Plasma proteomics improves prediction of coronary plaque progression.

Aims: Coronary computed tomography angiography (CCTA) offers detailed imaging of plaque burden and composition, with plaque progression being a key determinant of future cardiovascular events. As repeated CCTA scans are burdensome and costly, there is a need for non-invasive identification of plaque progression. This study evaluated whether combining proteomics with traditional risk factors can detect patients at risk for accelerated plaque progression.

Estimating inflammatory risk in atherosclerotic cardiovascular disease: plaque over plasma?

Inflammation is an important driver of disease in the context of atherosclerosis, and several landmark trials have shown that targeting inflammatory pathways can reduce cardiovascular event rates. However, the high cost and potentially serious adverse effects of anti-inflammatory therapies necessitate more precise patient selection. Traditional biomarkers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), show an association with cardiovascular risk on a population level, but do not have specificity for local plaque inflammation.

Plasma C-reactive protein is associated with a pro-inflammatory and adverse plaque phenotype.

Background And Aims: Systemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features.

Methods: Plaques were derived during carotid endarterectomy.

Apolipoprotein C-III Inhibition - Killing Two Birds with One Stone?

In this issue of , Gaudet et al. report on safety and efficacy of a strategy targeting apolipoprotein C-III (APOC3) using a silencing ribonucleic acid (RNA; ARO-APOC3). In a phase I trial comprising 52 healthy volunteers (triglycerides [TG], >80 mg/dl), 40 patients with hypertriglyceridemia (TG, >300 mg/dl), and 20 patients with chylomicronemia (TG, >880 mg/dl), ARO-APOC3 or placebo was administered subcutaneously either once or twice, with doses given on days 1 and 29.

ANGPTL3 (Angiopoietin-Like 3) Preferentially Resides on High-Density Lipoprotein in the Human Circulation, Affecting Its Activity.

Background ANGPTL3 (angiopoietin-like protein 3) is an acknowledged crucial regulator of lipid metabolism by virtue of its inhibitory effect on lipoprotein lipase and endothelial lipase. It is currently unknown whether and to which lipoproteins ANGPTL3 is bound and whether the ability of ANGPTL3 to inhibit lipase activity is affected by binding to lipoproteins. Methods and Results Incubation of ultracentrifugation-isolated low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions from healthy volunteers with recombinant ANGPTL3 revealed that ANGPTL3 associates with both HDL and LDL particles ex vivo.

Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction.

Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction.

Lipoproteins act as vehicles for lipid antigen delivery and activation of invariant natural killer T cells.

Invariant natural killer T (iNKT) cells act at the interface between lipid metabolism and immunity because of their restriction to lipid antigens presented on CD1d by antigen-presenting cells (APCs). How foreign lipid antigens are delivered to APCs remains elusive. Since lipoproteins routinely bind glycosylceramides structurally similar to lipid antigens, we hypothesized that circulating lipoproteins form complexes with foreign lipid antigens.

Lp(a): a New Pathway to Target?

Purpose Of Review: Over the past decades, genetic and observational evidence has positioned lipoprotein(a) as novel important and independent risk factor for cardiovascular disease (ASCVD) and aortic valve stenosis.

Recent Findings: As Lp(a) levels are determined genetically, lifestyle interventions have no effect on Lp(a)-mediated ASCVD risk. While traditional low-density lipoprotein cholesterol (LDL-C) can now be effectively lowered in the vast majority of patients, current lipid lowering therapies have no clinically relevant Lp(a) lowering effect.

Lipoprotein(a): An underestimated inflammatory mastermind.

Lipoprotein(a) [Lp(a)] has been established as an independent and causal risk factor for cardiovascular disease. Individuals with elevated levels of Lp(a) (>125 nmol/L; >50 mg/dl) display increased arterial wall inflammation characterized by activation of the endothelium by Lp(a)-carried oxidized phospholipids and recruitment of circulating monocytes. This results in increased secretion of chemoattractants and cytokines, upregulation of adhesion molecules and increased migration of leukocytes through the vessel wall.

Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives.

Introduction: Diabetes, chronic kidney disease (CKD) and cardiovascular disease (CVD) are cardiometabolic diseases that remain amongst the leading causes of morbidity and premature mortality. Here, we review the current understanding of how anti-inflammatory intervention via inhibition of the pro-inflammatory but pleiotropic cytokine interleukin (IL) 6 may benefit patients with these or related diseases or complications.

Areas Covered: Based on a PubMed literature search, this review integrates and contextualizes evidence regarding the clinical utility of anti-IL-6 intervention in the treatment of cardiometabolic diseases, as well as of the associated condition nonalcoholic hepatosteatosis.

Targeted proteomics improves cardiovascular risk prediction in secondary prevention.

Aims: Current risk scores do not accurately identify patients at highest risk of recurrent atherosclerotic cardiovascular disease (ASCVD) in need of more intensive therapeutic interventions. Advances in high-throughput plasma proteomics, analysed with machine learning techniques, may offer new opportunities to further improve risk stratification in these patients.

Methods And Results: Targeted plasma proteomics was performed in two secondary prevention cohorts: the Second Manifestations of ARTerial disease (SMART) cohort (n = 870) and the Athero-Express cohort (n = 700).

The iterative lipid impact on inflammation in atherosclerosis.

Purpose Of Review: Lipid-mediated atherogenesis is hallmarked by a chronic inflammatory state. Low-density lipoprotein cholesterol (LDL-C), triglyceride rich lipoproteins (TRLs), and lipoprotein(a) [Lp(a)] are causally related to atherosclerosis. Within the paradigm of endothelial activation and subendothelial lipid deposition, these lipoproteins induce numerous pro-inflammatory pathways.

Effects of dipeptidyl peptidase-4 inhibitor linagliptin versus sulphonylurea glimepiride on systemic haemodynamics in overweight patients with type 2 diabetes: A secondary analysis of an 8-week, randomized, controlled, double-blind trial.

Aim: To determine the glucose-independent effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D).

Materials And Methods: In this prespecified secondary analysis of a phase IV, double-blind trial, 46 metformin-treated, overweight patients with T2D were included and randomly assigned (1:1) to once-daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub-study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style).

HIV and Cognitive Impairment in Clinical Practice: The Evaluation of a Stepwise Screening Protocol in Relation to Clinical Outcomes and Management.

Neurocognitive impairment (NCI) is an increasingly important comorbidity in an ageing HIV+ population. Despite the lack of available treatment modalities, screening for NCI is recommended. In the UMC Utrecht, yearly NCI screening is done using the Montreal Cognitive Assessment (MoCA) tool and the HIV Dementia Scale (HDS).