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Background and Purpose - Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods - The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. Results - Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection. Conclusions - Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Physical inactivity is an important and modifiable cardiovascular disease risk factor. Little is known about the social determinants of physical inactivity in older, urban-dwelling populations. We collected socio-demographic and medical risk factor information and physical activity questionnaires in the Northern Manhattan Study. Logistic regression models were constructed to examine whether measures of social isolation, race-ethnicity, and sex were associated with physical inactivity. Physical inactivity was present in 40.5% of the cohort. In multivariable models adjusted for medical comorbidities, Hispanic race-ethnicity (compared to non-Hispanic white) was associated with higher odds of physical inactivity (OR 2.18, 95% CI 1.78, 2.67), while women were more likely to be inactive than men (OR 1.33, 95% CI 1.15, 1.54). Having Medicaid/being uninsured (OR 1.20, 95% CI 1.02, 1.42), and having fewer than 3 friends (1.41, 95% CI 1.15, 1.72) were also associated with physical inactivity. Physical inactivity is common, particularly in Hispanics, women, and those who are socially isolated. Public health interventions aimed at increasing physical activity in these more sedentary groups are required. [ABSTRACT FROM AUTHOR]

Objective: There is insufficient randomized trial data to support evidence-based recommendations for tight control of fasting blood glucose (FBG) among diabetic subjects in primary stroke prevention. We explored the relationship between FBG among diabetic subjects and risk of ischemic stroke in a multiethnic prospective cohort.Research Design and Methods: Medical and social data and FBG values were collected for 3,298 stroke-free community residents: mean age +/- SD was 69 +/-10 years; 63% were women, 21% were white, 24% were black, and 53% were Hispanic; and follow-up was 6.5 years. Baseline FBG levels were categorized: 1) elevated FBG: history of diabetes and FBG >or=126 mg/dl (7.0 mmol/l); 2) target FBG: history of diabetes and FBG <126 mg/dl (7.0 mmol/l); or 3) no diabetes/reference group. Cox models were used to calculate hazard ratios (HRs) and 95% CI for ischemic stroke and vascular events.Results: In the Northern Manhattan Study, 572 participants reported a history of diabetes and 59% (n = 338) had elevated FBG. Elevated FBG among diabetic subjects was associated with female sex (P < 0.04), Medicaid (P = 0.01), or no insurance (P = 0.03). We detected 190 ischemic strokes and 585 vascular events. Diabetic subjects with elevated FBG (HR 2.7 [95% CI 2.0-3.8]) were at increased risk of stroke, but those with target FBG levels (1.2 [0.7-2.1]) were not, even after adjustment. A similar relationship existed for vascular events: elevated FBG (2.0 [1.6-2.5]) and target FBG (1.3 [0.9-1.8].Conclusions: This prospective cohort study provides evidence for the benefits of tighter glucose control for primary stroke prevention. [ABSTRACT FROM AUTHOR]

Stroke is the third leading cause of death in the United States. It is also the leading cause of significant disability, and stroke rates double for every decade after age 55. Overall, stroke is about 30% more common in men than in women, but there are more American women with stroke than men, because of the longer life expectancy in women. Until recently, definitions stated that a stroke lasts 24 hours or longer, and a transient ischemic attack lasts less than 24 hours. This definition is now finally giving way to new evidence from modern imaging techniques, showing that even symptoms lasting a very short time can be associated with evidence of stroke on imaging. There are also advances in the approach to acute therapy, and strides have been made in controlling blood pressure and other risk factors. But more efforts are needed on all fronts to reduce the enormous clinical and financial impact of stroke and transient ischemic attack on patients and on the US healthcare system. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke., Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event. Kaplan-Meier statistics were used to estimate the cumulative incidence of a cancer diagnosis within the first year after randomization., Results: Among 878 participants without baseline history of cancer, 13 (1.5%) were diagnosed with incident cancer in the year after randomization, comprising 12 solid cancers (3 prostate, 2 breast, 2 gastrointestinal, and 5 other primary sites) and 1 hematologic cancer (non-Hodgkin lymphoma). The cumulative incidences of a cancer diagnosis were 0% at 3 months, 0.6% (95% CI 0.2%-1.5%) at 6 months, and 2.0% (95 CI 1.1%-3.4%) at 1 year. The median time from index stroke to cancer diagnosis was 261 days (interquartile range 183-358)., Discussion: In a multicenter cryptogenic stroke cohort with prospective follow-up, the 1-year cumulative incidence of a cancer diagnosis was 2%. This rate may be an underestimation because of the clinical trial population and exclusion of cancers diagnosed immediately after stroke., Trial Registration Information: ClinicalTrials.gov Identifier: NCT03192215. Registered June 20, 2017. First patient enrolled February 1, 2018.

Background and Objectives: The term "embolic stroke of undetermined source" (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared with antiplatelet therapy in secondary ischemic stroke prevention., Methods: A study-level meta-analysis was conducted on randomized controlled trials of patients with ESUS, comparing anticoagulation with antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke, and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled risk ratios (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 was used for risk-of-bias assessment., Results: A total of 7 randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I 2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I 2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I 2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy., Discussion: In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate-to-severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.

Background: Several studies investigated the risks of neurological conditions in patients with inflammatory bowel disease (IBD), with some variability in findings. We aimed to perform a systematic review and meta-analysis of available evidence to elucidate the association between IBD and the risks of common neurological disorders., Methods: We conducted a literature search through Embase, PubMed, Scopus, and ProQuest databases from inception to June 30, 2023, to identify cohort studies assessing the risk of developing stroke, all-cause dementia, Parkinson's disease (PD), multiple sclerosis (MS), seizure/epilepsy, and peripheral neuropathy in adult IBD patients compared with non-IBD population. We combined hazard ratios (HRs) with 95% confidence intervals (CIs) to compute pooled estimates using a random-effects model., Results: In total, 22 cohort studies were included, of which 9 studies reported 7074 stroke events in 202 460 IBD patients, 5 studies reported 3783 all-cause dementia diagnoses in 109 602 IBD patients, 7 studies reported 932 PD diagnoses in 354 792 IBD patients, and 1 study reported 6 MS events in 35 581 IBD patients. We observed increased risks of incident stroke (pooled HR = 1.19; 95% CI, 1.06-1.31), all-cause dementia (pooled HR = 1.22; 95% CI, 1.05-1.38), PD (pooled HR = 1.39; 95% CI, 1.20-1.58), and MS (HR = 2.89; 95% CI, 1.02-8.42). No eligible studies were found on peripheral neuropathy and seizure/epilepsy., Conclusions: Inflammatory bowel disease may be modestly associated with increased risks of stroke, all-cause dementia, and PD. Further longitudinal studies are warranted to investigate potential links with MS, seizure/epilepsy, and peripheral neuropathy, as well as their clinical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: While there are several completed clinical trials that address treatment strategies in patients with symptomatic and recurrent atrial fibrillation (AF), there are no randomized clinical trials that address first-line rhythm control of new-onset AF. Recent data suggest that early initiation of rhythm control within 1 year can improve outcomes., Methods: In this open-label pragmatic clinical trial nested within the Get with The Guidelines Atrial Fibrillation registry, approximately 3,000 patients with first-detected AF will be enrolled at approximately 200 sites. Participants will be randomized (1:1) to treatment with dronedarone in addition to usual care versus usual care alone. The primary endpoint will be time to first cardiovascular (CV) hospitalization or death from any cause through 12 months from randomization. Secondary endpoints will include a WIN ratio (all-cause death, ischemic stroke or systemic embolism, heart failure hospitalization, acute coronary hospitalization), CV hospitalization, and all-cause mortality. Patient reported outcomes will be analyzed based on change in Atrial Fibrillation Effect on Quality of Life (AFEQT) and change in Mayo AF-Specific Symptom Inventory (MAFSI) from baseline to 12 months., Conclusion: CHANGE AFIB will determine if treatment with dronedarone in addition to usual care is superior to usual care alone for the prevention of CV hospitalization or death from any cause in patients with first-detected AF. The trial will also determine whether initiation of rhythm control at the time of first-detected AF affects CV events or improves patient reported outcomes., Trial Registration: - NCT05130268., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Little is known about the incidence of late onset epilepsy (LOE) across different racial/ethnic groups in the USA, particularly in the Hispanic population. Stroke, a strong predictor of LOE, is more common in non-Hispanic Blacks (NHBs) and Hispanics than in non-Hispanic Whites (NHWs). We assessed the incidence of LOE across racial/ethnic groups and examined whether the associations of stroke with LOE risk differ by race/ethnicity., Methods: The Northern Manhattan Study is a population-based longitudinal study of older adults enrolled between 1993 and 2001. Participants free of history of stroke or epilepsy at baseline (n = 3419) were followed prospectively for incidence of LOE. We estimated LOE incidence per 1000 person-years in each racial/ethnic group. We used Cox proportional hazards regression to assess the association of race/ethnicity with LOE and multiplicative interactions of race/ethnicity with incident stroke in relation to LOE, adjusting for demographics and comorbid diagnoses., Results: During 51 176 person-years of follow-up, 183 individuals developed LOE. Incidence of LOE was significantly higher in NHBs (6.2 per 1000 person-years) than in NHWs (3.3 per 1000 person-years, p = .004). There was no significant difference in LOE incidence between NHWs (3.3 per 1000 person-years) and Hispanics (2.6 per 1000 person-years, p = .875). However, following incident stroke, the risk of LOE differed across racial/ethnic groups. Incident stroke was associated with 2.55 times the risk of LOE among NHWs (95% confidence interval [CI] = .88-7.35), 8.53 times the risk of LOE among Hispanics (95% CI = 5.36-13.57, p = .04 for stronger association than that in NHWs), and 6.46 times the risk of LOE among NHBs (95% CI = 3.79-11.01, p = .12 for stronger association than that in NHWs)., Significance: We found a stronger association of incident stroke with LOE risk in Hispanics and NHBs than in NHWs, offering some insight into the racial/ethnic disparities of LOE incidence., (© 2024 International League Against Epilepsy.)

Background: Heart failure (HF) prevalence is increasing, especially among older adults. Left atrial (LA) dysfunction is often associated with HF, but it is unclear whether it may contribute to its development. We investigated whether measures of LA function can predict the development of HF in older adults without a history of cardiovascular events., Methods and Results: Seven hundred ninety-five participants from a triethnic (white, Black, Hispanic) community-based cohort of adults age ≥55 without a history of cardiovascular events underwent standard, three-dimensional, and speckle-tracking echocardiography. Left atrial volumes, LA strain, LA stiffness, and LA coupling index (LACI) were measured. Longitudinal follow-up was conducted, and new-onset HF was ascertained through standardized interviews, in-person visits, and active hospital surveillance of admission and discharge ICD-9 codes. Risk analysis with a cause-specific hazards regression model was used to assess the association of LA variables with incident HF, adjusting for other HF risk factors. The mean age was 70.9 ± 9.2 years (297 men, 498 women). During a mean follow-up of 11.4 years, new-onset HF occurred in 345 participants (43.4%). All measures of LA morphology and function were associated with incident HF (all P < .05). In multivariable analysis, LA stiffness and LACI (adjusted hazard ratio = 2.06; 95% CI, 1.08-3.94; adjusted hazard ratio = 1.25; 95% CI, 1.09-1.43, respectively) remained associated with incident HF. After further adjustment for left ventricular global longitudinal strain, only LACI remained associated with incident HF (adjusted hazard ratio = 1.22; 95% CI, 1.05-1.42)., Conclusions: Left atrial coupling index is a stronger independent predictor for incident HF in older adults than LA volumes and strain and may improve HF risk stratification., Competing Interests: Conflicts of Interest None., (Copyright © 2024 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The American Heart Association (AHA), founded in 1924, is anchored in the core belief that scientific research can lead the way to better prevention, treatment, recovery, and ultimately a cure for cardiovascular disease. Historically, the association's involvement in international efforts centered on scientific cooperation. Activities mostly involved AHA leadership presenting at international scientific meetings and leaders from other countries sharing scientific and medical information at AHA meetings. Although the AHA's and American Stroke Association's international efforts have expanded substantially since those early days, global knowledge exchange remains the bedrock of its international endeavors. As the AHA turns 100, we reflect on the successful global efforts in prevention, resuscitation, global advocacy, quality improvement, and health equity that have guided the organization to a place of readiness for "advancing health and hope, for everyone, everywhere." Motivated by the enormous potential for population health gains in an aging world, the AHA is entering its second century with redoubled commitment to improving global cardiovascular and cerebrovascular health for all.

Objective: Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer., Methods: We studied patients with cancer and IS (CS; n = 42), stroke only (SO; n = 41), and cancer only (n = 28), and vascular risk factor-matched controls (n = 30). mRNA-Seq and miRNA-Seq data, analyzed with linear regression models, identified differentially expressed genes in CS versus SO and in cardioembolic versus noncardioembolic CS, and miRNA-mRNA regulatory pairs. Network-level analyses identified stroke etiology-specific responses in CS., Results: A total of 2,085 mRNAs and 31 miRNAs were differentially expressed between CS and SO. In CS, 122 and 35 miRNA-mRNA regulatory pairs, and 5 and 3 coexpressed gene modules, were associated with cardioembolic and noncardioembolic CS, respectively. Complement, growth factor, and immune/inflammatory pathways showed differences between IS etiologies in CS. A 15-gene biomarker panel assembled from a derivation cohort (n = 50) correctly classified 81% of CS and 71% of SO participants in a validation cohort (n = 33). Another 15-gene panel correctly identified etiologies for 13 of 13 CS-cardioembolic and 11 of 11 CS-noncardioembolic participants upon cross-validation; 11 of 16 CS-cryptogenic participants were predicted cardioembolic., Interpretation: We discovered unique mRNA and miRNA transcriptome architecture in CS and SO, and in CS with different IS etiologies. Cardioembolic and noncardioembolic etiologies in CS showed unique coexpression networks and potential master regulators. These may help distinguish CS from SO and identify IS etiology in cryptogenic CS patients. ANN NEUROL 2024;96:565-581., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: Approximately 10% to 15% of ischemic strokes are associated with cancer; cancer-associated stroke, particularly when cryptogenic, is associated with high rates of recurrent stroke and major bleeding. Limited data exist on the safety and efficacy of different antithrombotic strategies in patients with cancer and cryptogenic stroke., Objective: To compare apixaban vs aspirin for the prevention of adverse clinical outcomes in patients with history of cancer and cryptogenic stroke., Design, Setting, and Participants: Post hoc analysis of data from 1015 patients with a recent cryptogenic stroke and biomarker evidence of atrial cardiopathy in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial, a multicenter, randomized, double-blind clinical trial conducted from 2018 to 2023 at 185 stroke centers in North America. Data analysis was performed from October 15, 2023, to May 23, 2024., Exposures: Oral apixaban, 5 mg (or 2.5 mg if criteria met), twice daily vs oral aspirin, 81 mg, once daily. Subgroups of patients with and without cancer at baseline were examined., Main Outcomes and Measures: The primary outcome for this post hoc analysis was a composite of major ischemic or major hemorrhagic events. Major ischemic events were recurrent ischemic stroke, myocardial infarction, systemic embolism, and symptomatic deep vein thrombosis or pulmonary embolism. Major hemorrhagic events included symptomatic intracranial hemorrhage and any major extracranial hemorrhage., Results: Among 1015 participants (median [IQR] age, 68 [60-76] years; 551 [54.3%] female), 137 (13.5%) had a history of cancer. The median (IQR) follow-up was 1.5 (0.6-2.5) years for patients with history of cancer and 1.5 (0.6-3.0) years for those without history of cancer. Participants with history of cancer, compared with those without history of cancer, had a higher risk of major ischemic or major hemorrhagic events (hazard ratio [HR], 1.73; 95% CI, 1.10-2.71). Among those with history of cancer, 8 of 61 participants (13.1%) randomized to apixaban and 16 of 76 participants (21.1%) randomized to aspirin had a major ischemic or major hemorrhagic event; however, the risk was not significantly different between groups (HR, 0.61; 95% CI, 0.26-1.43). Comparing participants randomized to apixaban vs aspirin among those with cancer, events included recurrent stroke (5 [8.2%] vs 9 [11.8%]), major ischemic events (7 [11.5%] vs 14 [18.4%]), and major hemorrhagic events (1 [1.6%] vs 2 [2.6%])., Conclusions and Relevance: Among participants in the ARCADIA trial with history of cancer, the risk of major ischemic and hemorrhagic events did not differ significantly with apixaban compared with aspirin., Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Objective: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship., Methods: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships., Results: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia., Conclusions: Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

Background: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging., Methods and Results: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (β=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment., Conclusions: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases., (© 2024. Springer Nature Limited.)

Background: Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment., Methods: We used nationally representative health, economic, and demographic data to project health care costs attributable to key cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia) and conditions (coronary heart disease, stroke, heart failure, atrial fibrillation) through 2050. The human capital approach was used to estimate productivity losses from morbidity and premature mortality due to cardiovascular conditions., Results: One in 3 US adults received care for a cardiovascular risk factor or condition in 2020. Annual inflation-adjusted (2022 US dollars) health care costs of cardiovascular risk factors are projected to triple between 2020 and 2050, from $400 billion to $1344 billion. For cardiovascular conditions, annual health care costs are projected to almost quadruple, from $393 billion to $1490 billion, and productivity losses are projected to increase by 54%, from $234 billion to $361 billion. Stroke is projected to account for the largest absolute increase in costs. Large relative increases among the Asian American population (497%) and Hispanic American population (489%) reflect the projected increases in the size of these populations., Conclusions: The economic burden of cardiovascular risk factors and overt cardiovascular disease in the United States is projected to increase substantially in the coming decades. Development and deployment of cost-effective programs and policies to promote cardiovascular health are urgently needed to rein in costs and to equitably enhance population health.

Background: Cardiovascular disease and stroke are common and costly, and their prevalence is rising. Forecasts on the prevalence of risk factors and clinical events are crucial., Methods: Using the 2015 to March 2020 National Health and Nutrition Examination Survey and 2015 to 2019 Medical Expenditure Panel Survey, we estimated trends in prevalence for cardiovascular risk factors based on adverse levels of Life's Essential 8 and clinical cardiovascular disease and stroke. We projected through 2050, overall and by age and race and ethnicity, accounting for changes in disease prevalence and demographics., Results: We estimate that among adults, prevalence of hypertension will increase from 51.2% in 2020 to 61.0% in 2050. Diabetes (16.3% to 26.8%) and obesity (43.1% to 60.6%) will increase, whereas hypercholesterolemia will decline (45.8% to 24.0%). The prevalences of poor diet, inadequate physical activity, and smoking are estimated to improve over time, whereas inadequate sleep will worsen. Prevalences of coronary disease (7.8% to 9.2%), heart failure (2.7% to 3.8%), stroke (3.9% to 6.4%), atrial fibrillation (1.7% to 2.4%), and total cardiovascular disease (11.3% to 15.0%) will rise. Clinical CVD will affect 45 million adults, and CVD including hypertension will affect more than 184 million adults by 2050 (>61%). Similar trends are projected in children. Most adverse trends are projected to be worse among people identifying as American Indian/Alaska Native or multiracial, Black, or Hispanic., Conclusions: The prevalence of many cardiovascular risk factors and most established diseases will increase over the next 30 years. Clinical and public health interventions are needed to effectively manage, stem, and even reverse these adverse trends.

Fibrinolytic agents catalyze the conversion of the inactive proenzyme plasminogen into the active protease plasmin, degrading fibrin within the thrombus and recanalizing occluded vessels. The history of these medications dates to the discovery of the first fibrinolytic compound, streptokinase, from bacterial cultures in 1933. Over time, researchers identified two other plasminogen activators in human samples, namely urokinase and tissue plasminogen activator (tPA). Subsequently, tPA was cloned using recombinant DNA methods to produce alteplase. Several additional derivatives of tPA, such as tenecteplase and reteplase, were developed to extend the plasma half-life of tPA. Over the past decades, fibrinolytic medications have been widely used to manage patients with venous and arterial thromboembolic events. Currently, alteplase is approved by the U.S. Food and Drug Administration (FDA) for use in patients with pulmonary embolism with hemodynamic compromise, ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and central venous access device occlusion. Reteplase and tenecteplase have also received FDA approval for treating patients with STEMI. This review provides an overview of the historical background related to fibrinolytic agents and briefly summarizes their approved indications across various thromboembolic diseases., Competing Interests: Dr. O'Donoghue has received grant funding from Amgen, Novartis, and AstraZeneca and consulting fees from Amgen, Novartis, AstraZeneca, and Janssen. Dr. O'Donoghue has advisory roles at AstraZeneca, Janssen, and NovoNordisk. Dr. Jimenez is a member of the Steering Committee of the PEITHO III. Dr. Monreal reports nonrestricted research grants to sponsor the RIETE registry from Sanofi and Rovi Laboratories. Dr. Anderson is supported by NIH R01NS103924, U01NS069673, AHA 18SFRN34250007, AHA-Bugher 21SFRN812095, and the MGH McCance Center for Brain Health. Dr. Anderson has received sponsored research support from Bayer AG, Massachusetts General Hospital, and the American Heart Association and has consulted for ApoPharma Inc. Dr. Elkind is an employee of the American Heart Association and has received study drug-in-kind from the BMS-Pfizer Alliance for Eliquis and ancillary funding from Roche for an NIH-funded trial of stroke prevention; honoraria from the Atria Academy of Science and Medicine; and royalties for chapters on stroke from UpToDate. Dr. Baumann Kreuziger has received sponsored research support from NHLBI, the American Society of Hematology, Takeda, and CSL Behring. Dr. Lang receives research support from AOP-Health, and consulting fees from AOP-Health, J&J, MSD, and United Therapeutics. Dr. Lang receives lecture fees from AOP-Health, J&J, MSD, Pulnovo, and United Therapeutics, and support for attending meetings from Medtronic. Dr. Konstantinides reports personal lecture and advisory fees as well as research grants via his institution from Bayer AG, Boston Scientific, Daiichi-Sankyo, LumiraDx, and Penumbra; he also reports personal lecture/advisory fees from MSD and Pfizer—Bristol-Myers Squibb. Dr. Piazza has received research grants from BMS/Pfizer, Janssen, Alexion, Bayer, Amgen, BSC, Esperion, and 1R01HL164717–01. Dr. Piazza has advisory roles at BSC, Amgen, BCRI, PERC, NAMSA, BMS, Janssen, and Regeneron. Dr. Krumholz received expenses and/or personal fees from United-Health, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, and F-Prime; he is a co-founder of Refactor Health and Hugo-Health; and contracts through Yale New Haven Hospital from the Centers for Medicare & Medicaid Services and through Yale University from Johnson & Johnson. Dr. Braunwald reports research grants through his institution from Astra Zeneca, Daiichi Sankyo, and Novartis, and consultancy fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Cardurion, Edgewise, and Verve. Dr. Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814). Dr. Bikdeli was supported by the Scott Schoen and Nancy Adams IGNITE Award and is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women's Hospital. Dr. Bikdeli reports that he was a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. Dr. Bikdeli has not been involved in the litigation in 2022–2024 nor has he received any compensation in 2022–2024. Dr. Bikdeli reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum, and serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. Other authors report no disclosures., (Thieme. All rights reserved.)

Background and Aims: Most cancer patients require surgery for diagnosis and treatment. This study evaluated whether cancer is a risk factor for perioperative arterial ischaemic events., Methods: The primary cohort included patients registered in the National Surgical Quality Improvement Program (NSQIP) between 2006 and 2016. The secondary cohort included Healthcare Cost and Utilization Project (HCUP) claims data from 11 US states between 2016 and 2018. Study populations comprised patients who underwent inpatient (NSQIP, HCUP) or outpatient (NSQIP) surgery. Study exposures were disseminated cancer (NSQIP) and all cancers (HCUP). The primary outcome was a perioperative arterial ischaemic event, defined as myocardial infarction or stroke diagnosed within 30 days after surgery., Results: Among 5 609 675 NSQIP surgeries, 2.2% involved patients with disseminated cancer. The perioperative arterial ischaemic event rate was 0.96% among patients with disseminated cancer vs. 0.48% among patients without (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.90-2.13). In Cox analyses adjusting for demographics, functional status, comorbidities, surgical specialty, anesthesia type, and clinical factors, disseminated cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.37; 95% CI, 1.28-1.46). Among 1 341 658 surgical patients in the HCUP cohort, 11.8% had a diagnosis of cancer. A perioperative arterial ischaemic event was diagnosed in 0.74% of patients with cancer vs. 0.54% of patients without cancer (HR, 1.35; 95% CI, 1.27-1.43). In Cox analyses adjusted for demographics, insurance, comorbidities, and surgery type, cancer remained associated with higher risk of perioperative arterial ischaemic events (HR, 1.31; 95% CI, 1.21-1.42)., Conclusion: Cancer is an independent risk factor for perioperative arterial ischaemic events., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden., Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days., Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection., Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires., Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days., Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections., Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Background: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia., Methods: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population., Results: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages., Conclusions: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia., Competing Interests: Disclosures None.