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Curso de Atualização em Medicina Cardiovascular 2019
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Impact of LPA gene variation on the risk of Coronary Disease
Session:
CO3 - Doença Coronária
Speaker:
Andreia Pereira
Congress:
CPC 2019
Topic:
E. Coronary Artery Disease, Acute Coronary Syndromes, Acute Cardiac Care
Theme:
12. Coronary Artery Disease (Chronic)
Subtheme:
12.5 Coronary Artery Disease – Prevention
Session Type:
Comunicações Orais
FP Number:
---
Authors:
Andreia Pereira; Maria Isabel Mendonça; Joao Adriano Sousa; Flávio Mendonça; Micaela Rodrigues Neto; Ana Célia Sousa; Eva Henriques; Sónia Freitas; Sofia Borges; Ilídio Ornelas; Ana Isabel; A. Drumond de Freitas; Roberto Palma dos Reis
Abstract
<p>The rs3798220 variant of the LPA gene encoding lipoprotein (a) is strongly associated with increased plasma levels of Lp (a), reduction in the number of copies of type 2 Kringle IV and lower lipoprotein size, which leads to a more deleterious lipoprotein. It is not so clear the influence of LPA gene and coronary artery disease.</p> <p><strong>Objective:</strong> Investigate the association of LPA rs3798220 with plasma levels of Lp (a) and the risk of coronary disease (CAD) in our population. Estimate whether the inclusion of high levels of Lp (a), in a model with tradicional risk factors, increases the predictive capacity for CAD.</p> <p><strong>Methods:</strong> A case-control study was carried out with 3050 subjects (1619 coronary patients with 53.3 ±8 years; 77.8% male and 1431 controls with 52.8 ±7.8 years; 76.6% male) from the GENEMACOR study population. Traditional risk factors (TRF) were investigated, as well as the LPA rs3798220 and its plasma levels. Lp (a) ≥30 mg/dL was considered elevated. Bivariate and multivariate (logistic regression) analyzes estimated the risk of CAD. A ROC curve and respective AUC were designed to evaluate the predictive capacity of the addition of Lp (a) ≥30 mg / dl to the model with the TRF to predict CAD.</p> <p><strong>Results:</strong> In our population, there was an association between the LPA gene and Lp (a) plasma levels, being higher in the CT genotype (mean 81.09±64.2 mg/dL) than in the TT genotype (mean 30.30±33.7 mg/dL), with statistical significance (p<0.0001). After multivariate analysis, LPA gene was significantly and independently associated with CAD risk (OR=2.33; 95%CI: 1.52-3.62; p <0.0001). A second multivariate analysis indicated that high plasma levels (Lp (a)≥30) were significantly associated with CAD (OR=2.11, 95%CI: 1.77-2.52; p<0.0001), in contrast to Lp (a) <30, that was protective for CAD. The inclusion of high levels of Lp (a) to TRF model to predict CAD, the AUC increased from 0.768 to 0.780 (DeLong test p=0.0001), improving the predictive capacity of the initial model.</p> <p><strong>Conclusion:</strong> Our study confirmed that LPA rs3798220 variant is associated with CAD risk as well as with elevated plasma levels of Lp (a), which represent an independent risk factor for this disease. A better understanding of the regulation and metabolism of Lp (a) may lead to new pharmacological targets to reduce Lp (a) levels, with potential benefit in the treatment and prevention of CAD.</p>
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