Major Risk Factor For Stroke Research Articles

Identifying the optimal time period for detection of atrial fibrillation after ischaemic stroke and TIA: An updated systematic review and meta-analysis of randomized control trials.

Atrial fibrillation (AF) is a major risk factor for ischaemic stroke (IS) and transient ischaemic attack (TIA). The timely detection of first-diagnosed or "new" AF (nAF) would prompt a switch from antiplatelets to anticoagulation to reduce the risk of stroke recurrence; however, the optimal timing and duration of rhythm monitoring to detect nAF remains unclear. We searched MEDLINE, PubMed, Cochrane database, and Google Scholar to undertake a systematic review and meta-analysis of randomized controlled trials (RCT) between 2012 and 2023 investigating nAF detection after IS and TIA. Outcome measures were overall detection of nAF (control; (usual care) compared to intervention; (continuous cardiac monitoring >72 h)) and the time period in which nAF detection is highest (0-14 days, 15-90 days, 91-180 days, or 181-365 days). A random-effects model with generic inverse variance weights was used to pool the most adjusted effect measure from each trial. A total of eight RCTs investigated rhythm monitoring after IS, totaling 5820 patients. The meta-analysis of the studies suggested that continuous cardiac monitoring was associated with a pooled odds ratio of 3.81 (95% CI 2.14 to 6.77), compared to usual care (control), for nAF detection. In the time period analysis, the odds ratio for nAF detection at 0-14 days, 15-90 days, 91-180 days, 181-365 days were 1.79 (1.24-2.58); 2.01 (0.63-6.37); 0.98 (0.16-5.90); and 2.92 (1.30-6.56), respectively. There is an almost fourfold increase in nAF detection with continuous cardiac monitoring, compared to usual care. The results also demonstrate two statistically significant time periods in nAF detection; at 0-14 days and 6-12 months following monitoring commencement. These data support the utilization of different monitoring methods to cover both time periods and a minimum of 1 year of monitoring to maximize nAF detection in patients after IS and TIA.

Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: a multi-center study

Background and objectivesEndovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI.MethodsThis is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3).ResultsOf the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (n = 124) versus no RFI (n = 107). Older age (OR 1.041, 95% CI 1.004 to 1.073; p = 0.010), chronic kidney disease (OR 4.399, 0.904–21.412; p = 0.067), and higher 24-h NIHSS (OR 1.284, 1.201–1.373; p < 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178–0.909; p = 0.029).ConclusionIn conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.

The pathway to diagnosis and follow-up care for atrial fibrillation in Sri Lanka: a descriptive longitudinal study

Background Early diagnosis and continuity of care is vital for atrial fibrillation (AF), a major risk factor for stroke that requires regular monitoring when treated with warfarin; however, evidence on AF care in LMICs is lacking. We aimed to identify the AF patient pathway in Northern Province, Sri Lanka and to determine how the COVID-19 pandemic impacted AF care. Methods This descriptive longitudinal study utilised two questionnaires, which were previously used in India and Mongolia to quantitatively evaluate the AF pathway: one at baseline and one ≥3 months following baseline. Adults (≥18 years) with AF were recruited from the A&E department and outpatient clinics located at the Jaffna Teaching Hospital, the only tertiary hospital with cardiologists and 12-lead echocardiogram facilities in the Province. Data were collected between October 2020 and June 2021 and analysed using descriptive statistics. Results This study included 151 participants (median age 57 years, IQR 49-67; 70% female). Most participants were diagnosed in the A&E (38%) or inpatient department (26%), followed by an outpatient department (19%) or private facility (16%). Nearly all (97%) participants received follow-up care during the study period, with an average of 1.3 AF-related healthcare visits per person; most visited an outpatient department (88%). The COVID-19 pandemic negatively impacted 39% of participants’ care: fewer healthcare visits, delayed or unattainable medications, and longer intervals between blood tests; however, 24% of participants received their medication by ambulance, public health staff or post. Conclusions Primary care was not involved in the diagnosis of AF, leading to most diagnoses occurring after a medical emergency. The frequency of blood tests was lower than guideline recommendations and could in-part be due to the adverse impacts of the pandemic. Strengthening primary and community-based care may enable early diagnosis and improve continuity of care during and beyond future healthcare crises/emergencies.

Qualitative Study on Knowledge of Non-Pharmacological Interventions as Management Strategies for Hypertension Among Middle-Aged Adults in Rural Areas of Anambra State

Recent World Health Organization records show that hypertension is more common in Africa than in other parts of the world, and remains a major common risk factor for cardiovascular diseases, stroke, renal diseases, and death. However, little is known about hypertension management strategies among people in rural areas. Therefore, this phenomenological study aimed to investigate knowledge of hypertension management strategies among middle-aged adults in rural areas of Anambra state. Focus group discussions were used to collect data from 40 middle-aged adults (20 males and 20 females). The data were analysed thematically. Results showed that the participants were all aware of hypertension but lacked in-depth knowledge of disease management strategies. Most of the participants did not believe that engaging in regular physical exercise/activity, and other factors like reduction in salt and alcohol intake could help in controlling high blood pressure. Social workers who are also social service providers are needed to raise awareness among middle-aged people in rural areas about hypertension management strategies. This can be done through the provision of social services like education, health services, and transport services, as this will go a long way in helping rural dwellers gain more knowledge of hypertension management strategies. With the provision of health services, the rural population will not only know management strategies for hypertension but will also be able to check their blood pressure regularly, while transport services will make it possible for the rural population who do not have health centres in their community and means of transporting themselves to the neighbouring community for treatment to do so. Future research should focus on the importance of welfare/home visits as an avenue for awareness creation on hypertension management strategies, as this will be an avenue for the provision of better social services for people in rural areas and an improvement in social service research.

Abstract 17231: Importance of Intra Plaque Hemorrhage During Carotid Artery Revascularization

Introduction: The American Heart Association currently estimates that every 3 minutes a person dies from a stroke. Carotid artery stenosis, a major risk factor for new and recurrent strokes, can be treated with carotid artery revascularization. Vascular emboli released during this procedure are non-invasively detected by transcranial doppler (TCD) ultrasound as micro embolic signals (MES). In this study we aim to show the relationship between carotid plaque characteristics and MES rates that were detected by TCD-monitoring throughout the stages of the carotid artery revascularization procedures. Methods: Before elective carotid revascularization 30 patients (mean age 72±8 years; 16 males, 14 females) underwent 3-T MRI. After localization of the carotid bifurcation using phase contrast imaging, Time-of-Flight, 3D T1 weighting, transverse T1 and T2 weightings and proton density sequences were acquired. The different plaque components: lipid core, intraplaque hemorrhage, calcification and the characterization of the fibrous cap were assessed. While 20 patients underwent carotid endarterectomy (CEA), 10 patients had carotid artery stenting (CAS). CES was divided into 9 stages: 1- Pre-procedure, 2- Dissection, 3- IC clamp, 4- Shunt placement, 5- Shunt open, 6- Endarterectomy, 7- Clamped, 8- IC opened, 9- Post-procedure. Similarly, CAS was divided into 9 stages: 1- Pre-procedure, 2- Arch-carotid angiography, 3- Wire insertion, 4- Filter deployment, 5- Pre-dilation, 6- Stent deployment, 7- Post-dilation, 8- Final angiography, 9- Post-procedure. Patients were monitored continuously with TCD to detect pre-procedural, intra-procedural and post-procedural MES rates. Results: Intraplaque hemorrhage was observed in 18 patients (60%). Patients with intra plaque hemorrhage had more MES during carotid artery dissection/arch-carotid angiography (p=0.028) and IC clamping/wire insertion (p=0.009) compared to patients without intra plaque hemorrhage in the pre-procedural stage. Conclusions: Carotid plaques with intra plaque hemorrhage is associated with higher MES during carotid artery revascularization procedures.

Multicentre, national, investigator-initiated, randomised, parallel-group, register-based superiority trial to compare extended ECG monitoring versus standard ECG monitoring in elderly patients with ischaemic stroke or transient ischaemic attack and the effect on stroke, death and intracerebral bleeding: the AF SPICE protocol

IntroductionAtrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring...

A Randomized Trial of Three Homeopathic Drugs: Rauwolfia serpentina, Viscum album, and Spartium scoparium in Essential Hypertension

AbstractHypertension (HTN) remains one of the major risk factors for heart failure, stroke, and coronary heart disease worldwide. This study was undertaken to compare the antihypertensive effects produced by the mother tinctures (MTs) of three homeopathic drugs—Rauwolfia serpentina (RS), Viscum album (VA), and Spartium scoparium (SS; also known as Cytisus scoparius [CS]) in essential hypertension. This open-label, randomized, three parallel arm, pragmatic, pilot trial was conducted on 60 participants with essential hypertension in the outpatient department of D. N. De Homoeopathic Medical College and Hospital, Kolkata. Participants were randomized into three groups: RS, VA, and SS equally. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at baseline and after 30 and 60 minutes. Group differences at different time points and overall were measured using one-way analysis of variance (ANOVA) and three-way repeated measure ANOVA models, respectively, after adjusting for baseline differences using intention-to-treat approaches. A p value less than 0.05 was considered statistically significant. Endpoint analysis included 60 participants. Although the highest mean reductions in SBP and DBP with time were achieved in the RS group, all three medicines revealed similar antihypertensive effects without any significant differences (SBP: F 2, 57 = 1.710, p = 0.190; DBP: F 2, 57 = 0.732, p = 0.485). No harm or serious adverse events were reported from either of the groups. All three medicines (RS, VA, and SS) produced similar antihypertensive effects in essential hypertension. Trial registration: CTRI/2021/02/031548; UTN: U1111–1264–6856.

Identifying and understanding the care pathway of patients with atrial fibrillation in Brazil and the impact of the COVID-19 pandemic: A mixed-methods study.

Atrial fibrillation (AF) is a major risk factor for stroke. To enable improvements to AF diagnosis and follow-up care, understanding current patient pathways and barriers to optimal care are essential. We investigated the patient care pathways and their drivers, and the impact of the COVID-19 pandemic on patient pathways in a middle-income country setting, Brazil. This mixed-methods study in São Paulo, included adults (≥18y) with AF from 13 primary/secondary healthcare facilities. Surveys using baseline, follow-up (administered ≥two months after baseline) and COVID-19 questionnaires (quantitative), and three focus group discussions (FGDs) were conducted. Minimum sample size for the quantitative component was 236 and we aimed to reach saturation with at least three FGDs for the qualitative component. Descriptive statistics were used for quantitative data and a content analysis was used for qualitative data to identify themes related to AF diagnosis and follow-up care. 267 participants completed the baseline questionnaire: 25% were diagnosed in primary care, 65% in an emergency or inpatient department. At follow-up (n = 259), 31% visited more than one facility for AF care, and 7% had no follow-up. Intervals between international normalised ratio (INR) tests were increased during the pandemic, and the number of healthcare visits and availability of medication were reduced. Seventeen patients participated in three FGDs and revealed that AF diagnosis often occurred following a medical emergency and patients often delay care-seeking due to misconceptions about AF symptoms. Long waiting times, doctor/patient interactions and health system factors, such as doctor availability and the referral system, influence where participants visited for follow-up care. Lack of public awareness and underdeveloped primary healthcare lead to delayed diagnosis, which impacts clinical outcomes and excess patient and healthcare system costs. Health system, care-provider, and pandemic factors disrupt timely and effective continuity of care.

Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review.

Hyperlipidemia is a metabolic disorder, which is a major risk factor for atherosclerosis, stroke, and coronary heart disease. Although lipid-lowering treatments have been extensively studied, safer treatments with fewer adverse effects are needed. Rhubarb is a traditional Chinese medicine that has lipid-lowering, anti-inflammatory, and antioxidant properties. Disturbance in lipid metabolism is the basis of tissue damage caused by hyperlipidemia and plays a key role in the development of hyperlipidemia; however, the molecular mechanisms by which rhubarb regulates lipid metabolism to lower lipid levels are yet to be elucidated. We conducted this study to summarize the phytochemical constituents of Rheum officinale and provide a comprehensive review of the molecular mechanisms underlying the regulation of lipid metabolism during hyperlipidemia treatment. It was found that rhubarb extracts, including emodin, rhubarb acid, and rhubarb phenol, regulate total cholesterol, triglyceride, TNF-α, and IL-1β levels through signaling pathways such as C/EBP α, 3T3-L1, PPAR α, and AMPK, thereby improving the hyperlipidemic state. This suggests that rhubarb is a natural drug with lipid-lowering potential, and an in-depth exploration of its lipid-lowering mechanism can provide new ideas for the prevention and treatment of hyperlipidemia.

Serum Vitamin D Level as a Risk Factor and Prognostic Marker for Acute Ischemic Stroke: A Case-Control Study at a Tertiary Care Centre in Northern India.

Introduction Stroke is a predominant cause of death worldwide. Major risk factors for stroke in any age group are diabetes, hypertension, heart disease, smoking, and long-term alcohol abuse. It is of utmost importance to identify the risk factors for stroke to prevent recurrence. Vitamin D deficiency is identified as a risk factor for stroke. Therefore, we attempted to look for a correlation between vitamin D levels and acute ischemic stroke. Methods This observational case-control study was conducted with 150 patients (75 cases and 75 controls). On the day of admission, the National Institutes of Health Stroke Scale (NIHSS) score was calculated, and vitamin D levels were measured for each patient. The functional outcome was determined by the modified Rankin scale (mRS). Results The most common risk factors identified in this study were hypertension (61.3%), diabetes mellitus (41.3%), and smoking (37.3%). Out of 75 patients enrolled in the study, 49.4% had significant vitamin D deficiency, and 30.6% had insufficient vitamin D levels. Our study showed a significant correlation between vitamin D sufficiency in the body and the incidence of stroke (x2=3.888 and p=0.048). A significant correlation (p=0.03) was found between the NIHSS score and vitamin D levels in patients with acute ischemic stroke. Conclusion In this observational case-control study, we concluded that the increasing severity of vitamin D deficiency was associated with more deaths and poor outcomes.

Use of Oral Anticoagulants in Patients with Atrial Fibrillation: Preliminary Data from the Italian Atrial Fibrillation (ITALY-AF) Registry.

Atrial fibrillation (AFIB), the most frequent cardiac arrhythmia, is a major risk factor for stroke, heart failure, and death. Because of the recent advances in AFIB management and the availability of new oral anticoagulants (OACs), there is a need for a systematic and predefined collection of contemporary data regarding its management and treatment. The objective of the ongoing ITALY-AFIB registry is to evaluate the long-term morbidity and mortality in patients with AFIB and to verify the implementation of the current guidelines for stroke prevention in these patients. The registry includes consecutive in- and out-patients with first diagnosed, paroxysmal, persistent, or permanent AFIB. In patients in sinus rhythm at entry, the qualifying episode of AFIB, confirmed by ECG diagnosis, had to have occurred within 1 year before entry. The clinical record form is web-based and accessible by personal keyword. Enrolment into the registry started in the year 2013. In a current cohort of 2470 patients (mean age 75 ± 11 years, males 56%), the mean CHA2DS2-VASc score was 3.7 ± 1.8, and the mean HAS-BLED was 1.6 ± 0.9. There were no significant sex differences in the AFIB subtypes. At the end of the inclusion visit and after receiving knowledge of the web-based electronic estimate of risk for stroke and bleeding, the proportion of patients discharged with OACs was 80%. After exclusion of patients with first diagnosed AFIB (n = 397), the proportion of patients with prescription of OACs rose from 66% before the visit to 82% on discharge (p < 0.0001). Prescription of aspirin or other antiplatelet drugs fell from 18% before the visit to 10% on discharge (p < 0.0001). A web-based management of AFIB with automated estimation of risk profiles appears to favorably affect adherence to AFIB guidelines, based on a high proportion of patients treated with OACs and a substantial decline in the use of antiplatelet drugs.

Importance of assessment of carotid plaques in the managementof acute ischemic stroke: floating intracarotid plaque

Mobile atheromatous plaques affecting large arteries are a major risk factor for embolic strokes. We report a case of extensive embolic cerebral infarction secondary to a vulnerable internal carotid artery plaque. A 67-year-old female was admitted with sudden left-sided weakness. A computed tomography brain scan revealed early ischemic changes in the right middle cerebral territory. The ultrasound Doppler showed soft mobile plaque with thrombus in the right internal carotid artery causing 90% stenosis. Magnetic resonance imaging brain scan performed later showed extensive right cerebral infarction. A computed tomography angiogram revealed ulcerated non-occlusive soft tissue plaque in the right internal carotid artery. She was also diagnosed with bladder cancer during this admission and was managed medically due to her performance status. Unstable vulnerable plaques can be symptomatic even in the absence of significant carotid stenosis. Hence, early identification of the plaque vulnerability, using new imaging modalities, and its medical stabilization can help to reduce the risk of cerebrovascular insults. The etiopathogenesis of inflammation within unstable vulnerable plaques and its concordance with inflammatory markers is still unclear. It is feasible in our case the malignantprocess could also be contributing to the inflammation within the blood vessels promoting vulnerability of the plaques.

The Role of the Low-Density Lipoprotein/High-Density Lipoprotein Cholesterol Ratio as an Atherogenic Risk Factor in Young Adults with Ischemic Stroke: A Case-Control Study.

Dyslipidemia is a major atherogenic risk factor for ischemic stroke. Stroke patients tend to have high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). Therefore, it is noteworthy that there has been an increase in ischemic stroke cases in young and elderly individuals in recent years. This study investigated the TC/HDL-C ratio and the LDL-C/HDL-C ratio, which may be more specific and common lipid parameters in young patients with ischemic stroke. This study aimed to demonstrate the sensitivity and specificity of TC/HDL-C and LDL-C/HDL-C ratios as atherogenic markers for young adult ischemic strokes. This trial was conducted as a retrospective case-control study. A total of 123 patients (patient group) and 86 healthy individuals (control group) aged 18-50 years were randomly selected from four different hospitals. Lipid parameters and TC/HDL-C and LDL-C/HDL-C ratios were compared between these two groups. The mean age was 38.8 ± 7.3 years in patients and 37.7 ± 9 years in controls (p > 005). The HDL-C levels were 39.1 ± 10.8 mg/dL in patients and 48.4 ± 13.8 mg/dL in controls (p < 0.001). LDL-C/HDL-C ratios were 3.23 ± 1.74 and 2.38 ± 0.87, and TC/HDL-C ratios were 5.24 ± 2.31 and 4.10 ± 1.25 in the patient and control groups, respectively (p < 0.001). The LDL-C/HDL-C and TC/HDL-C cutoff values in ROC analyses were 2.61 and 4.40 respectively; the AUCs (95% CI) were determined to be 0.680 (0.608-0.753) and 0.683 (0.610-0.755) (p < 0.001), respectively. An increased risk of stroke was observed in those with a high LDL-C/HDL-C ratio (OR = 1.827; 95% CI = 1.341-2.488; p < 0.001). Our study obtained similar results when we compared the mean TC and LDL-C levels between the two groups. However, considering the TC/HDL-C and LDL-C/HDL-C ratios, it is noteworthy that there was a significant difference between the patient and control groups.

Biomarker, Imaging, and Clinical Factors Associated With Overt and Covert Stroke in Patients With Atrial Fibrillation.

Atrial fibrillation is a major risk factor for stroke and silent brain infarcts. We studied whether a multimodal approach offers additional insights to the CHA2DS2-VASc score in predicting stroke or new brain infarcts on magnetic resonance imaging (MRI) over a 2-year follow-up. Swiss-AF is a prospective, multicenter cohort study of patients with known atrial fibrillation. We included patients with available brain MRI both at enrollment and 2 years later. The dates of the baseline and follow-up visits ranged from March 2014 to November 2020. The primary outcome was assessed 2 years after baseline and was defined as a composite of clinically identified stroke or any new brain infarct on the 2-year MRI. We compared a multivariable logistic regression model including prespecified clinical, biomarker, and baseline MRI variables to the CHA2DS2-VASc score. We included 1232 patients, 89.8% of them taking oral anticoagulants. The primary outcome occurred in 78 patients (6.3%). The following baseline variables were included in the final multivariate model and were significantly associated with the primary outcome: white matter lesion volume in milliliters (adjusted odds ratio [aOR], 1.91 [95% CI, 1.45-2.56]), NT-proBNP (N-terminal pro-B-type natriuretic peptide; aOR, 1.75 [95% CI, 1.20-2.63]), GDF-15 (growth differentiation factor-15; aOR, 1.68 [95% CI, 1.11-2.53]), serum creatinine (aOR, 1.50 [95% CI, 1.02-2.22]), IL (interleukin)-6 (aOR, 1.37 [95% CI, 1.00-1.86]), and hFABP (heart-type fatty acid-binding protein; aOR, 0.48 [95% CI, 0.31-0.73]). Overall performance and discrimination of the new model was superior to that of the CHA2DS2-VASc score (C statistic, 0.82 [95% CI, 0.77-0.87] versus 0.64 [95% CI, 0.58-0.70]). In patients with atrial fibrillation, a model incorporating white matter lesion volume on baseline MRI and selected blood markers yielded new insights on residual stroke risk despite a high proportion of patients on oral anticoagulants. This may be relevant to develop further preventive measures.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

Vertebrobasilar Artery Calcification as a Risk Factor for the Development of Stroke: Case-Control Study From a Tertiary Care Center, Southern India.

Background Stroke is an important cause of morbidity and mortality in developing countries. Many risk factors are well-established for the development of stroke. Atherosclerosis involving the media and intima layer of vertebrobasilar arteries has not been studied well as a risk factor for stroke. Objective To assess the degree of calcification of vertebrobasilar arteries among patients with stroke (cases), age- and gender-matched controls, and the risk of the development of stroke. Methods This was a hospital record-based case-control study with individuals with stroke as cases and age- and gender-matched individuals without stroke as controls, who underwent computed tomography imaging. The degree of calcification of vertebrobasilar arteries was assessed among cases and controls. Various other risk factors for the development of stroke such as the presence of hypertension, diabetes mellitus, and impaired lipid profile were also assessed. Results Among the 150 cases and their age- and gender-matched controls, the mean age of the subjects was 58.38 (±14.06) years. Forty percent of the individuals were males. Among the cases, right vertebral, left vertebral, and basilar artery calcifications were observed among 114 (76%), 102 (68%), and 52 (34.7%), respectively. Among controls, 71 (47.3%), 77 (51.3%), and 29 (19.3%) individuals had right vertebral, left vertebral, and basilar artery calcifications, respectively. The degree of calcification was higher among the cases in the right and left vertebral arteries than the controls (adjusted odds (aOR) of 6.61 and 2.32 and p-value <0.001 and 0.032, respectively). The risk of stroke increased with higher degrees of calcification, the presence of diabetes mellitus, and raised cholesterol levels (aOR of 9.98, 2.32, and 4 and p-value <0.001, 0.007, and 0.001, respectively). The risk of stroke increases with the presence of multiple risk factors. Conclusion The presence of higher grades of calcifications in the vertebrobasilar arteries is a major risk factor for stroke. Hence, its presence in asymptomatic individuals needs to be taken as a warning sign for the development of stroke.

Contribution of Conventional Cardiovascular Risk Factors to Brain White Matter Hyperintensities.

Background White matter hyperintensities (WMHs) are a major risk factor for stroke and dementia, but their pathogenesis is incompletely understood. It has been debated how much risk is accounted for by conventional cardiovascular risk factors (CVRFs), and this has major implications as to how effective a preventative strategy targeting these risk factors will be. Methods and Results We included 41 626 UK Biobank participants (47.2% men), with a mean age of 55 years (SD, 7.5 years), who underwent brain magnetic resonance imaging at the first imaging assessment beginning in 2014. The relationships among CVRFs, cardiovascular conditions, and WMH volume as a percentage of total brain volume were examined using correlations and structural equation models. Only 32% of the variance in WMH volume was explained by measures of CVRFs, sex, and age, of which age accounted for 16%. CVRFs combined accounted for ≈15% of the variance. However, a large portion of the variance (well over 60%) remains unexplained. Of the individual CVRFs, blood pressure parameters together accounted for ≈10.5% of the total variance (diagnosis of hypertension, 4.4%; systolic blood pressure, 4.4%; and diastolic blood pressure, 1.7%). The variance explained by most individual CVRFs declined with age. Conclusions Our findings suggest the presence of other vascular and nonvascular factors underlying the development of WMHs. Although they emphasize the importance of modification of conventional CVRFs, particularly hypertension, they highlight the need to better understand risk factors underlying the considerable unexplained variance in WMHs if we are to develop better preventative approaches.

Percutaneous Left Atrial Appendage Closure Among Patients With Diabetes (Insights from a National Database)

Atrial fibrillation is a major risk factor for stroke. Left atrial appendage closure (LAAC) has emerged as an alternative to anticoagulation for patients with high risk of bleeding. Diabetes mellitus (DM) is associated with adverse events after cardiac procedures. We sought to compare procedural and hospital outcomes in patients who underwent LAAC with and without DM. The Nationwide Inpatient Database was queried for patients with atrial fibrillation who underwent LAAC between January 1, 2016, and December 31, 2019. The primary outcome was all adverse events that included in-hospital death, acute myocardial infarction, cardiac arrest, stroke, pericardial effusion, pericardial tamponade, pericardiocentesis, pericardial window, and postprocedural hemorrhage requiring blood transfusion. Analysis included 62,220 patients who underwent LAAC from 2016 to 2019; 34.9% of patients had DM. There was a slight increase in the percentage of patients who underwent LAAC who had DM during the study period, from 29.92% to 34.93%. In unadjusted and adjusted analysis, there was no significant difference in all adverse events between patients with and without DM who underwent LAAC (9.18% vs 8.77%, respectively, adjusted p=0.63), and no difference in length of stay. Patients with DM have higher risk of acute kidney injury (3.75 vs 1.96%, p<0.001). This nationwide retrospective study demonstrates that DM is not associated with an increase in adverse event rates in patients who underwent LAAC.

Pharmacokinetic Evaluation of Telmisartan and Cilnidipine Bilayer Tablet in A Rabbit Model

Hypertension is a chronic medical condition affecting a significant proportion of the global population. It is a major risk factor for cardiovascular diseases, stroke, and kidney failure. Telmisartan and cilnidipine combination are commonly used in managing hypertension due to their complementary mechanism of action. Therefore, a bilayer tablet design that enhances the pharmacokinetic profile of cilnidipine as a sustained-release drug while telmisartan act as an immediate-release drug may provide a better therapeutic option for hypertension management. We aim to evaluate the pharmacokinetic parameters of the bilayer tablet of Telmisartan and Cilnidipine. Our objective is to observe the bioavailability of the bilayer tablet in rabbit plasma. The formulation aims to achieve an immediate release effect for Telmisartan and a sustained release effect for Cilnidipine. The solubility and bioavailability of Telmisartan were enhanced by complexation with beta-cyclodextrin. To achieve our aim, we observe the drug concentration in rabbit plasma. Telmisartan is an angiotensin receptor blocker, while Cilnidipine is a calcium channel blocker. The pharmacokinetics of the drugs were evaluated in New Zealand rabbits following oral administration. Systemic drug bioavailability was assessed, and an HPLC method was developed to estimate Telmisartan and Cilnidipine's plasma concentration simultaneously. A Gemini C-18 column (250 mm X 4.6 mm X 5 microns) Phenomenex was used for peak separation. The mobile phase consisted of acetonitrile with phosphate buffer pH 3.5 v/v, with a flow rate of 1.5 ml per minute. The calibration curve analysis indicated a correlation coefficient of 0.9996 and 0.9997 for Telmisartan and Cilnidipine, respectively. The pharmacokinetics of the optimized batch, including Cmax, Tmax, and AUC values, were compared to those of the pure drug. Drug concentration was detected using a DAD detector with an excitation wavelength of 241nm. No interaction was observed between the drugs and excipients. The in-vivo study of the formulation showed higher bioavailability, indicating that the developed bilayer tablet formulation could be an effective means of delivering Telmisartan and Cilnidipine.

Predicting mechanisms of action at genetic loci associated with discordant effects on type 2 diabetes and abdominal fat accumulation.

Obesity is a major risk factor for cardiovascular disease, stroke, and type 2 diabetes (T2D). Excessive accumulation of fat in the abdomen further increases T2D risk. Abdominal obesity is measured by calculating the ratio of waist-to-hip circumference adjusted for the body-mass index (WHRadjBMI), a trait with a significant genetic inheritance. Genetic loci associated with WHRadjBMI identified in genome-wide association studies are predicted to act through adipose tissues, but many of the exact molecular mechanisms underlying fat distribution and its consequences for T2D risk are poorly understood. Further, mechanisms that uncouple the genetic inheritance of abdominal obesity from T2D risk have not yet been described. Here we utilize multi-omic data to predict mechanisms of action at loci associated with discordant effects on abdominal obesity and T2D risk. We find six genetic signals in five loci associated with protection from T2D but also with increased abdominal obesity. We predict the tissues of action at these discordant loci and the likely effector Genes (eGenes) at three discordant loci, from which we predict significant involvement of adipose biology. We then evaluate the relationship between adipose gene expression of eGenes with adipogenesis, obesity, and diabetic physiological phenotypes. By integrating these analyses with prior literature, we propose models that resolve the discordant associations at two of the five loci. While experimental validation is required to validate predictions, these hypotheses provide potential mechanisms underlying T2D risk stratification within abdominal obesity.