AB0345 A PILOT ATTEMPT TO USE THE CONSTANT GENETIC MARKERS IN CARDIOVASCULAR RISK STRATIFICATION IN RHEUMATOID ARTHRITIS
Authors: Vitaly Omelchenko, Elena Letyagina, Tatyana Pospelova, Maxim Korolev
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with early atherosclerosis and high mortality. Routine riskometers developed for a common population usually underestimate a true cardiovascular (CV) risk in RA-patients. For early prevention additional criteria is needed to evaluate CV risk in RA-patients. It's known, that early CV accidents in relatives relate to elevated risk. Nevertheless, specific constant genetic markers don't use in risk stratification. Single nucleotide polymorphisms in regulatory regions of genes, participating in immune interaction, can potentially play a role in progression atherosclerosis and used in CV-prevention algorithms. Objectives: to develop the model for cardiovascular risk stratification in RA-patients including constant genetic markers. <h3>Methods</h3> Two hundred and twelve Caucasian patients with RA (age – 58.0 yrs [48.3; 65.0]; DAS28 4.96 [3.86; 5.85]) were included in our study. Patients had American College of Rheumatology (ACR)-defined RA (1987 classification criteria). All patients gave written informed consent before enrollment. Traditional and "non-traditional" (e.g. RA-associated factors) were analyzed [1]. Carotid atherosclerotic plaques had been found by ultrasonography. Single nucleotide polymorphisms were determined by restriction fragment length polymorphism (<i>TNFA G-308A</i> (rs1800629), <i>TNFA C-863A</i> (rs1800630), <i>TNFA G-238A</i> (rs361525), <i>IL6 G-174C</i> (rs1800795), <i>VEGFA C-2578A</i> (rs699947), <i>MMP3 5-1171 6A</i> (rs 3025058), <i>MMP9 -1562T</i> (rs3918242)) and polymerase chain reaction (<i>IL1B T-31C</i> (rs1143627), <i>IL4 C-590T</i> (rs2243250), IL10 C-592A (rs1800872), <i>IL10 A-1082G</i> (rs1800896), <i>VEGFA C+</i><i>936</i><i>T</i> (rs3025039), <i>MMP2 C-1306</i><i>T</i> (rs2438650)). Descriptive statistics, Chi-squared test, logistic regression with Wald statistics were used for data analysis. Results are presented as median and 25th/75th percentiles (Me [25th percentile; 75th percentile]). <h3>Results</h3> Atherosclerotic plaques (APl) were found in 59 (27.8%) patients. APl revealed were strongly associated with age (66.0 yrs [59.0; 73.0] with APl vs 55.0 yrs [42.0; 61.0] without APl, p&lt;0.001) and sex (51.6% for man vs 23.8% for woman, p&lt;0.001). Then, a logistic regression was performed to determine which variables analyzed are predictors of a carotid atherosclerotic lesion. Regression results had demonstrated that the model was statistically reliable in distinguishing between patients with APl and without [-2 Log Likelihood = 146.53, p&lt;001]. The model correctly classified 85.3% of cases. The Wald statistics showed that at least 6 parameters were principal – age (B=0.123, p&lt;0.001), hypertension (B=3.114, p&lt;0.001), smoke (B=2.167, p&lt;0.001), positive rheumatoid factor (B=1.674, p=0.038), body mass index (B=-0.098, 0.019) and recessive allele in <i>TNFA C-863A</i> (B=1.338, p=0.005). Using parameters obtained the ROC-curve was constructed. Area under ROC curve were 0.900 (SE 0.022; 95%Cl 0.857-0.942, P&lt;0.001). Sensitivity and specificity calculated by Youden's Index were 79.7% and 87.5%, respectively. <h3>Conclusion</h3> Age, hypertension, smoke, positive rheumatoid factor, low body mass index and recessive allele in <i>TNFA C-863A</i> were associated with carotid atherosclerosis. <h3>References</h3> [1] Amaya-Amaya J. et al. Novel risk factors for cardiovascular disease in rheumatoid arthritis//Immunol. Res. 2013. Vol. 56, No 2–3. P. 267–286 <h3>Disclosure of Interests</h3> None declared