Higher Risk Of Cerebrovascular Disease Research Articles

#1490 Long-term health outcomes in non-dialysis dependent chronic kidney disease patients with cognitive impairment or dementia

Abstract Background and Aims A decline in cognitive function, with a spectrum ranging from mild cognitive impairment to dementia (CI-D), is common in patients with chronic kidney diseases (CKD), rendering them frailer. Whether the coexistence of CKD and CI-D increases the health risk profile remains unclear. Our work aims to clarify how this association increases adverse outcomes for CKD patients (stages 3-5). Method This retrospective observational cohort study was conducted on CKD patients (stages 3-5) from the Global Collaborative Network (GCN) of the TriNetX research platform between 2004 and 2024. TriNetX provides access to anonymized electronic medical records from over half a million CKD patients in large healthcare organizations (HCOs) across the world. Our report includes patients from 110 HCOs with different demographic backgrounds. The study compared outcomes of patients with CKD stages 3-5, aged 18-70 years, with and without pre-existent CI-D (diagnosed within 5 years). The two cohorts were propensity score-matched (PSM) for age, sex, ethnicity, comorbidities (neurological, haematological, musculoskeletal, respiratory including smoking history, oncological, cardiovascular, gastroenterological and endocrine conditions) and CKD stage. The proportional hazard assumption was tested using the generalized Schoenfeld approach built in the TriNetX platform. A 95% confidence interval (95% CI) was considered evidence of statistical significance throughout the analyses. Kaplan- Meier (KM) was used for survival probability. Statistical significance was defined as p-value < 0.05. Outcome events were included from 1 day after the index event (CKD diagnosis) until 3650 days after. Results Of the total of 503,298 CKD patients, 7,891 had a co-existent diagnosis of CI-D made within 5 years (prevalence rate 1.56%). A PSM generated a matched cohort of 7,890 patients each. The mean age of the cohort was 60.7 ± 7.0 years, with a predominance of white ethnicity (53.7%) and an equal male-to-female ratio. Standardized difference (Std diff) was used to evaluate the balance of baseline characteristics in the PSM populations. Generally, Std diff < 0.1 is considered a small difference and all comorbidities fell below this threshold after PSM (Table 1). The comparison of the outcomes at follow-up between the matched cohorts is illustrated in Table 2. CKD patients with concomitant CI-D had higher all-cause mortality (18.4% vs 12.1%, p < 0.0001), a higher risk of cerebrovascular disease (10.8% vs 7.8%), malnutrition (6.7% vs 4.3%), mood disorders (13.7% vs 8.9%), anxiety (13.2% vs 10.9%), encephalopathy (9.6% vs 4.5%), epilepsy (4.3% vs 1.3%). All findings were statistically significant with a p < 0.0001. Proportional hazard models showed that CI-D was a strong risk factor associated with all-cause mortality (HR: 1.761; 95% CI (1.621-1.913, p < 0.0001)) and other cerebrovascular and mental health illnesses. Conclusion Our “real-world data” demonstrate that a concomitant CI-D diagnosis is a strong risk factor for negative health outcomes and mortality in patients with CKD stages 3-5. These results highlight the need for routine cognitive assessments in patients with advanced CKD to deliver personalised care.

REDUCED AEROBIC FITNESS IS ASSOCIATED WITH IMPAIRED CEREBROVASCULAR FUNCTION IN INDIVIDUALS WITH ATRIAL FIBRILLATION

INTRODUCTION & AIMS Lower aerobic fitness (V̇O2peak) is associated with higher risk of cerebrovascular disease. However, the relationship between V̇O2peak and cerebrovascular function and cerebral blood velocity at rest and during exercise has not been investigated in adults with atrial fibrillation (AF). We aimed to compare resting and exercise cerebral blood velocity responses and cerebrovascular function in individuals with AF to healthy controls. METHODS Eight inactive adults either with AF or healthy age-matched controls (AF: n=4, 64±6 years, 50% female; control: n=4, 66±4 years, 75% female) completed a maximal graded exercise test to measure V̇O2peak. Transcranial Doppler was used to measure bilateral middle cerebral artery velocity (MCAv). Vascular function was assessed by measuring MCAv increases and time to peak following a 30s hypercapnia stimulus (9% CO2, 21% O2, and balanced nitrogen), and MCAv during aerobic exercise (3-minute stages at 40%, 60% and 80% V̇O2peak). Blood pressure, heart rate and end-tidal gases were collected alongside MCAv. RESULTS Compared to controls, individuals with AF (both P<0.01) had higher BMI (AF: 31.8±2.0 kg/m2; control: 27.3±0.6 kg/m2), lower V̇O2peak (AF: 19.9±2.5 mL/kg/min; control: 33.7±5.8 mL/kg/min), and similar blood pressure. Resting right and left MCAv was higher in the AF group (R: 66.6±34.0 cm/s; L: 44.2±10.1 cm/s) compared to the control (R: 36.1±6.7 cm/s; L: 34.9±8.7 cm/s); this was not significant (P=0.121 and 0.258). Right MCAv was higher than left MCAv in individuals with AF but this was not significant (P=0.247). Hypercapnia and exercise induced MCAv and time to peak were similar between groups (P>0.05). CONCLUSION Lower V̇O2peak may be associated with increased resting MCAv in individuals with AF. Furthermore, there may be regional disparities in MCAv in individuals with AF. Future studies with larger sample sizes investigating potential mechanisms and volumetric cerebrovascular changes (e.g., vessel diameter, arterial stiffness) in AF are warranted.

Cerebrovascular Complications in Spinal Fusion Surgery: A Nationwide 8-year Follow-up Study in South Korea.

This retrospective study investigated the long-term incidence and risk of postoperative complications following spinal fusion. This study included 640,366 participants from a National Health Examination cohort in the Republic of Korea. Among them, 11,699 individuals underwent spinal fusion, and 56,667 individuals who underwent non-fusion spinal procedures served as controls. Propensity score matching was used to account for patient characteristics including demographic factors, comorbidities, and other relevant variables. The participants were followed for 8 years to assess the occurrence of cerebrovascular disease (CVD), hemorrhagic infarction (HA), ischemic infarction (II), occlusion and stenosis, and ischemic heart disease (IHD). The incidence rates of CVD and IHD were found to be 27.58 and 31.45 per 1,000 person-years in the spinal fusion group compared to 18.68 and 25.73 per 1,000 person-years in the control group (p < .001), respectively. Patients who underwent spinal fusion had a higher risk of CVD, HA, and IHD than those in the control group (all p < .001). In the subgroup analysis, thoracolumbar and noncervical spinal fusion were associated with a higher risk of CVD, II, and IHD (all p < .005). Patients undergoing thoracolumbar fusion may have an increased association with CVD, II in cerebral arteries, and IHD. This suggests a need for careful consideration of vascular risks in such patient populations.

Risk of myocardial infarction, heart failure, and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan in patients.

There is a lack of studies comparing the risk of cardio-cerebrovascular disease between angiotensin receptor blockers (ARBs) of different half-lives. We aimed to compare the risks of myocardial infarction (MI), heart failure (HF), and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan with different half-lives in a national claim-based retrospective cohort of patients aged ≥ 40 years with hypertension. To establish a cohort exposed to valsartan, losartan, irbesartan, or telmisartan, we performed propensity score (PS) matching and used an as-treated approach to evaluate exposure. The Cox regression model was employed to calculate hazard ratios, which were based on the incidence rate for each newly occurring event of MI, heart failure, or cerebrovascular disease. These hazard ratios were calculated to compare the risk of MI, heart failure, and cerebrovascular disease associated with valsartan, losartan, and irbesartan in comparison to telmisartan. A PS-matched cohort of 148,229 patients was established for each of valsartan, losartan, irbesartan, or telmisartan. The matched cohort analysis showed that the adjusted hazard ratio (aHRs, 95% confidence interval) for MI was higher for valsartan use (1.39, 1.33-1.45) and losartan use (1.10, 1.05-1.15) but lower for irbesartan use (0.90, 0.86-0.94) compared with the reference (telmisartan). The aHRs for HF were not different among these ARBs (angiotensin receptor blockers). The aHR for cerebrovascular disease was lower for valsartan use (0.85, 0.83-0.87) and losartan use (0.80, 0.78-0.82) but higher for irbesartan use (1.11, 1.09-1.13) compared with the reference. We found differences in the risk of MI and cerebrovascular disease with the use of different ARBs compared to telmisartan use. Valsartan, and losartan with a short half-life, which showed a higher risk of MI, had a lower risk of cerebrovascular disease. Conversely, irbesartan with a long half-life, which showed a lower risk of MI, had a higher risk of cerebrovascular disease.

Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): Aortic stiffness & intracranial atherosclerosis

ObjectivesPrevious studies suggest an association between central arterial stiffness (CAS) and intracranial atherosclerotic disease (ICAD) among Asian participants with stroke or hypertension; this association has not been evaluated in United States populations. We assessed the cross-sectional association of CAS with ICAD presence and burden in late-life, and differences in association by age, sex, and race. Materials and methodsWe conducted a cross-sectional analysis of 1,285 Atherosclerosis Risk in Communities Study participants [mean age 75 (standard deviation: 5) years, 38 % male, 20 % Black] at Visit 5 (2011-2013). CAS was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus. ICAD was assessed using high-resolution vessel wall MRI and MR angiography. We evaluated associations of a 1 standard deviation (SD) cfPWV (3.02 m/s) and high vs. non-high cfPWV (≥ 13.57 m/s vs. < 13.57 m/s) with presence of plaques (yes/no) and plaque number (0, 1-2, and >2) using multivariable logistic and ordinal logistic regression models adjusted for covariates. ResultsEach one SD greater cfPWV was associated with higher odds of plaque presence (odds ratio (OR)=1.32, 95 % confidence interval (CI): 1.22, 1.43), and an incrementally higher odds of number of plaques (OR 1-2 vs. 0 plaques = 1.21, 95 % CI: 1.10, 1.33; OR >2 vs. 0 plaques = 1.51, 95 % CI: 1.33,1.71). Results suggested differences by race, with greater magnitude associations among Black participants. ConclusionsCAS was positively associated with ICAD presence and burden; cfPWV may be a useful subclinical vascular measure for identification of individuals who are at high risk for cerebrovascular disease.

Abstract 16971: Unraveling the Burden of Cerebrovascular Disease: Exploring the Role of Peripheral Vascular Disease and Kidney Transplant in End-Stage Renal Disease Hospitalization Rates (Insights From the National Inpatient Sample, 2005 to 2019)

Background: Patients with end-stage renal disease (ESRD) face a higher risk of cerebrovascular disease, but the impact of peripheral vascular disease (PVD) and a kidney transplant (KiTx) on hospitalization rates for cerebrovascular conditions remains uncertain. This study aimed to investigate the rates of hospitalization for cerebrovascular disease in patients with ESRD, PVD, KiTx, or a combination. Methods: Using the National Inpatient Sample (NIS), 2,713,194 ESRD hospitalizations (2005-2019) were analyzed. We focused on two cerebrovascular conditions of interest: 1) cerebral infarction due to thrombosis, embolism, and occlusion (CITO) and 2) artery occlusion resulting in cerebral ischemia (AOSI). Comparative analysis utilized t-tests and odds ratios. Results: Among ESRD hospitalizations, 66,927 (2.47%) had KiTx, 63,411 (2.34%) had PVD, and 1,406 (0.05%) had both. Key findings included: 1) ESRD patients with PVD had higher odds of hospitalization for CITO (OR 1.33, CI 1.1-1.8, p=0.009) or AOSI (OR 2.63, CI 2.5-2.8, p&lt;0.001) compared to those without PVD (Fig. 1AB); 2) ESRD patients hospitalized with CITO had higher odds of having KiTx and PVD compared to those without KiTx or PVD (OR 3.17, CI 1.0-9.3, p=0.035, Fig. 1AB); 3) ESRD patients with PVD had higher rates of being hospitalized with AOSI (7.29%) than those without AOSI (2.29%, p&lt;0.001); 4) ESRD patients hospitalized with CITO had higher odds of having KiTx and PVD compared to those without KiTx or PVD (OR 3.17, CI 1.0-9.3, p=0.035, Fig. 1AB) and 5) ESRD patients hospitalized with AOSI demonstrated a higher rate of having KiTx and PVD (0.09%) compared to those without AOSI (0.05%, p=0.002). Conclusion: This nationwide analysis reveals that the presence of PVD and KiTx is associated with increased rates of hospitalization for cerebrovascular conditions. These findings underscore the importance of proactive management to mitigate the risk of cerebrovascular disease in this vulnerable patient population.

Factors related to dietary quality among older stroke high-risk population in Tianjin community, China: a multicenter study

BackgroundStroke is a common and frequently-occurring disease in older people. It has the characteristics of high morbidity, high mortality, high recurrence rate and high disability rate. Most stroke risk studies are based on pathophysiology, however psychosocial factors such as diet quality are often understudied. The aim of this study was to assess stroke risk in urban community residents in Tianjin and investigate the factors that affect the dietary quality of older stroke high-risk populations.MethodsUsing a cross-sectional, multicenter study, recruit people aged 60 to 80 in Tianjin. Dietary intake data were obtained through a validated food frequency questionnaire, which were used to calculate Alternate Healthy Eating Index-2010 (AHEI-2010) and to analyze its association with sociodemographic characteristics, stroke risk factors and health marker variables.ResultsA total of 1068 participants from 4 community health service centers in Tianjin were recruited, including 300 low-risk individuals and 768 high-risk individuals. Compared with the low-risk group (62.75 ± 3.59), the AHEI-2010 mean score of the high-risk group (56.83 ± 6.54) was significantly lower. The top three most common risk factors among participants were dyslipidemia (80.3%), hypertension (60.6%), and physical inactivity (58.2%). Multiple logistic regression showed that diet quality was independently and significantly associated with stroke risk (OR = 0.765; 95%CI: 0.690–0.848, p < 0.001).ConclusionThe diet quality of high-risk stroke population in Tianjin is far from ideal. At the same time, public health knowledge needs to be disseminated and educated, especially among those at high risk of cerebrovascular disease, with a focus on improving psychosocial factors such as diet quality.

Association between proprotein convertase subtilisin/kexin type 9 and subclinical cerebrovascular disease in the community.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new target for reducing low-density lipoprotein cholesterol and incident cardiovascular disease, including stroke. However, the clinical relevance of circulating PCSK9 levels has been poorly elucidated in the general population, particularly in association with subclinical cerebrovascular disease including cerebral small vessel disease (CSVD) and intracranial artery stenosis (ICAS). In community-dwelling Japanese men (n=526) aged 46-82 years without a history of cardiovascular disease, the associations of serum PCSK9 levels with the prevalence of CSVD and ICAS were assessed using magnetic resonance imaging. CSVD included lacunar infarction, deep and subcortical white matter hyperintensity, periventricular hyperintensity and cerebral microbleeds. The median (interquartile range) age at baseline and serum PCSK9 levels were 69 (63-74) years and 240 (205-291) ng/ml, respectively. After adjusting for traditional cardiovascular risk factors including low-density lipoprotein cholesterol, multivariable Poisson regression with robust error variance revealed a significant association between PCSK9 levels (per 1 SD) and ICAS (relative risks 1.18, 95% confidence interval 1.02-1.37). Multivariable ordinal logistic regression for ICAS, with stenosis graded as mild (<50%) or moderate-severe (≥50%), revealed a similar association (common odds ratio 1.31, 95% confidence interval 1.04-1.64). However, no significant association was observed between serum PCSK9 levels and CSVD. Higher circulating PCSK9 levels were independently associated with an ICAS prevalence but not with CSVD prevalence. The quantification of circulating PCSK9 levels may help to identify individuals at high risk for cerebrovascular disease in the general population.

Circadian nutritional behaviours and risk of cardiovascular disease in NutriNet-Santé

Abstract Meal timings and daily night-time fasting periods can synchronise the circadian system, which regulates the cardiovascular system. The present study aims to evaluate the prospective associations between circadian nutritional behaviours, defined by meal timing and frequency, and the risk of cardiovascular diseases. We used data from 103,389 adults (79% females) in the French NutriNet-Santé study, 2009-2021. Circadian nutritional behaviours were assessed using repeated 24h food records during the first two years of follow-up. We examined the associations between circadian eating behaviours and risk of cardiovascular, coronary heart and cerebrovascular diseases by multivariable Cox proportional hazard models. During a median follow-up of 7.2 years, 2036 incident cardiovascular diseases were diagnosed. A later first meal of the day was associated with a higher risk of cardiovascular diseases (HR per hour increase = 1.06, 95% CI 1.01 - 1.12). A later last meal of the day was associated with a higher risk of cerebrovascular diseases (HR per hour increase = 1.08, 95% CI 1.01 - 1.15). Among women, a later last meal was also associated with a higher risk of cardiovascular disease (HR per hour increase = 1.08, 95% CI 1.01 - 1.15). We found no evidence for an association between night-time fasting duration nor meal frequency, with risk of cardiovascular diseases. This study suggests that the habit of eating a later first meal, and a later last meal (in women) could be associated with a higher risk of developing circulatory diseases. These results need to be confirmed in other largescale studies before they can be transferable to clinical practice. Key messages • Beyond nutritional quality of meals, meal timing could also be a risk factor for cardiovascular disease. • If confirmed in other largescale studies, early breakfast and dinner could be considered in preventive strategies of cardiovascular diseases.

Effects of intermittent hypoxia with thrombin in an in vitro model of human brain endothelial cells and their impact on PAR-1/PAR-3 cleavage

Patients with obstructive sleep apnea/hypopnea (OSA) are at high risk of cerebrovascular diseases leading to cognitive impairment. The oxidative stress generated by intermittent hypoxia (IH) could lead to an increase in blood–brain barrier (BBB) permeability, an essential interface for the protection of the brain. Moreover, in patients with OSA, blood coagulation could be increased leading to cardiovascular complications. Thrombin is a factor found increased in these populations that exerts various cellular effects through activation of protease activated receptors (PARs). Thus, we have evaluated in an in vitro BBB model the association of IH with thrombin at two concentrations. We measured the apparent BBB permeability, expression of tight junctions, ROS production, HIF-1α expression, and cleavage of PAR-1/PAR-3. Pre-treatment with dabigatran was performed. IH and higher thrombin concentrations altered BBB permeability: high levels of HIF-1α expression, ROS and PAR-1 activation compared to PAR-3 in such conditions. Conversely, lower concentration of thrombin associated with IH appear to have a protective effect on BBB with a significant cleavage of PAR-3. Dabigatran reversed the deleterious effect of thrombin at high concentrations but also suppressed the beneficial effect of low dose thrombin. Therefore, thrombin and PARs represent novel attractive targets to prevent BBB opening in OSA.

Association of SNP (rs1042579) in thrombomodulin gene and plasma thrombomodulin level in North Indian children with Kawasaki disease.

Kawasaki disease (KD) is the commonest systemic vasculitis in children. It predisposes to development of coronary artery abnormalities (CAAs). Thrombomodulin (THBD) gene polymorphism rs1042579 is associated with high risk of cerebrovascular diseases. However, association of THBD polymorphism (rs1042579) and plasma thrombomodulin (TM) levels with susceptibility to KD and CAAs remains unclear. Polymorphism in THBD gene (rs1042579) was analysed in 50 KD patients and 50 age, gender and ethnicity matched controls using Sanger sequencing. Plasma TM levels were measured by ELISA. Mean plasma TM level (± SD) in KD patients was 2549.41 (± 853.18) pg/ml and in controls was 2298.03 (± 869.14) pg/ml; p = 0.042. Mean plasma TM levels in CC genotype was 2299.98 (± 834.88) pg/ml and in CT/TT genotype was 2837.96 (± 857.14) pg/ml; p = 0.005. Genotyping data did not reveal significant differences in patients with KD as compared to controls (p = 0.25), and in KD patients with and without CAAs (p = 0.407). Odds of finding T allele in cases were 2.07 times greater than in controls (p = 0.093). This is the first study from India, and second in the world, that investigates association of THBD gene polymorphism with KD. This is also the first study to assess plasma TM levels in KD patients. Our data show that plasma TM levels were significantly higher in KD patients with CT/TT genotypes. Further, the polymorphism rs1042579 at exon 1 of THBD gene was found to be more common in KD patients than in controls although the difference was not statistically significant.

Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study

Diffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.

Is Morgellons an organic disease? structural and functional abnormalities implicated in the pathophysiology of delusional infestation

Little is known about the pathophysiology of delusional infestation (DI), a psychodermatologic condition in which patients have a fixed, false belief of being infested with parasites or inanimate material in their skin, despite lack of objective evidence. Because some delusional states, such as schizophrenia and psychotic state in bipolar disorder have been found to be associated with brain structural and functional abnormalities, a literature review was conducted to summarize available data on structural and functional abnormalities that are found to be associated with DI. A review of the literature found cases of brain imaging studies in patients with primary DI, as well as patients with secondary DI. Accumulating evidence from the studies reviewed suggests that dysfunction of the fronto-striato-thalamo-parietal network may explain how delusions manifest in DI and suggest that DI has an organic etiology. Abnormalities in the striato-thalamo-parietal network may cause false sensations of infestation through dysfunction in visuo-tactile regulation, whereas abnormalities in the frontal region may impair judgement. Delusional infestation patients also exhibit increased activation of brain structures implicated in itch processing. Furthermore, patients at high risk for cerebrovascular disease who present with secondary DI may benefit from brain imaging studies to rule out brain ischemic insult.

Early famine exposure and adult disease risk based on a 10-year prospective study of Chinese adults

ObjectiveTo comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age.MethodsThis study included 92 284 participants aged 39–51 years...

Assessing the protective effect of rosiglitazone against electronic cigarette/tobacco smoke-induced blood\u2013brain barrier impairment

BackgroundSmoking (TS) and recently e-cigarettes (EC) vaping, have been associated with vascular endothelial dysfunction primarily relevant to oxidative stress, exposure to nicotine, and smoking-induced inflammation. It is accepted that both EC and TS enhance glucose intolerance and the risk of developing type-2 diabetes mellitus which is also one of the causes of blood–brain barrier (BBB) damage and the higher risk of cerebrovascular diseases. Recent studies have shown how Metformin, the first common antidiabetic drug, can protect the BBB integrity through enhancement of nuclear factor erythroid 2-related factor (Nrf2) activity. Herein, we investigated the role of rosiglitazone (RSG; family of thiazolidinedione class used oral anti-diabetic drug) in TS/EC-induced BBB impairment.ResultsAlthough the exact mechanism of RSG is not fully understood, previous studies have revealed that RSG can promote counteractive protective mechanisms primarily associated with the enhancement of Nrf2 activity through activation of the peroxisome proliferator-activated receptor gamma. In line with these findings, our results show an increased expression of PPARy by RSG, enhancement of Nrf2 activity and BBB protection against TS/EC exposure including reduced inflammation, oxidative stress, tight junction downregulation and loss of BBB integrity.ConclusionsRSG could be considered as a promising therapeutic potential to prevent TS/EC induced cerebrovascular dysfunction and possibly other xenobiotic substances which may impact the BBB via oxidative stress-mediated effects. However, additional in vivo studies and clinical setting will be needed to validate our results and assess the full extent of RSG protective effects.

Vascular Arginase Is a Relevant Target to Improve Cerebrovascular Endothelial Dysfunction in Rheumatoid Arthritis: Evidence from the Model of Adjuvant-Induced Arthritis.

Emerging data revealed that rheumatoid arthritis (RA) is associated with higher risk of cerebrovascular diseases. Whereas cerebral endothelial dysfunction is acknowledged as a critical aspect of cerebrovascular diseases, its presence in RA and the mechanisms involved are currently unknown. By using the model of rat adjuvant-induced arthritis (AIA), the present study investigated cerebrovascular reactivity in pressurized middle cerebral arteries (MCA) on day 33 post-immunization. The results revealed that arthritis induced a dramatic decrease in the vasodilatory response to acetylcholine (ACh), ADP, and bradykinin (n = 7-9 arteries, p < 0.0001). By using nor-NOHA, L-NAME, BH4, and Tempol, the results showed that the reduced response to ACh relied on arginase overactivation (n = 8), low NOS activity (n = 8), BH4 deficiency (n = 9), and excessive superoxide production (n = 9). Immunohistological analysis revealed an endothelial upregulation of arginase 2 (p < 0.05, n = 5-6) and NADPH oxidase (p < 0.05, n = 5-7) while eNOS expression was unchanged in AIA (n = 6). To assess whether arginase inhibition may be a relevant therapeutic, AIA rats were treated with an arginase inhibitor (nor-NOHA, 40mg/kg/day, i.p., n = 20 rats) daily from day 10 to day 33 post-immunization. The treatment alleviated the impaired response of MCA to endothelium-dependent agonists, through an increase in NOS signaling and a suppression of BH4 deficiency and superoxide overproduction. By contrast, it did not change the course of arthritis. In conclusion, arthritis induced a cerebrovascular endothelial dysfunction involving an imbalance in the arginase/NOS pathway. Arginase inhibition appears as a promising therapy beyond anti-rheumatic drugs for reducing the risk of cerebrovascular diseases in RA.

Abstract TP463: Enhancing Access to Stroke Neurology Care for Patients With Sickle Cell Disease

Introduction: Patients with chronic illness have demonstrated non-adherence rates to clinic appointments ranging between 20-40%, however, few studies have documented non-adherence rates in patients with sickle cell disease. One study estimated that during an 8-month period non-adherence rates were as high as 46%. Patients with sickle cell disease and a history of prior stroke are at particularly high risk of recurrence for secondary stroke requiring routine follow up. This study aimed at examining the effect on non-adherence rates after the development of a combined stroke-sickle cell outpatient clinic. Methods: Non-adherence rates were examined in the separate stroke clinic and compared to the combined outpatient stroke-sickle cell clinic, staffed by a vascular neurology physician, an advanced practice nurse (APN) and a hematology physician. The APN was readily available for consultation and follow-up of patients with a history of stroke, suspected stroke, or transient ischemic attack. Non-adherence rates were calculated based on no show events over total scheduled clinic events. Descriptive statistics were used to compare groups of patients and a Chi-Square was used to compare non adherence between groups. Results: Since September 2015 to August 2018, there was a total of 34 total scheduled clinic visits in the separate stroke clinic, resulting in a non-adherence rate of 26.5%. Since the inception of the combined stroke-sickle cell clinic in September 2016 to August 2018, there was a total of 45 scheduled clinic visits, resulting in a non-adherence rate of 11.1%. The number of new consultations for the stroke clinic and combined clinic were 44.1% and 40.0% respectively. Conclusion: The development of a combined stroke-sickle cell outpatient clinic may be an effective, multidisciplinary method for improving non-adherence rates in patients with sickle cell disease and a history of stroke. In addition, creating a combined clinic both increases patient access for both sickle cell patients at high risk for cerebrovascular disease as well as stroke patients without a history of sickle cell disease.

Cerebral blood flow regulation and cognitive function in women with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is associated with structural and functional alterations in a number of interacting brain regions, but the physiological mechanism for the high risk of cerebrovascular disease or impairment in brain function remains unknown. Women are more likely to develop PTSD after a trauma than men. We hypothesized that cerebral blood flow (CBF) regulation is impaired in women with PTSD, and it is associated with impairment in cognitive function. To test our hypothesis, we examined dynamic cerebral autoregulation (CA) and cognitive function by using a transfer function analysis between arterial pressure and middle cerebral artery blood velocity and the Stroop Color and Word test (SCWT), respectively. We did not observe any different responses in these hemodynamic variables between women with PTSD ( n = 15) and healthy counterparts (all women; n = 8). Cognitive function was impaired in women with PTSD; specifically, reaction time for the neutral task of SCWT was longer in women with PTSD compared with healthy counterparts ( P = 0.011), but this cognitive dysfunction was not affected by orthostatic stress. On the other hand, transfer function phase, gain, and coherence were not different between groups in either the supine or head-up tilt (60°) position, or even during the cognitive challenge, indicating that dynamic CA was well maintained in women with PTSD. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that PTSD-related cognitive dysfunction may not be due to compromised CBF regulation. NEW & NOTEWORTHY Cognitive function was impaired; however, dynamic cerebral autoregulation (CA) as an index of cerebral blood flow regulation was not impaired during supine and 60° head-up tilt in women with PTSD compared with healthy females. In addition, there was no relationship between cognitive function and dynamic CA. These findings suggest that the mechanism of PTSD-related cognitive dysfunction may not be due to CBF regulation.

Assessment of risk factors for cerebrovascular disease among the elderly in Beijing: A 23-year community-based prospective study in China

IntroductionThere are few studies on how lifestyle factors and mental conditions modulate the cerebrovascular diseases (CBVD) mortality risk are rare in the Asian elderly. AimTo comprehensively assess the impact of lifestyle factors and mental conditions on the mortality risk of CBVD among the Chinese older adults.Material and methods: This community-based prospective cohort study was based on the Beijing Longitudinal Study of Aging. We included 2101 participants aged ≥55 years who were interviewed in August 1992 and followed until December 2015. Baseline sociodemographic variables, lifestyle behaviors, and medical conditions were collected using a standard questionnaire. In addition, biochemical parameters, the Activities of Daily Living (ADL) scale, Center for Epidemiological Studies Depression (CES-D) scale, and Mini-Mental State Examination (MMSE) were performed. Hazard ratio (HR) and 95% confidence intervals (CI) was estimated from the competing risk model. ResultsDuring the follow-up period, 576 (27.42%) CBVD events were documented. Multivariable analysis showed that hypertension (HR = 2.331, 95% CI = 1.652–3.288,P < 0.001), depression (HR=2.331, 95% CI=1.652-3.288, P < 0.001), cognitive impairment (HR=1.382, 95% CI=1.132-1.689, P < 0.001), and coronary heart diseases (HR=1.360, 95% CI=1.095-1.689, P = 0.005) were independently associated with CBVD, while body mass index, fasting blood glucose, triglycerides, drinking, and smoking were not associated with CBVD (all P > 0.05). ConclusionsMales were at higher risk of CBVD than females. Age, gender, hypertension, cognitive impairment, and depression were associated with CBVD among the elderly in Beijing, China.

Acute vestibular disorder in the elderly: stroke or peripheral vestibulopathy

Acute vestibular disorder is a frequent cause of urgent hospitalization in elderly patients. A CNS vascular disorder is often thought to be a cause of vertigo and a patient is diagnosed with stroke or transitory ischemic attack (TIA) or vertebral-basilar insufficiency. Despite the higher risk of cerebrovascular disease in the elderly, stroke and TIA are not the only cause of acute vestibular disorder. Hyperdiagnosis of cerebrovascular diseases in patients with acute vertigo often leads to underdiagnosis of peripheral vestibular disorders that could be successfully treated if timely diagnosed. The differential diagnosis of the lesions of central and peripheral vestibular systems is based on clinical examination of patients with acute vertigo including an analysis of cerebrovascular risk factors, characteristics of vertigo, nystagmus and careful identification of focal neurological symptoms.