PCSK9 Inhibitors: Is the Time Ripe for the "Fast Track" Use Independently on the LDL-C Baseline Values in Acute Coronary Syndrome?

The low-density lipoprotein cholesterol (LDL-C) lowering decreases the risk to develop major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). Therefore, the "fast track" use of PCSK9 inhibitors (PCSK9i) has been introduced in ACS patients not achieving LDL-C target (70 mg/dl) despite an ongoing lipid lowering therapy with statin at maximum tolerated dosage plus ezetimibe or stain-naïve (LDL-C > 130 mg/dl). PCSK9i "fast track" use has shown to achieve the regression of "non-culprit" atherosclerotic plaques leading to a further MACE decrease.

Obesity: the perfect storm for heart failure.

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction.

A method for the risk assessment of biomechanical overload in hospital physiotherapists.

Background: In physiotherapists, biomechanical overload risk assessment (RA) is particularly complex due to the tasks' variability. The present study aims to propose a new methodology, named Whole Body RA Biomechanical Overload (WB-RAMBO), to assess the risk in the activities performed by physiotherapists.

Methods: Each type of intervention was broken down into elementary operations.

Reducing Cardiac Injury during ST-Elevation Myocardial Infarction: A Reasoned Approach to a Multitarget Therapeutic Strategy.

The significant reduction in 'ischemic time' through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure.

Stress-Induced Hyperglycaemia in Non-Diabetic Patients with Acute Coronary Syndrome: From Molecular Mechanisms to New Therapeutic Perspectives.

Stress-induced hyperglycaemia (SIH) at hospital admission for acute coronary syndrome is associated with poor outcome, especially in patients without known diabetes. Nevertheless, insulin treatment in these subjects was not correlated with the reduction of mortality. This is likely due to the fact that SIH in the context of an acute coronary syndrome, compared to that in known diabetes, represents an epiphenomenon of other pathological conditions, such as adrenergic and renin-angiotensin system over-activity, hyperglucagonaemia, increase of circulating free fatty acids and pancreatic beta-cell dysfunction, which are not completely reversed by insulin therapy and so worsen the prognosis.

The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. Both these events trigger "cytokine storm" leading to acute lung and cardiovascular injury. A selective therapy for COVID-19 has not yet been identified.

The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction.

During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients.

Autocrine Bradykinin Release Promotes Ischemic Preconditioning-Induced Cytoprotection in Bovine Aortic Endothelial Cells.

The aims of this study were to assess whether ischemic preconditioning (PC) induces bradykinin (Bk) synthesis in bovine aortic endothelial cells (bAECs) and, if so, to explore the molecular mechanisms by which this peptide provides cytoprotection against hypoxia. PC was induced by exposing bAECs to three cycles of 15 min of hypoxia followed by 15 min of reoxygenation. Bk synthesis peaked in correspondence to the early and late phases of PC (10 M and 10 M, respectively) and was abolished by a selective tissue kallikrein inhibitor, aprotinin.

Correction to: Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up.

Following publication of the original article [1], the authors reported an error in Acknowledgment section. The last sentence should read as "All authors have read and approval the submission to Cardiovascular Diabetology.

Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up.

Objectives: We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients.

Background: The management of hyperglycemic patients during STEMI is unclear.

Methods: We undertook an observational cohort study of 3166 first STEMI.

Antiplatelet Therapy for Non-ST-Segment Elevation Myocardial Infarction in Complex "Real" Clinical Scenarios: A Consensus Document of the "Campania NSTEMI Study Group".

The incidence of ST-segment elevation myocardial infarction (STEMI) has significantly decreased. Conversely, the rate of non-STEMI (NSTEMI) has increased. Patients with NSTEMI have lower short-term mortality compared to patients with STEMI, whereas at long-term follow-up, the mortality becomes comparable.

Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway.

Aims: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated.

Pharmacological approach to cardiovascular risk in metabolic syndrome.

Metabolic syndrome is not a discrete entity with a single pathogenesis, but different complex mechanisms, especially those inducing oxidative stress, play a major role in the genesis of this condition. This consideration suggests that treatment of recognized cardiovascular risk factors alone cannot be enough to prevent cardiovascular events in patients with a diagnosed metabolic syndrome. However, it has been reported that oxidative stress is involved in the transduction of the effects of haemodynamic and metabolic pathological conditions.

Prevention and treatment of nonalcoholic fatty liver disease.

A better knowledge of the biochemical mechanisms implicated in the development and progression of nonalcoholic fatty liver disease, linking fatty liver to insulin resistance and the metabolic syndrome, has shifted the goal of treatment from a mere clearing of fat from the liver to a systematic treatment of metabolic risk factors for fatty liver. Any attempt to modify the "unhealthy" habits responsible for fatty liver requires an integrated approach, based on the cognitive theory of behaviour by a multidisciplinary team including physicians, psychologists, dieticians and physical exercise experts, and recent data demonstrate that this is feasible and effective. Whenever this goal is not attained, a treatment based on insulin-sensitizers remains the best option, to simultaneously tackle all metabolic alterations of the metabolic syndrome.

Cross-talk between PKA and Akt protects endothelial cells from apoptosis in the late ischemic preconditioning.

Objective: The aim of this study was to explore the molecular mechanisms involved in late preconditioning-induced cell protection in endothelial cells.

Methods And Results: Preconditioning (PC) was induced by exposing bovine aortic endothelial cells (BAECs) to 3 cycles of 15 minutes of hypoxia followed by 15 minutes of reoxygenation. A 12-hour period of hypoxia induced cell death in 60% of BAECs (48+/-5% apoptosis, 12+/-4% necrosis).

[Renin-angiotensin system modulation: instructions for use].

Angiotensin-converting enzyme (ACE) inhibitors and AT1 receptor blockers have long been considered as two classes of drugs with strictly comparable effect in cardiovascular diseases, on the assumption that both classes act on the renin-angiotensin-aldosterone system. The results of large clinical intervention trials, which failed to demonstrate any significant difference between the effects of these two pharmacological classes in patients with essential hypertension, acute myocardial infarction and heart failure, supported this concept. The recent observation that a combination of ACE-inhibitors and AT1 receptor blockers improves the prognosis of these pathological conditions better than monotherapy at higher doses focused on the difference between their mechanisms of action.

Retrospective analysis of coagulation factor II receptor (F2R) sequence variation and coronary heart disease in hypertensive patients.

Objectives: The purpose of this study was to evaluate the role of genetic variants within the coagulation factor II receptor (F2R) in the occurrence of coronary heart disease (CHD).

Methods And Results: Four SNPs (-1738 G/A, 2860 G/A, 2930 T/C, and 9113 C/A) and an ins/del polymorphism -506-/GGCCGCGGGAAGC (D/I), replicating a consensus sequence for Ets-1 transcription factor, and their related haplotypes were tested for association to CHD in 1600 hypertensive patients divided in 2 groups according to presence (cases, n=559) and absence (controls, n=1041) of CHD. Allele I at -506 locus was associated with increased risk of CHD under additive, dominant, and recessive models of inheritance (all P<0.

Akt mediates the cross-talk between beta-adrenergic and insulin receptors in neonatal cardiomyocytes.

Upregulation of the sympathetic nervous system plays a key role in the pathogenesis of insulin resistance. Although the heart is a target organ of insulin, few studies have examined the mechanisms by which beta-adrenergic stimulation affects insulin sensitivity in cardiac muscle. In this study, we explored the molecular mechanisms involved in the regulation of the cross-talk between beta adrenergic and insulin receptors in neonatal rat cardiomyocytes and in transgenic mice with cardiac overexpression of a constitutively active mutant of Akt (E40K Tg).