Background And Aims: Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with cardiovascular risk, but its prognostic relevance and mechanistic role in coronary artery disease (CAD) remains incompletely understood. This study investigated the association between CHIP and all-cause mortality in CAD and explored the cellular and molecular mechanisms, focusing on TET2 mutations.
Methods: Targeted deep sequencing of 13 CHIP driver genes in 8612 patients with angiographically confirmed CAD was performed.
Background: Accurate classification of aortic stenosis (AS) severity remains challenging despite detailed echocardiographic assessment. Adjudication of severity is informed by subjective interpretation of aortic leaflet motion from the first image parasternal long axis (PLAX) view, but quantitative metrics of leaflet motion currently do not exist. The objectives of the study were to echocardiographically quantify aortic leaflet motion using the PLAX view and correlate motion data with Doppler-derived hemodynamic indices of disease severity, and predict significant AS using these isolated motion data.
View Article and Find Full Text PDFCoronary artery disease (CAD) is a major cause of global morbidity and mortality. Macrophages play a central role in orchestrating this disease process. In 2016, we initiated the STARNET primary blood macrophage study, followed by the multi-ethnic NGS-PREDICT primary blood macrophage study in 2018.
View Article and Find Full Text PDFCarotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics differ. Here we run deep single-cell sequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex differences in major cell types, we identified a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females.
View Article and Find Full Text PDFBackground: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome or sudden cardiac death, primarily affecting relatively young women (median age, 51 years) without typical cardiovascular risk factors. SCAD has a genetic component, with genome-wide association studies identifying multiple risk loci. Thoracic aortic dissection (type A) shares some genetic overlap with SCAD, suggesting potential common predispositions.
View Article and Find Full Text PDFThe plasma proteome is the future for diagnostic markers for common diseases, like cardiometabolic disorders (CMDs) and coronary artery disease (CAD). The reliability of these markers requires identifying their source-organ(s). We profiled 974 plasma proteins in 532 CAD-patients of the STARNET study with arterial wall, major metabolic organ, and blood transcriptomic data.
View Article and Find Full Text PDFWe report a unique case involving cardiac manifestation of T-cell lymphoma and associated risk management of ventricular arrhythmia and sudden cardiac death. A 39-year-old woman presented with a syndrome consistent with fever in a returned traveler, ultimately diagnosed with stage IV peripheral T-cell lymphoma involving the myocardium with ventricular tachycardia. Management of risk of sudden cardiac death was complicated by hematological management with an antibody-drug conjugate chemotherapy regimen and later autologous stem cell transplant.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
Background: Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.
View Article and Find Full Text PDFSudden cardiac arrest (SCA) represents a major cause of premature mortality globally, with enormous impact and financial cost to victims, families, and communities. SCA prevention should be considered a health priority in Australia. National Cardiac Arrest Summits were held in June 2022 and March 2023, with inclusion from multi-faceted endeavours related to SCA prevention.
View Article and Find Full Text PDFNat Cardiovasc Res
September 2024
Aims: Vein grafts are used for many indications, including bypass graft surgery and arteriovenous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia, and adverse remodelling. Recently, endothelial-to-mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts.
View Article and Find Full Text PDFCereb Circ Cogn Behav
May 2024
Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression.
Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL.
Various forms of pollution carry a substantial burden with respect to increasing the risk of causing and exacerbating noncommunicable diseases, especially cardiovascular disease. The first part of this 2-part series on pollution and cardiovascular disease provided an overview of the impact of global warming and air pollution. This second paper provides an overview of the impact of water, soil, noise, and light pollution on the cardiovascular system.
View Article and Find Full Text PDFEnvironmental stresses are increasingly recognized as significant risk factors for adverse health outcomes. In particular, various forms of pollution and climate change are playing a growing role in promoting noncommunicable diseases, especially cardiovascular disease. Given recent trends, global warming and air pollution are now associated with substantial cardiovascular morbidity and mortality.
View Article and Find Full Text PDFTricuspid valve disease is an often underrecognized clinical problem that is associated with significant morbidity and mortality. Unfortunately, patients will often present late in their disease course with severe right-sided heart failure, pulmonary hypertension, and life-limiting symptoms that have few durable treatment options. Traditionally, the only treatment for tricuspid valve disease has been medical therapy or surgery; however, there have been increasing interest and success with the use of transcatheter tricuspid valve therapies over the past several years to treat patients with previously limited therapeutic options.
View Article and Find Full Text PDFEndothelial cells (ECs) line the luminal surface of blood vessels and play a major role in vascular (patho)-physiology by acting as a barrier, sensing circulating factors and intrinsic/extrinsic signals. ECs have the capacity to undergo endothelial-to-mesenchymal transition (EndMT), a complex differentiation process with key roles both during embryonic development and in adulthood. EndMT can contribute to EC activation and dysfunctional alterations associated with maladaptive tissue responses in human disease.
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