Trends in Black-White Differences of Antihypertensive Treatment in Individuals With and Without History of Stroke.

BACKGROUND: Recent hypertension guidelines for the general population have included race-specific recommendations for antihypertensives, whereas current stroke-specific recommendations for antihypertensives do not vary by race. The impact of these guidelines on antihypertensive regimen changes over time, and if this has varied by prevalent stroke status, is unclear. METHODS: The use of antihypertensive medications was studied cross-sectionally among self-identified Black and White participants, aged ≥45 years, with and without history of stroke, from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke). Participants completed an in-home examination in 2003-2007 (visit 1) with/without an examination in 2013-2016 (visit 2). Stratified by prevalent stroke status, logistic regression mixed models examined associations between antihypertensive class use for visit 2 versus visit 1 and Black versus White individuals with an interaction adjusted for demographics, socioeconomic status, and vascular risk factors/vital signs. RESULTS: Of 17 244 stroke-free participants at visit 1, Black participants had greater adjusted odds of angiotensin-converting enzyme inhibitor usage than White participants (odds ratio [OR], 1.51 [95% CI, 1.30-1.77]). This difference was smaller in the 7476 stroke-free participants at visit 2 (OR, 1.16 [95% CI, 1.08-1.25]). In stroke-free participants at visit 1, Black participants had lower odds of calcium channel blocker (CCB) usage than White participants (OR, 0.47 [95% CI, 0.41-0.55]), but CCB usage did not differ significantly between Black and White stroke-free participants at visit 2 (OR, 1.02 [95% CI, 0.95-1.09]). Among 1437 stroke survivor participants at visit 1, Black participants had lower odds of CCB use than White participants (OR, 0.34 [95% CI, 0.26-0.45]). In 689 stroke survivor participants at visit 2, CCB use did not differ between Black and White participants (OR, 0.80 [95% CI, 0.61-1.06]). CONCLUSIONS: Racial differences in the use of guideline-recommended antihypertensives decreased between 2003-2007 and 2013-2016 in stroke-free individuals. In stroke survivors, racial differences in CCB usage narrowed over the time periods. These findings suggest there is still a mismatch between race-specific hypertension guidelines and recent clinical practice.

Effects and Thresholds of Young to Midlife Vascular Risks on Brain Health.

BACKGROUND: Vascular risk factors, particularly hypertension, are important contributors to accelerated brain aging. We sought to quantify vascular risk factor risks over adulthood and assess the empirical evidence for risk thresholds. METHODS: We used SBP (systolic blood pressure) and diastolic blood pressure, total cholesterol, fasting blood glucose, and body mass index measurements collected from participants in the CARDIA study (Coronary Artery Risk Development in Young Adults) at 2- to 5-year intervals through year 30. The Montreal Cognitive Assessment and domain-specific cognitive tests were performed at year 30. White matter hyperintensity volume was measured by magnetic resonance imaging. We used a 2-step method to fit longitudinal vascular risk factor exposures to optimized spline functions with mixed-effects models, then used the participant-specific random effects that characterized individual exposures over time in cross-sectional models adjusted for sex, race, age, and education to study effects on midlife brain health. RESULTS: Change in SBP up to 33 years of age was negatively associated with Montreal Cognitive Assessment scores (-0.29 Montreal Cognitive Assessment Z score per mm Hg/y change [95% CI, -0.49 to -0.09]; P=0.005), with similar effects for SBP changes from 33 to 49 years of age (-0.08 [95% CI, -0.16 to 0.01]; P=0.08). We observed comparable, significant associations between SBP exposure during those ages, midlife performance on specific cognitive domains, and volume of white matter hyperintensity (all P<0.05). SBP ≤111 mm Hg was the estimated threshold below which no harmful association with midlife cognitive performance was identified. CONCLUSIONS: SBP in early adulthood is the vascular risk factor most strongly associated with midlife cognitive performance and white matter hyperintensity burden, with SBP 111 mm Hg suggested as a harm threshold.

Population-based approaches for reducing stroke risk: an update on their success and the challenges ahead.

INTRODUCTION: Stroke is a significant public health challenge as it is the second most common cause of death and the third leading cause of disability globally. Additionally, stroke incidence and the number of stroke deaths have been rising. Efforts to prevent stroke have been made, including high-risk approaches where patients are screened for cardiovascular risk factors, and population-based approaches which attempt to reduce stroke rates by improving overall population health. AREAS COVERED: We summarize studies of population-based approaches to stroke prevention involving greater than 1,000 participants identified on a PubMed database search. Based on these programs, challenges of population-based stroke prevention programs are discussed and potential keys to success are highlighted. EXPERT OPINION: Population-based stroke prevention programs face challenges including cost and interest of the public and certain stakeholders. Additionally, secular trends for improvement in risk factors and catastrophic adverse environmental circumstances add to the complexity of analyzing program success. Factors leading to successful programs include validated digital solutions for self-monitoring of risks, backing by global policy and legislation, flexibility to the needs of the population, intersectoral programs, community engagement, information dissemination back to the populations, and high-risk screening to develop a complementary combination approach to stroke prevention.

Network analysis of stroke systems of care in Korea.

Background: The landscape of stroke care has shifted from stand-alone hospitals to cooperative networks among hospitals. Despite the importance of these networks, limited information exists on their characteristics and functional attributes. Methods: We extracted patient-level data on acute stroke care and hospital connectivity by integrating national stroke audit data with reimbursement claims data. We then used this information to transform interhospital transfers into a network framework, where hospitals were designated as nodes and transfers as edges. Using the Louvain algorithm, we grouped densely connected hospitals into distinct stroke care communities. The quality and characteristics in given stroke communities were analysed, and their distinct types were derived using network parameters. The clinical implications of this network model were also explored. Results: Over 6 months, 19 113 patients with acute ischaemic stroke initially presented to 1009 hospitals, with 3114 (16.3%) transferred to 246 stroke care hospitals. These connected hospitals formed 93 communities, with a median of 9 hospitals treating a median of 201 patients. Derived communities demonstrated a modularity of 0.904, indicating a strong community structure, highly centralised around one or two hubs. Three distinct types of structures were identified: single-hub (n=60), double-hub (n=22) and hubless systems (n=11). The endovascular treatment rate was highest in double-hub systems, followed by single-hub systems, and was almost zero in hubless systems. The hubless communities were characterised by lower patient volumes, fewer hospitals, no hub hospital and no stroke unit. Conclusions: This network analysis could quantify the national stroke care system and point out areas where the organisation and functionality of acute stroke care could be improved.

Introduction to the special issue on brain health.

None.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

What will it take to achieve brain health globally?

Brain health initiatives and programs are gaining traction worldwide. Some are clinically based, others research based, and some are a combination of clinical and research action plans. Achievement of global brain health is a challenging endeavor with prerequisites including but not limited to multidisciplinary and multisectoral approaches, strengthening of neurologic policies at local and regional levels, global advocacy, leadership and collaboration amongst stakeholders, development of technical and guidance documents, and strengthening and interpretation of the relevant evidence. Over 1 billion persons worldwide are impacted by neurologic disorders, and brain health initiatives are needed to curb the human suffering and cost of these disorders. We provide a brief review of select brain health initiatives and programs and offer possible steps to achieve brain health globally.

What is brain health?

The call to optimize brain health is now a local, regional and global priority. Organizations such as the World Health Organization, Centers for Disease Control and Prevention and Alzheimer's Association, American Academy of Neurology, World Federation of Neurology, and others have developed recommendations for the maintenance of brain health. Brain health definitions range from broad to narrow in scope and may focus on cognition or encompass broader core components such as cerebral, mental and social domains. In this manuscript we will explore various definitions of brain health and its core components, the importance of cognitive and functional domains, and briefly introduce the concept of cognitive medicine in the context of brain health.

Improvement in Delivery of Ischemic Stroke Treatments but Stagnation of Clinical Outcomes in Young Adults in South Korea.

BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.

Genotype-guided dual antiplatelet therapy in cerebrovascular disease: assessing the risk and benefits for ethnic populations.

INTRODUCTION: Cerebrovascular disease is a leading cause of morbidity and mortality in the world and antiplatelet therapy is a main pharmacologic means of secondary prevention. Clinical information has accumulated about benefit of dual antiplatelet therapy in certain clinical scenarios, genetic causes of antiplatelet resistance and its effect on clinical outcomes, and ethnic and geographic distributions of genetic polymorphisms. AREAS COVERED: This review covers literature related to the pharmacogenomics of antiplatelet agents with a focus on ethnic variability, antiplatelet resistance, and dual antiplatelet therapy in cerebrovascular disease. EXPERT OPINION: Selecting patients for dual antiplatelet therapy and specific agents require consideration of multiple factors. Ethnic factors should be considered in certain circumstances, but additional research is needed to determine the generalizability of the findings.

Malpractice Lawsuits Relating to Mechanical Thrombectomy for Acute Ischemic Stroke: A Systematic Review.

Background and Purpose: Medical-legal claims for malpractice relating to the use of alteplase for acute ischemic stroke (AIS) are usually for failure to treat rather than for complications. The advent of mechanical thrombectomy (MT) as a standard of AIS treatment has added a new dimension to the medical-legal landscape as there is a need for the delivery of a higher level of care creating the potential for delays and errors associated with such treatment. Information on causes of malpractice related to mechanical thrombectomy (MT) is currently lacking. Methods: We conducted a systematic review of legal databases (Westlaw, LexisNexis, Google Scholar Case Law, and VerdictSearch) to identify medical malpractice cases with and without verdicts filed in the United States up to March 31, 2021 which pertained to performance or non-performance of MT for AIS. We collected various case characteristics, case outcomes, and root causes for malpractice claims. Results: We found 25 cases, 16 of which alleged failure to treat with MT, 8 for harm due to delay in treatment and 1 case that alleged complications. Root causes included delay in vascular imaging, communication breakdowns, and transportation delays. Eight cases had an outcome in favor of the defendant, 9 in favor of the plaintiff, and 8 remained to be determined. Conclusions: As with alteplase, malpractice allegations regarding MT for AIS are largely for failure to treat or delay in treatment as opposed to complications. Addressing root causes of diagnostic delay, communication breakdowns, and transportation delays may reduce subsequent malpractice risk.

Comparison of Hospital Performance in Acute Ischemic Stroke Based on Mortality and Functional Outcome in South Korea.

BACKGROUND: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke. METHODS: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea - National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed. RESULTS: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of -0.29 and Kendall rank coefficient of -0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures. CONCLUSIONS: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke.

Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial: Rationale and design.

RATIONALE: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. AIMS: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. METHODS AND STUDY DESIGN: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. STUDY OUTCOMES: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. DISCUSSION: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. TRIAL REGISTRATION: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.

Household income is associated with functional outcomes in a multi-institutional cohort of patients with ischemic stroke and COVID-19.

OBJECTIVES: The COVID-19 pandemic has heightened awareness of health disparities associated with socioeconomic status (SES) across the United States. We examined whether household income is associated with functional outcomes after stroke and COVID-19. MATERIALS AND METHODS: This was a multi-institutional, retrospective cohort study of consecutively hospitalized patients with SARS-CoV-2 and radiographically confirmed stroke presenting from March through November 2020 to any of five comprehensive stroke centers in metropolitan Chicago, Illinois, USA. Zip-code-derived household income was dichotomized at the Chicago median. Logistic regression was used to examine the relationship between household income and good functional outcome (modified Rankin Scale 0-3 at discharge, after ischemic stroke). RESULTS: Across five hospitals, 159 patients were included. Black patients comprised 48.1%, White patients 38.6%, and Hispanic patients 27.7%. Median household income was $46,938 [IQR: $32,460-63,219]. Ischemic stroke occurred in 115 (72.3%) patients (median NIHSS 7, IQR: 0.5-18.5) and hemorrhagic stroke in 37 (23.7%). When controlling for age, sex, severe COVID-19, and NIHSS, patients with ischemic stroke and household income above the Chicago median were more likely to have a good functional outcome at discharge (OR 7.53, 95% CI 1.61 - 45.73; P=0.016). Race/ethnicity were not included in final adjusted models given collinearity with income. CONCLUSIONS: In this multi-institutional study of hospitalized patients with stroke, those residing in higher SES zip codes were more likely to have better functional outcomes, despite controlling for stroke severity and COVID-19 severity. This suggests that area-based SES factors may play a role in outcomes from stroke and COVID-19.

Blood pressure variability, dementia, and role of antihypertensive medications in older adults.

INTRODUCTION: We assessed the association between visit-to-visit blood pressure variability (BPV) up to 12 years and subsequent dementia risk, and tested the modifying effect of antihypertensive medications. METHODS: We studied 2234 participants from two community-based cohorts of older adults with normal cognition or mild cognitive impairment. Participants were followed through annual assessments for up to 27 years. Visit-to-visit BPV was quantified over 3, 6, 9, and 12 years, respectively. RESULTS: Higher systolic BPV (SBPV) during 3, 6, 9, and 12 years was associated with a subsequent increased risk of dementia, with hazard ratios ranging from 1.02 (95% confidence interval [CI]: 1.01-1.04) to 1.10 (95% CI: 1.05-1.16). The association between SBPV and dementia risk was stronger among participants not taking calcium channel blockers (p-for interaction < 0.05). DISCUSSION: Among older adults, long-term exposure to higher visit-to-visit SBPV is associated with an increased risk of dementia later in life, and calcium channel blockers may modify this association. HIGHLIGHTS: Among adults aged >65, higher systolic blood pressure variability spanning 3-12 years is associated with an increased risk of dementia later in life. Single blood pressure measurement or mean blood pressure levels does not seem to associate with dementia risk among older adults. The association between systolic blood pressure variability and dementia risk is stronger among those not taking calcium channel blocker medications.

The Role of Vascular Risk Factors in Cognitive Impairment and Dementia and Prospects for Prevention.

One of the most challenging clinical expressions of population aging is cognitive impairment and dementia. Among risk factors for the development of dementia, modifiable vascular risk factors have emerged as contributors to both vascular and nonvascular types of dementia. Epidemiologic studies have been particularly informative in understanding the link between vascular risks and dementia across the life course. We discuss vascular risks for dementia and cognitive impairment and practical management recommendations.

Brain Reserve, Resilience, and Cognitive Stimulation Across the Lifespan: How Do These Factors Influence Risk of Cognitive Impairment and the Dementias?

In the absence of effective treatments for dementia, maintaining cognitive health in old age is one of the major challenges facing aging societies. Interventions for cognitive health that are tailored to the person are more likely to bring the best benefits with a minimum burden. We review the existing literature on this topic and discuss the role of the primary care physician.

Blood and Cerebrospinal Fluid Biomarkers in Vascular Dementia and Alzheimer's Disease: A Brief Review.

The Maintenance of brain health is a lifelong process whereby potentially deleterious exposures such as cardiovascular risks, amyloid beta, and phosphorylated tau may adversely affect the brain decades before there are clinical manifestations. Thus, the early structural and neuropathological foundation for the development of cognitive impairment and its allied features later in life may provide precursor targets such that interventions may be applied to prevent or slow cognitively impairing processes if the underlying mechanism(s) can be addressed in time.