Risk Factor For Vascular Disease Research Articles

Clonal haemopoiesis and venous thromboembolism risk.

Many cases of venous thromboembolism (VTE) are idiopathic and clonal haemopoiesis, a risk factor for atherosclerotic vascular disease, may be a contributing factor to VTE. The report by Englisch and colleagues suggests that clonal haemopoiesis is a risk factor for recurrent VTE, especially in people without identifiable thrombotic predisposition. Commentary on: Englisch etal. Association of clonal hematopoiesis with recurrent venous thromboembolism: A case-control study. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19871.

Individuation of a cut-off value of triglyceride-glucose index for incident diabetes mellitus in patients with essential hypertension.

The prevalence of obesity and diabetes, risk factors for atherosclerotic vascular diseases, is increasing worldwide; therefore, it is desirable to early identify them to reduce cardiovascular events. Thus, we investigated whether the triglyceride-glucose index (TyG index), a new marker of insulin resistance, is associated with incident diabetes in patients with newly diagnosed arterial hypertension. We selected 585 patients with newly diagnosed arterial hypertension referred to our tertiary Clinic of Catanzaro University Hospital for the evaluation of their cardiometabolic risk profile. None of the patients had diabetes mellitus at enrollment and took any drug known to affect glucose metabolism. Patients underwent medical history collection, clinical examination and laboratory tests. The TyG index was calculated as the ln [fasting TG (mg/dl) × FPG (mg/dl)/2], as previously suggested. During the follow-up [mean 8.5years (range 3.1-10.7)], there were 78 new cases of incident diabetes (1.57% patient-year). Patients who developed diabetes mellitus were older and had a higher body mass index (BMI), baseline blood pressure, fasting glucose, insulin, homeostatis model sssessment (HOMA) index, triglyceride, creatinine and hs-CRP mean values, while estimated glomerular filtration rate values were lower. At the Cox regression analysis, covariates significantly associated with incident diabetes were: BMI (HR = 2.842, 95%CI = 2.299-3.514), TyG index (HR = 2.392, 95%CI = 1.745-3.192), age (HR = 1.944, 95%CI = 1.527-2.474), hs-CRP (HR = 1.409, 95%CI = 1.153-1.722), and HOMA (HR = 1.325, 95%CI = 1,079-1.756). The best estimated cut-off value of TyG index in predicting diabetes was 4.71. In addition, we documented a significant relationship between TyG index and HOMA (r = 0.575; p < 0.0001). Present data demonstrate that TyG index, a simple and cost-effective marker of insulin resistance, is useful in predicting incident diabetes in patients with arterial hypertension.

Does having a patient attend a postpartum vascular risk reduction clinic improve physician knowledge and management of preeclampsia as a cardiovascular risk factor?

Background Preeclampsia is an independent risk factor for vascular diseases. The Postpartum Preeclampsia Clinic (PPPC) intervenes in the first year postpartum to address these risks. This study aims to characterize physicians’ understanding and management of the cardiovascular risk associated with preeclampsia and whether this differs in physicians who had a patient attend the PPPC. Methods Family physicians, obstetricians, internists, obstetric internists, and cardiologists in Edmonton were anonymously surveyed. Results were analyzed using SPSS. Results Sixty-four surveys were returned, with physicians correctly identifying preeclampsia as a vascular risk factor 73% of the time. Physicians who had a patient attend the PPPC were more likely to counsel patients on their increased cardiovascular risk, although increased knowledge did not reach statistical significance. Conclusion Vascular risk reduction clinics may benefit the long-term management of patients with a history of preeclampsia by improving counseling by physicians, which may reduce the disproportionate vascular morbidity these patients face.

The silent protector: Nucleoporin93's role in vascular health.

Nuclear envelope proteins have recently gained traction as novel regulators of endothelial and vascular function. Nuclear pore complexes (NPCs) stand as one of the largest protein complexes found at the nuclear envelope yet the role of component NPC proteins (i.e., nucleoporins) in vascular health remains unclear. In the issue of Aging Cell, Nguyen et al. (2024) identify Nucleoporin93, a major structural protein of the NPC, as an indispensable player in endothelial protection. This discovery raises the possibility that endothelial NPCs are susceptible to risk factors for consequent vascular disease.

A Study on Prevalence of Hypertension Among Patients Attending OPD of National Institute of Unani Medicine, Bengaluru, India.

Introduction: Hypertension is the leading modifiable cause of premature death and hence World Health Organization (WHO) has made it one of its global prevention priorities. It is a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease. The prevention and treatment of hypertension imposes a significant public health challenge owing to its related morbidity and mortality as well as the expense to society. Hypertension is referred to as a silent and an invisible killer and affects at least 1.4 billion people globally. Less than half of adults (42%) with hypertension are diagnosed and treated. Methodology The research design was an institution based single centered, observational descriptive study, cross sectional in design and was carried out for a duration of 28 days (4 weeks) from 01.06.2024 to 29.06.2024. The study was conducted in the Outpatient Department (OPD) of Regimenal therapies, National Institute of Unani Medicine (NIUM), Bengaluru. All people above 21 years of age attending OPD constituted study population. In present study, 524 patients were included in the study. The diagnosis of hypertension was done as per WHO guidelines. Data analysis was done using SPSS version 24. Results: The study revealed that prevalence of hypertension was 35.87% in the study population. In the present study, 53.20% of diagnosed hypertensive patients were females and rest 46.80% were males. Majority of diagnosed hypertensive patients (39.89%) belonged to the age group of above 60 years. Conclusion: Prevalence of hypertension is significantly increasing at a greater pace globally as well as in India. Periodic screening and raising awareness about hypertension in general population is necessary to reduce the prevalence of the disease and thereby the associated morbidity and mortality. Keywords: Hypertension, WHO, Prevalence, SPSS, OPD patients.

Lipoprotein(a) in Children and Adolescents: Risk or Causal Factor for Cardiovascular Disease? A Narrative Review.

The evaluation of serum Lp(a) values in childhood and adolescence has been widely debated, and in the last few years, many authors have tried to better define Lp(a) role in atherosclerosis pathogenesis, starting from childhood. In our narrative review, we have evaluated the main historical stages of Lp(a) studies in childhood, trying to focus on pathogenic mechanisms linked to elevated serum Lp(a) values, starting from ischemic stroke and vascular damage, and to its possible direct involvement in premature atherosclerosis from childhood onwards. Historic manuscripts on Lp(a) in pediatric patients have mainly focused on serum Lp(a) values and increased stroke risk. More recently, many studies have evaluated Lp(a) as a coronary vascular disease (CVD) risk factor starting from childhood, especially related to a positive family history of premature CVD. Finally, only a few studies evaluated the role of Lp(a) in premature atherosclerotic processes and endothelial and vascular damage in pediatric patients. Lastly, we have hypothesized a future perspective, with the hope that plasma Lp(a) levels will be treated with a tailored pharmacologic approach, and Lp(a) will become a precocious therapeutic target to control the atherosclerotic pathways from the first years of life.

Myocardin related transcription factor and galectin-3 drive lipid accumulation in human blood vessels

ObjectiveDiabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis. Approach and resultsHuman mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading. ConclusionEx vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.

Novel Role of YAP1 in Regulating Blood Pressure and Vascular Tone

Introduction: Hypertension is a major risk factor for occlusive vascular diseases, myocardial infarction, heart failure, stroke, and chronic kidney disease. In the U.S., ~30% of adults suffer from hypertension. Merely half of the individuals with hypertension have their blood pressure under control, despite the wide range of antihypertensive medications available, indicating an urgent need for a better understanding of the underlying causes of hypertension to identify novel therapeutic strategies for its treatment and prevention. Recent genome-wide association study (GWAS) has identified an unexpected association between a loss-of-function SNP in the YAP1 gene locus and decreased blood pressure (BP). Moreover, de novo analysis of publicly available RNAseq data revealed that the vascular tissues of hypertensive mice treated with Ang-II exhibit increased YAP1 expression. Suggesting a novel role of YAP1 in blood pressure regulation. However, whether Vascular smooth muscle cell (VSMC) expressed YAP1 has a specific role in VSMC contraction and BP regulation remains completely unknown. Therefore, we hypothesized that YAP1 could play a key role in regulating blood pressure. Methodology: We have generated a novel inducible SM-specific- Yap1 Knockout ( YAP1 iKO) mouse model and employed a pharmacological inhibitor of YAP1, Verteporfin, to delineate the functional role of VSMC-expressed YAP1 in hypertension in regulating vascular tone and BP. Vascular reactivity experiments were performed using wire myography. BP was measured in ambulant mice via radiotelemetry. In vitro gain- and loss-of-function studies utilizing human coronary artery SMCs were conducted to examine the impact of YAP1 on contractility signaling components using western blotting. Results: Consistent with GWAS and RNAseq data, we found that YAP1 is upregulated in vascular tissues of spontaneously hypertensive rats (SHRs). Using aortic rings from WT mice, we discovered that Verteporfin significantly reduced vasoconstrictive responses to Phenylephrine or Serotonin but did not alter endothelium-dependent vasorelaxant responses to Acetylcholine, suggesting a specific role of YAP1 in VSMCs. Consistently, YAP1 iKO exhibited attenuated responses to vasoconstrictors in isolated conduit and resistance vessels. Importantly, radiotelemetry studies demonstrated for the first time that YAP1 iKO mice exhibit a hypotensive phenotype. Mechanistically, YAP1 gain- and loss-of-function studies in human VSMCs showed that YAP1 activates multiple signaling pathways that play a key role in VSMC contractility including RhoA/ROCK1/actin polymerization and PKC/ERK signaling pathways. Summary/Conclusion: This is the first study to demonstrate that inhibition of SM-specific-Yap1 expression regulates BP and vascular tone, likely via the regulation of contractile machinery components. Together, our data suggest that YAP1 is a promising novel therapeutic target for ameliorating hypertension. This work is supported by a grant from National Heart, Lung, and Blood Institute (R00HL153896). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Medial and Lateral Burns With Concomitant Infection After Genicular Nerve Radiofrequency Ablation: A Case Report

BACKGROUND: Knee osteoarthritis management might include medication, intraarticular injections, physical therapy, and surgical intervention. Genicular nerve radiofrequency ablation (RFA) is an effective therapy for patients who do not receive benefit from conservative medical management and are not surgical candidates (secondary to medical comorbidity, patient preference, and other factors). Genicular nerve RFA is generally safe and has a low complication rate. However, there have been case reports of minor and major complications after RFA. We report a case of burns after genicular nerve RFA. CASE REPORT: A 49-year-old man (92 kg; body mass index [kg/m2] 28.3), with a history of coronary artery disease and chronic tobacco use, presented with 20 years of chronic knee pain. He previously had short-term relief with an intraarticular steroid knee injection. He was found to be a suitable candidate for genicular nerve RFA and underwent the procedure successfully without any immediate complications. His pain decreased from 9/10 before the procedure to 5/10 after his RFA. On postprocedure day 33, a 1 cm circular lesion with drainage was noted on the medial aspect of his knee. A lateral lesion was discovered at a subsequent follow-up appointment. He was treated with antibiotics, chlorhexidine cleansing, and dressing changes which resolved the lesions without any long-term sequelae. CONCLUSION: Our case represents an instance of full thickness skin burns with concomitant infection post genicular RFA, uniquely in both the medial and lateral sites. Our patient’s risk factors of low body mass index, smoking, and vascular disease may have led to a delayed healing response. In addition, needle depth may also have contributed to his injury. Ensuring adequate needle depth and patient selection can minimize these complications. KEY WORDS: Radiofrequency ablation, knee pain, osteoarthritis, chronic pain, genicular nerve, RFA, adverse event, complication

Elevated blood homocysteine increases the risk of incident Motoric Cognitive Risk syndrome: A two cohort study.

Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (> 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.

Profiles of Lifestyle Health Behaviors and Postmortem Dementia-Related Neuropathology.

High engagement in lifestyle health behaviors appears to be protective against cognitive decline in aging. We investigated the association between patterns of modifiable lifestyle health behaviors and common brain neuropathologies of dementia as a possible mechanism. We examined 555 decedents from the Rush Memory and Aging Project, free of dementia at their initial concurrent report of lifestyle health behaviors of interest (physical, social, and cognitive activities, and healthy diet), and who underwent a postmortem neuropathology evaluation. First, we used latent profile analysis to group participants based on baseline behavior patterns. Second, we assessed the associations of profile membership with each neurodegenerative (global Alzheimer's disease [AD] pathology, amyloid-beta load, density of neurofibrillary tangles, and presence of cortical Lewy bodies and TAR DNA-binding protein 43 cytoplasmic inclusions) and neurovascular pathologies (presence of chronic gross or microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), using separate linear or logistic regression models, adjusted for age at death, sex (core model), vascular disease risk factors, and vascular conditions (fully adjusted model). Participants had either consistently lower (N = 224) or consistently higher (N = 331) engagement across 4 lifestyle health behaviors. We generally found no differences in neuropathologies between higher and lower engagement groups in core or fully adjusted models; for example, higher engagement in lifestyle health behaviors was not associated with global AD pathology after core or full adjustment (both p > .8). In conclusion, we found no evidence of associations between patterns of lifestyle health behaviors and neuropathology. Other mechanisms may underlie protective effects of health behaviors against dementia.

Effects of Vascular Disease Risk Factors on Brain ATP in People with Multiple Sclerosis—A 3-year Longitudinal Study (P11-6.010)

Effects of Vascular Disease Risk Factors on Brain ATP in People with Multiple Sclerosis—A 3-year Longitudinal Study (P11-6.010)

395 A History of Smoking Is Not an Independent Risk Factor for Perioperative Outcomes in Nontraumatic Subarachnoid Hemorrhage

INTRODUCTION: Nontraumatic Subarachnoid Hemorrhage (NSAH) is a rupture leading to blood accumulating in the subarachnoid region. Smoking contributes to vascular pathogenesis which can ultimately end in an aneurysm. Smoking and history of smoking often is a risk factor for complications perioperatively for vascular procedures, however patients receiving treatment for NSAH may have different perioperative outcome profiles. METHODS: Patients with NSAH who underwent neurosurgery were identified using ICD codes (ICD10, I60; ICD9, 430) in the ACS-NSQIP database from 2005-2021. Subjects were stratified into two study groups based on documented prior history of smoking: smokers or non-smokers. Significant preoperative differences were present between groups so a multivariable logistic regression was performed between patients with and without a prior history of smoking. The 30-day perioperative outcomes of patients with a prior history of smoking were compared to that of control. Perioperative outcomes included death, major adverse cardiovascular events (MACE), cardiac complications, stroke, wound complications, renal complications, sepsis, clot formation, pulmonary complications, return to the operating room, operation time greater than four hours, length of stay longer than 7 days, discharge not to home, and bleeding. RESULTS: There were 626 patients with a prior smoking history and 1336 patients with no prior smoking history. We found no significant difference between these two groups across all adverse outcomes analyzed. CONCLUSIONS: This study shows that although history of smoking is commonly a risk factor for vascular diseases and perioperative complications, it is not a risk factor for the perioperative variables analyzed when treating NSAH. Additional research should be done to determine if different procedures to treat NSAH may have different outcomes among smokers.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Hypertension and other vascular risk factors in patients with functional seizures

ObjectiveRecent literature has suggested that functional seizures are associated with an elevated risk for vascular disease and mortality. We investigated the prevalence of risk factors for vascular disease in patients who were admitted to the epilepsy monitoring unit. MethodsPatients who were admitted to the epilepsy monitoring unit and received a definitive diagnosis of either functional seizures or epilepsy were identified. Data collected included demographic, clinical characteristics, medication list, comorbidities, and scheduled blood pressure measurements that occurred every 12 h during the admission. The mean blood pressures were calculated and if they were above the American College of Cardiology and the American Heart Association guideline cutoff of 130/80 mm Hg or the patient had a documented history of hypertension the patient was counted as having the condition. A multiple logistic regression model was developed to evaluate the independent association of the patient’s diagnosis (i.e., epilepsy or functional seizures) and vascular risk factors that controlled for the number of blood pressure measurements, age, sex, and if the patient was taking antihypertensive medications. Results270 patients were included in this study of which 147 patients had epilepsy and 123 had functional seizures. Among those with functional seizures, 57.72 % had either a history of hypertension or a mean blood pressure above 130/80 compared to 38.78 % of those with epilepsy (p = 0.0022). In addition, 30.89 % of functional seizures patients had hyperlipidemia and 63.41 % were obese. The logistic regression model indicated that functional seizures were independently associated with high blood pressure (OR: 2.47, 95 % CI 1.10–5.69), hyperlipidemia (OR: 3.38, 95 % CI 1.35–8.86), and obesity (OR: 4.25, 95 % CI 2.22–8.36) compared to those with epilepsy. There was no significant difference in the prevalence of diabetes (OR: 0.81, 95 % CI 0.24–2.77) or current tobacco use (OR: 1.04, 95 % CI 0.48–2.25) between the groups. SignificancePatients with functional seizures had an elevated prevalence of several vascular risk factors. These findings may partially account for complications associated with functional seizures and have implications related to their pathophysiology.

Comparative vascular effects of levetiracetam and valproate with hyperhomocysteinemia in rat models

Abstract Objectives Hyperhomocysteinemia (HHcy) a significant risk factor for vascular disease, often emerges in epilepsy with the use of antiepileptic drugs. In this relationship, our study investigates the combined effects of HHcy and antiepileptics on vascular function using a rat model. Methods Fourty two rats were included and divided into six groups as, 1-Control, 2-L-Met, 3-LEV injected, 4-LEV-injected + L-Met, 5-VAL-injected, 6-VAL injected + L-Met. L-Methionine (L-Met) was added to drinking water of rats for 1 month to develop HHcy. Simultaneously, intraperitoneal (ip) injections of sodium valproate (VAL) and levetiracetam (LEV) were administered. Effects were comparatively investigated, and noradrenaline (NA), followed by acetylcholine (ACh) and glyceryl trinitrate (GTN) were applied in organ bath system. Agonist doses were expressed as ten base logarithm (M) through 10−9, 10−8, 10−7, 10−6, 10−5, 10−4 mol/L in dose-response graph. Results NA contractions between LEV and LEV + L-Met groups showed statistical significance (LEV Emax=288.50 ± 46.54, LEV + L-Met Emax=480.40 ± 78.83) (p&lt;0.05) however, no significance was observed among the other groups. ACh relaxations between Control-L-Met (Control Inhmax=12.65 ± 2.09, L-Met Inhmax=50.05 ± 7.43) (p&lt;0.05), and Control-Val + L-Met (Control Emax=328.20 ± 52.83, VAL + L-Met Emax=452.60 ± 71.53) (p&lt;0.01), groups showed statistical significance. Between other groups, no significance was observed. In GTN relaxations, no statistical significance was observed. Conclusions This study highlights the adverse impact of HHcy on aortic relaxation. Further impairment was observed with VAL compared to other treatment and control groups. These findings underscore the importance of considering vascular side effects when selecting antiepileptic drugs. Ultimately, our study contributes valuable insights that may aid the choice of appropriate treatment strategies to mitigate potential vascular complications of HHcy.

Current Smoking Status Is Not a Risk Factor for Perioperative Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Who Underwent Craniotomy Repair

BackgroundAneurysmal subarachnoid hemorrhage is a rupture leading to blood accumulating in the subarachnoid region. Smoking status often is a risk factor for postoperative complications for vascular procedures. This study aims to retrospectively examine the effect of being a current tobacco smoker on postoperative outcomes in nontraumatic subarachnoid hemorrhage patients. MethodsPatients with aneurysmal subarachnoid hemorrhage who underwent craniotomy were identified in the ACS-NSQIP database. The 30-day perioperative outcomes of current smokers were compared to that of control, which was patients who have not smoked tobacco in the past year. Postoperative outcomes included death, cardiac complications, stroke, operation time greater than four hours, bleeding, and other events. Additionally, this studied examined the same surgical outcomes in patients over age 65. ResultsWe found no significant difference between these two groups across all adverse outcomes analyzed. In age>65, we again found no significant different between these two groups across all adverse outcomes analyzed. ConclusionsThis study shows that although current tobacco smoker status is commonly a risk factor for vascular diseases and postoperative complications, it is not a risk factor for the postoperative variables we analyzed during craniotomy for aneurysmal subarachnoid hemorrhage. Additional research should be conducted to determine if different procedures to treat aneurysmal subarachnoid hemorrhage may have different outcomes among smokers.

Associations between homocysteine, tau, and neurodegenerative markers in apolipoprotein ε4 non‐carriers with clinical Alzheimer’s disease

AbstractBackgroundHomocysteine (Hcy) is an amino acid generated as a byproduct of methionine metabolism. It is a risk factor for vascular and neurodegenerative diseases. This study investigated relationships between plasma Hcy concentrations and neurodegenerative biomarkers in people clinically diagnosed with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) due to AD.MethodParticipants were identified from the Ontario Neurodegenerative Disease Research Initiative. Brain parenchymal fraction (BPF) was quantified using T1‐ and T2‐weighted structural magnetic resonance imaging with an in‐house Semi‐Automated Brain Region Extraction and Lesion Explorer package. Plasma amyloid beta (Aβ) 42, Aβ40, phosphorylated tau 181 (p‐tau181), and neurofilament light chain (NfL) were measured with Single molecule array (Simoa) assays. Linear regression analyses were used to test associations between Hcy and neuroimaging or plasma biomarkers, controlling for age, sex, hypertension, hyperlipidemia, diabetes, cholesterol, and vitamin B12. Analyses were stratified by apolipoprotein E (APOE) ε4 carrier status (non‐carriers: n = 64, mean age = 70.9 years, 41% female; carriers: n = 62, mean age = 71.2 years, 50% female).ResultIn APOE ε4 non‐carriers, Hcy was associated negatively with BPF (β = ‐0.233, p = 0.047, 95% CI [‐0.460, ‐0.003]), notably in temporal lobe regions in exploratory regional analyses. Hcy was also associated positively with plasma concentrations of NfL (β = 0.403, p = 0.007, 95% CI [0.117, 0.688]) and p‐tau181 (β = 0.357, p = 0.023, 95% CI [0.051, 0.663]) in APOE ε4 non‐carriers. Also, in APOE ε4 non‐carriers, Hcy was associated positively with Aβ40 (β = 0.367, p = 0.015, 95% CI [0.074, 0.660]) and Aβ42 (β = 0.305, p = 0.041, 95% CI [0.012, 0.598]), but not with the Aβ42/40 ratio (β = 0.155, p = 0.339, 95% CI [‐0.166, 0.476]). None of these associations were seen in APOE ε4 carriers.ConclusionIn non‐carriers of the APOE ε4 allele clinically diagnosed with AD or MCI, homocysteine was associated with Amyloid, tau and neurodegeneration. The specificity of these relationships to ε4 non‐carriers identifies a unique risk factor profile for AD that is independent of APOE ε4 status.

Central positional nystagmus due to acute medial medullary infarction

A 70-year-old male with risk factors for vascular disease presented with dizziness and instability. The patient showed horizontal geotropic nystagmus when turning his head while lying down, with larger slow phase velocity observed when turning to the left. There were no other neurological deficits. Video head impulse tests and vestibular evoked myogenic potentials were normal. The initial magnetic resonance imaging (MRI) findings were negative; however, the patient experienced subsequent right-side weakness, right tilting, and recurrent episodes of vertigo. A follow-up MRI revealed an acute left medial medullary infarction, which seems to have caused the paroxysmal geotropic central positional nystagmus in this patient.