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A genetic risk score predicts cardiovascular mortality in young adults with coronary heart disease
Session:
Painel 8 -Doença Coronária 6
Speaker:
Flávio Mendonça
Congress:
CPC 2020
Topic:
E. Coronary Artery Disease, Acute Coronary Syndromes, Acute Cardiac Care
Theme:
12. Coronary Artery Disease (Chronic)
Subtheme:
12.2 Coronary Artery Disease – Epidemiology, Prognosis, Outcome
Session Type:
Posters
FP Number:
---
Authors:
Flávio Mendonça; Maria Isabel Mendonça; Andreia Pereira; Joel Monteiro; Joao Adriano Sousa; Marina Santos; Margarida Temtem; Ana Célia Sousa; Eva Henriques; Sónia Freitas; Ana Isabel Freitas; A. Drumond de Freitas; Roberto Palma dos Reis
Abstract
<p><strong>Background</strong></p> <p>The risk for Coronary Artery Disease (CAD) is determined by both genetic and environmental factors, as well as by the interaction between them. Young patients with CAD usually lack most of the clinical factors and almost invariantly have low cardiovascular risk. There is an increasing interest in the potential use of Genetic Risk Score (GRS) in cardiovascular disease.</p> <p>The aim of this study was to evaluate whether additive GRS (aGRS) improves the prediction of cardiovascular mortality in young nondiabetic patients with CAD and identifies a more aggressive form of atherosclerosis in this population.</p> <p><strong>Methods </strong></p> <p>A prospective study with consecutive inclusion of nondiabetic patients aged < 55 years (46.47±5.72, 84.1% male) with CAD angiographically proven. The primary outcome was cardiovascular mortality. We have included 12 genes associated to cell cycle, cellular migration and inflammation; genes involved in pro-oxidative status; genes associated with modifiable risk factors such as lipids metabolism, hypertension and diabetes/obesity. The GRS was constructed under an additive model. Genotyping was performed by TaqMan Real-Time PCR method. For statistical analysis, the GRS was divided into 4 quartiles and Kaplan-Meier survival curves were plotted for the primary outcome. The low-risk GRS (1<sup>st</sup> quartile) was used as the reference group. Cox regression models were constructed. </p> <p><strong>Results</strong></p> <p>A logistic regression under a Forward Wald method was performed including hypertension, dyslipidemia, smoker, multivessel coronary artery disease (MVCAD), serum creatinine and aGRS (1<sup>st</sup> vs. 4<sup>nd</sup> quartile). In this multivariable analysis, MVCAD (OR = 2.38; 95%CI: 1.05 – 5.39; p = 0.037) and aGRS (OR = 2.89; 95%CI: 1.19 – 7.06; p = 0.020) were independent predictors for cardiovascular mortality. Kaplan-Meier analysis showed that the cumulative survival rate of the 1st quartile was not significantly higher than 4th quartile of aGRS (p=0.065).</p> <p><strong>Conclusions</strong></p> <p>An additive genetic risk score identified nondiabetic young patients with CAD at higher risk for cardiovascular mortality. There was no difference in the cumulative survival rate between 1<sup>st</sup> and 4<sup>th</sup> quartile, low and high-risk aGRS, respectively; but Kaplan-Meier analysis showed a separation of survival curves at the beginning (see figure). The possibility to identify patients at higher risk represents an actionable goal to modify to a more aggressive secondary therapy. </p>
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