Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition associated with increased risk for ventricular arrhythmias and sudden cardiac death. Prior ARVC studies contained majority European-ancestry individuals; however, limited data have shown an increase in disease-associated variants in individuals of African ancestry. This study aimed to assess genotype/phenotype differences by ancestry across several cohorts.

We analyzed genomic and health record data from over 660,000 individuals from 4 population biobanks. We compared the prevalence of predicted pathogenic variants in 4 ARVC-associated genes across ancestries and the association with ARVC-related traits.

We observed that individuals with a PKP2 predicted pathogenic variant were 2 to 3 times as likely to be of African ancestry than European ancestry in MyCode, All of Us, and the UK Biobank. This difference was not seen in the Penn Medicine Biobank (PMBB). PKP2 predicted pathogenic heterozygotes were more likely to have an ARVC-related trait in the MyCode and All of Us cohorts but not in PMBB or UK Biobank.

Although individuals of African ancestry are more likely to carry a PKP2 predicted pathogenic variant, only European ancestry heterozygotes in MyCode and All of Us had increased odds of an ARVC-related trait, suggesting reduced penetrance or clinical underrecognition of disease in individuals of African ancestry.

Ginseng berry saponin (GBS), the primary bioactive constituent of Panax ginseng C.A. Mey (known as "Renshen" in Chinese) berries, exhibits cardioprotective properties, including anti-inflammatory, antioxidant, and anti-fibrotic effects. In traditional Chinese medicine, they are widely used to treat various cardiovascular diseases. Several randomized controlled trials (RCTs) have shown its efficacy for heart failure (HF).

To assess the clinical efficacy and safety of GBS as an adjunct therapy for HF through systematic review and meta-analysis.

A comprehensive and systematic literature search was conducted across seven electronic databases, with no language restrictions, from their respective inception dates through 31 March 2025. These databases included PubMed, the Cochrane Library, EMBASE, Web of Science China National Knowledge Infrastructure China Science and Technology Journal Database (VIP), and Wanfang Data. For quality assessment, the Cochrane Risk of Bias (ROB 2.0) tool was employed, and meta-analyses were performed using Review Manager (RevMan, version 5.4). Under a random-effects model, mean differences and their corresponding 95% confidence intervals (CI) were calculated. Additionally, the certainty of evidence for each outcome was systematically assessed using the GRADE methodology (GRADEpro software v3.6). The study has been registered in PROSPERO, with the registration number CRD420251003193.

The final analysis integrated 32 RCTs, comprising 3,476 HF patients for efficacy and safety assessment. Meta-analysis results indicated that adjunctive GBS therapy significantly improved the following outcomes compared with the control group (all P < 0.01): LVEF (MD = 8.91, 95%CI [6.78, 11.04]), 6MWTD (MD = 63.11, 95%CI [43.27, 82.95]), FS (MD = 2.63, 95%CI [2.04, 3.22]), SV (MD = 6.68, 95%CI [5.56, 7.80]), Cardiac Index (MD = 0.51, 95%CI [0.33, 0.70]), CO (MD = 0.68, 95%CI [0.38, 0.99]), NO (MD = 10.82, 95%CI [7.49, 14.15]), FMD (MD = 2.42, 95%CI [1.45, 3.39]), and NMD (MD = 2.13, 95%CI [1.04, 3.21]). Conversely, adjunctive GBS therapy significantly reduced the following parameters (all P < 0.01): LVEDD (MD = -5.71, 95%CI [-7.59, -3.82]), LVESD (MD = -6.30, 95%CI [-10.00, -2.59]), BNP (MD = -159.86, 95%CI [-199.17, -120.56]), NT-proBNP (MD = -529.13, 95%CI [-673.92, -384.33]), CRP (MD = -1.98, 95%CI [-2.25, -1.71]), hs-CRP (MD = -1.61, 95%CI [-2.66, -0.56]), TNF-α (MD = -20.42, 95%CI [-32.58, -8.26]), MMP-9 (MD = -34.76, 95%CI [-54.96, -14.56]), ET-1 (MD = -20.08, 95%CI [-30.18, -9.98]), SAS score (MD = -7.49, 95%CI [-11.43, -3.55]), SDS score (MD = -14.53, 95%CI [-17.26, -11.80]), HAMA score (MD = -4.48, 95%CI [-6.77, -2.20]), and HAMD score (MD = -5.79, 95%CI [-8.89, -2.68]).

This systematic review suggests that adjunctive GBS therapy may be associated with improvements in surrogate cardiac function measures and patient-reported outcomes in patients with HF. However, these findings should be considered preliminary, as they are derived predominantly from low- and very low-certainty evidence, with no data on hard clinical endpoints such as mortality or hospitalization. Given these substantial limitations, the available evidence does not support the routine clinical use of GBS in HF management. Individualized application may be considered only in the context of shared decision-making and acknowledgment of the underlying evidence uncertainty.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251003193.

Peripheral artery disease (PAD) confers elevated risk for major adverse cardiovascular events (MACE), yet accurate risk stratification remains a challenge, particularly among patients with advanced disease necessitating endovascular revascularization. This study aimed to improve the prediction of MACE in a clearly defined high-risk PAD population (hospitalized patients undergoing endovascular intervention) by identifying novel protein biomarkers and developing a robust risk model. We prospectively analyzed blood samples from 164 hospitalized PAD patients scheduled for endovascular revascularization, employing untargeted plasma proteomics and metabolomics. Differential protein and metabolite profiles were compared between patients with and without subsequent MACE. Several proteins, including MMP3, MMP19, and PRB2, were markedly elevated in patients who developed MACE. A proteomics-based risk model incorporating these biomarkers achieved high discriminative accuracy (area under the curve > 0.80) for identifying individuals at increased risk. Metabolomic profiling revealed additional pathway alterations, notably involving tryptophan and glycogen metabolism, which provided mechanistic insights into cardiovascular complications but were not directly incorporated into the prediction model. This study demonstrates that integrating protein biomarkers markedly improves risk stratification in advanced PAD patients undergoing surgical intervention. The findings offer promising tools for early detection and enable more personalized management for this high-risk subgroup, while also deepening understanding of disease pathophysiology. However, further validation in larger and more diverse prospective cohorts is warranted before these findings can be broadly applied in clinical practice.

Resveratrol, a flavonoid with antioxidant and anti-inflammatory properties, shows therapeutic potential in metabolic, neurological, cardiovascular, viral, allergic, and inflammatory diseases. Preclinical studies demonstrate its mechanisms, including modulation of oxidative stress and inflammatory pathways, while clinical trials suggest benefits in anti-cancer and cardioprotective applications. Resveratrol modulates inflammatory and survival pathways by inhibiting ROS production and suppressing NF-κB and JAK/STAT signaling through the prevention of key phosphorylation and nuclear translocation events. Concurrently, it affects metabolic signaling via AMPK-dependent inhibition of mTOR, leading to altered transcriptional activity. However, inconsistent clinical outcomes and potential side effects, such as gastrointestinal discomfort (e.g., nausea, diarrhea) and drug interactions at high doses, highlight significant limitations. This study reviews clinical data on the effects of resveratrol on disease-specific biomarkers, emphasizing its potential as an adjunct in cancer radiotherapy. The variability in efficacy and safety underscores the need for well-designed clinical trials to validate therapeutic benefits and assess risks. To address these gaps, we propose a comprehensive framework for future research, incorporating standardized methodologies, optimized dosing regimens, and rigorous safety evaluations. This framework aims to clarify resveratrol's efficacy, address its safety concerns, and facilitate its clinical application. By providing a structured roadmap for future investigations, this study seeks to balance the understanding of resveratrol's therapeutic potential with its limitations, paving the way for evidence-based clinical use.

Lipoprotein(a) [Lp(a)] is a useful marker for cardiovascular risk stratification. Previous studies have shown higher Lp(a) levels in women than in men and sex differences in its association with atherosclerosis. The aim of this study was to assess associations between Lp(a) levels and cardiovascular disease (CVD) in men and women with suspected familial hypercholesterolemia (FH). The study included 220 hypercholesterolemic patients (110 men) treated at an outpatient lipid clinic. Clinical data, anthropometric measurements, and laboratory tests were collected. Lipid concentrations were measured enzymatically and Lp(a) by latex-enhanced immunonephelometry. Coronary artery disease (CAD) was present in 27.3% of men and 14.5% of women; 30.9% were current smokers and 84.5% received statin therapy. Median Lp(a) levels were significantly higher in women with CAD than without CAD, whereas no significant difference was observed in men. After age standardization, mean Lp(a) levels did not differ by CAD status in either sex. In age-adjusted logistic regression, CAD in men was associated with smoking and hypertension, while in women it was associated with LDL-C, Lp(a), and smoking. These findings support sex-specific differences in the role of Lp(a) in CAD development and identify Lp(a) as a CVD risk factor in hypercholesterolemic women.

Despite advances in vessel recanalization, ischemic stroke remains a leading cause of mortality, highlighting the need for comprehensive neuroprotective strategies such as remote ischemic conditioning (RIC). This review evaluates the multitargeted mechanisms of RIC, its progress in clinical translation, and the key factors determining its efficacy. In preclinical models, RIC exerts neuroprotection by modulating neuroinflammation, preserving the blood-brain barrier, and promoting angiogenesis and remyelination. Notably, it suppresses multiple programmed cell death pathways, including pyroptosis, apoptosis, ferroptosis, and disulfidptosis. However, analyses of recent high-quality clinical trials (e.g., SERIC-EVT, RESIST, and RICAMIS) reveal heterogeneous efficacy, indicating that clinical success is highly dependent on the specific execution protocol and successful cerebral reperfusion. Furthermore, critical patient-specific variables such as circadian rhythms, baseline systemic inflammation, and levels of both lipoprotein(a) and mean corpuscular hemoglobin (MCH) significantly influence therapeutic outcomes. Ultimately, while RIC is a highly translatable therapeutic strategy, its successful clinical application relies on the standardization of treatment protocols, the use of precision medicine to identify optimal responders, and its integration with existing therapies to maximize long-term stroke recovery.

Despite advances in therapies targeting hemodynamic and neurohormonal axes in heart failure (HF), incomplete reverse remodeling (RR) characterized by persistent myocardial edema and fibrosis remains a major clinical challenge. This review posits that dysfunction of the cardiac lymphatic system, a critical but understudied pathway for interstitial fluid and immune cell clearance, constitutes a fundamental barrier to complete myocardial recovery. We synthesize current evidence outlining the anatomy, developmental biology, and physiological role of cardiac lymphatics in maintaining myocardial fluid homeostasis and immune surveillance. In the context of HF, the lymphatic system undergoes a dynamic evolution: an initial compensatory lymphangiogenic response in the acute phase facilitates the clearance of edema and inflammatory cells, while its subsequent exhaustion or impairment in chronic HF perpetuates a vicious cycle of inflammation, fibrosis, and adverse remodeling. Central molecular pathways, including the VEGF-C/VEGFR-3 axis and transcriptional regulators like PROX1/FOXC2, govern lymphatic growth, integrity, and function. Furthermore, lymphatics actively modulate post-injury immune responses via specialized mechanisms such as CCL21/CCR7-guided cell trafficking. Therapeutically, augmenting cardiac lymphangiogenesis presents a promising strategy to enhance fluid drainage, resolve maladaptive inflammation, and directly support cardiomyocyte survival, thereby creating a conducive milieu for RR. However, translating this potential requires overcoming translational hurdles related to intervention timing, comorbidity-specific lymphatic dysfunction, and the development of targeted delivery systems. This review concludes that harnessing the cardiac lymphatic system represents a paradigm-shifting therapeutic avenue, complementary to existing regimens, with the potential to promote more complete and sustainable reverse remodeling in heart failure.

Premature coronary atherosclerosis remains a primary driver of late-stage mortality in systemic lupus erythematosus (SLE), independent of traditional cardiovascular risk profiles. This mini-review outlines the multifaceted immunometabolic pathways that underpin accelerated atherogenesis in SLE patients. We examine how chronic systemic inflammation modifies the lipoprotein profile toward a pro-oxidant state, characterized by dysfunctional HDL and elevated oxidized LDL. Central to this vascular pathology are type I interferon-driven cascades, excessive neutrophil extracellular trap release, and biased macrophage polarization toward pro-atherogenic phenotypes. Furthermore, the roles of pathogenic autoantibodies, genetic susceptibility, and the metabolic impact of specific immunosuppressants are explored. Integrating these mechanistic insights is essential for refining cardiovascular risk assessment and identifying novel immunomodulatory interventions. Ultimately, understanding the unique SLE-atherosclerosis axis provides a foundation for reducing cardiovascular morbidity and improving long-term outcomes in this vulnerable population.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently identified autoimmune disorder of the central nervous system. It commonly manifests as meningitis, encephalitis, myelitis, or optic neuritis. However, presentations resembling stroke are exceedingly rare. Here, we report a case of autoimmune GFAP astrocytopathy initially misdiagnosed as acute ischemic stroke. The correct diagnosis was later established through the detection of GFAP antibodies in both the patient's serum and cerebrospinal fluid (CSF) using a cell-based assay (CBA). The patient initially responded to corticosteroid therapy; however, a relapse occurred during the tapering phase. After one year of treatment with oral prednisone and azathioprine, the patient achieved remission, with a subsequent negative result for GFAP antibodies. At the three-year follow-up, no recurrence was observed.

Atherosclerosis is characterized by the deposition of lipid within arterial walls, precipitating the initiation and progression of atherosclerotic lesions. Over time, these plaques enlarge and rupture, initiating thrombosis cascades that pose significant risks to patient safety. Conventional therapies, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (eg, statins) and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, predominantly target lipid reduction while overlooking the intricate microenvironment within atherosclerotic plaque. Statins possess limited lipid-lowering efficacy and may even exhibit insensitivity or intolerance in patients. While PCSK9 inhibitors, as adjuvant therapy, demonstrate potent lipid-lowering effects, they fail to further stabilize vulnerable plaques. In contrast, biomaterials have emerged as pivotal tools for addressing unstable plaques. By restoring endothelial cell (EC) function, inhibiting neutrophil activation, modulating macrophage behavior, and preventing the phenotypic transformation of smooth muscle cells, biomaterials effectively promote plaque regression. This review explores the pathogenesis of atherosclerosis and highlights recent advancements in biomaterial-based therapies for vulnerable plaques, aiming to offer novel insights and solutions to this pressing global health challenge.