Prevention of cardiovascular disease

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.

In this Review, Bäckhed and colleagues summarize the evidence for gut microbiome alterations in cardiometabolic and cardiovascular diseases and the rationale and potential benefit motivating translational approaches to target the gut microbiota and its metabolites for prevention and treatment.

The relationship between climate change and health outcomes is complex. In this Review, Rajagopalan and colleagues describe the environmental exposures associated with climate change and provide an overview of the consequences of climate change, including air pollution and extreme temperatures, on cardiovascular health and disease.

In this Review, Raitakari and colleagues discuss the importance of initiating the prevention of atherosclerosis in early life and summarize the major paediatric programmes for the prevention of atherosclerotic cardiovascular disease.

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, 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, 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.

In this Review, Elshazly and colleagues summarize the basic engineering principles of common wearable sensors and discuss their broad applications in cardiovascular disease prevention, diagnosis and management.

In this Review, Lucia and colleagues discuss the epidemiological evidence on the benefits of major lifestyle interventions in the prevention and adjuvant treatment of hypertension, including regular physical exercise, body weight management, healthy diet, adequate sleep patterns, circadian entrainment and stress management. The authors also describe the main physiological mechanisms underlying these benefits.

A strong relationship exists between exposure to air pollution and cardiovascular events. In this Review, Rajagopalan and colleagues summarize the evidence supporting the detrimental effects of air pollution on cardiovascular health and describe the potential mechanisms involved in air pollution-mediated cardiovascular mortality.

Dietary fats comprise heterogeneous molecules with diverse structures and complex health effects. This Review discusses the effects of different dietary fats on cell processes and cardiometabolic disease risk factors and clinical events, highlighting areas of controversy and future research directions to improve the prevention and management of cardiometabolic diseases through optimization of dietary fat intake.

This Review describes the effects of short sleep duration on cardiovascular health and diseases, and the authors discuss the main pathophysiological mechanisms involved, taking into account both experimental data and clinical evidence.

The benefits of regular exercise extend beyond its effect on cardiovascular disease (CVD) risk factors. In this Review, the authors outline the non-traditional mechanisms underlying the benefits of exercise in CVD and highlight the importance of a holistic view of exercise in cardiovascular health.

Reduction in salt consumption has long been recommended to lower blood pressure (BP) and the risk of cardiovascular disease (CVD). A linear relationship between salt intake and CVD risk has recently been challenged in some cohort studies; however, methodological issues exist with these studies. In this Review, He and MacGregor discuss the relationship between salt intake, BP, and CVD risk, and describe the benefits and challenges of reducing the population intake of salt.

This Review describes the relationship between urban and transport planning and the city environment, the main cardiovascular risk factors (including physical activity, hypertension, and obesity), and cardiovascular disease and mortality. Improved city planning that promotes physical activity, reduces levels of air pollution and noise, and increases green space could decrease the burden of cardiovascular disease.

In this Review, Kivimäki and Steptoe assess the current evidence on the association between stress and cardiovascular disease, covering the multiple roles of stress in the development and triggering of disease and as a determinant of prognosis and outcome. In addition, they discuss the clinical and public health importance of major stressors and the implications for prevention and treatment of cardiovascular disease.

Over the past decade, marijuana has been legalized for medicinal purposes or recreational use in many countries, and the potency of marijuana and synthetic cannabinoids has substantially increased. In this Review, Pacher and colleagues summarize the role of the endocannabinoid system in cardiovascular health and disease, and critically discuss the beneficial and detrimental cardiovascular effects of marijuana and synthetic cannabinoid use.

The use of electronic cigarettes has increased dramatically in the past decade, but its effects on cardiovascular health are still unknown. In this Review, Benowitz and Fraiman discuss the constituents, exposure, and potential mechanisms of cardiovascular toxicity of electronic cigarettes compared with conventional tobacco cigarettes.

This Review summarizes the existing knowledge on the effects of vitamin D on cardiovascular diseases and the associated risk factors. Pilz and colleagues provide an update on clinical studies on vitamin D and cardiovascular risk, discuss ongoing vitamin D research, and consider the management of vitamin D deficiency from the perspective of cardiovascular health.

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.

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, 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, Lutsey and Zakai describe the epidemiology of venous thromboembolism, including incidence, risk factors and outcomes; summarize opportunities for primordial, primary and secondary prevention; and highlight the importance of reducing disparities in venous thromboembolism incidence and management, and opportunities to reduce them.

In this Review, Roos-Hesselink and colleagues describe how the physiological adaptations during pregnancy can induce cardiometabolic complications or an exacerbation of existing cardiometabolic disease, and discuss the epidemiology, pathophysiology, diagnosis and management of cardiometabolic diseases acquired or presenting during pregnancy, including hypertensive disorders, gestational diabetes mellitus, thromboembolic disorders and peripartum cardiomyopathy.

The role of aspirin for the primary prevention of cardiovascular disease is controversial. In this Review, Patrono and Baigent discuss the new randomized trials on aspirin for the primary prevention of cardiovascular disease in the context of previous evidence, and appraise whether the new evidence is likely to enable a more targeted use of aspirin

The use of polypills containing multiple pharmaceutical agents targeting the cardiovascular system in the primary prevention of cardiovascular disease is controversial. In this Review, Chow and Meng discuss the barriers to the use of polypills and focus in detail on the use of fixed-dose combination pills containing low doses of multiple blood pressure-lowering drugs.

Three cardiovascular outcome trials have now demonstrated the clinical benefit of achieving lower plasma LDL-cholesterol levels with the addition of PCSK9 inhibitors to statin therapy. In this Review, Marc Sabatine discusses the safety and efficacy data from these trials and their possible implications, such as the definition of new plasma LDL-cholesterol targets.

The current guidelines recommending the use of higher-intensity statin therapy to reduce the risk of cardiovascular disease have raised concerns about potential adverse effects associated with long-term statin therapy. In this Review, Adhyaru and Jacobson discuss the evidence for the efficacy and safety of statins to help clinicians and patients make informed decisions about statin therapy.

Patients with diabetes mellitus have a prothrombotic status that increases the risk of cardiovascular events and worsens prognosis after these events. In this Consensus Statement, the Working Group on Thrombosis of the Italian Society of Cardiology proposes antithrombotic strategies for patients with diabetes in various cardiovascular settings.

Novel antisense oligonucleotide and small interfering RNA technology can be used to reduce levels of lipoproteins that cause cardiovascular disease. In this Review, Nordestgaard and colleagues describe the principles of these gene-silencing approaches and summarize the trials that have tested the efficacy of these approaches in patients at risk of cardiovascular disease.

Heart failure has emerged as the most common cardiovascular complication among patients with type 2 diabetes mellitus. In this Review, Nassif and Kosiborod describe the detrimental, neutral, or even beneficial effects of different classes of glucose-lowering medications on heart failure outcomes.

The left atrial appendage is known to be a source of thromboemboli in patients with nonvalvular atrial fibrillation, and the interventional or surgical occlusion or exclusion of this anatomical structure is an alternative approach to anticoagulation therapy for the prevention of stroke. In this Review, Caliskan et al. discuss the various methods for occlusion of the left atrial appendage, and provide an overview of the clinical studies investigating these techniques.

In this Perspectives article, Ruilope and colleagues discuss the relevance and caveats of the SPRINT trial, with particular focus on patient cohort characteristics, the method used to measure blood-pressure levels, and applicability of the SPRINT blood-pressure targets in real-world clinical practice and future hypertension management guidelines.

The cardiovascular benefits of weight loss in patients with obesity are well documented. Bariatric surgery is an effective and long-lasting strategy for weight loss, and can improve many cardiovascular risk factors such as hypertension and dyslipidaemia. In this Review, Beamish and colleagues highlight the effects of bariatric surgery on cardiovascular risk factors and outcomes.

Both the cardiovascular research and clinical communities are ideally positioned to develop and implement precision medicine to achieve more effective prevention and treatment. This Review highlights the advances in modern biomedicine that make possible the precision medicine era, provides current examples of the use of this approach in the cardiovascular field, and defines the goals and barriers to implementation of a precision medicine system.

Despite the high consumption of fermented foods and beverages worldwide, their role in a healthy diet is still up for debate. Some fermented beverages have been demonstrated to protect against cardiovascular disease, but many aspects of the effects of fermented foods on cardiovascular health are uncertain. Better-designed studies are warranted.

Statin nocebo effects have been demonstrated in numerous randomized, double-blind, placebo-controlled and active-controlled trials. Emerging evidence suggests that brain pathways might mediate statin nocebo hyperalgesia. Evidence-based pain-management approaches can be used to manage nocebo symptoms that occur during statin therapy.

Extreme heat events are now more frequent in many parts of the world as a result of climate change. The combined effects of heat, air pollution, individual age, and socioeconomic and health status are responsible for avoidable acute events of cardiovascular disease and need to be considered in order to prevent and treat cardiovascular diseases effectively.

In this Comment, Nikki Gillum Posnack discusses how the increasing use of plastics in everyday life has potentially harmful effects on cardiovascular health.

The notion that atherosclerosis can be prevented or mitigated by vaccination is now moving towards clinical trials. This strategy is based on the existence of autoimmunity to LDL, the cholesterol-carrying particles that accumulate in arteries. In this Comment, we discuss the underlying concepts, research basis and challenges for the development of a vaccine against atherosclerosis.

Yoga has been associated with improvements in numerous cardiovascular risk factors and has the potential to address the unmet needs of current cardiovascular prevention strategies. Large and well-designed clinical trials are needed to assess the benefits of yoga across the spectrum of cardiovascular diseases and to provide the evidence required for its widespread implementation.

Salt substitutes hold great potential for the control of blood pressure and prevention of chronic disease, but the evidence base remains inadequate. Data from a community-based trial in Peru add to this evidence base and support the conduct of large-scale trials to drive the global uptake of salt substitution.

The available literature suggests that electronic cigarettes (e-cigarettes), although not without risk, might decrease cardiovascular risk in chronic smokers of tobacco cigarettes who switch to e-cigarettes. However, to safeguard our youth, e-cigarettes must be required to meet product standards, all flavourings must be banned and laws regulating e-cigarette sales must be strictly enforced.

Awareness of the effect of the neighbourhood built environment on cardiovascular diseases is growing. In this Comment, we identify major conceptual, methodological and policy-relevant issues in research related to the built environment and describe potential future directions to improve the scientific rigour of research in this field.

The Apple Heart Study demonstrates that the Apple Watch can detect atrial fibrillation inferred from the smartwatch heart-rate sensor with a high positive predictive value. However, we must now contend with many clinically relevant unknowns that were not addressed by the study, such as the ramifications of a false-positive result.

The global burden of cardiovascular disease morbidity and mortality demands increased awareness of effective prevention strategies by patients, communities and health-care providers. The new 2019 ACC/AHA guidelines provide evidence-based, preventive recommendations for patients without known cardiovascular disease, focusing on risk estimation, a healthy lifestyle and selective indications for pharmacotherapy.

LDL cholesterol is an important contributor to the risk of coronary heart disease, and its measurement is central to evaluating the effects of lipid-modifying therapies. Several ‘LDL-cholesterol’ assays exist but their methodologies differ, leading to between-assay heterogeneity in values of ‘LDL cholesterol’. We advocate the need for awareness of the potential implications.

In a prespecified secondary analysis of the ACCELERATE trial, Puri and colleagues report a stepwise relationship between lipoprotein(a) levels and risk of major adverse cardiac events in patients with high-sensitivity C-reactive protein levels ≥2 mg/l.

Individuals with obesity have an increased prevalence of the Bacteroides 2 enterotype, which is associated with systemic inflammation and disease. However, statin therapy is associated with a reduced prevalence of this dysbiosis in individuals with obesity.

An adverse childhood family environment is associated with an increased rate of cardiovascular disease and death in middle age, according to a longitudinal cohort study.

The safety and durability of the LDL-cholesterol-lowering effects of inclisiran, a small interfering RNA that inhibits the synthesis of PCSK9 in the liver, have now been confirmed in three phase III clinical trials published in the New England Journal of Medicine.

Deficiency in the orphan G protein-coupled receptor 146 (GPR146) decreases blood lipid levels and protects against atherosclerosis in mice independently of LDL receptor activity, according to a new study.

A new study shows that regular physical activity exerts cardiovascular beneficial effects by reducing the proliferation of haematopoietic stem and progenitor cells via modulation of their niche, leading to a reduction in the systemic supply of inflammatory leukocytes.

Statin therapy initiated during childhood in patients with familial hypercholesterolaemia (FH) slows the rate of carotid intima–media thickening and reduces the risk of cardiovascular events and death.

In a socioeconomically vulnerable community in Alabama, USA, the use of a polypill containing four low-dose drugs produced greater reductions in blood pressure and LDL-cholesterol level than usual care.

Lifelong genetic exposure to lower levels of both LDL cholesterol and systolic blood pressure is associated with an independent, additive and dose-dependent decrease in the risk of major coronary events.

The REWIND, PIONEER 4 and PIONEER 6 trials of GLP1R agonists show the cardiovascular benefits of dulaglutide in patients with diabetes and no previous cardiovascular events and that oral semaglutide is safe and noninferior to subcutaneous injections of liraglutide.

Dual therapies combining a calcium-channel blocker with an angiotensin-converting enzyme (ACE) inhibitor or thiazide diuretic are more effective at lowering blood pressure in black African patients than the combination of an ACE inhibitor and a thiazide diuretic.

Both pharmacological and genetic inhibition of ATP citrate lyase can reduce plasma LDL-cholesterol levels

Fragmented sleep interferes with a novel neuroimmune axis involving hypocretin produced in the hypothalamus, leading to increased haematopoiesis and larger atherosclerotic lesions.

Statin therapy significantly reduces major vascular events irrespective of age, but less direct evidence is available on the benefit of statins for the primary prevention of cardiovascular disease in people aged >75 years, according to a meta-analysis by the Cholesterol Treatment Trialists' Collaboration.