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
Prevention of cardiovascular disease
Primary prevention is crucial to reducing the burden of cardiovascular disease, which is the leading cause of death worldwide. Primary prevention strategies, aimed at people at risk of but who do not yet have manifest cardiovascular disease, can be achieved by targeting modifiable cardiovascular risk factors. These modifiable targets include physiological factors such as dyslipidaemia, hypertension, and diabetes mellitus; behavioural factors including a poor diet, smoking, and physical inactivity; and environmental and social factors such as air pollution, stress, and financial inequalities. In the era of precision medicine, primary prevention strategies are increasingly focusing on fine-tuning the intensity of interventions to match individual patient risk.
This Series by Nature Reviews Cardiology features articles on the latest advances in the field of primary prevention, from lifestyle modification approaches to pharmacological and clinical interventions, to reduce the incidence of cardiovascular events.
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.
Prevention of atherothrombotic events in patients with diabetes mellitus: from antithrombotic therapies to new-generation glucose-lowering drugs
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.
Although patients with chronic kidney disease (CKD) are at high risk of developing cardiovascular disease, therapies proven to protect both the cardiovascular and renal systems are used only at low doses or not at all. Ruiz-Hurtado et al. describe available and emerging treatments that can provide adequate cardiorenal protection without adverse effects in patients with CKD.
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.
Nutraceuticals are natural compounds that are beneficial for the prevention or treatment of disease. In their Review, Moss and Ramji summarize the preclinical and clinical studies to evaluate the efficacy of various nutraceuticals, such as polyunsaturated fatty acids, flavanols, and vitamins C and E, for the prevention of atherosclerosis.
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.
News and comment
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.
More than 150 years after acetylsalicylic acid was synthesized by French chemist Charles Frédéric Gerhardt, aspirin is still one of the most prescribed medications worldwide. In 2018, several trials have suggested that the role of aspirin in the contemporary era might be less pre-eminent than in previous decades.
The VITAL trial showed that neither vitamin D nor fish oil supplementation significantly reduced the incidence of cardiovascular disease (CVD). Conversely, current evidence supports the benefits of multiple dietary patterns, especially the Mediterranean diet, in primary prevention of CVD. Health effects of low-carbohydrate diets depend on the food sources of macronutrients.
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.
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.
The radical new US hypertension guidelines, released 3 years after the previous scientific statement, have implications far beyond their intended recipients. They include a new definition for hypertension, lower treatment targets, and extended guidance on the implementation of multidisciplinary care, including self-monitoring of blood pressure. Some recommendations are likely to generate controversy.
Research on dyslipidaemias in 2017 reaffirmed the central role of reducing the levels of atherogenic apolipoprotein B-containing lipoproteins, predominantly LDL, in preventing ischaemic cardiovascular events. However, whether increasing HDL-cholesterol levels in isolation can reduce cardiovascular risk remains to be determined.
The recent publication of The Lancet Commission on pollution and health is a watershed moment for one of the greatest challenges to cardiovascular health. In this Comment article, we discuss the global burden of air pollution on cardiovascular health.
Cardiovascular disease is the world's leading cause of death, with a disproportionate burden in low-income and middle-income countries. The Resolve initiative — eliminating artificial trans fats, reducing dietary sodium, and improving treatment of elevated blood pressure — is a substantial step in the right direction, but more combined efforts will be required.
Initial randomized trials of cholesteryl ester transfer protein (CETP) inhibitors were terminated early owing to adverse effects or futility. The REVEAL trial now shows the benefit of CETP inhibition in coronary heart disease. Despite raising HDL-cholesterol levels, the cardiovascular effect of CETP inhibitors is probably due to lowering of non-HDL-cholesterol levels.