The Relationship of LDH and Hematological Parameters with Ischemic Volume and Prognosis in Cerebrovascular Disease.

OBJECTIVE: To determine whether lactate dehydrogenase (LDH), platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) values can be used as a prediction for their relationship with stroke volume (SV) and for in-hospital mortality in stroke patients in Emergency Department (ED). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Balikesir University, Turkey from 24/03/2021 to 30/06/2021. METHODOLOGY: Patients aged 18 years or older, diagnosed with stroke in ED, were included in the study. Stroke volumes were calculated from diffusion-weighted images (DWi) with 3D slicer software using image-based semi-automatic and manual segmentation methods. RESULTS: Of the 265 patients, 128 (48.3%) were males. SV was significantly higher in the non-survivor group than in the survivor group (p=0.007). NLR was significantly higher in the non-survivor group than in the survivor group (p=0.018). CONCLUSION: The ratios of NLR and SV stand out as practical parameters for the estimation of mortality, prognosis, and management of patients diagnosed with acute stroke. Taking into account, these parameters in the diagnosis process and prognosis management in EDs will provide convenience. Key Words: Ischemia, NLR, Stroke volume, Cerebrovasular accident, Prognosis.

Associations of Serum Magnesium with Brain Morphology and Subclinical Cerebrovascular Disease: The Atherosclerosis Risk in Communities-Neurocognitive Study.

Circulating magnesium has been associated with a lower risk of dementia, but the physiologic effects by which magnesium may prevent neurological insults remain unclear. We studied 1466 individuals (mean age 76.2 ± 5.3, 28.8% black, 60.1% female) free of prevalent stroke, with measured serum magnesium and with available MRI scans obtained in 2011-2013, participating in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Cross-sectional differences in frontal, temporal, parietal, and occipital lobe volume, along with deep grey matter, total brain, and white matter hyperintensity volume across serum magnesium (categorized into quintiles and per standard deviation increases) were assessed using multiple linear regression. We also examined associations of magnesium with the prevalence of cortical, subcortical, and lacunar infarcts using multiple logistic regression. After adjusting for demographics, biomarkers, medications, and cardiometabolic risk factors, higher circulating magnesium was associated with greater total brain volume and frontal, temporal, and parietal lobe volumes (volumes 0.14 to 0.19 standard deviations higher comparing Q5 to Q1). Elevated magnesium was also associated with lower odds of subcortical infarcts (OR (95%CI): 0.44 (0.25, 0.77) comparing Q5 to Q1) and lacunar infarcts (OR (95%CI): 0.40 (0.22, 0.71) comparing Q5 to Q1). Elevated serum magnesium was cross-sectionally associated with greater brain volumes and lower odds of subclinical cerebrovascular disease, suggesting beneficial effects on pathways related to neurodegeneration and cerebrovascular damage. Further exploration through prospective analyses is needed to assess increasing circulating magnesium as a potential neuroprotective intervention.

The association between triglyceride-glucose index, cardio-cerebrovascular diseases, and death in Korean adults: A retrospective study based on the NHIS-HEALS cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. METHODS: This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. RESULTS: Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024-1.204), and 1.151 (1.058-1.252) in men and 1.099 (0.986-1.226), 1.046 (0.938-1.166), and 1.063 (0.954-1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969-1.282), 1.185 (1.031-1.363), and 1.232 (1.068-1.422) in men and 1.238 (1.017-1.508), 1.183 (0.971-1.440), and 1.238 (1.018-1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850-1.187), 1.225 (1.041-1.441), and 1.232 (1.039-1.460) in men and 1.040 (0.821-1.316), 1.226 (0.981-1.532), and 1.312 (1.054-1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. CONCLUSIONS: Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.

The Impact of the Triglyceride-Glucose Index on Poor Prognosis in NonDiabetic Patients Undergoing Percutaneous Coronary Intervention.

Background: The triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI). Methods: We consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR). Results: A total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan-Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56-1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L. Conclusion: The TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.

Research on Association between Levels of Serum Adiponectin, Hs-CRP, and sICAM-1 and Hypertensive Cerebrovascular Complications.

The study is aimed at studying the association between the levels of serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), and soluble intercellular adhesion molecule-1 (sICAM-1) and hypertensive cerebrovascular complications. 50 patients with hypertensive cerebrovascular disease treated in Gansu Provincial Hospital from December 2016 to December 2018 were selected as the experimental group, and 50 normal people who underwent physical examination were selected as the control group. The blood pressure, heart rate, and the complications were recorded, and the serum blood lipid indexes were detected. Moreover, the content of serum ADPN, hs-CRP, and sICAM-1; the neurological indexes; brain-derived neurotrophic factor (BNDF); and neurone-specific enolase (NSE) were also determined using ELISA. The content of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCR) in the experimental group was significantly higher than that in control group (p < 0.05); the incidence of cerebrovascular complications, systolic blood pressure, diastolic blood pressure, and heart rate increased (p < 0.05); the content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and sICAM-1 obviously rose (p < 0.05); and the content of ADPN and HDL obviously declined (p < 0.05). Besides, the experimental group had evidently lower systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd), and mean blood flow velocity (Vm) and evidently higher pulsatility index (PI) (p < 0.05). The levels of S100 and NSE in the experimental group increased significantly, and the level of BNDF decreased significantly (p < 0.05). In patients with hypertensive cerebrovascular disease, the level of ADPN declines; the levels of hs-CRP and sICAM-1 rise; the incidence rate of cerebrovascular complications is elevated; and there are changes in the blood lipid, cerebrovascular hemodynamic, and neurological indexes, thereby further promoting the occurrence and development of hypertensive cerebrovascular disease.

Effects of chemerin and homocysteine levels and their associations with occurrence and development of ischemic cerebrovascular disease.

BACKGROUND: The current study was conducted to explore the effects of chemerin and homocysteine (Hcy) levels and their associations with the occurrence and development of ischemic cerebrovascular disease (ICVD). METHODS: There involved a total of 187 patients with ICVD and 190 healthy people for physical examination in Cangzhou Central hospital from January 2020 to April 2021. The participants enrolled were divided into four groups based on the digital subtraction angiography: mild stenosis group (64 cases, stenosis rate 30-49 %), moderate stenosis group (72 cases, stenosis rate 50-69 %), severe stenosis group (51 cases, stenosis rate 70-99 %) and control group (190 cases, in healthy condition). The laboratory indexes of ICVD group and control group were observed and the four groups were further compared. Pearson linear correlation was applied to analyze the link between chemerin and Hcy levels and the degree of cerebral vascular stenosis in ICVD patients, and multivariate logistic regression was used to analyze the influencing factors of ICVD. RESULTS: No significant difference was found in general information including age, gender, body mass index (BMI), heart rate, systolic blood pressure, diastolic blood pressure, smoking and drinking between the two groups (P > 0.05). Moreover, there was no significant difference in fasting blood glucose (FBG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels between the two groups (P > 0.05). However, the levels of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), chemerin and Hcy in ICVD group were significantly higher than those in control group (P < 0.05). When comparing the four groups, there was no significant difference in FBG and TC levels (P > 0.05). The levels of TG, LDL-C, chemerin and Hcy in mild, moderate and severe stenosis groups were higher than those in control group, the above levels in moderate and severe stenosis group were higher than those in mild stenosis group, and severe stenosis group higher than moderate stenosis group (P < 0.05). Chemerin and Hcy levels were positively correlated with the degree of cerebral vascular stenosis in ICVD patients (r = 0.612, 0.519, P < 0.001). ICVD was regarded as the dependent variable, and the abovementioned general data as well as significant laboratory indicators, including TG, LDL-C, chemerin and Hcy, as independent variables. The results of multivariate logistic regression analysis revealed that TG, LDL-C, chemerin and Hcy were independent influencing factors of ICVD. CONCLUSIONS: Chemerin and Hcy levels exerted a close link to the occurrence and development of ICVD as independent influencing factors.

Cerebrovascular events in patients with isolated anti-phosphatidyl-serine/prothrombin antibodies.

The interest of extra-criteria antiphospholipid antibodies is growing, especially in patients negative for conventional antibodies. In this study we aimed to assess the clinical utility of anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) testing in patients negative for Beta2-Glycoprotein 1(ß2GPI)-dependent tests, for identifying antiphospholipid syndrome (APS) patients that developed cerebrovascular events (CVE). When screening APS patients attending our center, out of 119 aPS/PT IgG/IgM-positive patients, thus patients negative for aß2GPI and aCL, 42 patients (35%) tested negative for ß2GPI-dependent tests and were tested with thrombin generation assay (TGA). Ten patients (24%), with isolated aPS/PT IgG/IgM, had a history of CVE. Lupus anticoagulant (LA)-positive test was more frequently observed in patients with CVE (8/22 vs. 2/20; p = 0.045). Out of the 10 patients who experienced CVE, 3 patients were aPS/PT IgG positive (all LA positive), and 8 patients were aPS/PT IgM positive (6/8 LA positive). One patient was positive for both aPS/PT IgG and IgM. LA-positive patients had only high titers of aPS/PT IgG/IgM, all of them being ≥ 80 U/ml, while the 2 LA-negative patients were aPS/PT IgM positive with medium titers [40-60 U/ml]. LA-positive patients had significantly altered TGA profile when compared to those who were LA negative, considering all TGA parameters. LA-positive patients had significantly higher tLag (8.4 ± 3.3 min vs. 6.6 ± 1.8 min; p = 0.046), higher tPeak (14 ± 4.3 min vs. 11 ± 2.7 min; p = 0.015) and lower Peak (207 ± 152 nM vs. 356.3 ± 104.7 nM; p < 0.001) and lower AUC (2109.7 ± 1006.9 nM vs. 2772.5 ± 776.8 nM; p = 0.033). The use of aPS/PT might be of help in identifying patients with CVE and APS, as also confirmed by TGA testing.

Cystatin C predicts the risk of incident cerebrovascular disease in the elderly: A meta-analysis on survival date studies.

BACKGROUND: Stroke is the third leading cause of global year of life lost in all-age and second-ranked cause of disability adjusted life years in middle-aged and elder population. Therefore, it is critical to study the relationship between vascular-related risk factors and cerebrovascular diseases. Several cross-sectional studies have shown that Cystatin C (Cys C) is an independent risk factor for cerebrovascular diseases and levels of Cys C are significantly higher in stroke patients than in healthy individuals. In this meta-analysis, we introduce a Cox proportional hazards model to evaluate the causality between Cys C and the risk of cerebrovascular accident in the elderly. METHODS: We searched PubMed, EMBASE, the Web of Science, and the Cochrane Library from 1985 to 2019 for studies on the relationship between serum Cys C and incidence stroke with Cox proportional hazards models. We conducted a subgroup analysis of the selected studies to determine a connection between atherosclerosis and stroke. Finally, 7 research studies, including 26,768 patients without a history of cerebrovascular, were studied. RESULTS: After comparing the maximum and minimum Cys C levels, the hazard ratio for all types of stroke, including ischemic and hemorrhagic stroke, was 1.18 (95% confidence interval 1.04-1.31) with moderate heterogeneity (I2 = 43.0%; P = .119) in a fixed-effect model after pooled adjustment for other potential risk factors. In the subgroup analysis, the hazard ratio and 95% confidence interval for Cys C stratified by atherosclerosis was 1.85 (0.97-2.72). As shown in Egger linear regression test, there was no distinct publication bias (P = .153). CONCLUSION: Increased serum Cys C is significantly associated with future stroke events in the elderly, especially in patients with carotid atherosclerosis. Thus, serum levels of Cys C could serve as a predicted biomarker for stroke attack.

Hyponatremia is a Prognostic Factor in Patients Receiving Nutrition Support.

BACKGROUND: Hyponatremia, the most common electrolyte disorder, has been reported to be related to increased mortality. However, the association between hyponatremia and prognoses remains unclear in patients with nutrition support team (NST) intervention. This study aimed to determine the prevalence of abnormal serum sodium levels, its relation to patient data, and the impact of hyponatremia on prognosis. METHODS: Patients who received nutrition support at Tokushima University Hospital for the first time and whose serum sodium levels were measured at the start of NST intervention were enrolled. Patients were classified into three groups according to their serum Na levels at the start of NST intervention: hyponatremia group, normonatremia group, and hypernatremia group. RESULTS: In the hyponatremia group compared to the normonatremia group, body weight and body mass index were significantly lower. C-reactive protein levels and urea nitrogen/creatinine ratios were significantly higher. Meanwhile, there was no significant difference in the estimated glomerular filtration rate among the groups. The prevalence of malnutrition and anemia were the highest in the hyponatremia group. The 3-year survival rate was approximately 45% in the hyponatremia group, which was the lowest of all three groups. The mortality risk ratio of the hyponatremia group to the normonatremia group was 2.29. CONCLUSIONS: Hyponatremia in NST intervention patients is an independent prognostic predictor. Therefore, adding an assessment of serum sodium at the beginning of NST intervention can identify patients at high risk at an early stage and may improve the quality of NST activity.

Blood-Based Cardiac Biomarkers and the Risk of Cognitive Decline, Cerebrovascular Disease, and Clinical Events.

Background and Purpose: Cardiac biomarkers, NT-proBNP (N-terminal probrain natriuretic peptide), hs-cTnT (high-sensitivity-cardiac troponin T), and GDF-15 (growth differentiation factor-15) have been proposed as important biomarkers of early vascular pathology. However, little is known of the longitudinal associations of these cardiac biomarkers with cerebrovascular disease and clinical events. We examine the association of blood-based cardiac biomarkers (NT-proBNP, hs-cTnT, and GDF-15) with cognitive decline, incident cerebrovascular disease, vascular events, and mortality. Methods: Four hundred thirty-four memory-clinic patients provided blood samples at baseline, underwent 3 annual neuropsychological assessments and brain magnetic resonance imaging scans at baseline and follow-up. NT-proBNP and hs-cTnT concentrations were measured by electrochemiluminescence immunoassay and GDF-15 by quantitative sandwich immunoassay. Baseline and follow-up magnetic resonance imagings were graded for white matter hyperintensities, lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Data on incident vascular events and mortality were obtained. Results: Patients with higher levels of NT-proBNP, hs-cTnT, and GDF-15 showed greater decline in memory domain. Additionally, hs-cTnT was associated with decline in global cognition, executive function, and visuomotor speed. Higher levels of NT-proBNP were associated with incident cerebral microbleeds and hs-cTnT with incident cortical infarcts. During a mean follow-up of 3 years, 26 (5.9%) patients died and 35 (8.1%) developed vascular events. Patients with higher levels of NTpro-BNP and hs-cTnT were at increased risk of vascular events whereas those with higher levels of NT-proBNP and GDF-15 were at risk of mortality. Conclusions: Higher levels of blood-based cardiac biomarkers were associated with decline in memory and risk of vascular events and mortality. Moreover, NT-proBNP and hs-cTnT were associated with incident cerebral microbleeds and cortical infarcts. Thus, these biomarkers are potentially useful in identifying patients at risk of adverse vascular events and death.

Effect of High-Density Lipoprotein Cholesterol Levels on Overall Survival and Major Adverse Cardiovascular and Cerebrovascular Events.

Several studies designed to augment high density lipoprotein (HDL) levels have so far been unsuccessful in reducing rates of major adverse cardiovascular and cerebrovascular events (MACCE). In this study, we report the effect of HDL-C levels on overall survival outcomes and rates of MACCE following percutaneous coronary intervention (PCI). We reviewed patients who underwent PCI at the Cleveland Clinic from 2005 to 2017 and followed them through the end of 2018. Restricted cubic splines incorporated into Cox proportional hazard regression models were used to assess the outcomes. The HDL-C level associated with the lowest mortality was used as a reference value.15,633 patients underwent PCI during the study period, of which 70% were male, 81% were white, and 73% were on statins. The mean age at the time of procedure was 65.8 ± 11.8 years. After adjusting for demographics, co-morbidities, lipid profile, statin use, and date of procedure, our model demonstrated a U-shaped association between HDL-C and overall mortality, with HDL-C levels of 30-50 mg/dl associated with the most favorable outcomes, and HDL-C levels < 30 mg/dl or > 50 mg/dl associated with worse outcomes. A sensitivity analysis in men yielded a similar U-shaped association. In conclusion, our study shows that both low and high levels of HDL-C are associated with worse overall survival, with no effect on rates of MACCE in PCI patients. Further studies are required to understand the mechanism of this association between elevated HDL-C levels with increased overall mortality in patients with atherosclerotic cardiovascular disease (ASCVD).

Lp-PLA2 evaluates the severity of carotid artery stenosis and predicts the occurrence of cerebrovascular events in high stroke-risk populations.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for cardiovascular disease. However, relationship between carotid artery stenosis and cerebrovascular events in high stroke-risk populations is still unclear. METHODS: A total of 835 people at a high risk of stroke were screened from 15,933 people aged >40 years in April 2013 and followed at 3, 6, 12, and 24 months. Finally, 823 participants met the screening criteria, and the clinical data and biochemical parameters were investigated. RESULTS: Among the 823 participants, 286 had varying degrees of carotid artery stenosis and 18 had cerebrovascular events. The level of Lp-PLA2 in the carotid artery stenosis group was higher than that in the no stenosis group, and the level in the event group was higher than that in the no event group (p < 0.05). Spearman correlation analysis showed that Lp-PLA2 was positively correlated with the degree of carotid artery stenosis (r = 0.093, p = 0.07) and stenosis involvement (r = 0.094, p = 0.07). The correlation coefficient between Lp-PLA2 and lipoprotein was the highest on the levels of sdLDL (r = 0.555, p < 0.001), followed by non-HDL, LDL, TC, and TG. Cox multivariate regression analysis revealed that, compared with the first quantile of Lp-PLA2 level (Q1, low level), the risk of cerebrovascular events in the fourth quantile of Lp-PLA2 was 10.170 times that of the first quantile (OR = 10.170, 95% CI 1.302-79.448, p = 0.027). CONCLUSIONS: Lp-PLA2 levels can evaluate carotid artery stenosis and predict the occurrence of cerebrovascular events in high stroke-risk populations and provide scientific guidance for risk stratification management.

Glutathione Peroxidase Activity Is Altered in Vascular Cognitive Impairment-No Dementia and Is a Potential Marker for Verbal Memory Performance.

BACKGROUND: Coronary artery disease (CAD) increases risk for vascular cognitive impairment-no dementia (VCIND), a precursor to dementia, potentially through persistent oxidative stress. OBJECTIVE: This study assessed peripheral glutathione peroxidase activity (GPX), which is protective against oxidative stress, in VCIND versus cognitively normal CAD controls (CN). GPX activity was also evaluated as a biomarker of cognition, particularly verbal memory. METHODS: 120 CAD patients with VCIND (1SD below norms on executive function or verbal memory (VM)) or without (CN) participated in exercise rehabilitation for 24 weeks. Neurocognitive and cardiopulmonary fitness (VO2peak) assessments and plasma were collected at baseline and 24-weeks. RESULTS: GPX was higher in VCIND compared to CN (F1,119 = 3.996, p = 0.048). Higher GPX was associated with poorer baseline VM (ß= -0.182, p = 0.048), and longitudinally with VM decline controlling for sex, body mass index, VO2peak, and education (b[SE] = -0.02[0.01], p = 0.004). Only CN participants showed improved VM performance with increased fitness (b[SE] = 1.30[0.15], p < 0.005). CONCLUSION: GPX was elevated in VCIND consistent with a compensatory response to persistent oxidative stress. Increased GPX predicted poorer cognitive outcomes (verbal memory) in VCIND patients despite improved fitness.

Renal-Cerebral Pathophysiology: The Interplay Between Chronic Kidney Disease and Cerebrovascular Disease.

OBJECTIVES: Cerebrovascular disease has increasingly been linked to overall vascular health. Pathologic conditions like diabetes, hypertension, and kidney disease have been shown to affect brain health and cerebrovascular and nervous systems. Acute kidney injury (AKI) and chronic Kidney Disease (CKD) represent a variety of vascular insults that can adversely affect cerebral health. Hypertension, fluctuations in blood pressure, and diabetic vasculopathy are known risk factors for cerebrovascular disease associated with CKD. Other emerging areas of interest include endothelial dysfunction, vascular calcification due to calcium and phosphorus metabolism dysregulation, and uremic neuropathy present the next frontier of investigation in CKD and cerebrovascular health. METHODS: It has become apparent that the interrelation of AKI and CKD with vascular health, chemical homeostasis, and hormonal regulation upset many aspects of cerebral health and functioning. Stroke is an obvious connection, with CKD patients demonstrating a higher proclivity for cerebrovascular accidents. Cerebral bleeding risk, uremic neuropathies, sodium dysregulation with impacts on nervous system, vascular calcification, and endothelial dysfunction are the next salient areas of research that are likely to reveal key breakthroughs in renal-cerebral pathophysiology. RESULTS: In this review nephrological definition are discussed in a neuro-centric manner, and the areas of key overlap between CKD and cerebrovascular pathology are discussed. The multifaceted effects of renal function on the health of the brain are also examined. CONCLUSION: This review article aims to create the background for ongoing and future neurological-nephrological collaboration on understanding the special challenges in caring for patients with cerebrovascular disease who also have CKD.

Cerebrovascular comorbidity, high blood levels of C-reactive protein and D-dimer are associated with disease outcomes in COVID-19 patients.

The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke.

Plasma Sulfur Amino Acids and Risk of Cerebrovascular Diseases: A Nested Case-Control Study in the EPIC-Norfolk Cohort.

BACKGROUND AND PURPOSE: B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases. METHODS: Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993-1997). Using baseline plasma samples, we assayed sulfur-containing compounds including methionine, homocysteine, cystathionine, cysteine, glutathione, and taurine with liquid chromatography-tandem mass spectrometry. We examined the association of concentrations of each of the compounds and the ratio of methionine to homocysteine (representing activity of one-carbon metabolism) with risk of incident cerebrovascular diseases, adjusted for potential confounders. RESULTS: Plasma methionine and the methionine/homocysteine ratio were inversely associated with risk of cerebrovascular diseases, with odds ratios per 1 SD of 0.83 (95% CI, 0.72-0.96) and 0.82 (95% CI, 0.71-0.95), respectively. The association of methionine remained significant after adjustment for homocysteine. None of the other examined compounds was significantly associated with incident cerebrovascular diseases. CONCLUSIONS: These findings suggest that greater availability of methionine, an essential amino acid, may play a role in the prevention of cerebrovascular diseases and explain the previously recognized link between elevated homocysteine and stroke. Further research is needed to determine causation and the potential of circulating methionine as a target in cerebrovascular disease prevention.

Circulating microRNAs Associated With Reversible Cerebral Vasoconstriction Syndrome.

OBJECTIVE: The purpose of this study was to investigate the significance of circulating micro RNAs (miRNAs) in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS). METHODS: We prospectively recruited 3 independent cohorts of patients with RCVS and age-matched and sex-matched controls in a single medical center. Next-generation small RNA sequencing followed by quantitative polymerase chain reaction (PCR) was used to identify and validate differentially expressed miRNAs, which was cross-validated in migraine patients in ictal stage or interictal stage. Computational analysis was used to predict the target genes of miRNAs, followed by in vitro functional analysis. RESULTS: We identified a panel of miRNAs including miR-130a-3p, miR-130b-3p, let-7a-5p, let-7b-5p, and let-7f-5p that well differentiated patients with RCVS from controls (area under the receiver operating characteristics curve [AUC] was 0.906, 0.890, and 0.867 in the 3 cohorts, respectively). The abundance of let-7a-5p, let-7b-5p, and let-7f-5p, but not miR-130a-3p nor miR-130b-3p, was significantly higher in patients with ictal migraine compared with that of controls and patients with interictal migraine. Target prediction and pathway enrichment analysis suggested that the transforming growth factor-ß signaling pathway and endothelin-1 responsible for vasomotor control might link these miRNAs to RCVS pathogenesis, which was confirmed in vitro by transfecting miRNAs mimics or incubating the patients' cerebrospinal fluid (CSF) in 3 different vascular endothelial cells. Moreover, miR-130a-3p was associated with imaging-proven disruption of the blood-brain barrier (BBB) in patients with RCVS and its overexpression led to reduced transendothelial electrical resistance (ie, increased permeability) in in vitro human BBB model. INTERPRETATION: We identified the circulating miRNA signatures associated with RCVS, which may be functionally linked to its headache, BBB integrity, and vasomotor function. ANN NEUROL 2021;89:459-473.

Admission hyperglycemia as an independent predictor of long-term prognosis in acute myocardial infarction patients without diabetes: A retrospective study.

AIMS/INTRODUCTION: The predictive value of admission hyperglycemia in the long-term prognosis of acute myocardial infarction patients is still controversial. We aimed to investigate this value based on the diabetes status. MATERIALS AND METHODS: We carried out a multicenter, retrospective study of 1,288 acute myocardial infarction patients enrolled in 11 hospitals between March 2014 and June 2019 in Chengdu, China. The patients were classified into those with diabetes and those without diabetes, each was further divided into: hyperglycemia and non-hyperglycemia subgroups, according to the optimal cut-off value of the blood glucose to predict all-cause mortality during follow up. The end-points were all-cause death and major adverse cardiovascular and cerebrovascular events, including all-cause death, non-fatal myocardial infarction, vessel revascularization and non-fatal stroke. RESULTS: In the follow-up period of 15 months, we observed 210 (16.3%), 6 (0.5%), 57 (4.4%) and 34 (2.6%) cases of death, non-fatal myocardial infarction, revascularization and non-fatal stroke, respectively. The optimal cut-off values of admission blood glucose for patients with diabetes and patients without diabetes to predict all-cause mortality during follow up were 14.80 and 6.77 mmol/L, respectively. We divided patients with diabetes (n = 331) into hyperglycemia (n = 92) and non-hyperglycemia (n = 239), and patients without diabetes (n = 897) into hyperglycemia (n = 425) and non-hyperglycemia (n = 472). The cumulative rates of all-cause death and major adverse cardiovascular and cerebrovascular events among the patients in each hyperglycemia group was higher than that in the corresponding non-hyperglycemia group (P < 0.001). In patients without diabetes, admission hyperglycemia was an independent predictor of all-cause mortality and major adverse cardiovascular and cerebrovascular events. CONCLUSION: Admission hyperglycemia was an independent predictor for long-term prognosis in acute myocardial infarction patients without diabetes.

Relationship between leukocyte counts and large vessel occlusion in acute ischemic stroke.

BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of acute ischemic stroke (AIS) and peripheral leukocyte counts have proved to be independent predictors of stroke severity and outcomes. Clinical significance of large vessel occlusion (LVO) in AIS is increasing, as these patients are potential candidates for endovascular thrombectomy and likely to have worse outcomes if not treated urgently. The aim of our study was to assess the relationship between on admission leukocyte counts and the presence of LVO in the early phase of AIS. METHODS: We have conducted a cross-sectional, observational study based on a registry of consecutive AIS patients admitted up to 4.5 h after stroke onset. Blood samples were taken at admission and leukocyte counts were measured immediately. The presence of LVO was verified based on the computed tomography angiography scan on admission. RESULTS: Total white blood cell (WBC) and neutrophil counts were significantly higher in patients with LVO than those without LVO (P < 0.001 respectively). After adjustment for potential confounders total WBC counts (adjusted OR: 1.405 per 1 × 109/L increase, 95% CI: 1.209 to 1.632) and neutrophil counts (adjusted OR: 1.344 per 1 × 109/L increase, 95% CI: 1.155 to 1.564) were found to have the strongest associations with the presence of LVO. Total WBC and neutrophil counts had moderate ability to discriminate an LVO in AIS (AUC: 0.667 and 0.655 respectively). No differences were recorded in leukocyte counts according to the size of the occluded vessel and the status of collateral circulation in the anterior vascular territory. However, total WBC and neutrophil counts tended to be higher in patients with LVO in the posterior circulation (p = 0.005 and 0.010 respectively). CONCLUSION: Higher admission total WBC and neutrophil counts are strongly associated with the presence of LVO and has moderate ability to discriminate an LVO in AIS. Detailed evaluation of stroke-evoked inflammatory mechanisms and changes according to the presence of LVO demands further investigation.