The residual recurrence risk after atrial fibrillation (AF)-related stroke is high despite anticoagulation, thereby necessitating new therapies. The importance of inflammation in AF is increasingly recognized. However, patients with AF-related stroke were excluded from recent trials of anti-inflammatory therapies. It is uncertain whether associations between IL-6/high-sensitivity C-reactive protein (hsCRP) and poststroke recurrence are modified by AF status. In this study, we aimed to analyze the association between IL-6/hsCRP and recurrence according to AF history.

We leveraged individual participant data from studies identified by systematic review. We analyzed associations between IL-6/hsCRP and recurrent stroke/major adverse cardiovascular events (MACEs) (defined as fatal or nonfatal recurrent stroke or major coronary events) using multivariable Cox regression analyses (conditional logistic regression for 1 study) adjusted for age, sex, index event, cardiovascular risk factors, and medication use, stratified by AF status.

Data from 11 prospective studies with 10,080 patients (2,134 with AF, mean age 70 years, 59.3% male) were included. During 21,080 person-years of follow-up, 1,677 patients had MACEs and 1,342 had recurrent stroke. Inflammatory markers were higher in patients with AF, irrespective of stroke severity and timing of measurement, with elevated levels persisting well beyond the acute phase. hsCRP was associated with recurrent MACEs in patients with AF (adjusted risk ratio [aRR] 1.14, 95% CI 1.04-1.25, per log_e-unit increase) and without AF (aRR 1.08, 1.03-1.13) (P_interaction 0.30). There were similar associations on per-quarter analysis in patients with AF (aRR 1.51, 1.04-2.18) and without AF (aRR 1.32, 1.10-1.59) (Q4 vs Q1). No association was observed between hsCRP and recurrent stroke in either group. For IL-6, there was no evidence of interaction according to AF status for MACEs (P_interaction 0.57) or recurrent stroke (P_interaction 0.82). The aRR per log_e unit for MACE was 1.17 (1.07-1.27) in patients without AF and 1.10 (0.91-1.34) in those with AF. The corresponding aRR for recurrent stroke was 1.15 (1.05-1.25) and 1.12 (0.91-1.37) in patients without and with AF, respectively.

These data highlight the importance of inflammatory mechanisms in vascular recurrence irrespective of AF, provide rationale for the inclusion of patients with AF in trials of anti-inflammatory therapy, and support a selection approach in future trials based on elevated inflammatory marker levels, rather than stroke etiology alone.

Describir la prevalencia de adultos con hipertensión arterial diagnosticada, tratada y controlada, a nivel nacional y por estados, además de estimar el número de personas que podrían desarrollar ECV por tener hipertensión. Material y métodos. Se analizó la información de 34 954 participantes en la Encuesta Nacional de Salud y Nutrición 2021-2024. Se estimaron prevalencias de hipertensión a nivel nacional y estatal. Utilizando la escala de riesgo Globorisk y de la OMS, se estimó el número de personas que podrían desarrollar ECV por tener hipertensión.

A nivel nacional la prevalencia de hipertensión en adultos fue de 29.1%. El 62.9% de los adultos con hipertensión ya había sido diagnosticado y de los que recibía tratamiento farmacológico, 60.1% tenía presión arterial (PA) bajo control. La prevalencia más baja de hipertensión se observó en Colima (20.7%) y la más alta en Sonora (40.6%). Podrían evitarse en los próximos 10 años 1 119 060 eventos de ECV si se normalizara la PA en adultos.

La hipertensión es un problema de salud pública en México y el desempeño del sistema de salud para controlar la PA de los adultos es más bajo en los estados del Norte. Se requieren estrategias poblacionales, prontas y concertadas para reducir la carga de la hipertensión en México.

Determinar la prevalencia de factores de riesgo cardiometabólico (FRCM) en adultos, por sexo y tamaño de localidad para proporcionar evidencia que apoye la planificación de programas preventivos y de atención de enfermedades cardiometabólicas. Material y métodos. Se analizaron datos de 1 880 adultos de 20 años o más participantes en la Encuesta Nacional de Salud y Nutrición Continua 2021, estudio representativo a nivel nacional y por localidad. Los análisis consideraron el diseño complejo de la encuesta.

La obesidad abdominal fue el FRCM más prevalente, el cual afectó a 74% de hombres y 88% de las mujeres. Entre las mujeres, 63% presentó hipoalfalipoproteinemia, 60% colesterol LDL elevado y 32% de las de 40 a 59 años presentó entre 6 y 11 FRCM. En los hombres, 52% mostró hipertrigliceridemia, 51% C-LDL elevado, y 29% de los de 40 a 59 años presentó de 6 a 11 FRCM. Por localidad, los hombres rurales mostraron mayor prevalencia de C-LDL elevado (70%) y las mujeres urbanas niveles bajos de C-HDL. Conclusión. Los resultados evidencian diferencias por sexo y tamaño de localidad en las prevalencias de los FRCM y la necesidad de estrategias preventivas diferenciadas.

Cardiovascular disease (CVD) prevalence is rising among younger women in the United States. Hypertensive disorders of pregnancy (HDP) are early indicators of cardiovascular risk, yet it remains unclear whether HDP independently increase CVD risk or reflect poor prepregnancy health. We aimed to quantify the association between HDP and incident CVD in a diverse, real-world population, with replication of findings across health systems.

We used data from the All of Us research program, encompassing >50 health systems across the United States, to identify women with longitudinal pregnancy and postpartum data (n=17 357; between 2007 and 2022). Multivariable Cox regression estimated adjusted hazard ratios (aHRs) of HDP with CVD (ischemic heart disease, heart failure, or stroke), overall and stratified by prepregnancy cardiometabolic risk factors (hypertension, obesity, diabetes, hyperlipidemia, or chronic kidney disease). Analyses were replicated in an independent health system (n=56 549; between 2016 and 2025) using the Observational Medical Outcomes Partnership Common Data Model.

Participants had a median [interquartile range] age of 30 [25, 35] years; 2719 (16%) identified as Black or African American, and 7267 (42%) identified as Hispanic or Latino. Among those who reported socioeconomic data, 4306 (35%) reported an income <$25 000, and 6429 (37%) a high school education at most. HDP occurred in 2098 (12%) of pregnancies. Over a median of 4.6 years of follow-up, 701 women developed CVD. Overall, HDP were associated with elevated CVD risk (aHR, 1.82 [95% CI, 1.49-2.22]). Regardless of prepregnancy cardiometabolic risk factors, HDP were independently associated with CVD risk (aHR, 2.06 [95% CI, 1.55-2.74] among women without risk factors, and aHR, 1.33 [95% CI, 1.00-1.77] among women with risk factors). Main findings showed similar effect estimates for the risk of HDP with composite CVD (aHR, 2.62 [95% CI, 2.17-3.16]) in the external replication cohort.

In a diverse, national sample of young US women, HDP were a significant marker of premature CVD risk, even in the absence of prepregnancy cardiometabolic risk factors. Integrating pregnancy complications into CVD risk stratification and promoting cardiometabolic health before, during, and after pregnancy may reduce the growing burden of early-onset CVD among women.

The clinical outcomes of bioresorbable vascular scaffolds (BVS) compared with everolimus-eluting stents (EES) beyond 5-year follow-up are unknown.

This study aims to investigate clinical outcomes of BVS 7 years after implantation.

The COMPARE-ABSORB trial is an investigator-initiated, prospective randomised study. Patients at high risk of restenosis were randomly assigned to receive either a BVS or an EES. A dedicated implantation technique was recommended for BVS. The primary endpoint was target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction (TVMI), or clinically indicated target lesion revascularisation (CI-TLR). The primary and co-primary objectives were non-inferiority at 1 year and superiority of BVS at 7 years after a 3-year landmark analysis.

Although enrolment was stopped at 1,670 patients (80% of the intended 2,100 patients; 848 patients receiving BVS and 822 EES) because of high thrombosis and TVMI rates in the BVS arm, non-inferiority for TLF at 1 year was met. At 7-year follow-up subsequent to a 3-year landmark analysis, the TLF rate of BVS was 6.7% versus 5.9% for EES (hazard ratio [HR] 1.14, 95% confidence interval [CI]: 0.76-1.77; p=0.53); therefore, superiority was not met. Cardiac death, TVMI, and device thrombosis rates did not differ between both groups; however, CI-TLR was significantly higher in the BVS arm (4.4% vs 2.2%; HR 1.97, 95% CI: 1.08-3.60; p=0.023).

After complete resorption, no benefit was observed with BVS compared with EES at 7-year follow-up, despite the use of a dedicated implantation protocol for BVS. In fact, after 3 years, more target lesion revascularisations occurred with BVS than with EES.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is critically involved in atherosclerotic plaque formation. Recent clinical evidence suggest that the LOX-1 polymorphisms are linked to the susceptibility and outcomes of ischemic stroke (IS). However, the mechanisms through which LOX-1 influences cerebral ischemia/reperfusion (I/R) injury are not fully understood. In this study, blood samples were obtained from 295 patients with acute IS (AIS), and parallel experimental models including middle cerebral artery occlusion and reperfusion (MCAO/R) in male C57BL/6 mice and oxygen glucose deprivation (OGD) in primary neurons, were used to simulate cerebral I/R injury. Elevated serum soluble LOX-1 (sLOX-1) levels were detected in patients with AIS and showed positive correlations with both infarct volume and the 3-month modified Rankin scale (mRS) score. In mice, LOX-1 overexpression increased infarct volume, aggravated neurological deficits, and reduced cerebral blood flow (CBF), whereas LOX-1 knockdown produced the opposite effects. Co-immunoprecipitation demonstrated that LOX-1 interacts with key autophagy-lysosome pathway proteins (LC3B, P62, and LAMP2) in primary neurons. Western blotting, immunofluorescence and transmission electron microscopy showed that LOX-1 overexpression suppresses neuronal autophagic flux in peri-infarct brain tissue, while LOX-1 knockdown restores it. Moreover, early activation of autophagy with rapamycin (RAPA) promoted LOX-1 degradation, reduced infarct volume, improved neurological deficits, and restored CBF following cerebral I/R. Collectively, these findings indicated that LOX-1 exacerbates cerebral I/R injury by inhibiting neuronal autophagic flux. Early autophagy activation may therefore represent a promising neuroprotective strategy by facilitating LOX-1 degradation during acute cerebral ischemia.

Diabetic foot ulcers (DFUs) are a chronic complication of diabetes associated with impaired healing and tissue ischemia.

This study explores the transcriptional effects of trimetazidine (TMZ) in wound-relevant human cell models to generate hypotheses regarding its potential mechanisms of action.

We conducted a secondary analysis of LINCS Phase 5 transcriptomic data to evaluate TMZ-induced gene expression in four human cell lines relevant to DFU pathophysiology: HUVEC (endothelial), THP1 (monocytic), A375 (keratinocytic-like), and MCF7 (epithelial-like).

TMZ induced 700-900 differentially expressed genes per cell line, with distinct yet convergent responses across models. A consistent activation of the PI3K-Akt signaling pathway was observed, along with modulation of noncanonical NF-κB components such as RELB and CXCL2. TMZ promoted metabolic reprogramming, including SIRT3 upregulation and glycolysis inhibition, and selectively regulated extracellular matrix remodeling genes. Importantly, pro-angiogenic and anti-inflammatory signatures emerged independently of VEGF, with notable downregulation of PTGS2 and TLR4.

These results highlight TMZ's potential to modulate gene networks associated with angiogenesis, inflammation, and metabolism. The findings are exploratory and warrant validation in preclinical models to assess their therapeutic relevance.

Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with misdiagnosis potentially leading to harmful treatment decisions. DOPA decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for DLB and Parkinson's disease (PD), but quantitative assays are needed for its clinical implementation. Here we report on the development of two DDC immunoassays and the extensive clinical validation of DDC across three clinical cohorts (n = 740), one biologically defined cohort (n = 253), one cohort with detailed dopamine transporter imaging information (n = 102) and one autopsy-confirmed cohort (n = 78). CSF DDC levels were significantly higher in DLB and PD (up to 2.5-fold versus controls; 1.9-fold versus AD), showing area under the curve values > 0.9 for differential diagnosis. Elevated CSF DDC was linked to the presence, but not severity, of motor impairment. In autopsy-confirmed DLB, higher CSF DDC correlated with progressing α-synuclein pathology and immunohistochemistry in DLB and PD brain tissue revealed colocalization of DDC and α-synuclein in the substantia nigra. These findings underscore DDC's value to support DLB and PD diagnosis, paving the way for its clinical implementation using the here-presented developed immunoassays.

The objective of this study was to investigate the effects of rituximab (RTX) intrathecal injection on antibody levels in serum and cerebrospinal fluid (CSF), hippocampal tissue and neuronal injury and the behaviour of central neuropsychological lupus erythematosus (cNPSLE) model mice and to further explore the effects of RTX on microglia (MG) polarisation and related signalling pathways.

Female MRL/lpr mice received intrathecal RTX, with C57BL/6 and MRL/mpj mice as controls. Behavioural performance was evaluated using the open field test, novel object recognition and Porsolt swim task. Autoantibody levels in serum and CSF were measured by ELISA. Hippocampal pathology was assessed by H&E and Nissl staining. M1-type MG activation (Iba-1⁺/CD32⁺), CD20⁺ B-cell infiltration and immunoglobulin G (IgG) deposition were examined via immunohistochemistry and immunofluorescence. Immune transcriptome sequencing and in vitro polarisation assays were used to identify regulatory pathways.

Intrathecal injection of RTX reduced the levels of antibodies in the serum and CSF of MRL/lpr mice and alleviated brain tissue injury and neuronal injury. Moreover, hippocampal MG M1 polarisation was inhibited, and the number of CD20⁺ B cells and expression of IgG were reduced. Transcriptome sequencing revealed that the cAMP-dependent protein kinase A (cAMP/PKA) pathway may be involved in the activation of M1-type MG in the hippocampus. In vitro cell experiments demonstrated that RTX could reduce the expression of kinase cAMP-activated catalytic subunit alpha and phosphorylated-cAMP response element-binding protein/cAMP response element-binding protein through the suppression of the cAMP/PKA pathway, thus inhibiting M1-type MG activation.

The data in this study revealed that the intrathecal injection of RTX can attenuate M1-type MG activation-mediated inflammatory neuronal injury in cNPSLE model mice.

Preeclampsia is a pregnancy-specific multisystem disorder. With a global incidence of 2%-8%, preeclampsia is a major contributor to maternal and neonatal morbidity and mortality. The pathogenesis of preeclampsia is commonly described by a two-stage model. The first stage involves defective placentation in early pregnancy, marked by insufficient extravillous trophoblast invasion, impaired spiral artery remodeling, dysregulated sphingolipid metabolism, and an imbalance in immune tolerance; these anomalies lead to placental ischemia and hypoxia. The second stage consists of systemic maternal responses in the mid-to-late gestation period, including angiogenic imbalance, systemic inflammation, and endothelial dysfunction, which manifest as the clinical symptoms. Recent advances in multi-omics technologies and liquid biopsy have accelerated the discovery of novel biomarkers enabling non-invasive early prediction. Emerging therapeutic strategies target key pathological pathways: low-molecular-weight heparin to restore angiogenic balance and reduce inflammation, complement system inhibitors to counter aberrant activation, and epigenetic modulators to ameliorate endothelial dysfunction. Despite this progress, significant challenges remain, including the heterogeneity of preeclampsia, limited clinical validation of biomarkers and therapeutic targets, and the management of long-term cardiovascular sequelae. Future research should prioritize developing precision prediction models, conducting large-scale clinical trials for targeted therapies, and establishing comprehensive postpartum follow-up systems to improve the prevention, diagnosis, and treatment of preeclampsia.