15th Anniversary

November 2019 marks 15 years since the launch of Nature Reviews Cardiology. To celebrate, we invited six of our Advisory Board members to discuss some of the highlights of cardiovascular research in the past 15 years and to make some projections about scientific research in the next 15 years.

Metabolites produced by gut microorganisms from dietary metabolism have been linked to the pathogenesis of heart failure, suggesting that the gut microbiome functions like an endocrine organ. In this Review, Tang and colleagues discuss the gut microbial metabolic pathways involved in heart failure and propose the gut microbiome as a therapeutic target.

Inflammageing is a chronic, pro-inflammatory state that develops with age and is a risk factor for cardiovascular disease, comorbidities, frailty, and death. In this Review, Ferrucci and Fabbri discuss whether therapies to modulate inflammageing can reduce the age-related decline in health.

The pathophysiology of heart failure is complex, but mitochondrial dysfunction is an emerging therapeutic target to improve cardiac function. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.

High-density lipoproteins (HDLs) have various antiatherosclerotic effects; however, inflammation can cause HDL to become dysfunctional, which impairs its protective properties. In this Review, Rosenson and colleagues discuss the mechanisms by which HDL and apolipoprotein A-I protect against atherosclerosis, and how diagnostic and therapeutic approaches might target these proteins when they become dysfunctional.

Venous thromboembolism, including deep-vein thrombosis and pulmonary embolism, is a common, often-recurring condition that is occurring with increasing frequency, despite the availability of prophylactic treatments. The epidemiology of VTE involves interactions between predispositions to thrombosis and a range of risk factors, including hospitalization, cancer, and pregnancy.

Myocardial infarction initiates an inflammatory response that is required for repair of, but also contributes to, heart failure. In this Review, Nikolaos Frangogiannis, outlines our current understanding of the inflammatory response in the infarcted heart, and highlights potential therapies that might counterbalance the destructive effects of this immune response.

In the diseased heart, cardiomyocytes undergo necrotic cell death. A healing response results in myofibroblast production of collagen and other matrix molecules, which initially serve to preserve the structural integrity of the myocardium. However, myofibroblast dispersion fails to occur in many cardiac diseases, and perpetual matrix formation leads to adverse remodelling of the heart. In this Review, Weber et al. discuss relevant mechanisms of cardiac fibrosis and consequent remodelling, and highlight potential strategies for cardioprotection.

Psychological stress is thought to contribute to the cardiovascular disease process at several stages, including the long-term development of coronary heart disease and acute triggering of cardiac events. In this Review, Steptoe and Kivimäki summarize the evidence for the association between stress and cardiovascular disease, with a focus on external work-related and social stressors. They also discuss the effects of stress-management strategies on cardiovascular health.

Heart failure (HF) is a clinical syndrome that carries substantial morbidity and mortality. The prevalence of HF is increasing and represents a large burden to the health-care system and society. The authors of this Review discuss the epidemiology of HF and the impact of HF on health services. The risk profile of HF is also examined, highlighting factors that contribute to HF and identifying those who are most at risk of developing this syndrome.

Plaque macrophages account for the majority of leukocytes in atherosclerotic plaques, and are believed to differentiate from monocytes recruited from circulating blood. In this Review, Dr Woollard and Dr Geissmann discuss the heterogenous population of monocytes involved in the pathogenesis of atherosclerosis.

Thirteen years after his seminal Review on flow-mediated endothelial mechanotransduction, Peter Davies reviews the complex spatiotemporal shear stress characteristics that can predict atherosclerosis susceptibility. He also examines endothelial flow-induced responses—collectively known as mechanotransduction—and the spatially decentralized mechanism of endothelial mechanotransduction.

Despite being an increasingly recognized clinical syndrome, the mechanism of stress or 'Takotsubo' cardiomyopathy remains unknown. In this thought-provoking Review, Lyon et al. present their novel hypothesis for the mechanism behind stress cardiomyopathy, and examine what implications this hypothetical pathophysiology could have for the use of drugs or devices in the treatment of patients with this syndrome.

Familial hypercholesterolemia (FH) is an inherited disorder characterized by raised serum LDL cholesterol, which leads to accelerated atherosclerosis and a steep rise in the risk of premature coronary heart disease. Here, Anne Soutar and Rossi Naoumova examine the genetic mechanisms behind FH and discuss what effect new discoveries will have on the clinical management of FH.

The relationship between cardiovascular disease and the metabolic syndrome is now well known but is not yet fully elucidated. In this review, Yuji Matsuzawa discusses the role of intra-abdominal visceral fat accumulation and the release of bioactive substances termed adipocytokines in the development of disorders contributing to the metabolic syndrome.

Although excessive epicardial fat increases the work of pumping, this visceral fat depot is important source of free fatty acids and various bioactive molecules, and constitutes a metabolically active organ. Iacobelliset al. discuss its role, in the context of regional fat distribution, in cardiac pathology and the assessment of cardiac disease.

Brief episodes of ischemia before total coronary occlusion can protect the heart in animals; a similar preconditioning effect might be seen in humans. Preinfarction angina, already an important part of cardiac assessment, might be a corollary of preconditioning before myocardial infarction. Rezkalla and Kloner discuss the impact of preinfarction angina in the clinical setting.