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Is genetic information helpful in predicting recurrent events in young patients after acute coronary syndrome?
Session:
Comunicações Orais - Sessão 07 - Genética em Cardiologia
Speaker:
Francisco Homem de Gouveia e Sousa
Congress:
CPC 2024
Topic:
O. Basic Science
Theme:
36. Basic Science
Subtheme:
36.6 Basic Science - Other
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Francisco Sousa; M.I. Mendonça; D. Sá; E. Henriques; S. Freitas; M. Rodrigues; S. Borges; G. Guerra; G. Abreu; A. Drumond; A.C. Sousa; R. Palma Dos Reis
Abstract
<p style="text-align:justify"><span style="font-size:11pt"><span style="background-color:white"><span style="font-family:Calibri,sans-serif"><strong><span style="color:black">Background:</span></strong><span style="color:black"> Coronary Artery Disease (CAD) shares environmental and genetic factors. Young patients with acute coronary syndrome (ACS) carry a poor long-term prognosis. The clinical utility of genetic information in predicting CAD events remains unknown. </span></span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="background-color:white"><span style="font-family:Calibri,sans-serif"><strong><span style="color:black">Aim:</span></strong><span style="color:black"> Evaluate the clinical utility of a multiplicative Genetic Risk Score (mGRS) to predict lifelong residual risk in CAD patients below 55 years with few risk factors.</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="background-color:white"><span style="font-family:Calibri,sans-serif"><strong><span style="color:black">Methods</span></strong><span style="color:black">: 475 non-diabetic patients with LDL cholesterol levels below 100mg/dL at the first admission who suffered a prior MI at age ≤55 years were followed prospectively for a mean of 5.6±5.3 years. A mGRS was performed with nine variants associated with CAD but not with traditional risk factors (TRF): <em>CDKN2B-AS1 </em>(rs1333049 and rs4977574), <em>TCF21</em> (rs12190287), <em>PHACTR1</em> (rs1332844), <em>MIA3</em> (rs17465637), <em>ADAMTS7</em> (rs3825807), <em>ZC3HC1</em> (rs11556924), <em>SMAD3</em> (rs17228212) and <em>GJA4</em> (rs618675). The mGRS was subdivided into terciles. Using Cox regression analysis, the predictive and discriminative score ability for events was evaluated. C-statistic discriminated cardiovascular events occurrence. Whether mGRS was included in the TRF model, Net Reclassification Improvement (NRI), or Integrated Discrimination Improvement (IDI) reclassified patients. Kaplan-Meier method estimated survival curves.</span></span></span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><span style="background-color:white"><span style="font-family:Calibri,sans-serif"><strong><span style="color:black">Results</span></strong><span style="color:black">. There were 153 patients with at least one cardiovascular event. The bivariate analysis showed the strongest correlation with second and third mGRS tercile, multivessel disease, left ventricular dysfunction, and inflammation represented by C-reactive protein. Multivariate Cox regression for events adjusted to traditional risk factors displayed an HR=2.00 (p=0.001) for the mGRS high-risk tercile together with low ejection fraction HR=1.61 (p=0.005) and multivessel disease HR=1.86 (p<0.0001). The mGRS inclusion improved C-statistic (C-index=0.010; p=0.004), NRI (35.4%; p<0.0001) and IDI (2.7%; p=0.0005).</span></span></span></span></p> <p style="text-align:justify"><strong><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif">Conclusions:</span></span></strong><span style="font-size:11.0pt"><span style="font-family:"Calibri",sans-serif"> Our 9-SNP mGRS better identified and reclassified younger CAD patients with a high probability of genetic events, improving clinical decision-making and reducing costs for therapeutic strategies.</span></span></p>
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