Ferroptosis, an iron-dependent form of regulated cell death, has been identified as a key factor in the pathogenesis and progression of various cardiovascular diseases (CVDs). The molecular basis of ferroptosis involves lipid peroxidation, iron dysregulation, and antioxidant pathways. Accumulating evidence suggests that ferroptosis is associated with various CVDs, including atherosclerosis, myocardial

Globally, hot weather and heatwaves are claiming lives and are predicted to become increasingly deadly under all future climate change scenarios. Rising global temperatures pose a significant risk on cardiovascular health, disproportionately impacting the elderly and people with cardiovascular disease (CVD). However, despite convincing epidemiological data demonstrating this increased cardiovascular

Obesity is one of the biggest risks to public health in both developed and developing countries, and yet incidence continues to skyrocket. Being the main risk factor for a large number of life-limiting conditions, obesity has the potential to cause enormous damage unless addressed urgently. Heart failure (HF) is the most common cardiovascular disease associated with obesity. The incidence of HF overall

Aims LIPC encodes hepatic lipase (HL), a liver-bound protein with both phospholipase and triglyceride lipase activity, and involved in the catabolism of circulating lipoproteins. We recently identified the gain-of-function variant HL-E97G, with selectively increased phospholipase activity, as a new genetic cause of familial combined hypocholesterolemia in humans. The role of HL in the development of

Aims Platelets contain non-coding RNAs (ncRNAs), and their measurement may complement platelet aggregometry. Methods and results In the community-based Bruneck Study (n = 338), we generated platelet-rich plasma (PRP), platelet-poor plasma (PPP) and platelets. PRP was subjected to aggregometry using various agonists and processed to platelet releasates thereafter. Releasates, PPP and platelets underwent

Aims A comprehensive understanding of the genome-wide regulatory landscape of the cardiac tissues post-myocardial infarction (MI) is still lacking. We therefore integrated single-cell RNA sequencing (scRNA-seq) and single-cell for transposase-accessible chromatin sequencing (scATAC-seq) to elucidate the epigenetic landscape of the heart post-MI. Methods and results We established MI mice through ligation

Ceramides are bioactive lipid mediators involved in apoptosis, inflammation, and fibrosis. This narrative review provides a concise overview of the emerging role of ceramides in cardiovascular disease with emphasis on atherosclerotic vascular disease and heart failure, suggesting a potential use of ceramides in risk stratification and as putative therapeutic targets. Recent developments based on observational

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Section snippets A New Chapter for Guidelines in JACC2055Harlan M. Krumholz Acute Coronary Syndromes: A Holistic View2057Elliott M. Antman, Eugene Braunwald The Long-Awaited American ACS Guideline: Closer to a Universal Document2061Valentin Fuster, Borja Ibanez A Quarter Century of ACS Guidelines: Gaps Within Evidence Gaps2064Celina M. Yong, Robert M. Califf The 2025 American College of Cardiology/American

Section snippets Funding Support and Author DisclosuresIn the past 3 years, Dr Krumholz has received options for Element Science and Identifeye and payments from F-Prime for advisory roles; was a co-founder of and held equity in Hugo Health; is a co-founder of and holds equity in Refactor Health and ENSIGHT-AI; and is associated with research contracts through Yale University from Janssen, Kenvue,

Section snippets Historical PerspectiveCoronary atherosclerosis, long believed to be a recently developed disorder, was identified in Egyptian mummies who lived >4,000 years ago.1 In 1879, Ludvig Hektoen, an American pathologist, proposed that coronary artery thrombosis was the basis of acute myocardial infarction (MI).2 In 1910, 2 Ukrainian physicians, Obraztsov and Strazhesko, described 3 patients

Section snippets Funding Support and Author DisclosuresThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Section snippets Funding Support and Author DisclosuresThe authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Section snippets Creating the Writing CommitteeGuideline writing committees comprise individuals of different but relevant expertise, representatives of collaborating professional societies, liaisons from the ACC/AHA Joint Committee on Clinical Practice Guidelines, and patients. For the 2025 ACS guideline, the expertise of the writing group spanned general cardiology, critical care cardiology, interventional

Section snippets Why the Patient Perspective?Patients often experience acute coronary syndromes as life-altering events that rapidly unfold, leaving them overwhelmed and relieved to defer decision making to clinicians, especially during the acute phase, when fear and mental stress may be high.2,3 Yet even in this acute phase, there may be clinical equipoise, and shared decisions are paramount. For

Section snippets Funding Support and Author DisclosuresDr Bikdeli is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814) outside of the submitted work; was supported by the Scott Schoen and Nancy Adams IGNITE Award; is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology

Section snippets Class 1 Recommendations Regarding DAPT During Hospitalization 1.Prasugrel or ticagrelor is recommended in non–ST-segment elevation acute coronary syndromes (NSTE-ACS) and ST-segment elevation MI patients undergoing percutaneous coronary intervention (PCI). 2.Ticagrelor is recommended for NSTE-ACS patients managed without planned invasive evaluation.The benefit of DAPT in patients with

Section snippets Evidentiary Landscape and Quality of TrialsSupportive evidence for shortened DAPT followed by ticagrelor monotherapy is derived primarily from 5 trials3, 4, 5, 6, 7 that are summarized in Table 1. The heterogeneity between the trials is demonstrated in Table 1: •Trial design—2 placebo-controlled, double-blind trials4,7 and 3 open-label trial3,5,6; •Target populations—2 in patients

Section snippets From Historical Dogma to Contemporary EvidenceFor nearly 2 decades, 12 months of DAPT has been the default strategy after ACS.2 This approach originated with the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which found that clopidogrel plus aspirin significantly reduced cardiovascular death, myocardial infarction (MI), or stroke compared with aspirin alone

Section snippets Funding Support and Author DisclosuresDr Ridker has received institutional research grant support from Kowa, Novartis, Amarin, Pfizer, Esperion, Novo Nordisk, and the National Heart, Lung, and Blood Institute; during the past 3 years has served as a consultant to Novartis, Agepha, Arrowhead, AstraZeneca, CSL Behring, CiVi Biopharma, Merck, SOCAR, Novo Nordisk, Eli Lilly, New Amsterdam

Section snippets Funding Support and Author DisclosuresDr Kaul is a consultant for Abbott, Amgen, Bayer, Edwards, Medtronic, ReCor, and Novo Nordisk.

Section snippets ACS Classification: An Unchanged Relic in Modern GuidelinesThe guideline writing committee has thoughtfully structured their recommendations around the management of ACS subtypes—unstable angina, NSTEMI, and STEMI—primarily attributed to atherosclerotic plaque erosion or rupture with subsequent thrombosis (type I myocardial infarction).2 However, a significant evidence gap persists

Section snippets IABP: An Overdue DowngradeRoutine intra-aortic balloon pump (IABP) use in AMI-CS has been downgraded from Class 2; Level of Evidence: A in the 2013 STEMI guideline2 to Class 3 (no benefit). This change was based on the IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial,3 which showed no mortality benefit at 30-day nor at 6-year follow-ups.4 Routine IABP use in AMI-CS

Section snippets Advancing LDL-C Targets and Combination TherapyThe new guidelines establish more stringent LDL-C targets, with therapy intensification considered reasonable if LDL-C falls between 55 and 69 mg/dL, in particular among patients with significant residual risk factors such as diabetes, polyvascular disease, elevated lipoprotein(a) [Lp(a)], or suspected familial hypercholesterolemia. This

Section snippets Universal health careAustralia has a universal health care system, with 2 primary sources of funding and coordination. The federal government is the primary funder, responsible for delivery of primary and outpatient care, provision of medications, and diagnostic services. State governments are responsible for direct funding and management of their own public hospitals, where 69% of

Section snippets East AsiaEast Asia faces rapidly aging populations and variable access to pharmaceutical agents and devices. Health systems are challenged by rising demand for complex care and the need to balance innovation with affordability. 1.Antithrombotic strategies for secondary prevention after acute coronary syndromes (ACS) vary across countries. In China, clopidogrel and ticagrelor are the

Section snippets Funding Support and Author DisclosuresDr Al Lamee has received an Intermediate Research Fellowship from the British Heart Foundation (FS/ICRF/22/26051); has served on the advisory boards of Janssen Pharmaceuticals, Abbott, Shockwave, and Philips; and has received speaker honoraria from Abbott, Philips, Medtronic, Servier, Omniprex, Shockwave, and Menarini. Dr Byrne has received research

Section snippets Cardiovascular Disease Burden in Latin AmericaThe Latin America and Caribbean region comprises almost one-tenth of the world’s population and 7% of the global gross domestic product.2 In the past, most deaths in Latin America were attributed to infectious diseases; however, Latin America now resembles more high-income countries with ischemic heart disease as the current leading cause

Aims Antibody Drug Conjugates(ADCs) are approved for use in cancers. Cardiovascular adverse reaction is a fatal adverse reactions associated with ADCs. The incidence of adverse cardiac events about ADCs have not been fully studied. We aimed to assess differences in cardiotoxicity among cancer patients treated with different ADCs. Methods and Results An observational retrospective pharmacovigilance

T lymphocytes expressing the CD8 coreceptor, often referred to as cytotoxic T-lymphocytes (CTL), are critical in defending against virus infections and cancers. CD8 encompasses a diverse family of proteins, including homodimers, heterodimers, isoforms, and splice variants. CD8αβ heterodimers are the predominant form of the CD8 membrane protein, often anchored to lipid rafts to facilitate the activation

Background and Aims Heart failure (HF) is a major public health issue, imposing substantial costs on healthcare systems and societies. This study aimed to provide a contemporary overview of its global economic impact. Methods A systematic search of four databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting direct cost

Background and Aims Oral anticoagulation reduces stroke risk in patients with atrial fibrillation (AF) but increases bleeding. Longer fibrin clot lysis time has been shown to predict adverse cardiovascular outcomes in acute coronary syndromes. This study explored relationships between fibrin clot lysis time at randomization and clinical outcomes in patients with AF enrolled in the Apixaban for Reduction

Background and Aims Cardiovascular disease is a leading cause of mortality, with significant investments in research to improve treatment and prevention. Data sharing enhances transparency, reproducibility, and collaboration, yet data sharing statement (DSS) inclusion remains inconsistent. This study evaluates DSS prevalence, content, and influencing factors in high-impact cardiology journals, examines

Hyperglycemia harms vascular health and promotes platelet aggregation. Reducing glucose concentration is crucial, and sugar alcohols may aid this effort. Used for over 50 years in food, cosmetic, and pharmaceutical industries, erythritol and xylitol minimally affect plasma glucose and insulin levels while promoting the release of beneficial gastrointestinal hormones such as e.g. glucagon-like peptide-1

Effective engagement with cardiovascular societies enhances professional development, academic growth and leadership opportunities. We describe practical strategies for cardiovascular professionals to connect with their peers, seek mentorship, advance professionally and contribute as active members of the cardiovascular society, to develop an impactful career and advance the field of cardiac medicine

Background and Aims The efficacy and safety of preventive percutaneous coronary intervention (PCI) for treating vulnerable plaques in diabetic patients remain unclear. Methods The PREVENT (Preventive Coronary Intervention on Stenosis with Functionally Insignificant Vulnerable Plaque) trial was a randomized clinical trial that compared preventive PCI plus optimal medical therapy with optimal medical

Background and Aims The randomized CENTURY trial tested the hypothesis that a comprehensive strategy integrating intense lifestyle modification and aggressive medical management to goals with revascularization reserved for severely reduced coronary flow capacity (CFC) by positron emission tomography (PET) would reduce risk factors, subsequent revascularization, death and myocardial infarction (MI)

BACKGROUND Sarcolemmal small conductance Ca2+-activated K+ channels have the unique capacity to translate intracellular Ca2+ signal into repolarization, while mitochondrial SK channels can link Ca2+ cycling to mitochondrial function. We hypothesize that pharmacological enhancement of SK channels can be protective against malignant cardiac arrhythmias associated with disturbances in Ca2+ handling machinery

Transcriptional regulation is essential for the development, homeostasis, and function of all organisms. Transcription factors and epigenetic modifiers play an indispensable role by direct or indirect interaction with DNA or chromatin. Although the role of transcription factor PRDM16 in adipose, hematopoietic, skeletal, and neural cell lineage specification is well-documented, its function within the

BACKGROUND Arterial stiffness, commonly assessed via pulse wave velocity (PWV), is marked by reduced arterial elasticity and serves as a significant risk factor for cardiovascular disease and an early indicator of hypertension. This study investigated the regulatory roles of long noncoding RNAs (lncRNAs) in modulating mRNAs associated with arterial stiffness and hypertension, with a particular focus

The control of blood pressure in patients with treatment-resistant hypertension is paramount and requires the use of thiazide or loop diuretics to enhance renal salt excretion and reduce expanded body fluid volumes. However, the use of diuretics in patients with treatment-resistant hypertension without suppressing the production of aldosterone and MR (mineralocorticosteroid receptor) activation and

We appreciate the opportunity to reply to the points raised by M. Zhou et al. (Neuroendocrine regulatory effects of sex hormones on salt sensitivity of blood pressure. Nat. Rev. Cardiol. https://doi.org/10.1338/10.1038/s41569-025-01175-6 2025)1 on our Review (Masenga, S. K. et al. Salt sensitivity of blood pressure: mechanisms and sex-specific differences. Nat. Rev. Cardiol. https://doi.org/10.103

We read with great interest the Review by S. K. Masenga et al. (Salt sensitivity of blood pressure: mechanisms and sex-specific differences. Nat. Rev. Cardiol. https://doi.org/10.1038/s41569-025-01135-0 2025)1. The authors summarized the interactions between sex hormones, the renin–angiotensin–aldosterone system and the epithelial Na+ channel in the development of salt-sensitive hypertension1. Oestrogen

BACKGROUND Pulmonary artery endothelial cell (PAEC) dysfunction is a pathological hallmark of pulmonary hypertension (PH). Yet, the roles of long noncoding RNAs (lncRNAs) driven by super-enhancers (SEs) in PAECs are not well understood. In this study, we focused on the PAEC-specific SE-associated lncRNA HCG20 (HLA complex group 20) and to elucidate its role and underlying mechanisms in the progression

ImportanceRecreational and medicinal cannabis legalization has led to increased cannabis use. To understand the consequences for vascular health, we initiated the CANnabis: Does It Damage Endothelium (CANDIDE) study.ObjectiveTo investigate whether cannabis use is associated with vascular endothelial dysfunction.Design, Setting, and ParticipantsIn this cross-sectional study, sex- and age- matched healthy

BACKGROUND Dilated cardiomyopathy (DCM) is substantially influenced by genetic factors. Sarcomere function is intricately associated with other organelles, particularly the reciprocal regulation between sarcomeres and mitochondria. Mitochondrial stress dysregulation is linked to DCM progression, yet mechanisms remain unclear. In this study, we investigated the effects of cTnT (cardiac troponin T) dysregulation

BACKGROUND Preeclampsia, a severe pregnancy complication with an incompletely deciphered cause, is strongly associated with hyperlipidemia. Our previous studies demonstrated that FTL (ferritin light chain) expression was diminished in preeclampsia placentas and that FTL downregulation inhibited trophoblast invasiveness and migration while promoting apoptosis, contributing to preeclampsia development

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