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Identifying plasma lipid signatures for cardiovascular risk assessment in HFpEF patients
Session:
Comunicações Orais - Sessão 16 - Ciência Básica
Speaker:
Sílvia O. Diaz
Congress:
CPC 2023
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.6 Basic Science - Other
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Sílvia O. Diaz; António S. Barros; Pedro Palma; António Angélico-Gonçalves; Francisco Vasques-Nóvoa; Francisca Saraiva; José A. Belo; Otília V. Vieira; Adelino F. Leite-Moreira
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Introduction:</strong> The role of plasma lipids is well-established in cardiovascular diseases (CVD). Lipids may contribute to the development and progression of HFpEF by increasing inflammation and impairing the ability of the heart to relax and fill with blood. Still, a comprehensive evaluation of the plasma lipidome in patients with Heart Failure with preserved Ejection Fraction (HFpEF) is missing, predominantly for cardiovascular risk stratification. </span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Aims: </strong>To profile the plasma lipidome of patients with stable HFpEF using top-down shotgun lipidomics and to explore its associations with CV events.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Methods:</strong> Sixty HFpEF patients from the <em>NetDiamond</em> cohort were included. A total of 101 lipids were measured, normalized to their total sum (to reduce bias between subjects), log-transformed (to reduce skewness) and standardized (to give the same importance to all lipids). The primary endpoint was a composite of cardiovascular death or hospitalization due to HF or acute HF episode. Clinical data (age, sex, estimated glomerular filtration rate (eGFR), BNP and use of statin) was condensed through principal component analysis (PCA) into a single score (PC1) to be leveraged as regression adjustment. The association between each plasma lipid and a cardiovascular event was explored through Cox regression analysis, adjusted to the clinical data score (PC1). Models were internally validated with bootstrapping (resampling with repetitions, recomputed 1000 times). Hazard ratios (HR), p-values and c-index were recovered.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Results:</strong> For a median follow-up of 39 months (maximum 59 months), 21 patients registered an event. A significant association was found and corroborated with bootstrapping for 8 lipids (4 phosphocholines (PC), 1 phosphoethanolamine (PE), 1 phosphatidylinositol (PI), 1 sphingomielin (SM), and 1 cholesterol ester (CE) and the primary endpoint event in our population. Lipids positively associated were (ordered by decreasing HR): PE18:0-18:2, PC18:0-22:5, PC14:0-18:1, PI18:0-18:2, PC(O)16:0-18:0, and PC16:0-22:5; while negative associations were found for SM42:1:2 and CE20:4. Median c-index ranged from 0.69 to 0.80, showing moderately robust predictive models.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="color:#000000"><strong>Conclusion:</strong> Despite the small cohort and the low number of events, we identified lipids potentially associated with a cardiovascular event. These preliminary results revealed that plasma lipidomic might help stratify patients at risk of cardiovascular death, HF hospitalization, and acute HF episodes.</span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span style="color:black"><strong>Acknowledgements:</strong> European Regional Development Fund (ERDF), through the North Regional Operational Program in the framework of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (reference NORTE-01-0145-FEDER-000039).</span></span></span></span></p>
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