Clonal Hematopoiesis and Risk of New-Onset Myocarditis and Pericarditis.

Importance: Clonal hematopoiesis of indeterminate potential (CHIP) is the age-related clonal expansion of hematopoietic stem cells with leukemia-associated mutations. Certain CHIP mutations promote atherosclerosis and heart failure through immune-related pathways.

Objective: To test whether CHIP is associated with the development of myocarditis and pericarditis.

Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion.

Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset.

Gut microbiota-derived imidazole propionate predicts cardiometabolic risk in patients with coronary artery disease.

Background And Aims: The gut microbiota is a modulator of cardiometabolic disease. Circulating imidazole propionate (ImP) is a microbiota-derived proatherogenic amino acid metabolite modulating the inflammatory response of myeloid cells, endothelial function and glucose metabolism. This study examined the prognostic value of ImP in patients with coronary artery disease (CAD).

Eicosapentaenoic acid (EPA) limits the more rapid oxidation of lipoprotein(a) [Lp(a)] compared with other ApoB particles.

Aims: Elevated Lp(a) levels increase cardiovascular (CV) risk. Lp(a) contains oxidized phospholipids that may promote lipid oxidation more than other lipoproteins. The highly unsaturated omega-3 fatty acid EPA has multiple double bonds that can trap free radicals in resonance structures.

Lipoprotein(a) and Venous Thromboembolism: Association, Causality, and Medications.

Lipoprotein(a) [Lp(a)] is a circulating plasma lipoprotein with structural similarities to low-density lipoprotein (LDL), distinguished by the addition of apolipoprotein(a) to the LDL structure. Lp(a) levels are approximately 80% genetically determined, and distinct components of this complex particle are thought to confer atherogenic, inflammatory, and antifibrinolytic properties contributing to cardiovascular risk. A growing body of evidence has shown a causal association between elevated Lp(a) levels and both atherosclerotic cardiovascular disease (ASCVD) and valvular aortic stenosis.

Myocardial infarction, stroke and arterial stenosis: time to reassess a major misunderstanding.

A misconception persisting among the scientific and clinical communities relates to the correlation between arterial stenosis and acute ischaemic events, including myocardial infarction and cerebral stroke. This Perspective article challenges the approach that most of the current guidelines codify, which is based on the concept that occlusive arterial stenosis generally provokes ischaemic events. We highlight the mechanistic differences between chronic or inducible ischaemia caused by flow-limiting stenoses and acute thrombotic events and question the traditional reliance on stenosis grading as a biomarker for therapeutic decision-making that many guidelines enshrine.

Multitargeted Reduction of Inflammation and Atherosclerosis in -deficient CHIP via XPO1 Inhibition and Atf3 restoration.

is the second most frequently mutated gene in clonal hematopoiesis of indeterminate potential (CHIP), driving hematopoietic stem cell clonal expansion and increasing the risk of myeloid malignancies. Affected individuals often develop atherosclerotic cardiovascular disease, exacerbated by hyperinflammatory -mutant macrophages. Here, we show that the XPO1 nuclear export inhibitor eltanexor significantly reduces atherosclerotic plaque formation in a mouse model of -mutant CHIP.

Vaccination as a new form of cardiovascular prevention: a European Society of Cardiology clinical consensus statement.

Vaccination is increasingly acknowledged as an effective preventive measure not only against specific infections, but also for the prevention of cardiovascular disease in high-risk patients. Specifically, a growing body of evidence suggests that vaccines against influenza, SARS-CoV-2, respiratory syncytial virus, herpes zoster, and other viruses significantly reduce infection and for influenza the incidence of major adverse cardiovascular events in vaccinated individuals. This clinical consensus statement examines the existing literature and accumulated evidence and offers practical clinical advice on vaccination timing and target demographics, specifically addressing complex clinical scenarios with a focus on cardiovascular conditions.

Enhanced Trained Immunity in Peripheral Monocytes in Unstable Angina With Elevated High-Sensitivity C-Reactive Protein.

Despite effective secondary prevention for coronary heart diseases, recurrent events remain high. Elevated high-sensitivity C-reactive protein (hsCRP) indicates increased inflammation risk. This study aimed to investigate the trained immunity of circulating monocytes in unstable angina (UA) patients with elevated hsCRP.

Vaccination in patients with heart failure in practice.

This narrative review underscores the pivotal role of vaccination in mitigating respiratory infections and associated acute decompensations in heart failure (HF) patients. It highlights the necessity for heightened awareness and proactive engagement among healthcare providers to bridge vaccination gaps and enhance preventive care for HF patients. Respiratory pathogens, such as influenza, pneumococcus, SARS-CoV2, and Herpes zoster virus (VZV), instigate systemic inflammation and increase cardiovascular events, markedly elevating the risk of HF and strokes, especially in individuals with preexisting conditions.

Direct Interleukin-6 Inhibition Blunts Arterial Thrombosis by Reducing Collagen-Mediated Platelet Activation.

Background: Recent clinical trials demonstrated a reduction in biomarkers of thrombosis and inflammation in patients with very high cardiovascular risk treated with the anti-IL-6 (interleukin 6) monoclonal antibody ziltivekimab. However, if and how direct IL-6 inhibition exerts antithrombotic effects remains unknown. This translational project aimed to investigate the effect of direct IL-6 inhibition on experimental arterial thrombus formation and its underlying cellular mechanisms.

Global Variation in Lipoprotein(a) Levels Among Patients With Coronary Heart Disease: Insights From the INTERASPIRE Study and Implications for Emerging Lp(a)-Lowering Therapies.

Background: Lipoprotein(a) [Lp(a)] is a common risk factor for atherosclerotic cardiovascular disease, potentially more atherogenic per particle than low-density lipoprotein. An estimated 1.5 billion individuals globally have elevated levels ≥125 nmol/L, considered as a risk-enhancing threshold.

Acute coronary syndromes: mechanisms, challenges, and new opportunities.

Despite advances in research and patient management, atherosclerosis and its dreaded acute and chronic sequelae continue to account for one out of three deaths globally. The vast majority of acute coronary syndromes (ACS) arise from either plaque rupture or erosion, but other mechanisms, including calcific nodules, embolism, spontaneous coronary artery dissection, coronary spasm, and microvascular dysfunction, can also cause ACS. This ACS heterogeneity necessitates a paradigm shift in its management that extends beyond the binary interpretation of electrocardiographic and biomarker data.

A Protein Corona-Based Diagnostic Tool for Eroded Atherosclerotic Plaques.

Superficial plaque erosion, distinct from plaque rupture, represents a cause of residual thrombotic complications in atherosclerosis. Being able to detect plaque erosion, a mechanism that now accounts for up to 30% of acute coronary syndromes, can lead to targeted therapies, and perhaps avoid the need for urgent invasive interventions required for plaque rupture cases, thus greatly affecting clinical management. Nanoparticles (NPs) exposed to biological fluids acquire a layer of proteins on their surface, the protein corona (PC).

Frequency of residual combined dyslipidemia and hypertriglyceridemia in patients with coronary heart disease in 13 countries across 6 WHO Regions: Results from INTERASPIRE.

Background And Aims: Hypertriglyceridemia (HTG) is independently associated with risk of atherosclerotic events, even when LDL-cholesterol levels appear controlled. This INTERASPIRE study determined the frequency of HTG and residual combined dyslipidemia and their related factors in patients with coronary heart disease (CHD) from 13 countries across six World Health Organization (WHO) regions.

Methods: Participants with CHD underwent a standardized study interview and examination, including a centralized analysis of fasting blood samples.

Implementation strategies for improving the care of familial hypercholesterolaemia from the International Atherosclerosis Society: next steps in implementation science and practice.

Familial hypercholesterolaemia (FH) is the most common monogenic condition associated with premature atherosclerotic cardiovascular disease. Early detection and initiation of cholesterol lowering therapy combined with lifestyle changes improves the prognosis of patients with FH significantly. The International Atherosclerosis Society (IAS) published a new guidance for implementing best practice in the care of FH.

Impact of Apolipoprotein A-I Infusions on Cardiovascular Events Post-MI by Neutrophil-Lymphocyte Ratio and LDL-Cholesterol Levels.

Background: The AEGIS-II (ApoA-I Event Reducing in Ischemic Syndromes-II; NCT03473223) trial evaluated CSL112, a human plasma-derived apolipoprotein A-I therapy, for reducing cardiovascular events after acute myocardial infarction (AMI). Given CSL112's potential anti-inflammatory properties, we conducted an exploratory post hoc analysis to determine if its efficacy is influenced by baseline neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation, and low-density lipoprotein cholesterol (LDL-C).

Objectives: The purpose of this study was to investigate the association of baseline NLR and cardiovascular events and explore whether NLR and LDL-C modify CSL112's efficacy in post-AMI patients.

Endothelial dysfunction drives atherosclerotic plaque macrophage-dependent abdominal aortic aneurysm formation.

Currently there is no effective pharmacotherapy to prevent the growth and rupture of abdominal aortic aneurysms. Using a mouse model that combines cigarette smoke exposure and hypercholesterolemia, we demonstrated that cigarette smoke exacerbated atherosclerosis, leading to elastin fragmentation, aneurysm formation, rupture and death. Arterial injury was driven by macrophages that accumulated within atherosclerotic plaques and exhibited tissue-degrading proteolytic activity in vivo (a process dependent on the endothelial cell-derived macrophage growth factor CSF-1).

Sex and the Garden of Eden.

Despite only one chromosome differing between men and women, sex makes an enormous difference in clinical cardiovascular diseases. Recent multi-omic data expand our understanding of the underlying mechanisms that may contribute to this disparity in humans.

Plaque erosion risk and JAK2 V617F variant.

Background And Aims: Clonal haematopoiesis of indeterminate potential (CHIP) can increase the risk of myocardial infarction (MI). Among various CHIP mutations, JAK2 V617F substantially elevated this risk. However, the specific associations between JAK2 V617F and two mechanisms of MI, plaque erosion and plaque rupture, remain unclear.

Vulnerable or High-Risk Plaque: A JACC: Cardiovascular Imaging Position Statement.

The concept of high-risk plaque emerged from pathologic and epidemiologic studies 3 decades ago that demonstrated plaque rupture with thrombosis as the predominant mechanism of acute coronary syndrome and sudden cardiac death. Thin-cap fibroatheroma, a plaque with a large lipidic core covered by a thin fibrous cap, is the prototype of the rupture-prone plaque and has been traditionally defined as "vulnerable plaque." Although knowledge on the pathophysiology of plaque instability continues to grow, the risk profile of our patients has shifted and the character of atherosclerotic disease has evolved, partly because of widespread use of lipid-lowering therapies and other preventive measures.