Stroke Cohort Research Articles

Interleukin-6, Diabetes, and Metabolic Syndrome in a Biracial Cohort: The Reasons for Geographic and Racial Differences in Stroke Cohort.

Black Americans have a greater risk of type 2 diabetes than White Americans. The proinflammatory cytokine interleukin-6 (IL-6) is implicated in diabetes pathogenesis, and IL-6 levels are higher in Black individuals. This study investigated associations of IL-6 with incident diabetes and metabolic syndrome in a biracial cohort. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White adults age ≥45 years in 2003-2007, with a follow-up ∼9.5 years later. Baseline plasma IL-6 was measured in 3,399 participants at risk of incident diabetes and 1,871 at risk of metabolic syndrome. Relative risk (RR) by IL-6 was estimated with modified Poisson regression for both groups. Incident diabetes occurred in 14% and metabolic syndrome in 20%; both rates rose across IL-6 quartiles. There was a three-way interaction of IL-6, race, and central adiposity for incident diabetes (P = 8 × 10-5). In Black participants with and without central adiposity, RRs were 2.02 (95% CI 1.00-4.07) and 1.66 (1.00-2.75) for the fourth compared with first IL-6 quartile, respectively. The corresponding RRs were 1.73 (0.92-3.26) and 2.34 (1.17-4.66) in White participants. The pattern was similar for IL-6 and metabolic syndrome. Although IL-6 was higher in Black than in White participants and those with central adiposity, the association of IL-6 with diabetes risk was statistically significant only among White participants without central adiposity. The association with metabolic syndrome risk was similarly stronger in low-risk groups. The results support the concept of interventions to lower inflammation in diabetes prevention, but to reduce race disparities, better biomarkers are needed.

Infection, Inflammation, and Poststroke Cognitive Impairment.

Infection and inflammation are dementia risk factors in population-based cohorts; however, studies in stroke are scarce. We determined the prevalence of infection after stroke and routinely measured inflammatory biomarkers during hospitalization and their associations with acute and 6-month cognitive impairment. A prospective stroke cohort completed the Oxford Cognitive Screen at ≤2 weeks and 6 months after stroke. Infection, inflammatory markers (C-reactive protein, white cell count, and neutrophil/lymphocyte ratio), and systemic inflammatory response syndrome were ascertained throughout admission with electronic patient records supplemented by hand searches. Associations with acute and 6-month global and domain-specific cognitive impairment were analyzed using multivariable regression, adjusting for demographic/vascular factors and stroke severity. Among 255 patients (mean age, 73.9 [SD, 12.6] years; 46.3% women; mean education, 12.6 [SD, 3.7] years; median National Institutes of Health Stroke Scale score 5 [range, minimum-maximum, 0-30]), infection was present in 90 patients (35.3%) at mean 4.4 (SD, 6.9) days after stroke, consisting predominantly of pneumonia (47/90; 52%) and urinary tract infection (39/90; 43%). Admission white cell count was elevated in 25.1% (n=64; mean, 9.5×109/L [SD, 3.2×109/L]), C-reactive protein in 41.2% (n=105; mean, 27.5 [SD, 50.9 mg/L]), neutrophil/lymphocyte ratio in 55.7% (n=97; mean, 5.5 [SD, 4.5]), and systemic inflammatory response syndrome in 26.6% (n=53 [45.2%] positive during hospitalization). Infection was associated with acute and 6-month poststroke cognitive impairment (P<0.05adj) with stronger associations acutely for severe infection (infection+systemic inflammatory response syndrome; P=0.03adj). Acute language, executive function and attention domain impairments, and 6-month number processing impairment were associated with infection (P<0.05adj). No significant relationships were found for any biomarker and cognitive impairment. Infection and elevations in routinely measured inflammatory biomarkers are common following stroke; however, only infection is associated with poststroke cognitive impairment, suggesting that increases in these biomarkers may be nonspecific. Infection may present a tractable target for reducing poststroke cognitive impairment.

Plasma proenkephalin A and incident chronic kidney disease and albuminuria in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort

BackgroundPlasma proenkephalin A (PENK-A) is a precursor of active enkephalins. Higher blood concentrations have been associated with estimated glomerular filtration rate (eGFR) decline in European populations. Due to the significant disparity in incident chronic kidney disease (CKD) between White and Black people, we evaluated the association of PENK-A with incident CKD and other kidney outcomes among a biracial cohort in the U.S.MethodsIn a nested cohort of 4,400 participants among the REasons for Geographic And Racial Differences in Stroke, we determined the association between baseline PENK-A concentration and incident CKD using the creatinine-cystatin C CKD-EPI 2021 equation without race coefficient, significant eGFR decline, and incident albuminuria between baseline and a follow-up visit 9.4 years later. We tested for race and sex interactions. We used inverse probability sampling weights to account for the sampling design.ResultsAt baseline, mean (SD) age was 64 (8) years, 49% were women, and 52% were Black participants. 8.5% developed CKD, 21% experienced ≥ 30% decline in eGFR and 18% developed albuminuria. There was no association between PENK-A and incident CKD and no difference by race or sex. However, higher PENK-A was associated with increased odds of progressive eGFR decline (OR: 1.12; 95% CI 1.00, 1.25). Higher PENK-A concentration was strongly associated with incident albuminuria among patients without diabetes mellitus (OR:1.29; 95% CI 1.09, 1.53).ConclusionWhile PENK-A was not associated with incident CKD, its associations with progression of CKD and incident albuminuria, among patients without diabetes, suggest that it might be a useful tool in the evaluation of kidney disease among White and Black patients.

Denoising task-correlated head motion from motor-task fMRI data with multi-echo ICA.

Motor-task functional magnetic resonance imaging (fMRI) is crucial in the study of several clinical conditions, including stroke and Parkinson's disease. However, motor-task fMRI is complicated by task-correlated head motion, which can be magnified in clinical populations and confounds motor activation results. One method that may mitigate this issue is multi-echo independent component analysis (ME-ICA), which has been shown to separate the effects of head motion from the desired blood oxygenation level dependent (BOLD) signal but has not been tested in motor-task datasets with high amounts of motion. In this study, we collected an fMRI dataset from a healthy population who performed a hand grasp task with and without task-correlated amplified head motion to simulate a motor-impaired population. We analyzed these data using three models: single-echo (SE), multi-echo optimally combined (ME-OC), and ME-ICA. We compared the models' performance in mitigating the effects of head motion on the subject level and group level. On the subject level, ME-ICA better dissociated the effects of head motion from the BOLD signal and reduced noise. Both ME models led to increased t-statistics in brain motor regions. In scans with high levels of motion, ME-ICA additionally mitigated artifacts and increased stability of beta coefficient estimates, compared to SE. On the group level, all three models produced activation clusters in expected motor areas in scans with both low and high motion, indicating that group-level averaging may also sufficiently resolve motion artifacts that vary by subject. These findings demonstrate that ME-ICA is a useful tool for subject-level analysis of motor-task data with high levels of task-correlated head motion. The improvements afforded by ME-ICA are critical to improve reliability of subject-level activation maps for clinical populations in which group-level analysis may not be feasible or appropriate, for example, in a chronic stroke cohort with varying stroke location and degree of tissue damage.

Association of Healthy Lifestyle and Incident Polypharmacy

BackgroundPolypharmacy, commonly defined as taking ≥5 medications, is an undesirable state associated with lower quality of life. Strategies to prevent polypharmacy may be an important priority for patients. We sought to examine the association of healthy lifestyle, a modifiable risk factor, with incident polypharmacy. MethodsWe performed a secondary analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study, including 15,478 adults aged ≥45 years without polypharmacy at baseline. The primary exposure was healthy lifestyle at baseline as measured by the Healthy Behavior Score (HBS), a cumulative assessment of diet, exercise frequency, tobacco smoking, and sedentary time. HBS ranges from 0-8, whereby 0-2 indicates low HBS, 3-5 indicates moderate HBS, and 6-8 indicates high HBS. We used multinomial logistic regression to examine the association between HBS and incident polypharmacy, survival without polypharmacy, and death. ResultsHigher HBS (i.e., healthier lifestyle) was inversely associated with incident polypharmacy after adjusting for sociodemographic and baseline health variables. Compared with participants with low HBS, those with moderate HBS had lower odds of incident polypharmacy (odds ratio [OR] 0.85; 95% confidence interval [CI], 0.73-0.98) and lower odds of dying (OR 0.74; 95% CI, 0.65-0.83). Participants with high HBS had even lower odds of both incident polypharmacy (OR 0.75; 95% CI, 0.64-0.88) and death (OR 0.62; 95% CI, 0.54-0.70). There was an interaction for age, where the association between HBS and incident polypharmacy was most pronounced for participants aged ≤65 years. ConclusionsHealthier lifestyle was associated with lower risk for incident polypharmacy.

Development and Validation of a New Nomogram Model for Predicting Acute Ischemic Stroke in Elderly Patients with Non-Valvular Atrial Fibrillation: A Single-Center Cross-Sectional Study.

Non-valvular atrial fibrillation (NVAF) patients face a 3-5 times greater risk of acute ischemic stroke (AIS) compared to those without NVAF. This study aims to establish a novel clinical prediction model for AIS in elderly patients with NVAF by incorporating relevant biomarker indicators. A total of 301 individuals diagnosed with NVAF were selected for this investigation at the Third Affiliated Hospital of Anhui Medical University. Based on the presence of AIS, patients were categorized into two groups: the Stroke Cohort and the Non-Stroke Cohort. Predictor screening was performed using the least absolute shrinkage and selection operation (LASSO) regression algorithm. The binary logistic regression equation was applied to fit the model, followed by internal validation using the bootstrap resampling method (1000 times). Receiver operating characteristic (ROC) curve, calibration degree curve plots, and clinical decision curve analysis (DCA) were generated, respectively. Finally, a nomogram was constructed to present the prediction model. The final results of this study revealed that neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), lipoprotein(a) (Lp(a)), systolic pressure, history of stroke, hyperlipidemia were independent risk factors for AIS in elderly patients with NVAF (P<0.05). And the high-density lipoprotein cholesterol (HDL-C) was an independent protective factor (P<0.05). By incorporating these indicators, a nomogram prediction model for predicting AIS in elderly patients with NVAF was constructed. Comparative analysis between the nomogram predictive model and CHA2DS2-VASc score revealed that the AUC of the nomogram predictive model surpassed that of the CHA2DS2-VASc score (AUC: 0.881vs 0.850). NLR, RDW, Lp(a), SP, history of stroke, hyperlipidemia, and HDL-C emerge as independent prognostic factors for acute ischemic stroke in elderly patients with non-valvular atrial fibrillation. The predictive utility of the nomogram model may potentially surpass that of the CHA2DS2-VASc scoring system.

Social and clinical vulnerability in stroke and STEMI management during the COVID-19 pandemic: a registry-based study

ObjectiveThis study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment...

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry

BackgroundA recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway ‘concept’ on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry. Methods and resultsThis analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan–Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway.We studied 2513 patients [median (IQR) age 71 (62–78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6–75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37–0.99), as well as a lower risk of MACE (HR: 0.59; 0.39–0.88) and death (aHR: 0.22; 95 %CI: 0.12–0.41). ConclusionFull adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

Reduced physical activity level was associated with poorer quality of life during the early phase of the COVID-19 pandemic: a sub-study of the last-long trial.

To assess how physical activity levels changed in a stroke cohort during the COVID-19 (SARS-CoV-2) pandemic, and how these changes were associated with quality of life (QoL). Between March and July 2021, 150 patients with stroke already included in the Life after Stroke (LAST-long) trial in Norway were invited to participate in this cross-sectional survey. Participants were asked to complete a questionnaire assessing changes in physical activity and self-reported health following the pandemic. Univariate and multivariate logistic regression analyses were used to explore the association between physical activity, loneliness, mental health, social activity and QoL. In all, 118 (79%) participants completed the questionnaire. A total of 80 (68%) reported less physical activity, 46 (39%) felt lonelier, and 43 (37%) reported worse mental health, while 50 (42%) reported reduced QoL compared with before the lockdown. In the univariate analyses less physical activity, feeling lonelier and changes in mental health were associated with reduced QoL. In the multivariate analysis only less physical activity odds ratio (OR) = 4.04 (95% confidence interval (95% CI) 1.44-11.34, p = 0.008) was significantly associated with reduced QoL. More than two-thirds of patients with stroke reported reduced physical activity during the COVID-19 pandemic, and less physical activity was strongly associated with reduced QoL.

Accordance to a MIND–Style Diet is Associated with Decreased Risk of Dementia Mortality in the REasons for Geographic and Racial Disparities in Stroke (REGARDS) Cohort

AbstractBackgroundThe Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet (high in nuts, seeds, vegetables, berries and low in meat, dairy, and butter) has been associated with reduced risk of dementia. However, no studies have examined the role of the MIND diet in a racially diverse population nor have there been studies that have examined the association of the MIND diet with dementia mortality.MethodWe examined data from Black and White adults (age 45‐98) in the US‐based REGARDS cohort. Dietary and covariate data were collected at baseline (2002‐2007). MIND diet score was created as described by other cohort studies (Table footnote). The primary outcome was dementia‐related mortality through December 31, 2020 from the National Death Index using ICD‐10 codes F00‐F03, G30, G31.0‐G31.1, and R54. Cox proportional hazards regression was used to model MIND diet score (in tertiles and as a continuous variable) and time to dementia death. To ensure robust association across sub‐groups, we tested for interactions of MIND diet with sex, race, age, obesity, history of stroke, and baseline cognitive impairment and adjusted for competing risks.ResultA total of 18,277 participants (mean age 64.9) had dietary data available to calculate the MIND diet score. MIND diet score was higher among females compared with males, White compared with Black participants, and college graduates. There were no differences in accordance by age. After a median of 12 years, participants with the highest MIND diet scores had the lowest risk of dementia death HR = 0.78 {95% CI; (0.66, 0.94)} comparing the 3rd tertile with the 1st tertile and after adjustment for age, race, sex, income, education, total energy, and other medical conditions (Table). This association was attenuated slightly when a competing risk analysis was considered HR = 0.84 {95%CI; (0.70, 1.00)}. There were no significant interactions observed.ConclusionThe MIND diet score is associated with dementia death in a large bi‐racial cohort in the US. This association is robust across race, age, and sex groups. Dietary interventions using the MIND diet may further clarify whether this association is causal and whether MIND diet may be an important tool in reducing rates of dementia.

Prevalence and prognosis of acute ischemic stroke coexisting with unruptured intracranial aneurysms.

The prevalence of unruptured intracranial aneurysms (UIAs) in the acute ischemic stroke (AIS) cohort is probably higher than in the general population. This study investigated the prevalence of UIAs in AIS patients and the management risk and prognosis when treating AIS. From January 2020 to January 2023, we conducted a single-center retrospective study at Tianjin Huanhu Hospital. Each patient underwent both brain MRI and MRA/CTA to diagnose AIS and UIAs. Clinical, radiologic, and therapeutic data during hospitalization and prognosis were analyzed. Propensity-score matching (PSM) was performed to evaluate the risk of in-hospital adverse events, unfavorable outcomes at discharge when receiving post-stroke treatment and stroke recurrence. In all, 2,181 AIS patients were included, of whom 270 had UIAs (12.4%; 95%CI 11.0-13.8%). From the unmatched and matched cohort, the incidence of in-hospital adverse events and unfavorable outcomes at discharge in patients with UIAs were not significantly different; the risk of stroke recurrence was significantly higher in patients with UIAs than in those without (unmatched: aHR, 1.71 [1.08-2.70]; matched: aHR, 2.55 [1.16-5.58]). Multivariable Cox regression models showed that aneurysm size and the presence of homoregional infarction associated with higher risk of recurrence (unmatched: aHR, 1.31 [1.21-1.41] and aHR, 3.50 [1.52-8.10]; matched: aHR, 1.28 [1.18-1.40]; p < 0.001 and aHR, 3.71 [1.12-12.34]). The UIAs may not increase the risk of in-hospital adverse events and unfavorable outcomes at discharge in receiving post-stroke treatment, but it may associated with a high risk of stroke recurrence.

Validation of a German-language modified Rankin Scale structured telephone interview at 3 months in a real-life stroke cohort

BackgroundThe modified Rankin scale (mRS) at 3 months is established as the primary outcome measure in clinical stroke trials. Traditionally, the mRS is assessed through an unstructured face-to-face interview. This approach can be labor-intensive and lead to suboptimal inter-rater reliability. Recently, the Covid-19 pandemic made face-to-face contact even more challenging. To address these issues, we developed and validated a structured German-language questionnaire for mRS testing by telephone.MethodsIn this prospective cohort study, we compared the mRS testing results of the standard face-to-face interview with those obtained in a structured interview by telephone using Cohen’s Kappa.ResultsAt our tertiary care stroke center, we included 108 patients who underwent both assessments. In 80.6% of cases (87/108) face-to-face and telephone interview reached identical scores. Linear weighted Kappa was 0.82 (p < 0.001). Unweighted Kappa for dichotomized mRS between fair (0–2) and poor (3–6) functional outcome was κ = 0.97 (p < 0.001).ConclusionsOur study validates the use of the German-language structured telephone interview as a reliable instrument for the use in clinical trials. We encourage others to utilize the questionnaire. It is available as an Appendix (Additional file 1) to this publication.

Social Determinants of Health and Cardiologist Involvement in the Care of Adults Hospitalized for Heart Failure

Involvement of a cardiologist in the care of adults during a hospitalization for heart failure (HF) is associated with reduced rates of in-hospital mortality and hospital readmission. However, not all patients see a cardiologist when they are hospitalized for HF. To determine whether social determinants of health (SDOH) are associated with cardiologist involvement in the management of adults hospitalized for HF. This retrospective cohort study used data from the Reasons for Geographic and Racial Difference in Stroke (REGARDS) cohort. Participants included adults who experienced an adjudicated hospitalization for HF between 2009 and 2017 in all 48 contiguous states in the US. Data analysis was performed from November 2022 to January 2023. A total of 9 candidate SDOH, aligned with the Healthy People 2030 conceptual model, were examined: Black race, social isolation, social network and/or caregiver availability, educational attainment less than high school, annual household income less than $35 000, living in rural area, living in a zip code with high poverty, living in a Health Professional Shortage Area, and living in a state with poor public health infrastructure. The primary outcome was cardiologist involvement, defined as involvement of a cardiologist as the primary responsible clinician or as a consultant. Bivariate associations between each SDOH and cardiologist involvement were examined using Poisson regression with robust SEs. The study included 1000 participants (median [IQR] age, 77.8 [71.5-84.0] years; 479 women [47.9%]; 414 Black individuals [41.4%]; and 492 of 876 with low income [56.2%]) hospitalized at 549 unique US hospitals. Low annual household income (<$35 000) was the only SDOH with a statistically significant association with cardiologist involvement (relative risk, 0.88; 95% CI, 0.82-0.95). In a multivariable analysis adjusting for age, race, sex, HF characteristics, comorbidities, and hospital characteristics, low income remained inversely associated with cardiologist involvement (relative risk, 0.89; 95% CI, 0.82-0.97). This cohort study found that adults with low household income were 11% less likely than adults with higher incomes to have a cardiologist involved in their care during a hospitalization for HF. These findings suggest that socioeconomic status may bias the care provided to patients hospitalized for HF.

Predictive value of functional disability scales among stroke survivors: A long-term mortality evaluation in a Brazilian stroke cohort

ObjectiveTo assess the influence of two functional scales- Modified Rankin Scale (m-RS) and Modified Katz Index (m-Katz Index) on long-term mortality in a stroke cohort. Material and methodsAmong 760 stroke survivors (median age: 66 (IQR:56–75), 56.4 % women) m-Katz Index and m-RS scales applied at 1 and 6 months after stroke, were investigated in relation to 12-years of all-cause mortality. Kaplan–Meier survival curves were computed, and time-varying covariate Cox regression models were fitted to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) in all sample and by sex. The prognostic ability of the fitted models was computed for each model by six different measures. ResultsAfter 12 years of follow-up (median survival time: 7.3 years), 311 participants died. Overall survival curves show lower survival rates among those with the highest levels of disability/dependence (all log-rank p-values <0.0001). These findings were confirmed in all regression models for both sexes, particularly in men who had higher levels of dependence on Activities of Daily Living (ADLs) by m-Katz Index and severe disability by m-RS and presented the highest HR of dying (HR: 3.34 (95 %CI: 2.27–4.92) and HR: 4.94 (95 % CI: 3.15–7.75), respectively). ConclusionsBoth the m-Katz Index and the m-RS scale were good predictors of long-term mortality, which is of importance for guiding the functional rehabilitation of stroke patients. Besides, high levels of disability and dependence were implicated with high mortality risks, regardless of sex.

Patent foramen ovale: high-risk echocardiographic features related to secondary stroke prevention

Abstract Introduction Patent foramen ovale (PFO) closure has long been a matter of debate concerning the impact of such procedure on preventing ischemic events recurrence. Recent reports support this strategy raising the issue of optimal patient selection based on anatomical high-risk characteristics evaluated by transoesophageal echocardiography (TEE) that may be associated with an increased risk of recurrence. Purpose Characterize PFO-related echocardiographic findings and clinical features of a cohort of Embolic Stroke of Undetermined Source (ESUS) patients (pts). Methods Unicentric, retrospective analysis of pts with ESUS diagnosis who underwent TEE between 1/2014 and 11/2019. Excluded pts aged older than 70 years. Clinical stroke characteristics and echocardiographic PFO features were analysed. Results A total of 124 pts were included in the analysis, presenting a mean age of 50±1.6 [20;68] years and female gender predominance (58.9%). 48.4% of ESUS pts had PFO (53% female). Regarding PFO pts, 38 (62.3%) had significant right-to-left shunt on TEE, which was statistically associated with cortical infarcts (78.9 vs 56.5%,p=0.037). 35pts (58.3%) had shunt occurring at rest and during the Valsalva manoeuvre; when associated to significant shunt there was a correlation with cortical located infarcts (82.1 vs 60.0%, p&amp;lt;0.001). 33 PFOs (54.1%) had tunnel-like morphology. Tunnel-like PFOs were associated with significant right-to-left shunt (78.8 vs 42.9%, p&amp;lt;0.001), atrial septum aneurysm (ASA) presence (68.8 vs 50.0%, p&amp;lt;0.001) and with haemorrhagic transformation of ischemic stroke (15.2 vs 3.6%, p=0.031). 34 PFO pts (60.7%) had ASA. Mean PFO length was 6.42±5.0mm and mean height was 3.2±2.0mm. Conclusion In this cohort, there was a similar number of pts with and without PFO. Regarding ESUS pts with PFO, the majority had significant right-to-left shunt that occurred at rest and during Valsalva manoeuvre and were associated with cortical located infarcts. Tunnel-like morphology and ASA were also frequent. Tunnel-like morphology were associated with haemorrhagic transformation of ischemic strokes. These findings support the proposal that PFO characterization should have an additional role in stratifying pts with ESUS and selecting them for device closure.

Abstract 18607: Sex-specific Metabolites Associated With Incident Stroke, Incident Coronary Heart Disease, Hypertension, And Chronic Kidney Disease In The Regards Cohort

Sex disparities continue to exist in cardiometabolic diseases. Metabolomic profiling offers the ability to gain insight into disease mechanisms. The purpose of the present analysis was to identify metabolites associated with sex and determine if sex-specific metabolites are associated with incident stoke, incident coronary heart disease (CHD), hypertension (HTN), and chronic kidney disease (CKD). Targeted metabolomics was conducted for 358 metabolites in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Weighted logistic regression models were used to test the association between sex and metabolites. Metabolites meeting the Bonferroni-corrected threshold were selected for replication in the Hypertension Genetic Epidemiology Network study. Cox proportional hazard models were used to calculate hazard ratios (HRs) per unit standard deviation (SD) of each replicated metabolite with incident stroke and incident CHD. Weighted logistic regression models were used to calculate odds ratios (ORs) per unit SD of each replicated metabolite with prevalent HTN and prevalent CKD. A total of 1,898 individuals were included in the analysis and 50.47% of the sample was male sex. The mean age was 68.40 ± 10.55 years and 43% of the sample was Black race. Sixteen metabolites were associated with sex, meeting the Bonferroni-adjusted p-value of 1.4 x 10 -4 . These included 8 lipids, 6 amino acids, 1 indole, and 1 quinoline. Of these 16 metabolites, none were associated with incident stroke or incident CHD. Kynurenic acid and leucine were associated with HTN in the base model adjusting for age, sex, and race (kynurenic acid: OR 1.45, 95% CI [1.19, 1.76], p=2.36 x 10 -4 ; leucine: OR 1.41, 95% CI [1.14, 1.76], p=2.03 x 10 -3 ). Indole-3-lactic acid and kynurenic acid were associated with CKD in the full model adjusting for age, sex, race, smoking, alcohol use, and BMI (indole-3-lactic acid: OR 3.83, 95% CI [2.77, 5.29], p=5.93 x 10 -16 ; kynurenic acid: OR 6.63, 95% CI [4.67, 9.41], p=1.50 x 10 -25 ). Our findings shed light on the sexual dimorphism of the metabolome and suggest that differences in biochemical pathways may contribute to sex disparities in cardiometabolic disease risk.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network

ObjectiveWorse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations. Research design and methodsWe conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania. We measured NSEE with a z-score sum of six census tract indicators within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). Community type-stratified models evaluated the likelihood of new diagnoses of T2D in each study sample using restricted cubic splines and quartiles of NSEE. ResultsAcross study samples, worse NSEE was associated with higher risk of T2D. We observed significant effect modification by sex and age, though evidence of effect modification varied by site and community type. Largely, stronger associations between worse NSEE and diabetes risk were found among women relative to men and among those less than age 45 in the VADR cohort. Similar modification by age group results were observed in the Geisinger sample in small town/suburban communities only and similar modification by sex was observed in REGARDS in lower density urban communities. ConclusionsThe impact of NSEE on T2D risk may differ for males and females and by age group within different community types.

White Matter Hyperintensity Volume and Poststroke Cognition: An Individual Patient Data Pooled Analysis of 9 Ischemic Stroke Cohort Studies.

White matter hyperintensities (WMH) are associated with cognitive dysfunction after ischemic stroke. Yet, uncertainty remains about affected domains, the role of other preexisting brain injury, and infarct types in the relation between WMH burden and poststroke cognition. We aimed to disentangle these factors in a large sample of patients with ischemic stroke from different cohorts. We pooled and harmonized individual patient data (n=1568) from 9 cohorts, through the Meta VCI Map consortium (www.metavcimap.org). Included cohorts comprised patients with available magnetic resonance imaging and multidomain cognitive assessment <15 months poststroke. In this individual patient data meta-analysis, linear mixed models were used to determine the association between WMH volume and domain-specific cognitive functioning (Z scores; attention and executive functioning, processing speed, language and verbal memory) for the total sample and stratified by infarct type. Preexisting brain injury was accounted for in the multivariable models and all analyses were corrected for the study site as a random effect. In the total sample (67 years [SD, 11.5], 40% female), we found a dose-dependent inverse relationship between WMH volume and poststroke cognitive functioning across all 4 cognitive domains (coefficients ranging from -0.09 [SE, 0.04, P=0.01] for verbal memory to -0.19 [SE, 0.03, P<0.001] for attention and executive functioning). This relation was independent of acute infarct volume and the presence of lacunes and old infarcts. In stratified analyses, the relation between WMH volume and domain-specific functioning was also largely independent of infarct type. In patients with ischemic stroke, increasing WMH volume is independently associated with worse cognitive functioning across all major domains, regardless of old ischemic lesions and infarct type.

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening.

Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2-10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes.