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Objectives: To determine the prevalence and distribution of intracranial vessel occlusion identified on computed tomography (CT) or magnet resonance (MR) angiography and to explore its association with functional outcome in patients with atrial fibrillation (AF) and ischemic stroke. Methods: Multicenter cohort study enrolling consecutive patients with AF with imaging‐confirmed ischemic stroke who underwent CT‐ or MR‐angiography on admission (2014–2022). Multivariable regression was used to explore the association between intracranial vessel occlusion and poor functional outcome (modified Rankin Scale score 3–6) at 90 days. Results: The analysis included 10,164 patients (median age 81.5 years, 47.8% female, median National Institutes of Health Stroke Scale score on admission 6; 14.7% on a vitamin K antagonist [VKA], 27.5% on a direct oral anticoagulant [DOAC], 57.8% not receiving oral anticoagulation). Angiography showed intracranial vessel occlusion in 5,190 patients (51.1%), affecting the anterior cerebral circulation in 87.4%. Overall, 29.2% and 29.4% of patients received thrombolysis and mechanical thrombectomy, respectively. The proportion of patients with poor functional outcome at 90 days was 60.6% and 42.7% in those with and without vessel occlusion, respectively. In multivariable analyses, vessel occlusion was associated with poor functional outcome (adjusted odds ratio [aOR]: 1.95, 95% confidence interval [CI]: 1.71–2.22) with consistent results in subgroups according to oral anticoagulation use (VKA, aOR: 1.98, 95% CI: 1.40–2.80; DOAC, aOR: 2.35, 95% CI: 1.83–3.03; none, aOR: 1.76, 95% CI: 1.49–2.09). Interpretation: Intracranial vessel occlusion is common in patients with AF with ischemic stroke, mainly affects the anterior circulation and is associated with poor functional outcome. ANN NEUROL 2024;96:1115–1123 [ABSTRACT FROM AUTHOR]

Background and purposeChronic infections and cardiac dysfunction are risk factors for stroke. We hypothesized that blood biomarkers of infection (procalcitonin) and cardiac dysfunction (midregional proatrial natriuretic peptide [MR-proANP]), previously associated with small vessel stroke and cardioembolic stroke are also associated with subclinical cerebrovascular damage, including silent brain infarcts and white matter hyperintensity volume.MethodsThe NOMAS (Northern Manhattan Study) was designed to assess risk factors for incident vascular disease in a multiethnic cohort. A subsample underwent brain magnetic resonance imaging and had blood samples available for biomarker measurement (n=1178). We used logistic regression models to estimate the odds ratios and 95% confidence intervals (95% CIs) for the association of these biomarkers with silent brain infarcts after adjusting for demographic, behavioral, and medical risk factors. We used linear regression to assess associations with log-white matter hyperintensity volume.ResultsMean age was 70±9 years; 60% were women, 66% Hispanic, 17% black, and 15% were white. After adjusting for risk factors, subjects with procalcitonin or MR-proANP in the top quartile, compared with the lowest quartile were more likely to have silent brain infarcts (adjusted odds ratio for procalcitonin, 2.2; 95% CI, 1.3-3.7 and for MR-proANP, 3.3; 95% CI, 1.7-6.3) and increased white matter hyperintensity volume (adjusted mean change in log-white matter hyperintensity volume for procalcitonin, 0.29; 95% CI, 0.13-0.44 and for MR-proANP, 0.18; 95% CI, 0.004-0.36).ConclusionsHigher concentrations of procalcitonin, a marker of infection, and MR-proANP, a marker of cardiac dysfunction, are independently associated with subclinical cerebrovascular damage. If further studies demonstrate an incremental value for risk stratification, biomarker-guided primary prevention studies may lead to new approaches to prevent cerebrovascular disease.

Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes. Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population. Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke. Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71–0.89; p < 0.01; I 2 = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70–0.92; p < 0.01; I 2 = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71–1.01; p = 0.06; I 2 = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61–0.86; p < 0.01; I 2 = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61–0.85; p < 0.01; I 2 = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered. Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents. Trial registration: PROSPERO CRD42024515966. [ABSTRACT FROM AUTHOR]

Background: Approximately one in four stroke patients suffer from recurrent vascular events, underlying the necessity to improve secondary stroke prevention strategies. Immune mechanisms are causally associated with coronary atherosclerosis. However, stroke is a heterogeneous disease and the relative contribution of inflammation across stroke mechanisms is not well understood. The optimal design of future randomized control trials (RCTs) of anti-inflammatory therapies to prevent recurrence after stroke must be informed by a clear understanding of the prognostic role of inflammation according to stroke subtype and individual patient factors. Aim: In this narrative review, we discuss (1) inflammatory pathways in the etiology of ischemic stroke subtypes; (2) the evidence on inflammatory markers and vascular recurrence after stroke; and (3) review RCT evidence of anti-inflammatory agents for vascular prevention. Summary of review: Experimental work, genetic epidemiological data, and plaque-imaging studies all implicate inflammation in atherosclerotic stroke. However, emerging evidence also suggests that inflammatory mechanisms are also important in other stroke mechanisms. Advanced neuroimaging techniques support the role of neuroinflammation in blood–brain barrier dysfunction in cerebral small vessel disease (cSVD). Systemic inflammatory processes also promote atrial cardiopathy, incident and recurrent atrial fibrillation (AF). Although several inflammatory markers have been associated with recurrence after stroke, interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) are presently the most promising markers to identify patients at increased vascular risk. Several RCTs have shown that anti-inflammatory therapies reduce vascular risk, including stroke, in coronary artery disease (CAD). Some, but not all of these trials, selected patients on the basis of elevated hsCRP. Although unproven after stroke, targeting inflammation to reduce recurrence is a compelling strategy and several RCTs are ongoing. Conclusion: Evidence points toward the importance of inflammation across multiple stroke etiologies and potential benefit of anti-inflammatory targets in secondary stroke prevention. Taking the heterogeneous stroke etiologies into account, the use of serum biomarkers could be useful to identify patients with residual inflammatory risk and perform biomarker-led patient selection for future RCTs. [ABSTRACT FROM AUTHOR]

Determining the cause of stroke is considered one of the main objectives in evaluating a stroke patient in clinical practice. However, ischemic stroke is a heterogeneous disorder and numerous underlying disorders are implicated in its pathogenesis. Although progress has been made in identifying individual stroke etiology, in many cases underlying mechanisms still remain elusive. Since secondary prevention strategies are tailored toward individual stroke mechanisms, patients whose stroke etiology is unknown may not receive optimal preventive treatment. Cardioembolic stroke is commonly defined as cerebral vessel occlusion by distant embolization arising from thrombus formation in the heart. It accounts for the main proportion of ischemic strokes, and its share to stroke etiology is likely to rise even further in future decades. However, it can be challenging to distinguish cardioembolism from other possible etiologies. As personalized medicine advances, stroke researchers' focus is increasingly drawn to etiology-associated biomarkers. They can provide deeper insight regarding specific stroke mechanisms and can help to unravel previously undetected pathologies. Furthermore, etiology-associated biomarkers could play an important role in guiding future stroke prevention strategies. To achieve this, broad validation of promising candidate biomarkers as well as their implementation in well-designed randomized clinical trials is necessary. This review focuses on the most-promising candidates for diagnosis of cardioembolic stroke. It discusses existing evidence for possible clinical applications of these biomarkers, addresses current challenges, and outlines future perspectives.