Chenchen Wei

Increased Serum Alkaline Phosphatase as a Predictor of Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease

BACKGROUND AND OBJECTIVE Elevated alkaline phosphatase (ALP) is considered as a marker of liver function in clinical practice. Furthermore, it has been identified that liver function can contribute to hemorrhagic transformation (HT). However, whether ALP levels play a role in HT after stroke remains an open question, especially in cardioembolic stroke patients. METHODS We prospectively and consecutively enrolled ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. Baseline data including ALP levels within 48 hours after admission were collected. ALP levels were divided into tertiles. The presence of HT, hemorrhagic infarction (HI), parenchymal hematoma (PH), and symptomatic HT was evaluated according to brain magnetic resonance imaging and European-Australasian Acute Stroke Study III definitions. We used logistic regression to examine the associations between ALP levels and risk of HT, HI, PH, and symptomatic HT. RESULTS Of the 130 patients (56 male; mean age: 63 years) included finally, 50 (38.5%) developed HT and 13 (10.0%) developed symptomatic HT. ALP levels were not associated with risk of HT, HI, and PH. However, compared with the first ALP tertile, patients in the third tertile were 8.96 times more likely to have symptomatic HT (95% confidence interval: 1.33-60.21; P = .02) after adjusting for age, gender, alanine aminotransferase levels, aspartate aminotransferase levels, antiplatelet therapy, anticoagulation therapy, and thrombolysis therapy. CONCLUSION Elevated ALP levels may help identify high-risk symptomatic HT in ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. However, further studies with larger cohorts are needed to identify our results.

A cohort study of relationship between serum calcium levels and cerebral microbleeds (CMBs) in ischemic stroke patients with AF and/or RHD

AbstractCalcium is an essential element for life and has cerebroprotective property in stroke patients. Low serum calcium levels were found to be related to large hematoma volumes in intracerebral hemorrhagic patients and hemorrhagic transformation in ischemic stroke patients after thrombolysis. However, their impact on hemorrhage-prone small vessel disease represented by cerebral microbleeds (CMBs) is uncertain. We aim to investigate whether low serum calcium levels are associated with presence and location of CMBs.Ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease admitted to our hospital were consecutively and prospectively enrolled. Demographic and clinical information were collected and analyzed according to the occurrence and location of CMBs, and levels of serum calcium. We used logistic regression analysis to estimate the multivariable adjusted relationship between serum calcium levels and the presence or location of CMBs.Among the 67 patients (28 males; mean age, 67.3 years) in the final analysis, 39 (58.2%) were found to have CMBs. After adjustment for age, sex, smoking habits, drinking habits, and renal impairment, the presence of CMBs and deep CMBs was, respectively, 4.96- and 4.83-fold higher in patients with lower serum calcium levels (⩽2.15 mmol/L) than in patients with higher serum calcium levels.Lower serum calcium levels (⩽2.15 mmol/L) are independently associated with the presence of CMBs and deep CMBs in ischemic stroke patients with AF and/or rheumatic heart disease, which should be verified and extended in large cohorts, with other types of stroke patients and the general population.

Association between leukoaraiosis and hemorrhagic transformation after cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease

Cardioembolic stroke due to atrial fibrillation (AF) and/or rheumatic heart disease (RHD) often involves hemorrhagic transformation (HT), and we examined whether leukoaraiosis (LA) was associated with HT in these cases. We prospectively enrolled 251 patients who were admitted to two hospitals within one month of experiencing cardioembolic stroke due to AF/RHD. LA severity was assessed using three visual rating scales. HT was identified in 99 patients (39.4%) based on baseline computed tomography (CT) and post-admission magnetic resonance imaging or second CT. Univariate analysis identified risk of HT as higher in the presence of frontal LA based on the age-related white matter changes scale and in the presence of anterior LA based on the VSS scale. Multivariate analysis confirmed that moderate to severe LA was independently associated with higher HT risk. Of the various sites affected in LA, frontal LA correlated with highest risk of HT (OR 3.199, 95%CI 1.555-6.580). These results suggest that moderate to severe LA, especially at periventricular and anterior sites, is associated with HT after cardioembolic stroke due to AF/RHD. These findings suggest the need to take LA into account as a HT risk factor when considering the use of anticoagulation and thrombolysis in these patients.

Association between Fibrinogen and Leukoaraiosis in Patients with Ischemic Stroke and Atrial Fibrillation

BACKGROUND Leukoaraiosis (LA), a surrogate of cerebral small-vessel diseases (CSVD), has been increasingly recognized because of its high prevalence and strong prognostic value in stroke. But the mechanism of LA is incompletely clarified. Fibrinogen is a crucial role in coagulation cascade and inflammation. There are inconsistent reports on the association of fibrinogen with LA in the general population. We aimed to investigate the association between fibrinogen and LA in patients with stroke and atrial fibrillation (AF), which was not ever reported before. METHODS Patients with ischemic stroke and AF were prospectively and consecutively recruited. Clinico-demographic data and fibrinogen levels were collected within 48 hours from stroke onsets and analyzed according to the presence and distribution of LA (periventricular hyperintensity [PVH] and deep white matter hyperintensity). RESULTS Of 186 patients (34.4% male; mean age, 68.76 ± 12.76 years) enrolled, 134 patients (72.0%) presented with LA. Elevated fibrinogen levels were associated with higher presence of LA (P = .005) and PVH (P = .002). After adjustment for the confounders, the fibrinogen levels were independently correlated with LA and PVH (all P <.05). Patients with elevated fibrinogen levels (≥3.5 g/L) were more likely to present with LA and PVH, with the odds ratios of 14.037 (95% confidence interval [CI] 2.588-76.131) and 12.567 (95% CI 2.572-61.395), respectively. CONCLUSION This study found that fibrinogen was independently and positively associated with LA and PVH in patients with stroke and AF. These results provide further evidence for the key role of fibrinogen in LA, even the total CSVD burden.

Cerebral Microbleeds Do Not Predict Hemorrhagic Transformation in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease

BACKGROUND AND PURPOSE Cerebral microbleeds (CMBs) are known to be potential risk factors for intracerebral hemorrhage (ICH), but there is controversy on the relationship between CMBs and hemorrhagic transformation (HT) after ischemic stroke. Besides, the question regarding whether the relationship between CMBs and HT can be affected by antithrombotic drugs in acute stage of ischemic stroke has not yet reached a consensus. METHODS 174 acute ischemic stroke patients with atrial fibrillation (AF) and/or rheumatic heart disease (RHD) were prospectively and consecutively enrolled in the study, of which 160 patients (mean 68.09 ±12.59 years) were finally included in the final analysis (West China Hospital, Sichuan University, n=125; Peoples Hospital of Deyang City, n=35).We assessed the presence, location and number of CMBs by using susceptibility-weighted imaging (SWI) within 7 days after admission, and the incidence of hemorrhagic transformation was evaluated by magnetic resonance imaging(MRI) during hospitalization. The univariate and multivariate analyses were used to analyze the relationship between CMBs and HT. RESULTS CMBs were detected in 90 patients (56.3%). HT was found in 62 (38.8%) patients, among which 43 were hemorrhagic infarction (HI) and 19 were parenchymal haemorrhage (PH). The presence of CMBs was not significantly different among different HT subtypes (no HT, HI and PH; 59.2%, 51.2%, versus 52.6%, P=0.64). There was no relationship between the number/location of CMBs and hemorrhagic transformation subtypes (P=0.38). In the 2 subgroups of patients treated with anticoagulants and antiplatelets after admission, the incidence of HT was not significantly different between patients with and without CMBs (anticoagulants, 13.3% versus 18.2%, P=0.71; antiplatelets, 29.2% versus 40.3%, P= 0.21). CONCLUSION The present study suggests that CMBs do not predict the presence of hemorrhagic transformation in acute ischemic stroke patients with AF and/or RHD. The results were not affected by anticoagulant or antiplatelet agents used in acute stage of ischemic stroke.

Association between Coagulation Function and Cerebral Microbleeds in Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease

Cerebral microbleeds (CMBs), which indicate hemorrhage-prone disease, may associate with hemostatic abnormalities, but the association between CMBs and coagulation function is uncertain. We aimed to examine this possible association. The following coagulation function indicators were evaluated in 85 consecutive ischemic stroke patients diagnosed with atrial fibrillation and/or rheumatic heart disease: prothrombintime (PT), activated partial thromboplastin time (APTT), and levels of D-dimer and fibrinogen. Indicators were assessed within 24 h after admission. CMBs were identified based on published criteria by two experienced stroke neurologists working independently. PT, APPT, and levels of D-dimer and fibrinogen were compared between patients with and without CMBs using univariate and multivariate analysis. CMBs were detected in 48 patients (56.5%), and fibrinogen levels in these patients were independently and significantly higher than in patients without CMBs after adjustment (OR 2.16, 95% CI 1.20-3.90, P=0.01), whereas the two types of patients did not differ significantly in PT, APPT, or D-dimer levels. The presence of CMBs in ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease is associated with elevated levels of fibrinogen. Larger prospective studies are needed to verify this association and explore the mechanisms involved.

High-sensitivity cardiac troponin T levels and risk of cerebral microbleeds in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease

BACKGROUND AND OBJECTIVE Elevated high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with coronary disease and small-vessel ischemic stroke through their associations with atherosclerosis. Considering the relationship between atherosclerosis and cerebral microbleeds (CMBs), the purpose of this study was to examine associations between serum hs-cTnT levels and risk of CMBs in acute ischemic stroke patients. METHODS This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at a large tertiary care hospital in southwestern China. Clinico-demographic data were collected and analyzed by logistic regression to identify the relationship between serum hs-cTnT levels and CMB occurrence and location. RESULTS In the final analysis, of 66 patients (27 males; mean age, 68.7years), 39 (59.1%) had CMBs. Hs-cTnT levels were not associated with risk of strictly lobar CMBs. However, after adjusting age, sex, current alcohol consumption, total cholesterol, hypertension, diabetes mellitus, prior antithrombotic therapy and NIHSS on admission, patients in the higher tertile were more likely to have CMBs and deep or infratentorial CMBs (P<0.05) compared with the lower hs-cTnT tertile. CONCLUSION Hs-cTnT may be an independent predictor for the occurrence of CMBs, particularly of deep or infratentorial CMBs. This finding justifies further research into how hs-cTnT levels may contribute to CMBs and potentially other subclinical small-vessel diseases.

High Serum Alkaline Phosphatase Levels in Relation to Multi-Cerebral Microbleeds in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease.

Elevated alkaline phosphatase (ALP) levels are associated with cerebral small vascular diseases, such as silent brain infarction and cerebral white matter hyperintensity (cWMH), but few prospective data are available for cerebral microbleeds (CMBs). The aim of the study was to investigate associations between serum ALP levels and CMBs in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease. This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at two large tertiary care hospitals in southwestern China. We used logistic regression to examine the relationships between ALP levels and CMBs. Of 128 patients (56 males; mean age, 68 years) included, 71 (55.5%) patients had CMBs. Compared with the first tertile of ALP concentration, participants in the third tertile were 3.59 times more likely to have multi-CMBs (≥2) [95% confidence interval (CI): 1.21-10.71; P = 0.02] after adjusting for age, gender, smoking habits, drinking habits, ALT (alanine transaminase) levels, AST (aspartate transaminase) levels, renal impairment and cWMH.

Prognostic Significance of Intraventricular Hemorrhage in Vascular Structural Abnormality-Related Intracerebral Hemorrhage

BACKGROUND The prognostic significance of intraventricular hemorrhage (IVH) in patients with vascular structural abnormality-related intracerebral hemorrhage (VSARICH) is poorly understood. METHOD We prospectively included consecutive patients diagnosed with VSARICH. Imaging of initial brain computed tomography (CT) scans within 48 hours of symptom onset was analyzed. The presence and severity of IVH were recorded. Severity of IVH was measured using the modified Graeb (mGraeb) score. Baseline characteristics and 3-month outcomes were compared between the IVH and non-IVH groups. Multivariate logistic regression was used to examine the independent association between IVH and 3-month outcomes. RESULTS A total of 132 VSARICH patients were included for analysis, and 71 (53.8%) of them had IVH on initial CT imaging. IVH patients had a median mGraeb score of 15 (6-21), and compared to non-IVH patients, they had shorter delay to first CT scan and higher stroke severity on admission (all P ≤ .005). At 3 months, IVH patients had higher death rates (30.3% versus 7.0%; P = .001) and poor outcome rates (48.5% versus 21.1%; P = .002) than non-IVH patients. After multivariate analysis, IVH severity was associated with 3-month death (Model 1 OR 1.112, 95% CI [1.027-1.204], P = .009; Model 2 OR 1.110, 95% CI [1.027-1.200], P = .009) and poor outcome (Model 2 OR 1.053, 95% CI [1.001-1.108], P = .047), although no independent association between IVH presence and outcomes was observed. CONCLUSION IVH severity measured by mGraeb score independently predicts death and poor functional outcome in patients with VSARICH.