Reviews & Analysis

In this Review, the authors present an overview of the role of fibroblast growth factor 23 (FGF23) and klotho in normal mineral homeostasis, discuss disordered mineral homeostasis in chronic kidney disease (CKD), and explore CKD-associated FGF23 excess and klotho deficiency as novel risk factors and potential therapeutic targets for cardiovascular disease.

In this Review, Riksen and colleagues discuss the molecular and cellular mechanisms of trained immunity, the activation of these mechanisms by cardiovascular risk factors, and how trained immunity might contribute to atherosclerosis and atherosclerotic cardiovascular disease. The authors also propose potential strategies for the therapeutic modulation of trained immunity in atherosclerotic cardiovascular disease.

Familial hypercholesterolaemia (FH) is a preventable cause of premature coronary artery disease and death. This guidance article from the International Atherosclerosis Society provides a comprehensive overview of FH care that includes recommendations on the detection and management of patients with FH, as well as strategies to maximize implementation.

The benefits of oxygen therapy for the treatment of cardiovascular disease are unclear, and findings from preclinical studies have suggested potential adverse effects associated with its excessive use. In this Review, Eltzschig and colleagues provide an overview of studies on oxygen therapy for various cardiovascular conditions and describe alternative therapeutic strategies that target oxygen-sensing pathways.

In this Consensus Statement, Dewey and the other members of the Quantitative Cardiovascular Imaging Study Group provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations to detect and assess coronary artery stenosis and atherosclerosis.

In this Review, Ritterhoff and Tian describe the metabolic reprogramming that occurs in cardiac hypertrophy and heart failure; discuss the contribution of metabolism to energy-generating and non-energy-generating functions, including signalling, protein function and gene expression regulation; and highlight the role of metabolism in non-cardiomyocytes and the potential to develop metabolic therapies for heart failure.

Acute coronary syndromes (ACS) are a major contributor to death from cardiovascular disease. In this Review, Timmis and colleagues present data on mortality from ACS for 122 countries and examine the regional and temporal changes in the epidemiology of ACS over the past 20 years.

In this Review, Jo and colleagues discuss blood flow-induced mechanisms involved in endothelial cell dysfunction and atherosclerosis, including the emerging concept of disturbed-flow-induced reprogramming of endothelial cells as a pro-atherogenic mechanism, and highlight the therapeutic potential of targeting of flow-sensitive genes, proteins and pathways.

In this Review, Kroemer and colleagues describe eight molecular hallmarks of cardiovascular ageing: disabled macroautophagy, loss of proteostasis, genomic instability, epigenetic alterations, mitochondrial dysfunction, cell senescence, dysregulated neurohormonal signalling and inflammation. Therapeutically targeting these hallmarks might attenuate residual cardiovascular risk in older individuals.

Individuals with type 2 diabetes mellitus are at high risk of developing cardiovascular disease (CVD). In the context of type 2 diabetes mellitus, Wong and Sattar discuss established and novel mechanisms of CVD, risk assessment and patient stratification, and strategies to reduce multiple risk factors to prevent CVD.

Pulmonary embolism is the leading cause of in-hospital death and the third most frequent cause of cardiovascular death. In this Review, Mahfoud and colleagues discuss the growing range of interventional, catheter-based approaches for the treatment of pulmonary embolism as well as risk stratification and patient selection for these procedures.

In this Review, Gaillard and Jaddoe describe how maternal cardiovascular disorders, occurring before and during pregnancy, can influence cardiovascular health in the offspring from embryonic life until adulthood. Furthermore, the authors highlight critical periods for cardiovascular adaptations, including preconception, early pregnancy and infancy, and how the events occurring during these periods can have an effect on future cardiovascular health.

In this Review, Münzel and colleagues describe the exposome concept with a focus on environmental physical and chemical exposures and their effects on the burden of cardiovascular disease. Additionally, they discuss selected exposome studies and the relevance of the exposome concept for future health research and preventive medicine.

A bidirectional relationship exists between atrial fibrillation (AF) and myocardial infarction (MI) as a result of shared risk factors and both direct and indirect mechanisms. In this Review, Frederiksen and colleagues discuss the pathogenesis, prevention and management of AF in patients with MI and of MI in patients with AF.

In this Review, the authors discuss current treatment regimens for lowering plasma LDL cholesterol levels to reduce the risk of cardiovascular disease, highlight treatment gaps and challenges, as well as describe opportunities raised by novel available therapies and potential future therapeutic approaches.

In this Review, Gawaz and colleagues discuss the pathophysiological role of platelets in acute myocardial ischaemia, vascular inflammation and atherosclerotic progression, summarize the current clinical concepts in antiplatelet therapy and describe novel therapeutic targets for antiplatelet drugs that are currently in development.

Glucagon-like peptide 1 (GLP1) receptor agonists reduce the rate of major adverse cardiovascular events in people with type 2 diabetes mellitus. In this Review, Ussher and Drucker discuss the possible mechanisms of cardiovascular benefit of GLP1 receptor agonists and highlight the novel GLP1-based multi-agonists currently in development.

In this Review, Lucia and colleagues explain why obesity is an evolutionarily novel condition, summarize the epidemiological evidence for its detrimental cardiometabolic consequences, discuss the major mechanisms involved in the association between obesity and the risk of cardiometabolic diseases, and examine the evidence for potential ‘healthy’ phenotypes associated with obesity.

In this Review, Redline and colleagues summarize our understanding of the shared risk factors and causal links between obstructive sleep apnoea (OSA) and cardiovascular disease and emerging knowledge on the heterogeneity of OSA. They also explore the potential role of new biomarkers for cardiovascular risk stratification in patients with OSA.

Understanding how adverse professional life experiences affect the mental well-being of cardiologists is important. An unmet and equally important need is to design and implement strategies to prevent emotional harassment and discrimination at health-care workplaces and to effectively support cardiologists who have been exposed to adverse professional life experiences. These strategies are especially needed for female, younger or divorced cardiologists.