend <0.001) for cognitive impairment and the severity of cognitive impairment, respectively. Adding these 3 biomarkers to conventional model significantly improved the risk prediction of cognitive impairment (C statistic 0.729 vs. 0.688, p = 0.004; net reclassification improvement = 33.67%, p < 0.001; integrated discrimination index = 4.61%; p < 0.001). Similar significant findings were observed when cognitive impairment was defined by MoCA score. Combination of rheumatoid factor, matrix metalloproteinase-9 and total homocysteine can improve the risk prediction of cognitive impairment among ischemic stroke patients with elevated blood pressure. Further studies are warranted to validate our findings and explore their roles as potential therapeutic targets. Image 1 • The first study using multiple biomarkers to examine improvement in risk prediction for post-stroke cognitive impairment. • This prospective study is by far the largest biomarker study of post-stroke cognitive impairment. • Combination of RF, MMP-9 and tHcy might improve the risk prediction of post-stroke cognitive impairment. • RF, MMP-9 and tHcy should be measured simultaneously among ischemic stroke patients in future clinical practice. • Further studies are warranted to explore their roles as potential therapeutic targets. [ABSTRACT FROM AUTHOR]