In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%–15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion.

Importance: The magnitude of cognitive change after incident myocardial infarction (MI) is unclear.Objective: To assess whether incident MI is associated with changes in cognitive function after adjusting for pre-MI cognitive trajectories.Design, Setting, and Participants: This cohort study included adults without MI, dementia, or stroke and with complete covariates from the following US population-based cohort studies conducted from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Data were analyzed from July 2021 to January 2022.Exposures: Incident MI.Main Outcomes and Measures: The main outcome was change in global cognition. Secondary outcomes were changes in memory and executive function. Outcomes were standardized as mean (SD) T scores of 50 (10); a 1-point difference represented a 0.1-SD difference in cognition. Linear mixed-effects models estimated changes in cognition at the time of MI (change in the intercept) and the rate of cognitive change over the years after MI (change in the slope), controlling for pre-MI cognitive trajectories and participant factors, with interaction terms for race and sex.Results: The study included 30 465 adults (mean [SD] age, 64 [10] years; 56% female), of whom 1033 had 1 or more MI event, and 29 432 did not have an MI event. Median follow-up was 6.4 years (IQR, 4.9-19.7 years). Overall, incident MI was not associated with an acute decrease in global cognition (−0.18 points; 95% CI, −0.52 to 0.17 points), executive function (−0.17 points; 95% CI, −0.53 to 0.18 points), or memory (0.62 points; 95% CI, −0.07 to 1.31 points). However, individuals with incident MI vs those without MI demonstrated faster declines in global cognition (−0.15 points per year; 95% CI, −0.21 to −0.10 points per year), memory (−0.13 points per year; 95% CI, −0.22 to −0.04 points per year), and executive function (−0.14 points per year; 95% CI, −0.20 to −0.08 points per year) over the years after MI compared with pre-MI slopes. The interaction analysis suggested that race and sex modified the degree of change in the decline in global cognition after MI (race × post-MI slope interaction term, P = .02; sex × post-MI slope interaction term, P = .04), with a smaller change in the decline over the years after MI in Black individuals than in White individuals (difference in slope change, 0.22 points per year; 95% CI, 0.04-0.40 points per year) and in females than in males (difference in slope change, 0.12 points per year; 95% CI, 0.01-0.23 points per year).Conclusions: This cohort study using pooled data from 6 cohort studies found that incident MI was not associated with a decrease in global cognition, memory, or executive function at the time of the event compared with no MI but was associated with faster declines in global cognition, memory, and executive function over time. These findings suggest that prevention of MI may be important for long-term brain health.

Atrial myopathy, which is characterized by changes in left atrial function and size, may precede and promote atrial fibrillation and cardiac thromboembolism. This study assesses the association bet... Visual Left Atrial Function and Stroke. Atrial myopathy, which is characterized by changes in left atrial function and size, may precede and promote atrial fibrillation and cardiac thrombo... Background: Atrial myopathy—characterized by changes in left atrial function and size—may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or str...

Background: Out‐of‐hospital cardiac arrest ( OHCA ) results in significant morbidity and mortality, primarily from neurologic injury. Predicting neurologic outcome early post‐ OHCA remains difficult in patients receiving targeted temperature management. Methods and Results: Retrospective analysis was performed on consecutive OHCA patients receiving targeted temperature management (32–34°C) for 24 hours at a tertiary‐care center from 2008 to 2012 (development cohort, n=122). The primary outcome was favorable neurologic outcome at hospital discharge, defined as cerebral performance category 1 to 2 (poor 3–5). Patient demographics, pre‐ OHCA diagnoses, and initial laboratory studies post‐resuscitation were compared between favorable and poor neurologic outcomes with multivariable logistic regression used to develop a simple scoring system ( C‐ GRA pH ). The C‐ GRA pH score ranges 0 to 5 using equally weighted variables: ( C ): coronary artery disease, known pre‐ OHCA ; ( G ): glucose ≥200 mg/dL; ( R ): rhythm of arrest not ventricular tachycardia/fibrillation; ( A ): age >45; ( pH ): arterial pH ≤7.0. A validation cohort (n=344) included subsequent patients from the initial site (n=72) and an external quaternary‐care health system (n=272) from 2012 to 2014. The c‐statistic for predicting neurologic outcome was 0.82 (0.74–0.90, P <0.001) in the development cohort and 0.81 (0.76–0.87, P <0.001) in the validation cohort. When subdivided by C‐ GRA pH score, similar rates of favorable neurologic outcome were seen in both cohorts, 70% each for low (0–1, n=60), 22% versus 19% for medium (2–3, n=307), and 0% versus 2% for high (4–5, n=99) C‐ GRA pH scores in the development and validation cohorts, respectively. Conclusions: C‐ GRA pH stratifies neurologic outcomes following OHCA in patients receiving targeted temperature management (32–34°C) using objective data available at hospital presentation, identifying patient subsets with disproportionally favorable ( C‐ GRA pH ≤1) and poor ( C‐ GRA pH ≥4) prognoses.

Background and Objectives: Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities, or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission, and higher risk of mortality, compared to thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex. Methods: Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic versus thrombotic) and admission NIHSS category [minor (≤5), mild (6-10), moderate (11-15), severe (16-20), very severe (>20)] adjusted for covariates from visits most-proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019). Results: Participants (N=940) were mean age 71years [SD=9] at incident stroke, 51% female and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke versus thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (OR=1.95, 95%CI=1.14-3.35) to very severe strokes (OR=4.95, 95%CI=2.34-10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic versus thrombotic strokes, but with attenuation of effect (very severe stroke OR=3.91, 95%CI=1.76-8.67). Sex modified the association between stroke subtype and severity (embolic versus thrombotic stroke, p-interaction=0.03, per severity category, females OR=2.38, 95%CI=1.55-3.66; males OR=1.75, 95%CI=1.09-2.82). Risk of death (median follow-up 5 years, IQR 1-12) was also increased for embolic versus thrombotic stroke patients (HR 1.66, 95%CI 1.41-1.97). Discussion: Embolic stroke was associated with greater stroke severity at the time of the event, and higher risk of death versus thrombotic stroke, even after careful adjustment for patient-level differences.

Background and Purpose: We aim to determine, in healthy high-risk adults, the association between subclinical coronary artery disease and white matter hyperintensity (WMH) volume and location, independent of atherosclerotic risk factors. Methods: Seven hundred eighty-two asymptomatic first-degree relatives of index cases with early-onset coronary artery disease (<60 years old) from GeneSTAR (Genetic Study of Atherosclerosis Risk) with contemporaneous coronary computed tomography angiography and brain magnetic resonance imaging were analyzed. Multilevel mixed-effects linear regression models, accounting for family structure, evaluated the association of total WMH volume and 3 regions (deep WMH, periventricular WMH [PVWMH], or borderzone [cuff]) with markers of coronary artery disease. Separate models were created for total WMH, deep WMH, PVWMH, and cuff volumes, each, as dependent variables, across coronary computed tomography angiography variables, adjusted for covariates. Results: Mean age was 51 years ±10, with 58% women and 39% African American people. Participants with any coronary plaque had 52% larger WMH volumes than those without plaque (95% CI, 0.24–0.59). Per 1% greater coronary plaque volume, total WMH volumes were 0.07% larger (95% CI, 0.04–0.10). Every 1% higher total coronary plaque volume was associated with 5.03% larger deep WMH volume (95% CI, 4.67–5.38), 5.10% PVWMH larger volume (95% CI, 4.72–5.48), and 2.74% larger cuff volume (95% CI, 2.38–3.09) with differences in this association when comparing deep WMH to PVWMH ( P interaction, 0.001) or cuff ( P interaction, <0.001), respectively. Conclusions: In healthy, high-risk individuals, the presence and volume of coronary artery plaque are associated with larger WMH volumes, appearing the strongest for PVWMH. These findings in high-risk families suggest a disease relationship in 2 different vascular beds, beyond traditional risk factors, possibly due to genetic predisposition.