Review Articles

The menopausal transition period, which begins with irregular menstrual cycles and ends with the final menstrual period, is associated with an increase in cardiovascular risk. In this Review, Mehta and Manson describe the metabolic and cardiovascular changes that occur during the menopausal transition period and summarize the evidence on the use of targeted interventions to slow the progression of atherosclerosis.

In this Review, Swirski and co-workers discuss how lifestyle factors modulate haematopoiesis and leukocyte migration in the context of cardiovascular homeostasis and disease, with particular focus on the role of the nervous system as the key executor connecting environmental influences to leukocyte behaviour.

In this Review, the authors discuss the clinical and experimental data on immunomodulatory effects of evidence-based treatments for heart failure and their primary mechanisms of action, and highlight potential therapeutic targets and opportunities for the development and application of novel immunomodulatory treatments for heart failure.

Some species have a greater capacity for cardiac regeneration than others. In this Review, Weinberger and Riley summarize the diverse array of vertebrates that have been studied for their cardiac regenerative potential and the core mechanisms that regulate cardiac regeneration across vertebrate species.

In this Review, Marsan et al. discuss the different clinical scenarios in which valvular heart diseases and cardiomyopathies coexist, either as the cause of one another or because of a common aetiology, to highlight the need for an improved classification of these diseases with potential repercussions in clinical management and personalized treatment.

In the infarcted heart, pericytes have crucial roles in inflammatory signalling, angiogenesis, and scar formation and stabilization. In this Review, Avolio and colleagues discuss the numerous roles of cardiac pericytes in homeostasis and disease and describe the potential of pericyte-based therapy for restoring the perivascular niche after myocardial infarction.

Heart transplantation for patients with advanced heart failure is limited by a shortage of donor organs. In this Review, Jou and colleagues explore the options to increase the supply of donor hearts, including transplantation from donors with HCV, HIV or SARS-CoV-2 infection, national opt-out organ donation policies, donation after circulatory death, and xenotransplantation.

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.

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 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.