Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study.

Background And Aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification.

Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH.

Epidemiology of cardiovascular risk factors in two population-based studies.

We aimed to compare cardiovascular risk factors prevalence in Italy and Russia through cross-sectional database analysis. The study has been based on data from ESSE-RF and from baseline of PLIC study, two population-based epidemiological studies aimed to investigate prevalence of risk factors and evaluating contribution of traditional and new risk factors into morbidity and cardiovascular mortality. A total of 2203 patients with left and right intima-media thickness (IMT) measurements constituted the source population (1205 from PLIC study and 998 from ESSE-RF study).

Biological Consequences of Dysfunctional HDL.

Epidemiological studies have suggested an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular disease. HDLs promote reverse cholesterol transport (RCT) and possess several putative atheroprotective functions, associated to the anti-inflammatory, anti-thrombotic and anti-oxidant properties as well as to the ability to support endothelial physiology. The assumption that increasing HDL-C levels would be beneficial on cardiovascular disease (CVD), however, has been questioned as, in most clinical trials, HDL-C-raising therapies did not result in improved cardiovascular outcomes.

Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.

Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

Methods And Results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.

Proprotein Convertase Subtilisin Kexin 9 Inhibitors.

High levels of low-density lipoprotein cholesterol (LDL-C) are directly associated with an increased risk of cardiovascular disease. Reducing LDL-C levels reduces the incidence of cardiovascular events. Several lipid-lowering approaches are available to achieve the LDL-C levels recommended by current guidelines, statins being the first-line therapy.

The Interplay of Lipids, Lipoproteins, and Immunity in Atherosclerosis.

Purpose Of Review: Atherosclerosis is an inflammatory disorder of the arterial wall, in which several players contribute to the onset and progression of the disease. Besides the well-established role of lipids, specifically cholesterol, and immune cell activation, new insights on the molecular mechanisms underlying the atherogenic process have emerged.

Recent Findings: Meta-inflammation, a condition of low-grade immune response caused by metabolic dysregulation, immunological memory of innate immune cells (referred to as "trained immunity"), cholesterol homeostasis in dendritic cells, and immunometabolism, i.

Proprotein Convertase Subtilisin-Kexin type-9 (PCSK9) and triglyceride-rich lipoprotein metabolism: Facts and gaps.

After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants.

Disease trends over time and CD4CCR5 T-cells expansion predict carotid atherosclerosis development in patients with systemic lupus erythematosus.

Background And Aim: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study.

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study).

Anti-PCSK9 antibodies for the treatment of heterozygous familial hypercholesterolemia: patient selection and perspectives.

Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce the cardiovascular burden in this population. Phase I-III clinical trials showed the benefit of proprotein convertase subtilisin kexin 9 inhibitors, both alirocumab and evolocumab, in these patients with an average low-density lipoprotein cholesterol reduction ranging from -40% to -60%.

World Heart Federation Cholesterol Roadmap.

Background: The World Heart Federation has undertaken an initiative to develop a series of Roadmaps.

Objectives: The aim of these is to promote development of national policies and health systems approaches and identify potential roadblocks on the road to effective prevention, detection and management of cardiovascular disease (CVD) in low-and middle-income countries (LMIC), and strategies for overcoming these. This Roadmap focuses on elevated blood cholesterol, a leading risk factor for myocardial infarction, stroke, and peripheral arterial disease.

PCSK9 deficiency results in increased ectopic fat accumulation in experimental models and in humans.

Background Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several tissues. Here we evaluated whether PCSK9 may modulate the handling of triglycerides in the liver and peripheral tissues. Methods Subjects from the PLIC cohort were genotyped for the loss-of-function PCSK9 R46L variant and characterized for clinical and biochemical parameters, total and android fat mass, hepatic steatosis and epicardial fat thickness.

Pitavastatin and HDL: Effects on plasma levels and function(s).

Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported.

Statin use and risk of new-onset diabetes: A meta-analysis of observational studies.

Background And Aims: Meta-analyses of randomized control trials investigating the association between incident diabetes and statin use showed an increased risk of new-onset diabetes (NOD) from 9% to 13% associated with statins. However, short follow-up period, unpowered sample size, and lack of pre-specified diagnostic criteria for diabetes detection could be responsible of an underestimation of this risk. We conducted a meta-analysis of published observational studies to evaluate the association between statins use and risk of NOD.

Vascular inflammation and low-density lipoproteins: is cholesterol the link? A lesson from the clinical trials.

Unlabelled: For long time, the role of LDL and inflammation in the pathogenesis of atherosclerosis have been studied independently from each other and only more recently a common platform has been suggested. Accumulation of excess cholesterol due to the presence of increased circulating LDL promotes endothelium dysfunction and activation, which is associated with increased production of pro-inflammatory cytokines, overexpression of adhesion molecules, chemokines and C-reactive protein (CRP), increased generation of reactive oxygen species and reduction of nitric oxide levels and bioavailability. All these processes favour the progressive infiltration of inflammatory cells within the arterial wall where cholesterol accumulates, both extracellularly and intracellularly, and promotes vascular inflammation.

Translating the microRNA signature of microvesicles derived from human coronary artery smooth muscle cells in patients with familial hypercholesterolemia and coronary artery disease.

Aims: To analyze the impact of atherogenic lipoproteins on the miRNA signature of microvesicles derived from human coronary artery smooth muscle cells (CASMC) and to translate these results to familial hypercholesterolemia (FH) and coronary artery disease (CAD) patients.

Methods: Conditioned media was collected after exposure of CASMC to atherogenic lipoproteins. Plasma samples were collected from two independent populations of diagnosed FH patients and matched normocholesterolemic controls (Study population 1, N=50; Study population 2, N=24) and a population of patients with suspected CAD (Study population 3, N=50).

Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: Gaps and open questions.

Aim: Critically discuss the available data, to identify the current gaps and to provide key concepts that will help clinicians in translating the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases.

Data Synthesis: Adipose tissue is nowadays recognized as an active endocrine organ, a function related to the ability to secrete adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines (tumor necrosis factor alpha and resistin). Studies in vitro and in animal models have observed that obesity status presents a chronic low-grade inflammation as the consequence of the immune cells infiltrating the adipose tissue as well as adipocytes.

Lp(a) and cardiovascular risk: Investigating the hidden side of the moon.

Aims: This article reports current evidence on the association between Lp(a) and cardiovascular (CV) disease and on pathophysiological mechanisms. The available information on therapy for reduction of lipoprotein(a) is also discussed.

Data Synthesis: Although some evidence is conflicting, Lp(a) seems to increase CV risk through stimulation of platelet aggregation, inhibition of tissue factor pathway inhibitor, alteration of fibrin clot structure and promotion of endothelial dysfunction and phospholipid oxidation.