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Aims: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA)., Methods and Results: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P-values = 0.005, 0.016, and 0.004, respectively)., Conclusion: The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis., Competing Interests: Conflict of interest: A.S. received fees for consultancy or lectures from Abbot, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Molecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.

Background and Aims: Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients., Methods: 73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, n ° = 30), CAD2 (non-obstructive CAD, n ° = 21), and CAD3 (obstructive CAD, n ° = 22). Flow cytometry for CD14, CD16, and CCR2 was used to quantify Mon1, Mon2, and Mon3 subsets. Expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, and CXCR4 was also measured. Adhesion molecules and cytokines were quantified by ELISA., Results: Total cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF- α levels. IL-10 levels were lower at greater stenosis severity, while the IFN- γ /IL-10 ratio, a marker of a systemic pro-inflammatory imbalance, was directly correlated to stenosis degree and number of noncalcified plaques., Conclusions: The results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Silverio Sbrana et al.)

Background Progression of coronary artery disease using serial coronary computed tomography angiography (CTA) is of clinical interest. Our primary aim was to prospectively assess the impact of clinical characteristics and statin use on quantitatively assessed coronary plaque progression in a low-risk study population during long-term follow-up. Methods Patients who previously underwent coronary CTA for suspected coronary artery disease were prospectively included to undergo follow-up coronary CTA. The primary end point was coronary artery disease progression, defined as the absolute annual increase in total, calcified, and noncalcified plaque volume by quantitative CTA analysis. Results In total, 202 patients underwent serial coronary CTA with a mean interscan period of 6.2±1.4 years. On a per-plaque basis, increasing age (β=0.070; P =0.058) and hypertension (β=1.380; P =0.075) were nonsignificantly associated with annual total plaque progression. Male sex (β=1.676; P =0.009), diabetes mellitus (β=1.725; P =0.012), and statin use (β=1.498; P =0.046) showed an independent association with annual progression of calcified plaque. While hypertension (β=2.259; P =0.015) was an independent determinant of noncalcified plaque progression, statin use (β=-2.178; P =0.050) was borderline significantly associated with a reduced progression of noncalcified plaque. Conclusions Statin use was associated with an increased progression of calcified coronary plaque and a reduced progression of noncalcified coronary plaque, potentially reflecting calcification of the noncalcified plaque component. Whereas hypertension was the only modifiable risk factor predictive of noncalcified plaque progression, diabetes mellitus mainly led to an increase in calcified plaque. These findings could yield the need for intensified preventive treatment of patients with diabetes mellitus and hypertension to slow and stabilize coronary artery disease progression and improve clinical outcome.

Aim: Proteomics is considered a promising tool in the discovery of new biomarkers and/or therapeutic targets. The aim of this study was to identify proteins expressed in the plasma of survivors of myocardial infarction and possible correlations between expression of some proteins and the severity of coronary artery disease (CAD) in this population., Methods: The study included 17 survivors (15 men; age=53±9 years) of myocardial infarction at young age (age<60 years) classified for the severity of CAD graded according to angiography and 10 healthy volunteers (nine men; age=54±9 years). Proteomic analysis was carried out using a high-throughput technology and MALDI TOF/TOF mass spectrometry., Results: Compared with the healthy population, 14 proteins were differentially expressed in patients, and were classified in three principal categories: contraction, inflammation, and coagulation. Results show a correlation between the angiographic severity, the extension of CAD, and the expression of some proteins. In particular decreased levels of vitamin D binding protein (VDBP) in the plasma of patients statistically correlated with the number of affected coronary arteries. Enzyme-linked immunosorbent assay test confirmed modulation of VDBP., Conclusion: Our results suggest that some proteins are differentially expressed in atherosclerotic patients and their disregulation is strongly dependent on the severity of the artery disease. The down regulation of VDBP is confirmed and marked in multivessel disease patients., (© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.)