Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study.

Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease.

Acute myocardial infarction preferentially alters low-abundant, long-chain unsaturated phospholipid and sphingolipid species in plasma high-density lipoprotein subpopulations.

Aim: High-density lipoprotein (HDL) particles in ST-segment elevation myocardial infarction (STEMI) are deficient in their anti-atherogenic function. Molecular determinants of such deficiency remain obscure.

Methods: Five major HDL subpopulations were isolated using density-gradient ultracentrifugation from STEMI patients (n = 12) and healthy age- and sex-matched controls (n = 12), and 160 species of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylglycerol, phosphatidylserine, phosphatidic acid, sphingomyelin and ceramide were quantified by LC-MS/MS.

Two-Year Follow-Up of Chronic Ischemic Heart Disease Patients in a Specialized Center in Brazil.

The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil.

Insights into the Role of Inflammation in the Management of Atherosclerosis.

Atherosclerosis is the biological basis of ischemic heart disease and ischemic stroke, the leading causes of death in the world. After decades of studies, the understanding of atherosclerosis has evolved dramatically, and inflammation has been recognized as one of the most relevant pillars in all phases of atherosclerotic disease. Nevertheless, only recently, the trial CANTOS, and subsequent outcome studies with colchicine, finally provided proof-of-concept evidence that anti-inflammatory therapies were able to reduce cardiovascular events with no influence on lipid levels.

Evaluation of cardiovascular risk biomarkers after moderate consumption of red wine and cachaça in a randomized crossover trial: The Wine and Cachaça Study (WICAS).

Introduction: Moderate daily consumption of alcohol (MDCA) is associated with cardiovascular risk (CVR) reduction in observational studies. Some researches have suggested that this benefit may be associated not only with red wine consumption but also with other beverages. However, there are no clinical trials evaluating the possible CVR benefit of Brazilian spirit (cachaça) in humans.

Beyond Statins and PCSK9 Inhibitors: Updates in Management of Familial and Refractory Hypercholesterolemias.

Purpose Of Review: Elevation in apolipoprotein B-containing lipoproteins in the blood is a cause of atherosclerosis. Statins have changed the preventive cardiology scenario, and more recently monoclonal proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors were added as robust agents to further reduce pro-atherogenic lipoproteins and therefore prevent cardiovascular events. However, despite this many dyslipidemic individuals persist with inadequate LDL-C levels and still at risk.

Phospholipid transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis is directly correlated with HDL-cholesterol levels and is not associated with cardiovascular risk.

Background And Aims: While low concentrations of high-density lipoprotein-cholesterol (HDL-C) represent a well-established cardiovascular risk factor, extremely high HDL-C is paradoxically associated with elevated cardiovascular risk, resulting in the U-shape relationship with cardiovascular disease. Free cholesterol transfer to HDL upon lipolysis of triglyceride-rich lipoproteins (TGRL) was recently reported to underlie this relationship, linking HDL-C to triglyceride metabolism and atherosclerosis. In addition to free cholesterol, other surface components of TGRL, primarily phospholipids, are transferred to HDL during lipolysis.

The Role of Statins in Current Guidelines.

Purpose Of Review: The causal association of LDL-cholesterol (LDL-C) with atherosclerotic cardiovascular disease (ASCVD) has been demonstrated in robust experimental, epidemiological, genetic, and interventional randomized controlled trials (RCTs). The goal of this review is to show how the knowledge acquired from statin RCTs influenced and was recommended on guidelines for prevention of ASCVD during the last three decades.

Recent Findings: Guideline recommendations have evolved with accruing information derived mostly from statin RCTs, and as decades passed, more intensive LDL-C lowering was recommended according to a given ASCVD risk.

Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease.

Background: Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown.

Distinct phospholipid and sphingolipid species are linked to altered HDL function in apolipoprotein A-I deficiency.

Background: Familial apolipoprotein A-I (apoA-I) deficiency (FAID) involving low levels of both apoA-I and high-density lipoprotein (HDL) cholesterol is associated with accelerated atherosclerosis.

Objective: The objective of this study was to define distinctive patterns in the lipidome of HDL subpopulations in FAID in relationship to antiatherogenic activities.

Methods: Five HDL subfractions were isolated by ultracentrifugation from plasma of FAID Caucasian patients (n = 5) and age-matched healthy normolipidemic Caucasian controls (n = 8), and the HDL lipidome (160 molecular species of 9 classes of phospholipids and sphingolipids) was quantitatively evaluated.

Impact of Lipoproteins on Atherobiology: Emerging Insights.

Apolipoprotein B-containing lipoproteins and low-density lipoprotein play a key role in atherosclerotic vascular disease. Modified forms of low-density lipoprotein drive inflammation, an integral aspect of plaque progression. High-density lipoprotein particles are equipped to protect low-density lipoprotein from enzymatic and nonenzymatic modification.

Defective functionality of small, dense HDL3 subpopulations in ST segment elevation myocardial infarction: Relevance of enrichment in lysophosphatidylcholine, phosphatidic acid and serum amyloid A.

Background: Low plasma levels of high-density lipoprotein-cholesterol (HDL-C) are typical of acute myocardial infarction (MI) and predict risk of recurrent cardiovascular events. The potential relationships between modifications in the molecular composition and the functionality of HDL subpopulations in acute MI however remain indeterminate.

Methods And Results: ST segment elevation MI (STEMI) patients were recruited within 24h after diagnosis (n=16) and featured low HDL-C (-31%, p<0.

HDL particle subpopulations: Focus on biological function.

Low levels of high-density lipoprotein-cholesterol (HDL-C) constitute an independent biomarker of cardiovascular morbi-mortality. However, recent advances have drastically modified the classical and limited view of HDL as a carrier of 'good cholesterol', and have revealed unexpected levels of complexity in the circulating HDL particle pool. HDL particles are indeed highly heterogeneous in structure, intravascular metabolism and biological activity.

Defective functionality of HDL particles in familial apoA-I deficiency: relevance of alterations in HDL lipidome and proteome.

To evaluate functional and compositional properties of HDL in subjects from a kindred of genetic apoA-I deficiency, two homozygotes and six heterozygotes, with a nonsense mutation at APOA1 codon -2, Q[-2]X, were recruited together with age- and sex-matched healthy controls (n = 11). Homozygotes displayed undetectable plasma levels of apoA-I and reduced levels of HDL-cholesterol (HDL-C) and apoC-III (5.4% and 42.

Radial augmentation index is a surrogate marker of atherosclerotic burden in a primary prevention cohort.

Arterial stiffness is linked to cardiovascular risk and predicts clinical events independently of peripheral blood pressure. The potential relationship between the augmentation index measured at the radial artery and asymptomatic atherosclerosis remains unclear however. In order to assess relationship between the peripheral augmentation index and traditional risk factors, we estimated cardiovascular risk and presence of subclinical atherosclerosis in a large asymptomatic population in primary prevention.

Small, dense high-density lipoprotein-3 particles are enriched in negatively charged phospholipids: relevance to cellular cholesterol efflux, antioxidative, antithrombotic, anti-inflammatory, and antiapoptotic functionalities.

Objective: High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality.

Approach And Results: Using an original liquid chromatography-mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamine>phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatidic acid.

Lack of clopidogrel-statin interaction in patients undergoing coronary stent implantation.

Background: Some studies have suggested reduced activity of clopidogrel on platelet activation and adherence in patients using statins.

Objective: To assess whether platelet activation and aggregation decrease with clopidogrel, and whether there is a reduction of the action of clopidogrel when associated with atorvastatin or simvastatin.

Methods: This prospective study included 68 patients with stable angina with previous use of simvastatin, atorvastatin, or no statin (control group), with previous elective indication of percutaneous coronary intervention (PCI).

Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin.

Aim Of The Study: This study sought to evaluate the effect of nLDL concentrations on monocyte adhesion molecule expression in hypercholesterolemic patients with stable coronary artery disease (CAD) and to determine whether lipid-lowering therapy with simvastatin would change this effect.

Methods: Blood samples from patients with hypercholesterolemia (mean LDL 152 mg/dL) and CAD (HC, n = 23) were collected before and after a 12-week treatment with 40 mg of simvastatin. Healthy individuals (mean LDL 111 mg/dL) were used as controls (CT, n = 15).