Venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular death worldwide and a major contributor to costly and debilitating non-fatal complications. Despite the changing landscape of risk factors, preventive and diagnostic strategies, risk stratification and therapies, no contemporary global summary of the burden of VTE is available. In a collaborative, multinational effort, we provide a global overview of the incidence and outcomes of VTE. Reliable data were available for only a limited number of countries (predominantly in Northern America, Western Europe and Oceania), with notable regional differences. During 2012-2016, the global annual incidence of deep-vein thrombosis ranged from 25.1 to 131.5 per 100,000 of the population. The incidence of pulmonary embolism rose from 2012-2016 to 2017-2022 in Northern America and Asia but remained stable in Oceania. Among patients with pulmonary embolism, 30-day all-cause mortality ranged globally from 1.0% to 9.0%, and the 1-year cumulative incidence of recurrent VTE ranged from 2.9% to 8.1%. These findings reveal the substantial global burden of VTE, sources of heterogeneity and stark regional gaps in the data, demanding coordinated surveillance, standardized reporting and research into local and global drivers to curb worldwide morbidity and mortality.

In the setting of myocardial ischaemia-reperfusion injury, ischaemia induces severe myocardial hypoxia, whereas the abrupt reintroduction of oxygen during reperfusion further amplifies tissue injury through redox imbalance. This dynamic stabilizes hypoxia-inducible factors (HIFs), which become transcriptionally active and induce hypoxia-responsive gene networks. In turn, HIF-dependent programmes orchestrate adaptive responses to acute hypoxia, including metabolic reprogramming towards glycolysis, promotion of extracellular adenosine signalling, induction of epidermal growth factor pathways and integration with circadian regulatory circuits. Collectively, these programmes increase myocardial resistance to ischaemic stress and limit ischaemia-reperfusion injury. In this Review, we examine the functional roles of HIFs in cardioprotection, with a particular focus on their contributions to ischaemic preconditioning or remote preconditioning and the HIF-dependent pathways that drive these cardioprotective effects. Given that pharmacological HIF stabilizers are already in clinical use for the treatment of renal anaemia, these insights provide a clear translational framework, positioning HIF activation as a plausible and immediately actionable therapeutic approach to prevent or treat myocardial ischaemia-reperfusion injury.

The introduction of intracoronary imaging (ICI) into clinical practice has been one of the major advances in percutaneous coronary intervention (PCI) for patients with atherosclerotic coronary artery disease. However, because the procedural advantages of ICI in routine clinical practice can be offset by higher costs and longer procedural times, high-quality evidence demonstrating the net clinical benefits of ICI guidance has long been awaited. The publication of eight large (n > 1,000 patients), international, randomized studies (the ILUMIEN IV, IVUS-ACS, IVUS-CHIP, IVUS-XPL, OCCUPI, OCTOBER, RENOVATE-COMPLEX-PCI and ULTIMATE trials) has provided substantial data on the clinical use of ICI guidance to improve the safety and outcomes of patients undergoing PCI. However, the heterogeneity of the study populations, lack of standardized criteria across ICI protocols and the mixed results of randomized trials have left uncertainty about why and when the use of ICI confers a benefit in real-world settings. In this Review, by discussing the study characteristics and procedural aspects that contributed to the consistency and heterogeneity across trials, we provide a practical and comprehensive appraisal of the appropriateness - why, when, how and which - of ICI guidance in the clinical decision-making process for contemporary PCI, with the overall aim of improving clinical outcomes.

Dyslipidaemia and hepatic steatosis are interconnected metabolic disorders, often associated with obesity and diabetes mellitus, that contribute to the burden of cardiovascular disease. Hepatic steatosis is now recognized as a specific subset of metabolic dysfunction-associated steatotic liver disease (MASLD). Several processes contribute to lipid deposition in the liver, including increased de novo lipogenesis, impaired fatty acid oxidation and reduced lipoprotein biosynthesis. Hepatic lipid accumulation can also result from lipid-lowering therapies that impair lipoprotein production, thus requiring careful monitoring of hepatic lipid content in patients taking these medications. By contrast, drugs that lower plasma levels of lipids by increasing hepatic expression of the LDL receptor do not lead to lipid accumulation in the liver; however, some patients are less responsive than others to these therapies. Therefore, new therapeutics that decrease lipoprotein production without causing steatosis are needed. Indeed, balanced modulation of hepatic lipoprotein production and secretion, as well as systemic and cellular lipid catabolism, is crucial for hepatic lipid homeostasis. Strategies that target both plasma and hepatic lipid levels will help to reduce the burden of atherosclerosis and MASLD. In this Review, we discuss mechanistic links between dyslipidaemia and hepatic steatosis, emphasizing lipid-lowering therapies and their effects on hepatic lipid accumulation.