Inflammatory residual risk. An emerging target to reduce cardiovascular disease

Cardiovascular Residual Risk and Cardiovascular Preventio

Synergistic effects of cardiac resynchronization therapy and drug up-titration in heart failure. is this enough?

This editorial refers to ‘Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival’, by C.T. Witt et al., on page 18

Natriuretic Peptides in the Cardiovascular System. Multifaceted Roles in Physiology, Pathology and Therapeutics

The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches

Is early and fast blood pressure control important in hypertension management?

Control of blood pressure (BP) in hypertension is recognized as a key measure in the management of cardiovascular (CV) risk and is a cornerstone of preventive strategies. It is not defined, however, whether an initiation of the antihypertensive treatment in the early stages of hypertension (such as prehypertension or high-normal BP), may bring benefits for the long-term prevention of CV events. In addition, it has not been thoroughly addressed the issue whether achievement of a prompt BP reduction in hypertensive patients may contribute to reduce CV damage and events. The aim of this article is to critically examine data from studies exploring these important questions. Our conclusion is that the available evidence, though not very extensive, supports the prevailing benefits associated with early BP control. We also discuss the therapeutic strategies to achieve early control of BP. Finally, we believe that this aspect deserves to be more thoroughly addressed in upcoming international guidelines

Integrated preclinical cardiovascular prevention: a new paradigm to face growing challenges of cardiovascular disease

Cardiovascular disease (CVD) still represents the leading cause of mortality and morbidity worldwide. Despite considerable improvements in the prognosis of CVD and the significant reduction of CVD mortality obtained during the past half century, patients developing CVD, even though satisfactorily treated, still carry coronary artery disease and remain at risk for advanced CVD. Thus, the healthcare and socioeconomic burden linked to CVD remains high. As a result, more effective CVD prevention strategies remain crucial. 'Population strategies' and 'high-risk' approaches both have limitations and have often been viewed as alternative solutions. This persistent dualism could be overcome with the promotion of integrated prevention strategies based on a systematic evaluation of the total risk of disease, at both a population and an individual level. New approaches are also needed to reach people earlier in the course of the vascular disease and, possibly, to prevent risk factors and reduce CVD clinical manifestation

Blood pressure control versus atrial fibrillation management in stroke prevention

Hypertension is one of the major risk factors for atrial fibrillation which in turn is the most prevalent concomitant condition in hypertensive patients. While both these pathological conditions are independent risk factors for stroke, the association of hypertension and atrial fibrillation increases the incidence of disabling strokes. Moreover, documented or silent atrial fibrillation doubles the rate of cardiovascular death. Lowering blood pressure is strongly recommended, particularly for primary stroke prevention. However, a relatively small percentage of hypertensive patients still achieve the recommended blood pressure goals. The management of atrial fibrillation with respect to stroke prevention is changing. New oral anticoagulants represent a major advancement in long-term anticoagulation therapy in non valvular atrial fibrillation. They have several benefits over warfarin, including improved adherence to the anticoagulation therapy. This is an important issue since non-adherence to stroke prevention medications is a risk factor for first and recurrent strokes

Hypertension in the elderly. Which are the blood pressure threshold values?

Managing blood pressure is often difficult in the elderly, not only because of comorbidities, but also due to vascular remodelling and the changes in the renal and endocrine physiology. The structural and functional arterial modifications lead to impaired vessel’s compliance and increased systolic blood pressure (SBP), often with reduction of diastolic blood pressure (DBP)

Natriuretic peptides and cardiovascular damage in the metabolic syndrome. Molecular mechanisms and clinical implications

Natriuretic peptides are endogenous antagonists of vasoconstrictor and salt- and water-retaining systems in the body's defence against blood pressure elevation and plasma volume expansion, through direct vasodilator, diuretic and natriuretic properties. In addition, natriuretic peptides may play a role in the modulation of the molecular mechanisms involved in metabolic regulation and cardiovascular remodelling. The metabolic syndrome is characterized by visceral obesity, hyperlipidaemia, vascular inflammation and hypertension, which are linked by peripheral insulin resistance. Increased visceral adiposity may contribute to the reduction in the circulating levels of natriuretic peptides. The dysregulation of neurohormonal systems, including the renin-angiotensin and the natriuretic peptide systems, may in turn contribute to the development of insulin resistance in dysmetabolic patients. In obese subjects with the metabolic syndrome, reduced levels of natriuretic peptides may be involved in the development of hypertension, vascular inflammation and cardio vascular remodelling, and this may predispose to the development of cardiovascular disease. The present review summarizes the regulation and function of the natriuretic peptide system in obese patients with the metabolic syndrome and the involvement of altered bioactive levels of natriuretic peptides in the pathophysiology of cardiovascular disease in patients with metabolic abnormalities

Molecular Implications of natriuretic peptides in the protection from hypertension and target organ damage development

The pathogenesis of hypertension, as a multifactorial trait, is complex. High blood pressure levels, in turn, concur with the development of cardiovascular damage. Abnormalities of several neurohormonal mechanisms controlling blood pressure homeostasis and cardiovascular remodeling can contribute to these pathological conditions. The natriuretic peptide (NP) family (including ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide), and CNP (C-type natriuretic peptide)), the NP receptors (NPRA, NPRB, and NPRC), and the related protease convertases (furin, corin, and PCSK6) constitute the NP system and represent relevant protective mechanisms toward the development of hypertension and associated conditions, such as atherosclerosis, stroke, myocardial infarction, heart failure, and renal injury. Initially, several experimental studies performed in different animal models demonstrated a key role of the NP system in the development of hypertension. Importantly, these studies provided relevant insights for a better comprehension of the pathogenesis of hypertension and related cardiovascular phenotypes in humans. Thus, investigation of the role of NPs in hypertension offers an excellent example in translational medicine. In this review article, we will summarize the most compelling evidence regarding the molecular mechanisms underlying the physiological and pathological impact of NPs on blood pressure regulation and on hypertension development. We will also discuss the protective effect of NPs toward the increased susceptibility to hypertensive target organ damage

The T2238C human atrial natriuretic peptide molecular variant and the risk of cardiovascular diseases

Atrial natriuretic peptide (ANP) is a cardiac hormone which plays important functions to maintain cardio-renal homeostasis. The peptide structure is highly conserved among species. However, a few gene variants are known to fall within the human ANP gene. The variant rs5065 (T2238C) exerts the most substantial effects. The T to C transition at the 2238 position of the gene (13-23% allele frequency in the general population) leads to the production of a 30-, instead of 28-, amino-acid-long α-carboxy-terminal peptide. In vitro, CC2238/αANP increases the levels of reactive oxygen species and causes endothelial damage, vascular smooth muscle cells contraction, and increased platelet aggregation. These effects are achieved through the deregulated activation of type C natriuretic peptide receptor, the consequent inhibition of adenylate cyclase activity, and the activation of Giα proteins. In vivo, endothelial dysfunction and increased platelet aggregation are present in human subjects carrying the C2238/αANP allele variant. Several studies documented an increased risk of stroke and of myocardial infarction in C2238/αANP carriers. Recently, an incomplete response to antiplatelet therapy in ischemic heart disease patients carrying the C2238/αANP variant and undergoing percutaneous coronary revascularization has been reported. In summary, the overall evidence supports the concept that T2238C/ANP is a cardiovascular genetic risk factor that needs to be taken into account in daily clinical practice