Stroke Study Research Articles

Olanzapine-Induced Hypothermia: A Case Report in an Elderly Black Male Patient Diagnosed with Bipolar 1 Type Disorder

There are few reports that describe incidence of hypothermia in patients treated with olanzapine. We report a case of an elderly 83-year-old black male, readmitted to the state psychiatric hospital December 2023 due to psychiatric exacerbation after 6 months of successful discharge to community, who experienced a fall and profound hypothermia with bradycardia that resulted in a 10-day acute hospitalization in January 2024. Medical workup was unrevealing except for multivessel disease found on CT stroke study of the brain. When patient returned to inpatient psychiatric hospital, his psychiatric medications, including both quetiapine and olanzapine, were restarted at half the dose. The next morning, the patient was again hypotensive, bradycardic and hypothermic. For this patient, only the olanzapine was new upon the most recent admission, and thus this case report supports the other few reports already published, implicating olanzapine in the pharmacologic adverse effect of drug induced hypothermia.

Tenecteplase vs Alteplase for Patients With Acute Ischemic Stroke

Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited. To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset. The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement. Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg). The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality. Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]). In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting. ClinicalTrials.gov Identifier: NCT04915729.

Prehospital stroke detection scales: A head-to-head comparison of 7 scales in patients with suspected stroke.

Several prehospital scales have been designed to aid paramedics in identifying stroke patients in the ambulance setting. However, external validation and comparison of these scales are largely lacking. To compare all published prehospital stroke detection scales in a large cohort of unselected stroke code patients. We conducted a systematic literature search to identify all stroke detection scales. Scales were reconstructed with prehospital acquired data from two observational cohort studies: the Leiden Prehospital Stroke Study (LPSS) and PREhospital triage of patients with suspected STrOke (PRESTO) study. These included stroke code patients from four ambulance regions in the Netherlands, including 15 hospitals and serving four million people. For each scale, we calculated the accuracy, sensitivity and specificity for a diagnosis of stroke (ischemic, hemorrhagic or TIA). Moreover, we assessed the proportion of stroke patients who received reperfusion treatment with intravenous thrombolysis or endovascular thrombectomy that would have been missed by each scale. We identified 14 scales, of which seven (CPSS, FAST, LAPSS, MASS, MedPACS, OPSS, and sNIHSS-EMS) could be reconstructed. Of 3317 included stroke code patients, 2240 (67.5%) had a stroke (1528 ischemic, 242 hemorrhagic, 470 TIA) and 1077 (32.5%) a stroke mimic. Of ischemic stroke patients, 715 (46.8%) received reperfusion treatment. Accuracies ranged from 0.60 (LAPSS) to 0.66 (MedPACS, OPSS and sNIHSS-EMS), sensitivities from 66% (LAPSS) to 84% (MedPACS and sNIHSS-EMS), and specificities from 28% (sNIHSS-EMS) to 49% (LAPSS). MedPACS, OPSS and sNIHSS-EMS missed the fewest reperfusion-treated patients (10.3-11.2%), whereas LAPSS missed the most (25.5%). Prehospital stroke detection scales generally exhibited high sensitivity but low specificity. While LAPSS performed poorest, MedPACS, sNIHSS-EMS and OPSS demonstrated the highest accuracy and missed the fewest reperfusion-treated stroke patients. Use of the most accurate scale could reduce unnecessary stroke code activations for patients with a stroke mimic by almost a third, but at the cost of missing 16% of strokes and 10% of patients who received reperfusion treatment.

Associations among claims-based care fragmentation, self-reported gaps in care coordination, and self-reported adverse events

BackgroundFragmentation of care (that is, the use of multiple ambulatory providers without a dominant provider) may increase the risk of gaps in communication among providers. However, it is unclear whether people with fragmented care (as measured in claims) perceive more gaps in communication among their providers. It is also unclear whether people who perceive gaps in communication experience them as clinically significant (that is, whether they experience adverse events that they attribute to poor coordination).MethodsWe conducted a longitudinal study using data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, including a survey on perceptions of healthcare (2017–2018) and linked fee-for-service Medicare claims (for the 12 months prior to the survey) (N = 4,296). We estimated correlation coefficients to determine associations between claims-based and self-reported numbers of ambulatory visits and ambulatory providers. We then used logistic regression to determine associations between claims-based fragmentation (measured with the reversed Bice-Boxerman Index [rBBI]) and self-reported gaps in care coordination and, separately, between claims-based fragmentation and self-reported adverse events that the respondent attributed to poor coordination.ResultsThe correlation coefficient between claims-based and self-report was 0.37 for the number of visits and 0.38 for the number of providers (p < 0.0001 for each). Individuals with high fragmentation by claims (rBBI ≥ 0.85) had a 23% increased adjusted odds of reporting any gap in care coordination (95% CI 3%, 48%) and, separately, a 61% increased adjusted odds of reporting an adverse event that they attributed to poor coordination (95% CI 11%, 134%).ConclusionsMedicare beneficiaries with claims-based fragmentation also report gaps in communication among their providers. Moreover, these gaps appear to be clinically significant, with beneficiaries reporting adverse events that they attribute to poor coordination.

Differential efficacy of remote ischaemic conditioning in anterior versus posterior circulation stroke: A prespecified secondary analysis of the RICAMIS trial.

The benefit of remote ischaemic conditioning (RIC) in acute moderate ischaemic stroke has been demonstrated by the Remote Ischaemic Conditioning for Acute Moderate Ischaemic Stroke (RICAMIS) study. This prespecified exploratory analysis aimed to determine whether there was a difference of RIC efficacy in anterior versus posterior circulation stroke based on RICAMIS data. In this analysis, eligible patients presenting within 48 h of stroke onset were divided into two groups: anterior circulation stroke (ACS) and posterior circulation stroke (PCS) groups. The primary endpoint was an excellent functional outcome, defined as a modified Rankin Scale (mRS) score 0-1 at 90 days. In all, 1013 patients were included in the final analysis, including 642 with ACS and 371 with PCS. Compared with the control group, RIC was significantly associated with an increased proportion of mRS scores 0-1 within 90 days in the PCS group (unadjusted odds ratio 1.6, 95% confidence interval 1.0-2.4, p = 0.04; adjusted odds ratio 2.0, 95% confidence interval 1.2-3.3, p = 0.005), but not in the ACS group (p = 0.29). Similar results were found regarding secondary outcomes including mRS score 0-2 at 90 days, mRS distribution at 90 days and change in National Institutes of Health Stroke Scale score at day 12 from baseline. However, there was no significant interaction effect between stroke location and intervention on the primary outcome (pinteraction = 0.21). Amongst patients with acute PCS who are not candidates for reperfusion treatment, RIC may be associated with a higher probability of improved functional outcomes. These findings need to be validated in prospective trials.

The Aphasia Recovery Cohort, an open-source chronic stroke repository

Sharing neuroimaging datasets enables reproducibility, education, tool development, and new discoveries. Neuroimaging from many studies are publicly available, providing a glimpse into progressive disorders and human development. In contrast, few stroke studies are shared, and these datasets lack longitudinal sampling of functional imaging, diffusion imaging, as well as the behavioral and demographic data that encourage novel applications. This is surprising, as stroke is a leading cause of disability, and acquiring brain imaging is considered standard of care. The first release of the Aphasia Recovery Cohort includes imaging data, demographics and behavioral measures from 230 chronic stroke survivors who experienced aphasia. We also share scripts to illustrate how the imaging data can predict impairment. In conclusion, recent advances in machine learning thrive on large, diverse datasets. Clinical data sharing can contribute to improvements in automated detection of brain injury, identification of white matter hyperintensities, measures of brain health, and prognostic abilities to guide care.

Recent advances in Del Nido cardioplegia: A comprehensive analysis of randomized clinical trials in adult cardiac surgery.

Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: -6.01, 95% CI [-11.14, -0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: -537.17, 95% CI [-758.89, -315.45]), troponin T (MD: -1.71, 95% CI [-2.11, -1.32]), creatine phosphokinase-MB (MD: -2.96, 95% CI [-5.84, -0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Effect of salt substitution on fracture—a secondary analysis of the Salt Substitute and Stroke Study (SSaSS)

BackgroundAssociations of dietary sodium and potassium intake with fracture risk are inconsistent and the effects of salt substitute on fracture incidence are unknown. We assessed the effect of salt substitute compared to regular salt intake on fracture incidence using data from the Salt Substitute and Stroke Study (SSaSS).MethodsSSaSS was a cluster-randomized controlled trial conducted in 600 villages in northern China. Villages were randomly allocated into intervention and control groups in a 1:1 ratio. Salt substitute was provided to intervention villages and control villages continued regular salt use for 5 years. The primary outcome for this secondary analysis was the incidence of all fractures. Secondary outcomes included incidence of vertebral fracture, non-vertebral fracture, and fracture of unknown or non-specific location.Results20,995 participants were included in this study, and 821 fractures occurred during follow-up. Intention-to-treat analyses showed no differences between the salt substitute and regular salt groups in the incidence of all fractures (rate ratio (RR) 0.96; 95% CI 0.81 to 1.14), vertebral fracture (RR 0.82; 95% CI 0.53 to 1.26), non-vertebral fracture (RR 1.05; 95% CI 0.86 to 1.29), or fracture of unknown or non-specific location (RR 0.80; 95% CI 0.54 to 1.18).ConclusionsUse of salt substitute compared to regular salt had no detectable effect on the incidence of fracture in a population at high risk of cardiovascular disease and fracture.Trial registrationClinicalTrials.gov, NCT02092090. Registered on March 12, 2014.

Signaling roles of sphingolipids in the ischemic brain and their potential utility as therapeutic targets

Sphingolipids comprise a class of lipids, which are composed of a sphingoid base backbone and are essential structural components of cell membranes. Beyond their role in maintaining cellular integrity, several sphingolipids are pivotally involved in signaling pathways controlling cell proliferation, differentiation, and death. The brain exhibits a particularly high concentration of sphingolipids and dysregulation of the sphingolipid metabolism due to ischemic injury is implicated in consecutive pathological events. Experimental stroke studies revealed that the stress sphingolipid ceramide accumulates in the ischemic brain post-stroke. Specifically, counteracting ceramide accumulation protects against ischemic damage and promotes brain remodeling, which translates into improved behavioral outcome. Sphingomyelin substantially influences cell membrane fluidity and thereby controls the release of extracellular vesicles, which are important vehicles in cellular communication. By modulating sphingomyelin content, these vesicles were shown to contribute to behavioral recovery in experimental stroke studies. Another important sphingolipid that influences stroke pathology is sphingosine-1-phosphate, which has been attributed a pro-angiogenic function, that is presumably mediated by its effect on endothelial function and/or immune cell trafficking. In experimental and clinical studies, sphingosine-1-phosphate receptor modulators allowed to modify clinically significant stroke recovery. Due to their pivotal roles in cell signaling, pharmacological compounds modulating sphingolipids, their enzymes or receptors hold promise as therapeutics in human stroke patients.

Association between optic disc pallor and lacunar stroke

ObjectiveTo test for associations between optic disc pallor and two clinical variables: ischaemic stroke subtype (cortical and lacunar) and cerebral small vessel disease (SVD) scores in a cohort of hospital...

Wellbeing in stroke and aphasia (WISA): protocol for a feasibility study setting up an accessible service offering psychological therapy to people with post-stroke aphasia

Background and aimFollowing a stroke, around a quarter of people will have aphasia, a language disability. Aphasia can have a devastating long-term impact on a person’s psychological wellbeing, yet their language difficulties make it challenging to access mental health care. The Wellbeing In Stroke and Aphasia (WISA) study aims to evaluate the feasibility of setting up an accessible psychological service for people with aphasia.MethodsThe service will be open to people with post-stroke aphasia (n = 30) who live in the UK, are able to access the service either in the university clinic or via telehealth and are not currently receiving therapy from a mental health professional. Participants will be offered up to 8 therapy sessions over 6 months, either one-to-one, with family, or in a group. The intervention is Solution Focused Brief Therapy (SFBT), a brief psychological therapy, delivered by speech and language therapists with training in SFBT under the supervision of a stroke-specialist clinical psychologist. As part of this service, a protocol for addressing mental health care has been developed. Feasibility will be assessed by monitoring referral rates, therapy received, discharge processes, resource capability, costs, challenges, and adverse events. Patient-reported outcome measures collected pre and post intervention will assess mental wellbeing, mood, participation, and satisfaction with therapy and the service. A purposive sample will take part in in-depth interviews following therapy.DiscussionGiven the high levels of psychological distress in this client group, there is a need to investigate innovative ways to provide accessible and acceptable psychological support.

Profiling biomanufactured extracellular vesicles of human forebrain spheroids in a Vertical-Wheel Bioreactor.

Extracellular vesicles (EVs) secreted by human brain cells have great potential as cell-free therapies in various diseases, including stroke. However, because of the significant amount of EVs needed in preclinical and clinical trials, EV applicationis still challenging. Vertical-Wheel Bioreactors (VWBRs) have designed features that allow for scaling up the generation of human forebrain spheroid EVs under low shear stress. In this study, EV secretion by human forebrain spheroids derived from induced pluripotent stem cells as 3D aggregates and on Synthemax II microcarriers in VWBRs were investigated with static aggregate culture as a control. The spheroids were characterized by metabolite and transcriptome analysis. The isolated EVs were characterized by nanoparticle tracking analysis, electron microscopy, and Western blot. The EV cargo was analyzed using proteomics and miRNA sequencing. The in vitro functional assays of an oxygen and glucose-deprived stroke model were conducted. Proof of concept in vivo study was performed, too. Human forebrain spheroid differentiated on microcarriers showed a higher growth rate than 3D aggregates. Microcarrier culture had lower glucose consumption per million cells and lower glycolysis gene expression but higher EV biogenesis genes. EVs from the three culture conditions showed no differences in size, but the yields from high to low were microcarrier cultures, dynamic aggregates, and static aggregates. The cargo is enriched with proteins (proteomics) and miRNAs (miRNA-seq), promoting axon guidance, reducing apoptosis, scavenging reactive oxygen species, and regulating immune responses. Human forebrain spheroid EVs demonstrated the ability to improve recovery in an in vitro stroke model and in vivo. Human forebrain spheroid differentiation in VWBR significantly increased the EV yields (up to 240-750 fold) and EV biogenesis compared to static differentiation due to the dynamic microenvironment and metabolism change. The biomanufactured EVs from VWBRs have exosomal characteristics and more therapeutic cargo and are functional in in vitro assays, which paves the way for future in vivo stroke studies.

Oxidative balance and mental health: Exploring the link between prooxidant-antioxidant balance and depression in hypertensive and normotensive individuals, accounting for sex differences

BackgroundExisting studies have suggested a link between oxidative stress levels and depression. Additionally, factors such as gender and conditions like hypertension have been shown to influence oxidative stress. This ten-year follow-up cohort study aims to examine the association between prooxidant-antioxidant balance (PAB) and the onset of depression and its symptoms in both hypertensive and normotensive individuals, while considering gender differences. MethodsThe data for this study was obtained from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, a cohort study conducted in eastern Iran. Serum PAB levels were measured in 1702 hypertensive and 4096 normotensive individuals aged 35 to 65 years. After ten years, the participants' depression status was evaluated using the Beck questionnaire, and depression symptoms were investigated using the BDI-II structural model, which includes somatic, affective, and cognitive symptoms. ResultThe analysis indicates that in hypertensive male participants, the highest tertile of PAB is associated with an increased risk of depression (β: 1.22, 95 % CI: −0.046, 2.485; P = 0.059) and symptoms of depression, including cognitive (β: 2.937, 95 % CI: 0.511, 5.362; P = 0.018) and somatic (β: 2.654, 95 % CI: 0.37, 4.939; P = 0.023) symptoms. However, there was no significant association between affective symptoms and PAB tertiles. Additionally, there was no significant link between depression and depressive symptoms in female hypertensive and normotensive individuals. ConclusionIn male hypertensive patients, but not in normotensive individuals of both genders and hypertensive women, depression and its associated symptoms, including somatic and cognitive symptoms, are associated with elevated levels of oxidative stress, as evidenced by higher serum PAB values. PAB is not associated with affective symptoms. Future studies should focus on the gender-specific nature of this relationship and work to clarify its underlying mechanisms.

Magnitude of systolic blood pressure reduction following endovascular treatment and clinical outcomes in acute large artery occlusion stroke

BackgroundThe impact of lowering systolic blood pressure (SBP) following endovascular treatment (EVT) in acute large vessel occlusion stroke (LVOS) patients remains unclear. We aimed to explore the effect of the...

Efficacy and safety of mesenchymal stem cell therapies for ischemic stroke: a systematic review and meta-analysis.

The efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of ischemic stroke (IS) remains controversial. Therefore, this study aimed to evaluate the efficacy and safety of MSCs for IS. A literature search until May 23, 2023, was conducted using PubMed, EMBASE, the Cochrane Library, and the Web of Science to identify studies on stem cell therapy for IS. Interventional and observational clinical studies of MSCs in patients with IS were included, and the safety and efficacy were assessed. Two reviewers extracted data and assessed the quality independently. The meta-analysis was performed using RevMan5.4. Fifteen randomized controlled trials (RCTs) and 15 non-randomized trials, including 1217 patients (624 and 593 in the intervention and control arms, respectively), were analyzed. MSCs significantly improved patients' activities of daily living according to the modified Rankin scale (mean difference [MD]: -0.26; 95% confidence interval [CI]: -0.50 to -0.01; P = .04) and National Institutes of Health Stroke Scale score (MD: -1.69; 95% CI: -2.66 to -0.73; P < .001) in RCTs. MSC treatment was associated with lower mortality rates in RCTs (risk ratio: 0.44; 95% CI: 0.28-0.69; P < .001). Fever and headache were among the most reported adverse effects. Based on our review, MSC transplantation improves neurological deficits and daily activities in patients with IS. In the future, prospective studies with large sample sizes are needed for stem cell studies in ischemic stroke. This meta-analysis has been registered at PROSPERO with CRD42022347156.

The Association Between Experienced Discrimination and Pain in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

The relationship between experienced discrimination and its effects on pain interference and management among racial disparities is not well explored. This research investigated these associations among Black and White U.S. adults. The analysis involved 9369 Black and White adults in the REasons for Geographic and Racial Differences in Stroke (REGARDS), assessing experiences of discrimination, pain interference (SF-12), and pain treatment, incorporating factors like demographics, comorbidities, and stress. Black participants experiencing moderate discrimination were found to have a 41% increased likelihood of pain interference (aOR 1.41, 95% CI 1.02-1.95), similaritythose facing high levels of discriminationalso showed a 41% increase (aOR 1.41, 95% CI 1.06-1.86) compared to those without such experiences. White individuals reporting moderate discrimination also faced a heightened risk, with a 21% greater chance of pain interference (aOR 1.21, 95% CI 1.01-1.45). Notably, the presence of moderate discrimination among Black participants correlated with a 12% reduced probability of receiving pain treatment (aOR 0.88, 95% CI 0.56-1.37). Furthermore, Black, and White individuals who reported discrimination when seeking employment had a 33% (aOR 0.67, 95% CI 0.45-0.98) and 32% (aOR 0.68, 95% CI 0.48-0.96) lower likelihood, respectively, of receiving treated pain. The study elucidates how discrimination exacerbates pain interference and restricts access to treatment, affecting Black and White individuals differently. These findings underscore an urgent need for strategies to counteract discrimination's negative effects on healthcare outcomes. Addressing these disparities is crucial for advancing health equity and improving the overall quality of care.

Temporal Trends and Racial Disparities in Long-Term Survival After Stroke.

Few studies have examined trends and disparities in long-term outcome after stroke in a representative US population. We used a population-based stroke study in the Greater Cincinnati Northern Kentucky region to examine trends and racial disparities in poststroke 5-year mortality. All patients with acute ischemic strokes (AISs) and intracerebral hemorrhages (ICHs) among residents ≥20 years old were ascertained using ICD codes and physician-adjudicated using a consistent case definition during 5 periods: July 1993-June 1994 and calendar years 1999, 2005, 2010, and 2015. Race was obtained from the medical record; only those identified as White or Black were included. Premorbid functional status was assessed using the modified Rankin Scale, with a score of 0-1 being considered "good." Mortality was assessed with the National Death Index. Trends and racial disparities for each subtype were analyzed with logistic regression. We identified 8,428 AIS cases (19.3% Black, 56.3% female, median age 72) and 1,501 ICH cases (23.5% Black, 54.8% female, median age 72). Among patients with AIS, 5-year mortality improved after adjustment for age, race, and sex (53% in 1993/94 to 48.3% in 2015, overall effect of study year p = 0.009). The absolute decline in 5-year mortality in patients with AIS was larger than what would be expected in the general population (5.1% vs 2.8%). Black individuals were at a higher risk of death after AIS (odds ratio [OR] 1.23, 95% CI 1.08-1.39) even after adjustment for age and sex, and this effect was consistent across study years. When premorbid functional status and comorbidities were included in the model, the primary effect of Black race was attenuated but race interacted with sex and premorbid functional status. Among male patients with a good baseline functional status, Black race remained associated with 5-year mortality (OR 1.4, 95% CI 1.1-1.7, p = 0.002). There were no changes in 5-year mortality after ICH over time (64.4% in 1993/94 to 69.2% in 2015, overall effect of study year p = 0.32). Long-term survival improved after AIS but not after ICH. Black individuals, particularly Black male patients with good premorbid function, have a higher mortality after AIS, and this disparity did not change over time.

Race, social determinants of health, and comorbidity patterns among participants with heart failure in the REasons for geographic and racial differences in stroke (REGARDS) study

BackgroundAmong individuals with heart failure (HF), racial differences in comorbidities may be mediated by social determinants of health (SDOH).MethodsBlack and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 were included in this cross-sectional analysis. We assessed whether higher prevalence of comorbidities in Black participants compared to White participants were mediated by SDOH in socioeconomic, environment/housing, social support, and healthcare access domains, using the inverse odds weighting method.ResultsBlack (n = 240) compared to White (n = 293) participants with HF with preserved ejection fraction (HFpEF) had higher prevalence of diabetes [1.38 (95% CI 1.18–1.61)], chronic kidney disease [1.21 (95% CI 1.01–1.45)], and anemia [1.33 (95% CI 1.02–1.75)] and lower prevalence of atrial fibrillation [0.80 (95% CI (0.65–0.98)]. Black (n = 314) compared to White (n = 367) participants with HF with reduced ejection fraction (HFrEF) had higher prevalence of hypertension [1.04 (95% CI 1.02–1.07)] and diabetes [1.26 (95% CI 1.09–1.45)] and lower prevalence of coronary artery disease [0.86 (95% CI 0.78–0.94)] and atrial fibrillation [0.70 (95% CI 0.58–0.83)]. Socioeconomic status explained 14.5%, 26.5% and 40% of excess diabetes, anemia, and chronic kidney disease among Black adults with HFpEF; however; mediation was not statistically significant and no other SDOH substantially mediated differences in comorbidity prevalence.ConclusionsSocioeconomic status partially mediated excess diabetes, anemia, and chronic kidney disease experienced by Black adults with HFpEF, but differences in other comorbidities were not explained by other SDOH examined.

Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank.

Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke. We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; ncases=51 929; ncontrols=39 980) and subsequent arterial ischemic stroke (AIS; ncases=45 120; ncontrols=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (protein quantitative trait loci) to determine the effect of 1463 plasma protein abundances on subsequent MACE using Mendelian randomization. Two variants were significantly associated with subsequent cardiovascular events: rs76472767 near gene RNF220 (odds ratio, 0.75 [95% CI, 0.64-0.85]; P=3.69×10-8) with subsequent AIS and rs13294166 near gene LINC01492 (odds ratio, 1.52 [95% CI, 1.37-1.67]; P=3.77×10-8) with subsequent MACE. Using Mendelian randomization, we identified 2 proteins with an effect on subsequent MACE after a stroke: CCL27 ([C-C motif chemokine 27], effect odds ratio, 0.77 [95% CI, 0.66-0.88]; adjusted P=0.05) and TNFRSF14 ([tumor necrosis factor receptor superfamily member 14], effect odds ratio, 1.42 [95% CI, 1.24-1.60]; adjusted P=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation. We found evidence that 2 proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.

Risk of recurrent stroke and dementia following acute stroke by changes in kidney function: results from the Perindopril Protection Against Recurrent Stroke Study.

Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the aims of the study were to investigate functional relationships between dynamic kidney function change and cardiovascular outcomes, and clarify whether adding kidney parameters to conventional cardiovascular risk factors improves model discrimination. Post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) clinical trial of blood pressure lowering for the secondary prevention of stroke. We examined the association between dynamic kidney function defined as percentage change (declines of >30%, and >0 to ≤30%, and increases of ≥0 to <30%, and ≥30%) in estimated glomerular filtration rate (eGFR) over 2 years and recurrent stroke, major cardiovascular events, dementia and all-cause death over the next 2 years using Cox proportional hazard models controlling for eGFR at registration and potential confounders. Restricted cubic splines were used to assess the functional relationships. C-statistics and Net Reclassification Improvement (NRI) at 2 years were used to assess model discrimination. In 4591 patients followed for a mean of approximately 2 years, 254 (5.5%) developed recurrent stroke, 391 (8.5%) had a major cardiovascular event, 221 (4.8%) developed dementia, and 271 (5.9%) died. Reverse J-like or U-like relationships were observed for percent declines in eGFR and outcomes. Using declines in eGFR of >0 to ≤30% as a reference, increased risks were evident for a greater decline (>30%) in relation to recurrent stroke [adjusted hazard ratio 1.85, 95% confidence interval (CI) 1.20-2.85], major cardiovascular event (2.24, 1.62-3.10) and all-cause death (2.09, 1.39-3.15). A larger increase (≥30%) in eGFR was also associated with a greater risk of all-cause death (1.96, 1.14-3.37). Improvements in the C-statistic were found by adding baseline eGFR and percent change compared with a model with conventional cardiovascular risk factors alone, for major cardiovascular events, dementia, and all-cause mortality. Declining kidney function following an incident cerebrovascular event is associated with additional risk of a major cardiovascular events, dementia, and 2-year mortality. However, a large increase in kidney function was also found to be associated with a higher risk of mortality.