Banca de DEFESA: MARIANA UBALDO BARBOSA PAIVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARIANA UBALDO BARBOSA PAIVA
DATE: 30/03/2023
TIME: 09:00
LOCAL: Auditório da Pós-Graduação da Faculdade de Medicina
TITLE:

Metabolomics and Leaman CT score as non-invasive methods for risk stratification in asymptomatic patients with intermediate Framingham score: a translational pilot study

KEY WORDS:

CT-LeSc score, metabolomics, Coronary Arterial Disease (CAD), cardiovascular risk stratification, translational research, mass spectrometry, GC and LC-QTOF/MS.

PAGES: 159
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Early detection of subclinical atherosclerosis on patients with Framingham intermediate risk is a major unmet clinical need and additional tests are recommended to personalize the risk estimates. A prognostic revelation of CT-adapted Leaman score coupled with the analysis of potentials candidates for biomarkers by comprehensive metabolomic profile can deepen the current knowledge of the phenotype of patients and be used as a complementary technique for re-stratification of the risk. To test the hypothesis that CT-LeSC is able to discriminate different metabolomic profiles in intermediate risk subjects and aid physicians in the decision-making in order to better stratify these patients. We studied 40 subjects with an intermediate CV risk profile, subdividing them according to the presence or absence of CAD, assessed by computed tomography angiography. They were recruited into three groups according to CT-LeSc score (Low: < 5 and High > 5), and Control, and another analysis in four groups according to CT-LeSc tertiles (T1: 0.3-3.7; T2: 3.8-8.2; T3: 8.3-24.1 and Control). Metabolomic analysis of serum from patients in each group was performed with a global approach based on undirected performance liquid chromatography coupled with time-of-flight mass spectrometry (LC-QTOF/MS) and gas chromatography (GC MSMS). Data were analyzed between January 2018 and July 2020. Among the patients, 28 (70%) had identifiable plaques in the coronary tree; of these, 16 patients (40%) were high-risk, 12 (30%) were low-risk, and 12 (30%) were controls. In the GC MSMS approach, high concentrations of pipecolic acid, 2-hydroxy-3-methylbutyric acid, palmitic acid, oleic acid, asparagine, linoleic acid, L-phenylalanine, L-glutamic acid were found in the control group, while L-5- oxoproline was expressed more intensely in the High CT-LeSc group when compared to the Low CT-LeSc and Control groups. The sPLS-DA model had a low misclassification error rate and the value of the Area Under Curve (AUC) from ROC curves was 0.789 (95% CI: 0.559-0.952), 0.734 (95% CI: 0.424-0.955) and 0.654 (95% CI: 0.389-0.812) in the plaque group vs control, High-CT LeSc group vs control and High-CT LeSc group vs Low-CT LeSc, respectively. In the LC MSMS approach, the data show a discriminating metabolite profile between the extreme phenotypes of the intermediate group (High CT-LeSc versus Control and T3 versus Control), with AUC of 0.926 and 0.967, respectively. In this pilot, prospective, translational study, metabolomics analysis revealed discriminatory metabolic fingerprints of high CT-LeSc and T3 phenotypes, despite comparable intermediate CV risk profiles with controls, which seems to indicate, even in this global analysis, a hint of there may be a discriminating molecular signature for these patients. Ultimately, a specific grouping of metabolites, rather than a single marker, may improve the biological understanding of CVD risk.

BANKING MEMBERS:
Externo ao Programa - 1561942 - CARLOS HENRIQUE REIS ESSELIN RASSI
Externo à Instituição - DANIEL FRANCA VASCONCELOS - HUB
Presidente - 149.136.268-50 - FERNANDO ANTIBAS ATIK - USP
Externo à Instituição - FRANCISCO RAFAEL MARTINS LAURINDO - USP
Externo à Instituição - GUILHERME URPIA MONTE - ICTDF