Vascular Risk Research Articles (Page 1)

Intracranial atherosclerosis disease (ICAD) accounts for 30% of ischemic strokes, has the highest stroke recurrence rate, and is associated with accelerated cognitive decline. This study investigates associations between diet patterns and the risk of ICAD. Participants in a longitudinal clinical neuropathologic cohort study, with complete dietary, medical history, and neuropathology data, were included. Diet scores were computed (median interval to death = 5.9 [3.0-8.7] years). History of hypertension (HTN) and myocardial infarction (MI) were self-reported. Large vessel ICAD was evaluated at the circle of Willis, and severity of ICAD was assessed based on number of atherosclerotic plaques, extent of vessel involvement, and degree of vessel occlusion to create a 4-level grading system (0-3). All regression models were adjusted for age, sex, education, caloric intake, and APOE4. Of the 676 participants (mean age at death = 91.1 years, SD = 6.1, 71% women), 361 (53%) had mild, 142 (21%) had moderate, and 28 (4%) had severe ICAD. There was no direct relationship between diet and ICAD. The association between ICAD and MI (OR 1.38, 95% CI 0.95-2.00) was not significant. HTN (OR 1.598, 95% CI 1.15-2.18) was positively associated with ICAD. The association of diet with ICAD differed by history of MI (Mediterranean-DASH intervention for neurodegenerative delay [MIND] [p = 0.007], MedDiet [p = 0.006]). The association between ICAD and the MIND diet also differed by whether HTN was reported (β = -0.212, SE = 0.111, p = 0.055) as did the relationship between ICAD and the MedDiet (β = -0.077, SE = 0.035, p = 0.029). In stratified analysis, among individuals with preexisting MI (N = 130), those with a better diet had lower odds of ICAD (MedDiet: OR 0.88, 95% CI 0.81-0.96; MIND: OR 0.69, 95% CI 0.53-0.90). A direct relationship between diet and ICAD was not seen. Stratified analysis suggested that healthy diet may be of value for individuals with HTN or MI: In these high-risk individuals, a healthy dietary pattern is associated with lower odds of severe large vessel ICAD. In vivo studies of dietary habits and brain health, specifically in those at high vascular risk, are needed.

Ischemic stroke caused by atherosclerosis is associated with the highest risk of recurrence among stroke etiologies, highlighting a residual risk that current secondary prevention strategies fail to address. Multiple lines of research implicate inflammation in the pathogenesis of atherosclerosis, including recent large cardiovascular outcome trials demonstrating that anti-inflammatory therapies can lower residual vascular risk in patients with coronary artery disease. Notably, low-dose colchicine, a long-used anti-inflammatory drug, has received approval for cardiovascular risk reduction in patients with atherosclerosis. However, translation of anti-inflammatory treatments to patients with ischemic stroke has been challenging, with the first colchicine trials showing neutral or conflicting results. In this study, we review the preclinical, genetic, and epidemiologic literature linking inflammation to atherosclerotic stroke; examine key findings of cardiovascular outcome trials for stroke prevention; and summarize completed and ongoing stroke-specific trials. We discuss the etiologic heterogeneity of ischemic stroke that may obscure anti-inflammatory treatment effects, highlighting the need for precision medicine approaches targeting patients with established atherosclerosis and vascular inflammation. Finally, we provide an overview of the emerging anti-inflammatory therapeutics that are under development for atheroprotection and outline a translational roadmap to accelerate clinical impact in stroke prevention.

Evaluating and managing patients with recurrent stroke presents a significant challenge, particularly in individuals with underlying autoimmune or rheumatologic conditions. We present a case of a 56-year-old woman with a long-standing history of medically controlled systemic lupus erythematosus (SLE) who has experienced multiple ischemic strokes and a subarachnoid hemorrhage. Despite an unremarkable standard stroke workup and adherence to secondary prevention medications, including antithrombotic and lipid-lowering therapies, the patient continued to experience recurrent strokes, warranting further investigation. Serial follow-up imaging including CT angiography, magnetic resonance angiography, and conventional angiography revealed progressive intracranial vascular narrowing, prompting a broad workup and differential diagnosis. This case highlights the importance of a stepwise and comprehensive diagnostic approach that integrates traditional vascular risk factors with those related to underlying autoimmune disease. It provides an insight into the diagnostic strategies and management of this high-risk population, ultimately supporting the need for personalized patient care to address the multifactorial causes of stroke.

Glymphatic system (GS) alterations has been increasingly associated with cognitive impairment in cerebral small vessel disease (CSVD). Comprehensive and quantifiable markers of GS function remain limited. GS was assessed using three non-invasive MRI-based metrics including analysis along perivascular space (ALPS) index, coupling between global blood-oxygen-level-dependent (gBOLD) signal and cerebrospinal fluid (CSF) movement, and choroid plexus volume (CPV). Correlations between GS metrics and CSVD markers were examined, along with their associations with cognition. A weighted glymphatic composite score (GCS) was subsequently derived based on relative cognitive contributions. We recruited 350 participants (65.53 ± 7.65 years), with 160 CSVDs and 190 healthy controls (HC). Compared with CSVD-normal cognition (CSVD-NCI), the CSVD-mild cognitive impairment (CSVD-MCI) group exhibited significantly lower ALPS indices and higher CPV (p < 0.001). CSVD markers including periventricular (β = -0.350; β = 0.404) and deep (β = -0.330; β = 0.324) white matter hyperintensities, microbleeds (β= -0.255; β = 0.191), lacunes (β = -0.194; β = 0.177), and perivascular spaces (β = -0.335; β = 0.390) were associated with ALPS index and CPV (p < 0.01).Linear analyses revealed a significant interaction between ALPS and CSVD on cognition (p < 0.05), which remained robust after further adjustment for vascular risk factors. Compared to CSVD-NCI, CSVD-MCI exhibited significantly lower GCS (p < 0.05). The GCS was significantly associated with MCI status after adjustment for clinical factors (OR = 0.31, p = 0.024). Combining multiple GS-related MRI markers into a composite index effectively reflects cognitive status in CSVD and may serve as a non-invasive biomarker for CSVD-MCI discrimination.

Fabry disease (FD) is an X-linked disorder caused by deleterious variants in GLA. Cardiovascular disease (CVD) causes premature mortality in FD. Hope for aspirin (acetylsalicylic acid, ASA) to reduce CVD risks in FD as primary prevention may have been tempered by the 2018 ARRIVE, ASCEND, and ASPREE clinical trials. It is unclear how new ASA guidance applies to FD patients, who have a high rate of young-onset, small vessel stroke compared with the general population. Longitudinal data spanning 2007-2023 from patients in the Canadian Fabry Disease Initiative (CFDI) were analyzed retrospectively. Incident stroke and transient ischemic attack (TIA), other CVD events, FD-specific risk factors, and ASA/antiplatelet ("ASA/AP") prescription before and after 2018 were compared between groups who never had an event ("primary prevention group") to those who had incident stroke/TIA during the study. Stroke/TIA rates were compared within CFDI by sex and GLA variant severity, and in the CFDI compared to Canadian statistics by sex. Ten-year atherosclerotic CVD (ASCVD) risk was calculated using the 2013 ACC/AHA risk calculator. ASA/AP prescription rate was compared before and after 2018. Out of 641 patients, 57 had an incident stroke/TIA during the study, and 193 with complete data remained in the primary prevention group. Stroke/TIA rates were significantly higher among male patients (0.026 events per patient-year) than females (0.0098 events per patient-year), and higher among patients with severe GLA variants (males: 0.031 events per patient-year, females: 0.0096 events per patient-year) compared to those with attenuated variants (males: 0.011 events per patient-year, females: 0.0088 events per patient-year). No patients under 60 years at their incident stroke/TIA had high (≥ 10%) calculated 10-year ASCVD risk. Fewer patients were prescribed ASA/AP for primary prevention after 2018. There was a high incidence of stroke/TIA in the younger CFDI cohort compared to the general Canadian population, despite low levels of traditional vascular risk factors as represented in 10-year estimated ASCVD risk. Primary prevention use of ASA has declined.

Diet influences brain health through many connected metabolic and molecular pathways, and these effects are stronger in obesity. This review links diet quality with cognitive decline and dementia risk. Ultra-processed, high-fat, high-sugar diets drive weight gain, insulin resistance, and chronic inflammation. These changes trigger brain oxidative stress, reduce DNA repair, deplete NAD+, disturb sirtuin/PARP balance, and alter epigenetic marks. Gut dysbiosis and leaky gut add inflammatory signals, weaken the blood–brain barrier, and disrupt microglia. Mediterranean and MIND diets, rich in plants, fiber, polyphenols, and omega-3 fats, slow cognitive decline and lower dementia risk. Trials show extra benefit when diet improves alongside exercise and vascular risk control. Specific nutrients can help in certain settings. DHA and EPA support brain health in people with low omega-3 status or early disease. B-vitamins slow brain shrinkage in mild cognitive impairment when homocysteine is high. Vitamin D correction is beneficial when levels are low. A practical plan emphasizes healthy eating and good metabolic control. It includes screening for deficiencies and supporting the microbiome with fiber and fermented foods. Mechanism-based add-ons, such as NAD+ boosters, deserve testing in lifestyle-focused trials. Together, these measures may reduce diet-related brain risk across the life span. At the same time, artificial intelligence can integrate diet exposures, adiposity, metabolic markers, multi-omics, neuroimaging, and digital phenotyping. This can identify high-risk phenotypes, refine causal links along the diet–obesity–brain axis, and personalize nutrition-plus-lifestyle interventions. It can also highlight safety, equity, and privacy considerations. Translationally, a pattern-first strategy can support early screening and personalized risk reduction by integrating diet quality, adiposity, vascular risk, micronutrient status, and microbiome-responsive behaviors. AI can aid measurement and risk stratification when developed with privacy, equity, and interpretability safeguards, but clinical decisions should remain mechanism-aligned and trial-anchored.

The burden of atherosclerosis may have prognostic implications for patients affected by venous thromboembolism (VTE). We aimed to assess the association of the presence and extent of atherosclerotic disease with long-term clinical outcomes in patients with acute pulmonary embolism (PE). In patients with PE from the Hokusai-VTE trial, we assessed the association between the presence of atherosclerotic disease in multiple (polyvascular disease), one, or no vascular territories (coronary, cerebral, and/or peripheral arteries) and 1-year risk of VTE or PE recurrence, major bleeding, and all-cause death. We used univariable and multivariable Cox regression analysis, with adjustment for relevant comorbidities and anticoagulation modeled as a time-varying covariate. Of 2800 patients, 67 (2.4%) had polyvascular and 357 (12.7%) had single vascular atherosclerotic disease. During 12-month follow-up, recurrent VTE was reported for a total of 356 patients, including 208 PE events. A total of 52 patients had a major bleeding event and 91 deaths were recorded. Polyvascular atherosclerotic disease was strongly associated with VTE (adjusted hazard ratio,1.91 [95% CI, 1.05-3.49]) and PE recurrence (adjusted hazard ratio, 2.06 [95% CI, 1.03-4.16]). Polyvascular and single vascular disease were associated with major bleeding and all-cause death in univariable analysis; however, these associations attenuated after adjustment. The pre-existing burden of atherosclerosis may have prognostic value with respect to secondary prevention in patients who experienced an acute PE. Optimization of overall cardiovascular risk may be considered by management studies in the follow-up of this patient population. URL: www.clinicaltrials.gov; Unique identifier: identifier: NCT00986154.

Background Although traditional vascular risk factors, such as hypertension and diabetes, are incorporated into stroke risk prediction models, a significant proportion of stroke events remain unexplained by these models. Increasing evidence suggests that accelerated biological aging, as measured by DNA methylation clocks, may reflect reduced organ function and heightened susceptibility to disease. However, the relationship between epigenetic age acceleration (EAA) and stroke risk remains poorly understood, with limited comprehensive synthesis of the available evidence. Methods We conducted a systematic search of PubMed, Embase, Web of Science, and Cochrane Library databases (up to January 10, 2025) for observational studies examining the relationship between DNA methylation-derived EAA and stroke risk. The study protocol was registered with PROSPERO (CRD420251010621). Results Thirteen studies met the inclusion criteria. Random-effects meta-analysis revealed a significant positive association between accelerated biological aging and stroke risk (OR = 1.16, 95% CI 1.13–1.19, I 2 = 98.9%, p &amp;lt; 0.001). Stratified analysis by stroke event demonstrated a stronger association with incident stroke (OR = 1.28, 95% CI 1.25–1.35, I 2 = 92.6%, p = 0.001) compared to stroke recurrence (OR = 1.11, 95% CI 1.06–1.16, I 2 = 63.6%, p = 0.041). Sensitivity analyses confirmed the robustness of these findings. Conclusion DNA methylation-derived measures of accelerated biological aging are robust predictors of stroke. These findings provide new insights into stroke risk assessment and emphasize potential biomarkers for early detection and prevention. Further large-scale prospective studies are needed to validate these associations and examine the role of additional modifying factors.

Vascular sites have distinct susceptibility to atherosclerosis and aneurysm, yet the biological underpinning of vascular site-specific disease risk is largely unknown. Vascular tissues have different developmental origins that may influence global chromatin accessibility, and understanding differential chromatin accessibility, gene expression profiles, and gene regulatory networks (GRN) on single cell resolution may give key insight into vascular site-specific disease risk. Here, we performed single cell chromatin accessibility (scATACseq) and gene expression profiling (scRNAseq) of healthy adult mouse vascular tissue from three vascular sites, 1) aortic root and ascending aorta, 2) brachiocephalic and carotid artery, and 3) descending thoracic aorta. Through a comprehensive analysis at single cell resolution, we discovered key regulatory enhancers to not only be cell type, but vascular site specific in vascular smooth muscle (SMC), fibroblasts, and endothelial cells. We identified epigenetic markers of embryonic origin with differential chromatin accessibility of key developmental transcription factors such as Tbx20 , Hand2 , Gata4 , and Hoxb family members and discovered transcription factor motif accessibility to be cell type and vascular site specific. Notably, we found ascending fibroblasts to have distinct epigenomic patterns, highlighting SMAD2/3 function to suggest a differential susceptibility to TGFβ, a finding we confirmed through in vitro culture of primary adventitial fibroblasts. Finally, to understand how vascular site-specific enhancers may regulate human genetic risk for disease, we integrated genome wide association study (GWAS) data for ascending and descending aortic dimension, and through using a distinct base resolution deep learning model to predict variant effect on chromatin accessibility, ChromBPNet, to predict variant effects in SMC, Fibroblasts, and Endothelial cells within ascending aorta, carotid, and descending aorta sites of origin. We reveal that although cell type remains a primary influence on variant effects, vascular site modifies cell type transcription and highlights genomic regions that are enriched for specific TF motif footprints — including MEF2A, SMAD3, and HAND2. This work supports a paradigm that the epigenomic and transcriptomic landscape of vascular cells are cell type and vascular site-specific and that site-specific enhancers govern complex genetic drivers of disease risk.

Introduction: Cerebrovascular disease and vascular risk factors have important contributions to Alzheimer’s disease (AD) risk, and greater understanding of cognitive changes in vascular versus non-vascular populations may help reveal complementary and overlapping clinical changes. The aim of this work was to evaluate how cognitive changes in middle to later aged vascular and non-vascular cohorts are related to AD pathology. Methods: A subset of the National Alzheimer’s Coordinating Center (NACC) cohort with pTau217 testing available (ages 50-90, n=444) was included as a general population cohort. The first 167 participants enrolled in our prospective Carotid and Minds (CAM) study (participants aged 50-85 with ≥2 vascular comorbidities with/without asymptomatic carotid stenosis were included as a vascular disease cohort. Both cohorts were assessed using a full UDS neurocognitive battery and compared to plasma pTau217 adjusting for demographics and APOE ε4 status. Dementia and other neurological disorders were exclusionary. Results: Demographics of NACC cohort shown (Table1). When adjusted for age, sex, education, race, ethnicity and APOE ε4 status, pTau217 was associated with significantly worse memory (β=-0.15, p=0.003) while no significant association with domains of language, executive function, visuospatial and processing speed was seen. Demographics of CAM are shown (Table 2). Within CAM, pTau217 was associated with significantly worse non-amnestic domains including language (β=-0.18, p=0.02), executive function (β=-0.19, p=0.013) and processing speed (β=-0.18, p=0.02), but not memory (β=-0.07, p=0.36) independent of age, sex, education, race, ethnicity and APOE ε4 status. Poorer cognition was associated with age, sex and education in both cohorts; in contrast, worse processing speed and executive function in CAM cohort is associated with carotid stenosis (β=-0.24, p&lt;0.001) and a history of stroke (β=-0.47, p=0.02), but not APOE ε4 status or cerebral white matter lesion volumes. Conclusion: Within a vascular disease cohort, association of AD pathology with non-amnestic domains of processing speed, executive function and language complements and contrasts with memory domain impacts often associated with the classic notion of AD. Further assessment of these pathways associated with AD pathology could help understand unique and potentially complimentary cognitive changes relevant in understanding vascular contributions to cognitive impairment and dementia.

Background: Carotid ultrasound is convenient and widely used for CVD risk assessment. Plaques—especially in the internal carotid artery (ICA) or bulb—predict atherosclerotic cardiovascular disease (ASCVD) events, but plaque burden alone may miss vascular vulnerability or microvascular disease; additional biomarkers are needed to refine risk prediction. Hypothesis: We hypothesized that coronary artery calcium score (CACS) and a deep learning–based retinal biomarker (Dr.Noon CVD) would each associate with carotid plaque and predict ASCVD events, independently and in combination. Methods: We analyzed 1,075 high-risk adults from the CMERC-HI cohort with carotid ultrasound, CACS, and Dr.Noon CVD scores. Plaque was defined as any ICA/bulb lesion. ASCVD events (nonfatal or fatal) included stroke, heart failure, and myocardial infarction, and cardiovascular deaths. Age- and sex-adjusted logistic regression assessed associations of plaque with CACS (low: 0; moderate: 1–99; high: 100-400, very high: ≥400) and Dr.Noon CVD (low: &lt;31; moderate: 31-40; high: 41-50; very high: ≥51). For ASCVD event prediction, Cox models compared high and very high vs. low+moderate for CACS and Dr.Noon CVD, and plaque presence vs. absence. Performance was evaluated using hazard ratios (HRs), C-indices, and Kaplan–Meier curves. Results: Plaque was present in 719 (66.8%) participants. Over 8.8 years (median), 72 ASCVD events occurred. Incidence rates ranged from 0–14.6 per 1,000 PYs (Dr.Noon CVD), 2.6–19.7 per 1,000 PYs (CACS), and 5.6–9.3 per 1,000 PYs (plaque). Each 1-point Dr.Noon CVD increase was associated with plaque (OR 1.06; 95% CI 1.04–1.08; p&lt;0.001). Participants at moderate, high, and very high Dr.Noon CVD risk had ORs of 2.21, 3.71, and 7.01 for plaque (all p&lt;0.001). Similar trends were seen for CACS: moderate, high, and very high categories had ORs of 2.65, 3.91, and 5.17, respectively (all p&lt;0.001). In Cox models, the C-index was 0.680 for Dr.Noon CVD, 0.676 for CACS, and 0.661 for plaque alone. Combining plaque with Dr.Noon CVD or with CACS improved the C-index by Δ +0.060 and +0.038 versus plaque only (both p&lt;0.001). Kaplan–Meier curves confirmed clear risk stratification (log-rank p&lt;0.001). Conclusion: Dr.Noon CVD and CACS each associate with carotid plaque and predict ASCVD events. The greatest improvement in discrimination occurred when combining Dr.Noon CVD with plaque, underscoring its potential for practical vascular risk stratification.

Introduction: Standard cardiovascular testing relies primarily on medical history and coronary imaging, which may fail to detect the full extent of systemic vascular disease. Using AI in non-coronary vascular blood vessel areas, such as the carotid, aortic, and peripheral systems, may offer a thorough investigation and provide a better understanding of one's risk. Currently, manual assessments require a significant amount of time, and the varying interpretations of different experts often influence their accuracy. Hypothesis: Applying AI to the automated analysis of imaging for vascular diseases across multiple territories yields more accurate predictions of major adverse cardiovascular events than traditional risk scores and image analysis from a single area. Methods: Using PRISMA standards, we searched a range of databases (from 2018 to 2024) for studies focused on AI algorithms in non-coronary vascular imaging. Two researchers evaluated the studies and pulled out the information on predicting cardiovascular death, heart attack and stroke. Secondary outcomes included measuring the frequency with which each test produces the same result, assessing the time required for processing, and evaluating how well they correlate with established vascular biomarkers. A review of study quality was conducted using the QUADAS-2 and NOS. Results: All 23 selected studies (n = 28,894) found that AI-enhanced analysis of vascular parameters consistently predicted risk more accurately than traditional risk scales. Measurements of carotid thickness and stiffness of the aorta and arteries of the legs were highly reproducible and required much less analysis time using automation. Authors across various studies found that models using data from multiple areas performed better than models trained solely on one area. Conclusion: This analysis demonstrates that AI features in the automated analysis of imaging from multiple locations outside the heart enhance both the accuracy and efficiency of cardiovascular risk estimation. It enables thorough surveying of the vascular system for precision cardiology.

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment, yet limited research has been conducted in subtropical regions of China. Objective To examine the characteristics of cognitive impairment and identify the potential risk factors in patients with T2DM in Xiamen. Methods This cross-sectional observational study included 84 patients with T2DM from Zhongshan Hospital Xiamen University. Patients were grouped based on their Montreal Cognitive Assessment (MoCA) scores into a cognitively impaired group (T2DM-CI group, n = 52) and a cognitively normal group (T2DM-NCI group, n = 32). Multivariate logistic regression was used to identify independent risk factors. Results Among the 52 patients in the T2DM-CI group, the most commonly affected cognitive domains were executive function (82.7%), language (75.0%), memory (61.5%), and attention (48.1%), with 59.6% exhibiting impairments in three or more domains. Compared with the T2DM-NCI group, the T2DM-CI group showed poorer performance in most MoCA subdomains—including visuospatial/executive function, language, delayed recall, abstraction, and orientation—as well as in individual cognitive domain tests (all P &lt; 0.05), except for the Clock Drawing Test. Older age (OR = 1.167, 95% CI [1.045–1.303], P = 0.006) and higher lipoprotein (a) levels (OR = 1.109, 95% CI [1.020–1.205], P = 0.015) were independently associated with cognitive impairment in T2DM patients. Conclusion Cognitive impairment in T2DM affects multiple domains, with executive dysfunction most prominent. Age and elevated lipoprotein(a) may increase risk. Routine cognitive screening is warranted, particularly in older patients and those with vascular risk factors.

Background/Objectives: Cerebral small vessel disease (cSVD) and vascular cognitive impairment (VCI) are major contributors to stroke and dementia. Despite their importance, there are few effective treatments for cSVD and VCI. Variability in cSVD/VCI populations, intervention targets, and outcome selection may contribute to inconsistencies and challenges in clinical trial design. We reviewed the design of cSVD and VCI clinical trials to describe current practice in the selection of populations, interventions, and outcomes. Methods: We systematically searched Ovid Medline, Embase, and PsychInfo databases for recently completed cSVD/VCI trials and searched online trial registries (ClinicalTrials.gov, European Union Clinical Trials Register, and International Clinical Trials Registry Platform) for ongoing cSVD/VCI trials. We determined the use of specific categories of inclusion and exclusion criteria, interventions, and outcomes in the included trials and described these as counts and percentages. Results: We included a total of 82 cSVD trials and 120 VCI trials. Neuroimaging features were most frequently used as inclusion criteria for cSVD (88%) and cognition for VCI (88%). There was substantial variation in eligible ages for participation. Both cSVD and VCI trials largely excluded patients with comorbidities, vascular risk factors, and neuropsychiatric disorders, with a notable proportion of cSVD trials excluding on the basis of functional impairment. The most studied intervention classes were repurposed cardiovascular drugs (40%) for cSVD and Traditional Chinese Medicine (35%) in VCI. The most common primary outcome category was neuroimaging for cSVD (53%) and cognition for VCI (86%). Notably, functional outcomes were underused in both cSVD and VCI trials (13% and 12%, respectively, for primary outcomes). Conclusions: We have identified substantial variability in all aspects of cSVD and VCI clinical trial design. Inconsistent neuroimaging criteria and exclusions based on common long-term conditions limit the generalisability of findings. There is a need for greater focus on clinical outcomes, particularly functional ability, to better reflect treatment impact. Increased integration and standardisation of cSVD and VCI trial design is needed to accelerate progress in developing treatments.

Introduction: Extravascular implantable cardioverter defibrillators (EV-ICD) utilize a substernal lead to provide the benefits of ICDs without associated vascular risks. Only a few currently exist, and one such is the Aurora EV-ICD TM (Medtronic, Minneapolis, MN). Device-related, real-world complication data remains limited. Objectives: We reviewed the United States Food and Drug Manufacturer and User Facility Device Experience (MAUDE) database for adverse events involving the Aurora EV-ICD. Methods: The MAUDE database is a real-world registry of device-related adverse events. We reviewed this on 6/4/2025 for all events since 10/1/2023 – shortly after it was approved for use. Duplicate reports were removed, and adverse events and device issues were categorized and analyzed. Results: A total of 215 reports were identified, with an average age of 48.3±16.8 years and 75.0% male gender. Adverse events were analyzed as device- and patient-related. The most common device problem was sensing issues (40.4%), which included over- (11.1%) and under-sensing (2.3%); adverse events without an identified problem also occurred frequently (30.7%). The most common patient events occurred without clinical signs or symptoms (35.3%) but were followed by infection (37.3%) and inappropriate shocks (24.7%). This resulted in injury in 77.7% of cases, with death occurring in rare (1.9%) cases. Conclusion: EV-ICDs are an alternative defibrillator option but have shown notable early challenges, including frequent sensing issues, inappropriate shocks, and a high rate of infections. These findings underscore the need for careful patient selection and follow-up. However, the reliance on the MAUDE limits generalizability, and further studies are needed to evaluate its safety and efficacy.

Background: Insulin resistance is central to metabolic dysfunction and a recognized risk factor for cardiovascular disease. Surrogate markers of insulin sensitivity, such as estimated glucose disposal rate (eGDR), derived from routine clinical variables, have gained attention for vascular risk stratification. Although multiple studies across diverse populations suggest an association between lower eGDR and stroke risk, the magnitude and consistency of this relationship remain uncertain. Hypothesis: We hypothesized that lower eGDR reflecting higher insulin resistance is associated with an increased risk of stroke, and that this inverse relationship would remain consistent across populations stratified by age and diabetes status. Methods: We systematically searched PubMed, Scopus, and Cochrane through May 2025 for studies evaluating the association between eGDR and stroke. Hazard ratios (HRs) were pooled using a random-effects model. Heterogeneity was assessed using the I 2 statistic, and leave-one-out sensitivity analysis was performed. Subgroup analyses were conducted by diabetes status and age group (&lt;60/65 vs ≥60/65 years). Publication bias was assessed using the Luis Furuya-Kanamori (LFK) index. Results: Of 158 studies found on initial screening, 4 observational studies with a total population of 485,382 were included in the meta-analysis. Pooled analysis showed that individuals with higher eGDR had significantly lower risk of stroke (HR 0.52, 95% CI 0.36-0.74; P &lt; 0.01). Heterogeneity was high (I 2 = 89.9%), but leave-one-out analysis confirmed the stability of our results. Subgroup analysis by diabetes status revealed consistent inverse associations in both diabetic (HR 0.82, 95% CI 0.79-0.86) and non-diabetic populations (HR 0.78, 95% CI 0.67-0.92), with no significant interaction (P = 0.54). Similarly, inverse associations were observed in both younger (&lt;60/65 years: HR 0.81, 95% CI 0.78-0.84) and older (≥60/65 years: HR 0.83, 95% CI 0.75-0.92) subgroups, with no significant subgroup difference (P = 0.66). The LFK index (-1.32) suggested minor asymmetry, indicating no major publication bias. Conclusion: Lower eGDR is significantly associated with increased stroke risk across age groups and diabetic status. These findings support the role of insulin sensitivity, as captured by eGDR, in stroke risk assessment. Incorporating eGDR into routine clinical evaluation may improve identification of high-risk individuals and inform targeted prevention strategies.

Background: Dysglycemia is a well-established risk factor for cognitive decline. The association of long-term glucose control with early neuroimaging markers of dementia remains largely unexplored. Hypothesis: Higher visit-to-visit variability in glucose and HbA1c, indicating worse glucose control, are associated with lower total and regional gray matter volume (GMV) and higher white matter hyperintensity (WMH) volume. Methods: Fasting glucose (FG) was measured in MESA participants at Exam 1 (2000–02) and each of 5 follow-up exams through Exam 6 (2016-18), and HbA1c was measured at Exam 2 (2002–04), Exam 5 (2010–12), and Exam 6. We calculated intraindividual variability in FG and HbA1c as the SD (SD FG ; SD A1c ), average real variability (ARV FG ; ARV A1c ), and variability independent of the mean (VIM FG ; VIM A1c ) through Exam 6. Total and regional GMV and WMH volume were assessed by 3T brain MRI (2017-22). We report the SD difference in GMV and log-unit difference in WMH volume per two-fold increment in glucose or HbA1c variability with 95% CI from multivariable linear regression models adjusted for total intracranial volume, study site, age, sex, race/ethnicity, education, vascular risk factors, and APOE ε4 allele status. Results: A total of 1,424 Exam 6 participants (mean (SD) age 72 (8) yrs; 46% men; 28% with diabetes at Exam 6) had ≥3 FG measurements (mean: 5.9 measurements) and MRI data. Two-fold increments of SD FG , ARV FG , and VIM FG were associated with –0.08 (–0.11, –0.06), –0.09 (–0.12, –0.06), and –0.10 (–0.14, –0.06) SD differences in total GMV and 0.13 (0.06, 0.19), 0.13 (0.06, 0.20), and 0.16 (0.05, 0.26) log-unit differences in WMH volumes, respectively (Table 1). Associations appeared strongest with frontal lobe GMV. Further adjustment for mean FG through Exam 6 only modestly attenuated results. In 839 participants with 3 HbA1c measurements, two-fold increments of SD A1c , ARV A1c , and VIM A1c were associated with –0.20 (–0.30, –0.10), –0.77 (–1.20, –0.38), and –0.26 (–0.39, –0.12) SD differences in total GMV and 0.3 (0.04, 0.55), 1.40 (0.38, 2.3), and 0.36 (0.02, 0.70) log-unit differences in WMH volumes, respectively (Table 2). Neither glucose nor HbA1c variability were associated with temporal lobe or hippocampal volumes. Associations did not differ by diabetes status. Conclusion: Higher variability of glucose and HbA1c over 16–18 years were associated with lower GMV and higher WMH volumes in a diverse, community dwelling sample of older adults.

Background: Aβ1-42 and APOE concentrations, as well as Aβ42/40 ratio, may be considered as a link between hypertension (HTN) or diabetes mellitus (DM), brain amyloidosis, and dementia. HTN and DM are associated with cognitive impairment and may contribute to the development of Alzheimer’s disease (AD). This preliminary study aimed to evaluate the impact of vascular risk factors on the concentration of biochemical AD markers and cognitive state. As it is a cross-sectional study in nature, causal relationships cannot be established. Methods: The study was conducted in the south of Poland among a rural population over 65 years of age. A total of 58 patients qualified into the study were divided into groups according to the presence of HTN (n = 18) or HTN coexisting with DM (n = 40). A healthy control group was also formed (n = 20), resulting in 78 study participants. The study population was also divided based on M-ACE results, forming a normal cognition group (NC) and a deteriorated cognition group (DC). Biochemical tests, neurological scales assessments, and ultrasound examinations were conducted. Results: Patients who scored in the normal range on the M-ACE had higher Aβ1-42 (median 38.52 vs. 27.35 pg/mL, p = 0.02) and apoE concentrations (median 125.0 vs. 65.73 μg/mL, p = 0.002), and a higher Aβ42/40 ratio (median 0.39 vs. 0.29 p &lt; 0.000) compared to the DC group. Considering the study groups, the highest Aβ42/40 ratio was found among the HC group (median 0.47). The median score for the M-ACE scale was 3 points lower when HTN and DM coexisted, compared to the sole diagnosis of HTN (25 points and 28 points, respectively). A higher number of years of education correlated with better M-ACE results. Lipid and uric acid concentrations were not related to M-ACE or MMSE scores. An inverse relationship connected Aβ1-40 and Aβ1-42 to BMI, the duration of HTN treatment, and glycated hemoglobin. Conclusions: Aβ1-42, APOE, and Aβ42/40 are not only correlated with cognition but also related to patient’s disease profile. The coexistence of DM and HTN was associated with the most significant decline in cognitive functioning. However, a higher number of years of education may protect against the development of dementia in old age. The roles of cholesterol and uric acid in cognitive decline are still inconclusive.

Rationale: Pulmonary hypertension is a serious cardiopulmonary complication of sickle cell disease, but the prognostic impact of hemodynamic parameters remains poorly defined. Objectives: This study aimed to assess the clinical and long-term prognostic relevance of hemodynamic parameters in sickle cell disease. Methods: Data were analyzed from the French ETENDARD cohort. All 398 participants underwent echocardiography; those with tricuspid regurgitation velocity ⩾2.5 m/s proceeded to right heart catheterization. Over a minimum 10-year follow-up, we examined the clinical and prognostic significance of hemodynamic variables. Measurements and Main Results: Pulmonary hypertension defined by a mean pulmonary arterial pressure (mPAP) >20 mm Hg was identified in 44 patients (11%). Among them, 26 (6.5%) had a pulmonary arterial wedge pressure ⩽15 mm Hg, and 18 (4.5%) had a pulmonary arterial wedge pressure >15 mm Hg. Mortality during follow-up was 11.1%. A significant association was found between pulmonary vascular resistance (PVR) levels and mortality risk, with a threshold identified at 1.5 Wood units (WU) through receiver operating characteristic curve analyses. In patients with mPAP >20 mm Hg and PVR ⩾1.5 WU, the adjusted hazard ratio for mortality was 4.27 (95% confidence interval, 1.88-9.74; P < 0.001). A hemolytic phenotype and the presence of systemic complications, including hypertension, left ventricular diastolic dysfunction, renal impairment, and leg ulcers, were associated with elevated PVR and increased mortality risk. Conclusions: A PVR threshold of 1.5 WU emerges as a key predictor of mortality in patients with an mPAP above 20 mm Hg, particularly when assessed in conjunction with markers of hemolysis and systemic complications.

Seizure outcome and anti-seizure medication use in post-stroke epilepsy: A retrospective cohort study.