Variantes genéticas e variabilidade da frequência cardíaca em pacientes com antecedente de síndrome coronariana aguda

Abstract

Lipid metabolism genes are involved with coronary artery disease (CAD) and acute coronary syndrome (ACS) as well as low heart rate variability (HRV). Given thus, the identification of genetic markers, HRV and risk factors may contribute to better knowledge. Objective - To evaluate the association of genetic variants involved in the lipid metabolism pathway and their relation to biochemical and anthropometric profile, HRV, and lifestyle (smoking, drinking and physical inactivity) in patients with CAD and dyslipidemia, with or without ACS. Patients and Methods - We studied 80 patients with dyslipidemia and atherosclerotic CAD, under treatment with potent statins, aged> 45 years, divided into: Group 1 = 63 with a history of previous ACS and Group 2 = 17 with a CAD without a history of ACS. Patients underwent peripheral blood sampling for genetic profile analysis (DNA microarray), and three genes related to the lipid metabolism pathway were selected with subsequent analysis of seven polymorphisms (APOB-rs693, APOB-rs1042031, PCSK9- rs505151, PCSK9-rs11591147, PCSK9-rs11206510, RLDL-rs688, RLDL-rs6511720) by real time polymerase chain reaction (PCR) (TaqMan SNP Genotyping). The biochemical profile was obtained from electronic medical records. HRV was analyzed with the aid of time series recorded with Polar RS800 CX using linear and nonlinear methods. Data were analyzed using T-test or Mann-Whitney, Fisher's exact test or Chi-square. A 5% α error was assumed. Results - There was no significant difference between the groups for smoking, hypertension, BMI and physical inactivity (P> 0.05). Genetic polymorphisms – RLDL: Presence of wild genotype was observed in G2 (67%) when compared to G1 (0%; P <0.0001); In G1, the genotype (65%; TT) and the polymorphic allele (83% T; P <0.0001) stood out. The genotypic and allelic distribution was similar between groups for the other genes. Regarding the lipid profile, there was similarity between the median values for TC, HDLc and TG. LDLc prevailed in G2 (83.0mg / dL) compared to G1 (74.0mg / dL; P <0.025). Regarding HRV, of the analyzed variables, there was a statistically significant difference for: RRi (817 ± 103 x 961.6 ± 136.8 ms; P <0.0001); SDNN (141 ± 39 x 36.4 ± 30.7 ms; P <0.0001); TotalPowerms2 (21,222 ± 11,663 x 1827.1 ± 4869.1; P <0.0001); LnTotalPowerms2 (9.83 ± 0.51 x 7.5 ± 8.5; P = 0.0211); VLFPowerms2 (1782 ± 965 x 911.0 ± 2562.3; P = 0.0053). Lipid profile and HRV showed similarity between the variables. Conclusion: Polymorphisms of RLDL rs688 and rs6511720 are associated with previous SCA. Patients with coronary artery disease have reduced heart rate variability. Patients who have at least one polymorphic genotype of the PCSK9-rs11206510 gene, their heart rate variability is worse. The reduction in HRV may be associated with a worse lipid profile.