Usefulness of Combined Renin-Angiotensin System Inhibitors and Diuretic Treatment In Patients Hospitalized with COVID-19.

Antecedent use of renin-angiotensin system inhibitors (RASi) prevents clinical deterioration and protects against cardiovascular/thrombotic complications of COVID-19, for indicated patients. Uncertainty exists regarding treatment continuation throughout infection and doing so with concomitant medications. Hence, the purpose of this study is to evaluate the differential effect of RASi continuation in patients hospitalized with COVID-19 according to diuretic use.

New insights into the role of bempedoic acid and ezetimibe in the treatment of hypercholesterolemia.

Purpose Of Review: A number of new cholesterol-lowering drugs have been recently developed and approved, enriching the pharmacological armamentarium beyond and above statins. Ezetimibe, available since two decades, and bempedoic acid, a new drug inhibiting the same biosynthetic pathway targeted by statins but at an early step, represent valuable tools for the treatment of hypercholesterolemia, particularly in specific groups of patients.

Recent Findings: Bempedoic acid, either alone or in combination with ezetimibe, appears to reduce significantly LDL-C levels, an effect that has been observed also in patients with statin intolerance.

Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors.

Purpose Of Review: Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action.

HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases.

High density lipoproteins (HDL) are heterogeneous particles composed by a vast array of proteins and lipids, mostly recognized for their cardiovascular (CV) protective effects. However, evidences from basic to clinical research have contributed to depict a role of HDL in the modulation of immune-inflammatory response thus paving the road to investigate their involvement in other diseases beyond those related to the CV system. HDL-C levels and HDL composition are indeed altered in patients with autoimmune diseases and usually associated to disease severity.

Global epidemiology of dyslipidaemias.

Dyslipidaemias are alterations to the plasma lipid profile that are often associated with clinical conditions. Dyslipidaemias, particularly elevated plasma LDL-cholesterol levels, are major risk factors for cardiovascular disease, but some forms, such as hypertriglyceridaemia, are associated with severe diseases in other organ systems, including non-alcoholic fatty liver disease and acute pancreatitis. Dyslipidaemias can be genetically determined (primary or familial dyslipidaemias) or secondary to other conditions (such as diabetes mellitus, obesity or an unhealthy lifestyle), the latter being more common.

Improving lipid management in patients with acute coronary syndrome: The ACS Lipid EuroPath tool.

Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath Survey, performed in collaboration with 555 European cardiologists, identified a sub-optimal LDL-C management in post-ACS patients. Based on these premises, the ACS EuroPath II project led to the development of a self-assessment tool to improve lipid management in these very high risk patients, taking into consideration the new 2019 ESC/EAS guidelines.

Implementation of clinical practices and pathways optimizing ACS patients lipid management: Focus on eight European initiatives.

Post-acute coronary syndrome (ACS) patients are at very high cardiovascular risk. Despite current guidelines strongly recommend to reduce LDL-C levels and initiation of high-intensity statins as early as possible in patients admitted with an ACS, less than half of ACS patients receive a high intensity statin, and a high percentage of has LDL-C well above the goal despite therapy. There are multiple reasons for that, including physician lack of guideline adherence, patient lack of compliance with treatment, and lack of standardized procedures.

Lipid-lowering therapy and low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS patient pathway project.

Background And Aims: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. Aim of this survey was to evaluate the compliance to ESC/EAS guidelines during the management of ACS patients and the effectiveness of secondary prevention in seven European countries.

Methods: By means of an online questionnaire, data on 2775 ACS patients (either acute case or follow-up patients) were collected, including data on lipid profile, medications, follow-up visit planning, screening for familial hypercholesterolemia.

Hypercholesterolemia and cardiovascular disease: Focus on high cardiovascular risk patients.

The widespread use of statins has largely improved the treatment of hypercholesterolemia, but many patients still fail to achieve the LDL-C targets recommended by guidelines. Furthermore, some patients continue to present a very high cardiovascular (CV) risk or even an extreme risk despite being well treated, mainly due to the presence of co-morbidities such as diabetes or peripheral artery disease, which significantly increase their global CV risk. For these very high CV risk patients, the most recent European guidelines have reviewed the LDL-C goals and recommend an LDL-C reduction of at least 50% and a goal of <55 mg/dL or even <40 mg/dL.

Hypercholesterolemia and cardiovascular disease: What to do before initiating pharmacological therapy.

The availability of efficient lipid-lowering drugs has substantially reduced the incidence and mortality for cardiovascular disease (CVD). Despite that, CVD still represents a major cause of death and disability; efforts are thus required to prevent this disease, since reducing the established CV risk factors may slow or prevent the onset of cardiovascular events. Current guidelines recommend a healthier lifestyle for all CV risk categories, as it may have a beneficial impact on several risk factors; in individuals with a low-to-moderate hypercholesterolemia, which are not eligible for a pharmacological approach and are not far from the cholesterol target recommended for their risk category, functional foods or nutraceuticals may be considered as supplement to reduce their CV risk status.

Similarities and differences between European and American guidelines on the management of blood lipids to reduce cardiovascular risk.

The 2018 American Heart Association/American College of Cardiology/Multi-Society (AHA/ACC/MS) Guideline on the Management of Blood Cholesterol and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias: Lipid Modification to Reduce Cardiovascular Risk, that were recently released by the United States and Europe, provide new recommendations for the management of blood lipid levels based on the latest evidence. Despite many common points, there are several differences in the recommendations, including the definition of very-high-risk patient category, the recommendations for some categories of patients, such as those with diabetes, familial hypercholesterolemia, chronic kidney disease, and aged patients, and the use of ezetimibe and PCSK9 inhibitors. These differences suggest that multiple approaches can be used to manage lipid abnormalities in the context of cardiovascular risk reduction.

Recent insights into low-density lipoprotein metabolism and therapy.

Purpose Of Review: Elevated levels of low-density lipoprotein cholesterol (LDL-C) are causal to atherosclerosis and, thus, the reduction of LDL-C represents a major objective for the prevention of cardiovascular disease. Aim of this review is to provide an overview on novel strategies to lower LDL-C.

Recent Findings: Although inhibiting liver cholesterol biosynthesis by statins is used as the main therapeutic approach to increase hepatic LDL-receptor expression and lower plasma cholesterol levels, novel insights into lipid and lipoprotein biology have led to the development of additional lipid-lowering therapies that can be used in combination with or as an alternative to statins in patients with statin-intolerance.

Antecedent Administration of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Antagonists and Survival After Hospitalization for COVID-19 Syndrome.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme-2 (ACE-2) receptor to enter human cells. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID-19).

Omega n-3 Supplementation: Exploring the Cardiovascular Benefits Beyond Lipoprotein Reduction.

Purpose Of Review: Hypertriglyceridaemia is a highly prevalent disorder worldwide. Genetic and Mendelian randomization studies have suggested that triglyceride (TG)-rich lipoproteins are causal risk factors for coronary heart disease and contribute to the residual cardiovascular risk observed in patients optimally treated with statins. However, clinical trials failed to show cardiovascular benefits of TG-lowering; in this context, trials with omega-3 fatty acids provided contrasting results.

Mortality Risk Assessment Using CHA(2)DS(2)-VASc Scores in Patients Hospitalized With Coronavirus Disease 2019 Infection.

Early risk stratification for complications and death related to Coronavirus disease 2019 (COVID-19) infection is needed. Because many patients with COVID-19 who developed acute respiratory distress syndrome have diffuse alveolar inflammatory damage associated with microvessel thrombosis, we aimed to investigate a common clinical tool, the CHA(2)DS(2)-VASc, to aid in the prognostication of outcomes for COVID-19 patients. We analyzed consecutive patients from the multicenter observational CORACLE registry, which contains data of patients hospitalized for COVID-19 infection in 4 regions of Italy, according to data-driven tertiles of CHA(2)DS(2)-VASc score.

Impact of protein glycosylation on lipoprotein metabolism and atherosclerosis.

Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis.

New Pharmacological Approaches to Target PCSK9.

Purpose Of Review: Proprotein convertase subtilisin kexin 9 (PCSK9) plays a crucial role in regulating circulating levels of LDL-C as a consequence of its ability to inhibit LDL receptor recycling in the liver. Loss of function variants in the PCSK9 gene result in low LDL-C levels and associate with reduced cardiovascular risk, whereas gain of-function variants associate with hypercholesterolemia and increased risk of early cardiovascular events. Thus, PCSK9 inhibition has been established as an additional approach for the treatment of hypercholesterolemia.

LDL-Cholesterol-Lowering Therapy.

The causal relation between elevated levels of LDL-C and cardiovascular disease has been largely established by experimental and clinical studies. Thus, the reduction of LDL-C levels is a major target for the prevention of cardiovascular disease. In the last decades, statins have been used as the main therapeutic approach to lower plasma cholesterol levels; however, the presence of residual lipid-related cardiovascular risk despite maximal statin therapy raised the need to develop additional lipid-lowering drugs to be used in combination with or in alternative to statins in patients intolerant to the treatment.