Review Articles

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.

Calcific aortic valve disease (CAVD) is a common disorder characterized by thickening, fibrosis and mineralization of the aortic valve leaflets. In this Review, Mathieu and colleagues summarize the risk factors, genetics and molecular mechanisms involved in CAVD and the implications for treatment of the condition.

Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for the detoxification of alcohol-derived acetaldehyde, has been implicated in the pathogenesis of various types of cardiovascular disease. In this Review, Xu and colleagues present the latest evidence showing a link between the inactivating ALDH2 rs671 polymorphism and an increased or decreased risk of cardiovascular disease such as coronary artery disease.

Alternative splicing determines which exons are included in mature RNA and accounts for the majority of transcriptomic diversity. In this Review, Gotthardt and colleagues discuss how alternative splicing is regulated in the heart and how it differs in cardiac development, physiological adaptation and pathological remodelling. They also summarize technological advances in the field and potential applications of splicing data in cardiovascular medicine.

The prevalence of hypertension in China has risen steadily in the past two to three decades. In this Review, Wang and colleagues summarize the latest epidemiological data on hypertension in China, describe the risk factors for hypertension that are relevant to this population, and provide an overview of initiatives aimed at improving awareness, treatment and control of hypertension, especially in the low-resource rural setting.

Macrophages are one of the most active cell types during all stages after myocardial infarction. In this Review, Boisvert and co-workers describe the populations of cardiac macrophage involved in myocardial infarction, their cardioprotective functions and their interactions with other cardiac cell types. The authors also explore potential therapeutic approaches to target macrophage-mediated inflammation in myocardial infarction.

In this Review, Ntusi and colleagues examine the mechanistic links between dysbiosis of the oral microbiome and the pathogenesis of cardiovascular diseases, and explore potential strategies for prevention and treatment.

In this Review, Packer summarizes the latest advances in our understanding of the mechanisms that underlie the benefits of sodium–glucose cotransporter 2 (SGLT2) inhibitors in heart failure, identifies specific pathways that are likely to mediate a direct effect of SGLT2 inhibitors on cardiomyocytes and proposes a novel conceptual framework that explains the findings from experimental studies and clinical trials.

In this Review, the authors summarize the evidence for physiological and pathological cardiac hypertrophy regression from clinical and basic science studies, discussing therapies and mechanisms involved in regression of cardiac hypertrophy and highlighting knowledge gaps and questions for future investigation to design specific therapies to promote regression of pathological hypertrophy.