Reviews & Analysis

In this Review, Fernandez and Giannarelli discuss how single-cell technologies can advance our understanding of the cellular and molecular composition of atherosclerotic plaques and how these approaches can guide the design of new, personalized immunotherapies and immune monitoring tools for the management of patients with atherosclerotic cardiovascular disease.

Nanotherapies are emerging rapidly as options to treat cardiovascular disease. However, insufficient and heterogeneous delivery remain critical issues. Novel strategies to boost targeted delivery of systemically administered nanoparticles by optimizing the particle physical properties or using immune cells as carriers promise to increase nanotherapeutic effectiveness in cardiovascular and other inflammatory diseases.

Fatty acids affect the pathogenesis of atherosclerosis, and accumulating evidence shows that fatty acids also modulate T cell functions and processes. This Review summarizes the effects of circulating fatty acids on the metabolism, activation, proliferation and polarization of T cells and how these changes influence the subsequent functions of T cells in the pathogenesis of atherosclerosis.

In this Review, Maack and colleagues discuss the pathophysiology of angina in the context of the underlying cardiovascular condition as well as the modes of action of antianginal drugs to provide the clinician with a rationale and compass of when to use which compound or combination of drugs.

Mounting evidence from the SPRINT trial and the Blood Pressure Lowering Treatment Trialists points towards the use of absolute cardiovascular risk assessment to guide blood-pressure management. But who will fall between the cracks? We need to be pragmatic in keeping blood-pressure targets, if only to serve the >1 billion people at risk of cardiovascular disease living in low-resource settings.

Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. In this Review, Prendergast and colleagues discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.

Surgical mitral valve repair produces exceptional long-term survival, durable relief from mitral regurgitation, and physiological valve performance. Percutaneous mitral valve repair might prohibit subsequent surgical reconstruction. This finding has important implications, including for patient consent and clinical trial design. The objectives of mitral valve intervention must focus on life expectancy and long-term valve function.

Novel peroxisome proliferator-activated receptor (PPAR) agonists are providing new opportunities in the management of metabolic and cardiovascular diseases. In this Review, Staels and colleagues discuss the physiological regulation and actions of the PPAR family and their modulation of the atherogenic lipid profile, atherosclerosis and cardiac remodelling.

In this Review, Weldy and Ashley summarize the biology of heart failure (HF), the mechanisms of action of HF drugs, and both the Mendelian genetics of cardiomyopathies and the complex genetics of HF. Finally, they present a roadmap for the future of precision medicine in HF.

In this Review, Essien and colleagues discuss the contributions of social determinants, including race/ethnicity, financial resources, and rural or residential environment, to the evaluation, treatment and management of atrial fibrillation, identify gaps in the literature, and propose future directions to investigate and address social determinants of atrial fibrillation.

In this Review, Zhou and colleagues summarize the current data on the global epidemiology of blood pressure and hypertension and evaluate changes over time. They also present estimates of the mortality effects of elevated blood pressure and discuss interventions that can reduce the burden of high blood pressure.

Epidemiological studies indicate a genetic component to the risk of sudden cardiac death (SCD). In this Review, Behr and colleagues evaluate monogenic and polygenic contributions to the risk of SCD in the young and SCD associated with drug therapy and analyse the potential clinical role of genomic testing in the prevention of SCD in the general population.

In this Review, Dunstan and colleagues make a case for an approach to preventing and managing cardiovascular disease that involves sitting less and moving more, which will build on the well-established role of exercise in cardiovascular disease prevention and rehabilitation.

In this Review, Stark and Massberg discuss how the interplay between innate immunity, platelet activation and coagulation, known as immunothrombosis, functions as a host defence mechanism to limit pathogen spreading, yet its aberrant activation, termed thromboinflammation, results in thrombotic complications, highlighting the therapeutic potential of anti-inflammatory strategies in cardiovascular pathologies.

In this Review, Cavallari and colleagues examine the evidence supporting pharmacogenetic testing in cardiovascular medicine, describe guidelines for the use of cardiovascular pharmacogenetics and provide examples of the clinical implementation of genotype-guided therapies.

Atherosclerotic plaque erosion is becoming an increasingly common characteristic of culprit lesions in acute coronary syndromes. In this Review, Fahed and Jang discuss the patient phenotype and the molecular characteristics in plaque erosion and provide their vision for a potential major shift in the management of patients with plaque erosion.

Sequencing studies demonstrate a strong clinical association between clonal haematopoiesis driven by acquired mutations and atherosclerotic disease. Previous research supports the idea that this association reflects a direct contribution of some clonal haematopoiesis-related mutations to atherosclerosis. Now, mathematical modelling suggests that atherosclerosis could instead accelerate clonal haematopoiesis.

In this Review, Gotto and colleagues summarize the evolution of our understanding of HDL structure and function, current models of atheroprotection by HDL involving reverse cholesterol transport, and their identification of a correlation between the bioavailability of free cholesterol contained in HDL and atherogenesis.

Dyslipidaemias, particularly hypercholesterolaemia, are major risk factors for cardiovascular disease. In this Review, Catapano and colleagues summarize the latest data on plasma lipid levels and associated deaths and trends in these parameters over the past four decades in different regions of the world.

In this Review, Münzel and colleagues summarize the epidemiological evidence on transportation noise pollution as a cardiovascular risk factor, discussing mechanistic insights for the adverse cardiovascular effects of noise pollution and highlighting new risk markers of noise-induced cardiovascular effects as well as promising noise-mitigation strategies.