Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Lower total protein and absence of neuronavigation are novel poor prognostic factors of endoscopic hematoma removal for intracerebral hemorrhage.

OBJECTIVES: Endoscopic hematoma removal is widely performed for the treatment of intracerebral hemorrhage. We investigated the factors related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. MATERIALS AND METHODS: From 2013 to 2019, we retrospectively analyzed 75 consecutive patients with hypertensive intracerebral hemorrhage who underwent endoscopic hematoma removal. Their characteristics, including neurological symptoms, laboratory data, and radiological findings were investigated using univariate and multivariate analysis. Complications during hospitalization, Glasgow Coma Scale (GCS) score on day 7, and modified Rankin Scale (mRS) score at 6 months were considered as treatment outcomes. RESULTS: The mean age of the patients (33 women, 42 men) was 71.8 (36-95) years. Mean GCS scores at admission and on day 7 were 10.3 ± 3.2 and 11.7 ± 3.8, respectively. The mean mRS score at 6 months was 3.8 ± 1.6, and poor outcome (mRS score ranging from 3 to 6 at 6 months) in 53 patients. Rebleeding occurred in 4 patients, and other complications in 15 patients. Multivariate analysis revealed that older age, hematoma in the basal ganglia, lower total protein level, higher glucose level, and absence of neuronavigation were associated with poor outcomes. Of the 75 patients, 9 had cerebellar hemorrhages, and they had relatively favorable outcomes compared to those with supratentorial hemorrhages. CONCLUSION: Several factors were related to the prognosis of intracerebral hemorrhage after endoscopic hematoma removal. Lower total protein level at admission and absence of neuronavigation were novel factors related to poor outcomes of endoscopic hematoma removal for intracerebral hemorrhage.

Association of Sex with Serum Potassium, Sodium, and Calcium Disorders after Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: To determine the association of sex with serum potassium, sodium, and calcium disorders in patients with hypertensive intracerebral hemorrhage, and meanwhile investigate other risk factors. METHODS: A total of 516 patients with hypertensive intracerebral hemorrhage were retrospectively enrolled. The clinical characteristics were collected. Serum potassium, sodium, and calcium levels were measured. Multivariate analysis was performed to identify risk factors. RESULTS: Hypokalemia is the most common electrolyte disorder (50.2%) after hypertensive intracerebral hemorrhage, followed by hyponatremia (19.8%), hypocalcemia (13.8%), hypernatremia (12.0%), hyperkalemia (2.5%), and hypercalcemia (0.4%). Most of the electrolyte disorders occurred within 1 week after the onset of hypertensive intracerebral hemorrhage. The incidence rate of hypokalemia was higher in women than in men (61.7% vs. 42.3%, χ2 = 18.676; P < 0.001), but the incidence rates of hyponatremia, hypocalcemia, and hypernatremia were not statistically different between women and men (all P > 0.05). Sex was associated with hypokalemia with women having increased risk, whereas sex was not associated with hypernatremia, hypocalcemia, and hyponatremia. In addition, surgical treatment was a risk factor of hypokalemia, hyponatremia, hypocalcemia, and hypernatremia, both breaking into ventricle and age were risk factors of hyponatremia and hypocalcemia, and bleeding site was a risk factor of hypocalcemia and hypernatremia. CONCLUSIONS: In the treatment of female patients with hypertensive cerebral hemorrhage, the clinician should pay attention to potassium chloride supplementation and monitor its intensity. Within 1 week after intracerebral hemorrhage, individuals most prone to electrolyte disorders determined according to the identified risk factors should be monitored as early as possible, and the disorders should be promptly corrected.

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis.

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)-induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

Hemoglobin Concentration Affects Hypertensive Basal Ganglia Hemorrhage After Surgery: Correlation Analysis in a High-Altitude Region.

OBJECTIVE: Hypertensive cerebral hemorrhage leads to greater mortality and worse functional outcomes at high altitudes. Experimental studies have suggested that hemoglobin can lead to increased perihemorrhagic edema after intracerebral hemorrhage. METHODS: Patients were divided into a high-hemoglobin (H-H) group (>180 g/L) and a low-hemoglobin (L-H) group (≤180 g/L). The distance from the cortex to the midline was used to indicate the degree of edema. At 1, 7, 14, and 21 days, the patients' status was scored using the Glasgow coma scale, and survival was plotted using Kaplan-Meier survival curves. Pearson correlation analysis showed that the difference between the postoperative and preoperative Glasgow coma scale score correlated with the hemoglobin concentration. The Glasgow outcome scale was used to assess neurological recovery after 6 months. RESULTS: On days 7, 14, and 21, the edema of the H-H group was significantly greater than that of the L-H group (P < 0.01 and P < 0.001, respectively). The edema of the H-H group peaked at 14 and 21 days, but that of the L-H group peaked at 7 days. The hemoglobin concentration and postoperative neurological recovery had a linear relationship in the H-H group. The L-H group had greater survival compared with the H-H group (P < 0.05). The L-H group had higher Glasgow outcome scale scores compared with the H-H group (P < 0.05). CONCLUSION: The hemoglobin concentration affects the mortality and morbidity from hypertensive cerebral hemorrhage in high-altitude regions, and a linear relationship exists between hemoglobin concentration and neurological recovery in the H-H group.

Different Techniques of Minimally Invasive Craniopuncture for the Treatment of Hypertensive Intracerebral Hemorrhage.

OBJECTIVE: Efficacy of minimally invasive craniopuncture with the YL-1 puncture needle (hard-channel) and soft drainage tube (soft-channel) in treating hypertensive intracerebral hemorrhage (HICH). MATERIALS AND METHODS: A total of 150 patients with HICH were randomly assigned into 3 groups: conservative group (n = 50), hard-channel group (n = 50), and soft-channel group (n = 50). Computed tomography, National Institutes of Health Stroke Scale (NIHSS) and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum and in drainage fluid were examined on days 2, 4, and 6 after operation. RESULTS: Compared with the conservative group, the serum levels of IL-6, TNF-α, and MDA were decreased and SOD was increased (P < 0.05); volumes of hematoma and perihematomal edema as well as NIHSS were reduced (P < 0.05) in minimally invasive groups on days 7, 14, and 28 after operation. Compared with the hard-channel group, the serum levels of IL-6, TNF-α, MDA, and SOD showed the same trend as above in the soft-channel group. In the soft-channel group, MDA was reduced and SOD was increased in brain drainage fluid on days 2, 4, and 6 (P < 0.05); volumes of hematoma and perihematomal edema on days 14 and 28 were found to be reduced compared with the hard-channel group (P < 0.05). There was no significant difference of volumes of hematoma and perihematomal edema on day 7 between minimally invasive groups. NIHSS of the soft-channel group appeared to be significantly reduced on days 7, 14, and 28 after operation (P < 0.05). CONCLUSIONS: Soft-channel minimally invasive craniopuncture is an ideal technique for treating HICH, with advantages of alleviating cerebral edema, reducing oxidative stress, and inhibiting inflammatory response.

Predicting Recurrent Hypertensive Intracerebral Hemorrhage: Derivation and Validation of a Risk-Scoring Model Based on Clinical Characteristics.

OBJECTIVE: To develop and validate a risk-scoring model for predicting recurrent hypertensive cerebral hemorrhage (RHCH) occurring within 1 year after initial hypertensive cerebral hemorrhage and to facilitate preemptive clinical intervention for the prevention of secondary hemorrhage. METHODS: Patient gender, age, blood pressure, Glasgow Coma Scale (GCS) score, location of cerebral hemorrhage, surgery, past medical history, blood biochemical parameters, and Glasgow Outcome Scale score were analyzed using logistic regression analysis to determine independent predictors of RHCH. A risk-scoring model was constructed by assigning coefficients to each predictor and validating it in another independent cohort. The accuracy of the model was then assessed by the area under the receiver operating characteristic curve (AUC), and the calibration ability of the model was assessed by the Hosmer-Lemeshow test. RESULTS: Of 520 patients in the derivation cohort, 38 developed RHCH within 1 year after discharge. Independent risk factors of RHCH were age >60 years; stage 3 hypertension at admission; GCS score 9-12 (admission); GCS score 3-8 (discharge); history of cerebral ischemic stroke, smoking, alcoholism; and plasma homocysteine (Hcy) level ≥10 µmol/L. The recurrence rates for the low-risk (0-13 points), intermediate-risk (14-26 points), and high-risk (27-39 points) groups were 1.73%, 6.11%, and 57.14%, respectively (P < 0.001). The corresponding rates in the validation cohort, of whom 10/107 (9.35%) developed RHCH, were 3.45%, 7.14%, and 71.43%, respectively (P < 0.001). The risk-scoring model showed good discrimination in both the derivation and validation cohorts, with an AUC of 0.802 versus 0.863. The model also showed good calibration ability (the Hosmer-Lemeshow P values of the two cohorts were 0.532 vs. 0.724). CONCLUSIONS: This model will help identify high-risk groups for RHCH in order to facilitate and improve preemptive clinical intervention.

Serum calcium levels at admission is associated with the outcomes in patients with hypertensive intracerebral hemorrhage.

BACKGROUND/OBJECTIVE: Hypertensive spontaneous intracerebral hemorrhages (ICH) cause significant morbidity and mortality. In this study, we aimed to investigate the association between calcium level at admission and outcome in hypertensive ICH patients. METHODS: 658 hypertensive ICH patients were enrolled from January 2012 to January 2016 in this retrospective study, and demographic, clinical, laboratory, radiographic, and outcome data were collected. The associations between serum calcium level and initial hematoma volume, hematoma enlargement and functional outcome were assessed. RESULTS: Lower calcium level at admission was associated with larger initial hematoma volumes, baseline NIHSS and mRSscore (p < .05), but not with platelet count, activated partial thromboplastin time and international normalized ratio on admission (p > .05). For outcome assessment, 30 days mortality and 6 months mRS were adjusted for age, gender and time from onset to admission, cigarette smoking, alcohol drinking, history of hypertension, baseline NIHSS score, Baseline mRS score and hematoma position, lower calcium level at admission was associated with worse outcomes. CONCLUSION: Low calcium level at admission is associated with worse outcome and might be a prognostic factor for acute ICH.

Development and validation of the hypertensive intracerebral hemorrhage prognosis models.

To develop and validate the prognosis model of hypertensive intracerebral hemorrhage based on admission characteristics, which would be applied to predict the 3-month outcome.For developing the prognosis models, we studied data from 325 patients with retrospectively consecutive hypertensive intracerebral hemorrhage admitted between 2012 and 2016. The predictive value of admission characteristics was tested in logistic regression models, presenting 3-month outcome as the primary outcome. The performance of the models was tested by discrimination and calibration. After development, internal and external validations were used to test the function.The multivariate analysis of logistic regression indicated that age, Glasgow coma scale score, pupillary light reflex, hypoxemia, intracerebral hemorrhage volume, blood glucose, and D-dimer level were independent factors of the hypertensive intracerebral hemorrhage prognosis model. The prognosis model based on those admission risk factors worked well. The receiver operating characteristic curve was used to analyze the discriminant ability of model A, model A + B, and model A + B + C. Specifically, the area under the receiver operating characteristic curve increased from 0.816 (model A; 95% CI, 0.760-0.872) to 0.913 (model A + B + C; 95% CI, 0.881-0.946), and the models were not overoptimistic and were applicably confirmed by internal and external validations respectively.This prognosis model could be used to predict the prognosis of patients with hypertensive intracerebral hemorrhage early, simply and accurately, contributing to the clinical treatment eventually.

Lower Ionized Calcium Predicts Hematoma Expansion and Poor Outcome in Patients with Hypertensive Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVE: We tested the hypothesis that ionized calcium levels at admission are associated with early hematoma expansion and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH). METHODS: Patients presenting with HICH were enrolled in the observational cohort study that prospectively collected age, sex, blood pressure, history of diabetes and smoking, time from symptom onset to initial computed tomography (CT), admission ionized calcium (iCa) and total calcium (tCa), coagulation function, Glasgow Coma Scale (GCS), and postoperative modified Rankin Scale score. Hematoma reconstruction on CT was performed to measure hematoma volumes. Hematoma expansion (HE) was defined as an increase of more than 30% or 6 mL in HICH volume. We performed univariate and multivariate analyses to assess for association of iCa level with early HE and functional outcome. RESULTS: We included 111 patients with HICH for analysis. Admission serum iCa was 1.10 mmol/L in patients with HE and 1.17 in patients without HE. Univariate analysis indicated significant difference of GCS, initial HICH volume, iCa, and tCa between the HE and non-HE groups (P < 0.05). Lower admission iCa (less than 1.12 mmol/L) was associated with HE (odds ratio [OR] 0.300, 95% confidence interval [CI] 0.095-0.951, P = 0.041) after adjustment for age, blood pressure, GCS score, time to initial CT scan, baseline HICH volume, prothrombin time, and tCa. Furthermore, predictive factors of poor outcome included iCa (OR 0.192, 95% CI 0.067-0.554, P = 0.002) and GCS score (OR 0.832, 95% CI 0.722-0.959, P = 0.011). CONCLUSIONS: These data support the hypothesis that lower ionized calcium is associated with early hematoma expansion and poor outcome in patients with hypertensive intracerebral hemorrhage.

Serum Copper Homeostasis in Hypertensive Intracerebral Hemorrhage and its Clinical Significance.

This study was to investigate the alterations of serum copper homeostasis after hypertensive intracerebral hemorrhage (ICH), which is not yet clear. We recruited 85 hypertensive ICH patients and determined their serum levels of total copper (TCu), small molecule copper (SMC), and ceruloplasmin (Cp). Sera from 32 healthy persons and 12 primary hypertension patients were collected and analyzed as well. Serum TCu levels in ICH patients were tested at three time points (on admission, day 3, and day 7) and found to be higher than that in hypertension patients (p < 0.05). The serum SMC levels in hypertension patients and ICH patients at three time points were higher than that in healthy controls (p < 0.05). Higher serum SMC levels on days 3 and 7 were associated with death in the hospital. Additionally, higher serum SMC levels on the seventh day were associated with poor outcome at discharge. High serum Cp levels on admission, as well as low serum Cp levels on the seventh day, were associated with death in the hospital (p = 0.002 and p = 0.034, respectively). Our findings indicated that declines in serum Cp and increases in serum SMC are correlated with lethal or poor outcome in hypertensive ICH patients, possibly as a result of contributions to secondary injury of brain after hemorrhage due to impairment of iron transport and enhanced oxidative stress.

N-Terminal Pro-Brain Natriuretic Peptide Concentrations After Hypertensive Intracerebral Hemorrhage: Relationship With Hematoma Size, Hyponatremia, and Intracranial Pressure.

INTRODUCTION:: The role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with hypertensive intracerebral hemorrhage (HICH) is poorly understood. This study aimed to investigate the secretion pattern of NT-proBNP in patients with HICH and to assess its relationship with hematoma size, hyponatremia, and intracranial pressure (ICP). METHODS:: This prospective study enrolled 147 isolated patients with HICH. Blood samples were obtained from each patient, and values of serum NT-proBNP, hematoma size, blood sodium, and ICP were collected for each patient. RESULTS:: The peak-to-mean concentration of NT-proBNP was 666.8 ± 355.1 pg/mL observed on day 4. The NT-proBNP levels in patients with hematoma volume >30 mL were significantly higher than those in patients with hematoma volume <30 mL ( P < .05). In patients with severe HICH, the mean concentration of NT-proBNP was statistically higher than that in patients with mild-moderate HICH ( P < .05), and the mean level of NT-proBNP in hyponatremia group was significantly higher than that in normonatremic group ( P < .05). In addition, the linear regression analysis indicated that serum NT-proBNP concentrations were positively correlated with ICP ( r = .703, P < .05) but negatively with blood sodium levels only in patients with severe HICH ( r = -.704, P < .05). The serum NT-proBNP levels on day 4 after admission were positively correlated with hematoma size ( r = .702, P < .05). CONCLUSION:: The NT-proBNP concentrations were elevated progressively and markedly at least in the first 4 days after HICH and reached a peak level on the fourth day. The NT-proBNP levels on day 4 were positively correlated with hematoma size. There was a notable positive correlation between plasma NT-proBNP levels and ICP in patients with severe HICH. Furthermore, only in patients with severe HICH, the plasma NT-proBNP levels presented a significant correlation with hyponatremia, which did not occur in patients with mild-moderate HICH.

The Relationship of Hematoma Growth to Red Blood Cell Distribution Width in Patients with Hypertensive Intracerebral Hemorrhage.

AIM: Hypertension is a primary risk factor for intracerebral hemorrhage (ICH) and is thought to be responsible for about 55% of all ICH cases. Thus, the primary goal of the study was to examine whether the status of vascular rheological factors upon admission to the hospital was associated with hypertensive ICH growth and early outcomes. MATERIAL AND METHODS: Over a 2-year period, the present study evaluated 60 ICH patients who were admitted within the first 12 hours of symptom onset. Brain computed tomography scans were performed at admission and then 24 hours later as a control. Hematoma growth was classified as an volume increase more than 6.5 ml or > 33%, and good outcome was defined using the modified Rankin Scale (mRS) score (? 2 at 3 months). RESULTS: The mean age of the study population was 65.07 ± 11.659 years, with 34 men and 26 women. The leading vascular risk factor was hypertension (86.7%). There were significant associations between the initial red blood cell distribution width (RDW) and hematoma growth (p=0.038). Therefore, hematoma growth in the first 24 hours after symptom onset was significantly related to a poor clinical outcome at 3 months (p = 0.050). CONCLUSION: The study identified significant relationships between the initial RDW and poor outcome as well as the initial RDW and hypertensive hematoma growth. Additionally, this study demonstrated that these parameters are easily obtainable and could be used to effectively evaluate outcomes in ICH patients.

Activating blood circulation to remove stasis treatment of hypertensive intracerebral hemorrhage: A multi-center prospective randomized open-label blinded-endpoint trial.

OBJECTIVE: To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH). METHODS: This was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. RESULTS: After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups (P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group (P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 (P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment (P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment (P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. CONCLUSION: The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.

Elevated serum IL-11, TNF α, and VEGF expressions contribute to the pathophysiology of hypertensive intracerebral hemorrhage (HICH).

To study the changes in serum interleukin-11 (IL-11), tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) expressions following hypertensive intracerebral hemorrhage (HICH), and explore their associations with disease severity and prognosis. Serum IL-11, TNF-α, and VEGF levels after 1, 3, 7, and 14 days after HICH were assayed using enzyme-linked immunosorbent assay (ELISA), and neurological deficit score (NDS) were recorded at admission and discharge for 99 HICH cases. Then 45 healthy controls were included and assayed for serum IL-11, TNF-α, and VEGF levels. Serum IL-11, TNF-α, and VEGF levels were higher in HICH patients than healthy controls (all P < 0.05). TNF-α was higher at the 3rd day following disease onset than other time points (all P < 0.05), while IL-11 and VEGF peaked at the 7th day and dropped below baseline values at the 14th day (all P < 0.05). Serum IL-11 was positively correlated with TNF-α (r = 0.70, P < 0.05) and VEGF (r = 0.72, P < 0.05). Serum TNF-α was positively correlated with VEGF (r = 0.46, P < 0.05). Serum IL-11, TNF-α, and VEGF were associated with disease severity in HICH patients. Patients with more severe disease tended to have higher NDS at admission, and higher IL-11, TNF-α, and VEGF during treatment were associated with higher NDS at discharge. Serum IL-11, TNF-α, and VEGF may involve in the pathophysiology of HICH, thus IL-11, TNF-α, and VEGF may be prognostic factors for post HICH neurologic damage.

Relationship of plasma matrix metalloproteinase-9 and hematoma expansion in acute hypertensive cerebral hemorrhage.

In the present study, we aimed to investigate the relationship of plasma matrix metalloproteinase-9 (MMP-9) and hematoma expansion (HE) in acute hypertensive cerebral hemorrhage (AHCH) (HE-in-AHCH). Patients with hypertensive cerebral hemorrhage, confirmed by head computed tomography (CT) within 12 h of onset, were prospectively collected. Venous blood was sampled within 4 h of the confirmation to determine the serum MMP-9 concentration. The blood pressure and National Institute of Health Stroke Score of the patients were recorded on hospital admission. CT re-scanning was performed within 42-54 h of the first head CT examination or immediately after worsening of the patients' consciousness disorder. The relationship between MMP-9 level and HE was analyzed. A total of 186 patients were included. Of these patients, 41 had HE (22.0%). Multivariate logistic regression analysis showed that, in addition to the short interval between onset and the first CT examination, and the irregularity of hematoma shape, increasing MMP-9 level was an independent risk factor for HE-in-AHCH (OR value = 15.65, 95% CI: 5.30-46.15). Moreover, increasing plasma MMP-9 level was identified as an independent risk factor in patients with HE-in-AHCH.

Role of catecholamines in acute hypertensive response: subarachnoid hemorrhage versus spontaneous intracerebral hemorrhage.

BACKGROUND AND OBJECTIVE: Acute hypertensive response, defined as systolic blood pressure (SBP) 140 mmHg or more within 24 h of onset, is frequently observed in hemorrhagic stroke patients. Although catecholamine surge is pivotal in its pathogenesis, few studies have evaluated the relationship between admission SBP and plasma catecholamine levels. PATIENTS AND METHODS: A prospective observational study was carried out to investigate potential differences in the acute hypertensive reaction between subarachnoid hemorrhage (SAH) and spontaneous intracerebral hemorrhage (SICH) by analyzing 200 SAH and 200 SICH patients. In each category, patients were quadrichotomized on the basis of their SBPs in emergency department: less than 140 mmHg, 140-184 mmHg, 185-219 mmHg, and 220 mmHg or more. The plasma catecholamine levels were compared among the four groups. Furthermore, multivariate regression analyses were carried out to identify variables correlated with hypertensive emergency (SBP≥185 mmHg). RESULTS: In SAH patients, there was a proportional increase in norepinephrine levels relative to the graded SBPs, and norepinephrine levels in the 220 mmHg or more group were significantly higher than those in the less than 140 mmHg group (1596±264 vs. 853±124 pg/ml, P=0.03). By contrast, no proportional increase in norepinephrine levels to the graded SBPs was observed in SICH patients. Multivariate regression analyses showed that the initial Glasgow Coma Scale scores of 8 or less (odds ratio 2.251, 95% confidence interval 1.002-5.117) and plasma norepinephrine levels (odds ratio 1.002, 95% confidence interval 1.001-1.003) were correlated with hypertensive emergency in SAH patients. By contrast, none of the variables evaluated were correlated with hypertensive emergency in SICH patients. CONCLUSION: An acute hypertensive response may be more complex, multifactorial, and less catecholamine dependent in SICH patients compared with SAH patients.

The China Stroke Secondary Prevention Trial (CSSPT) protocol: a double-blinded, randomized, controlled trial of combined folic acid and B vitamins for secondary prevention of stroke.

RATIONALE: Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial. AIMS: The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions. DESIGN: This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients (n = 8000, α = 0.05, ß = 0.10) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level ≥ 15 µmol/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0.8 mg, vitamin B6 10 mg, and vitamin B12 500 µg) or matching placebo daily with a median follow-up of three-years. STUDY OUTCOMES: Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event 'stroke, myocardial infarction, or death from any vascular cause', whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations. DISCUSSION: This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification.

HindIII polymorphism in the lipoprotein lipase gene and hypertensive intracerebral hemorrhage in the Chinese Han population.

BACKGROUND: To investigate the relationship between the HindIII polymorphism and hypertensive intracerebral hemorrhage (HIH) and lipid metabolism. METHODS: A polymerase chain reaction-restriction fragment length polymorphism assay and the chain termination DNA sequencing method were used to determine the HindIII genotypes of 267 subjects, which included 120 cerebral hemorrhagic patients and 147 controls. The fasting levels of lipids and glucose in the plasma were used to measure the effect of genotype on HIH risk factors. RESULTS: The frequency of the T allele of the HindIII polymorphism in the HIH group was 90.8%. The frequency of the G allele was 9.2%. In the control group, the frequencies were 82.3% T and 17.7% G, which indicated that the proportion of the G allele in the HIH patient group was significantly lower than in the control group (P<.05). The frequency of GG+GT genotypes in HIH patients (P<.05) and the plasma triglyceride (TG) levels in these patients (P<.05) were also lower than in the control group. The levels of plasma TG, low-density lipoprotein cholesterol, glucose, systolic blood pressure, and diastolic blood pressure in the HIH group were higher than in the controls (P<.05). After controlling for risk factors related to HIH, the HindIII G allele was negatively correlated with the incidence of HIH (odds ratio=.417, 95% confidence interval: .193-.901). CONCLUSIONS: The HindIII G allele may be a protective factor against the development of HIH among the Han Chinese population.

Hold the heparin.

Dynamic ischemic-type electrocardiographic T-wave inversions raise the possibility of myocardial ischemia or infarction but are actually a nonspecific finding. We present a case of a young man presenting with headache and dizziness found to have marked hypertension, deepening T-wave inversions, and troponin elevation. Initial concerns were for acute coronary syndrome (ACS); however, before anticoagulant and antithrombotic therapy was instituted, further evaluation with noncontrast computed tomography of the head showed intraventricular hemorrhage. Electrocardiographic T-wave inversions are nonspecific and have a broad differential diagnosis, but ACS is of the highest concern especially in the setting of elevated troponin. However, as in this case, T-wave inversion and troponin elevation have been well described in intracranial bleeds as well, and full evaluation is required for such findings before initiation of therapy for presumed ACS to avoid a potentially catastrophic outcome.