Prevalence of Polymorphisms of Genes Responsible for Coagulation System and Folate Metabolism and Their Predictive Value for Thrombosis Development in MINOCA Patients: Immediate and Long-Term Prognoses

IF 0.5 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiogenetics Pub Date : 2023-04-07 DOI:10.3390/cardiogenetics13020006

S. Kruchinova, V. Shvartz, A. Namitokov, Milana Gendugova, Maria Karibova, E. Kosmacheva

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引用次数: 1

Abstract

(1) Background. One of the causes of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is thrombus formation in situ followed by lysis, resulting in a morphologically normal angiogram but with an underlying prothrombotic state that is potentially predisposed to recurrence. Recent studies have shown that a subset of MINOCA patients may have thrombophilic conditions at screening. Objective: To compare the prothrombotic trend in MINOCA patients with that of subjects with MI and obstructive coronary arteries (MIOCA) by testing for known congenital thrombophilias and markers of coagulation activation. (2) Materials and methods. Screening included congenital thrombophilias (factor V Leiden; assessment of protein C, protein S, and antithrombin III) and eight genes. Of these, four genes represented the folate pathway enzymes: MTHFR 677 C>T (rs1801133), MTHFR 1298 A>C (rs1801131), MTR 2756 A>G (rs1805087), and MTRR 66 A>G (rs1801394). The other four genes represented the blood coagulation system: F13 (163 G>T) rs5985, F1 (−455 G>A) rs1800790, GP IIb–IIIa (1565 T>C) rs5918, and PAI-I (−675 5G>4G) rs1799889. Additionally, we examined the levels of homocysteine and lipoprotein (LP) (a). (3) Results. Our study included 269 patients: 114 MINOCA patients and 155 MIOCA patients with lesions of one coronary artery. The frequencies of polymorphisms in the genes of the blood coagulation system and the folate pathway did not differ between the groups. The following genes were associated with in-hospital mortality in the MINOCA group: MTHFR 1298 A>C rs1801131 (OR 8.5; 95% CI 1.67–43.1) and F1 (−455 G>A) rs1800790 (OR 5.8; 95% CI 1.1–27.8). In the MIOCA group, the following genes were associated with in-hospital mortality: MTHFR 1298 A>C rs1801131 (OR 9.1; 95% CI 2.8–28.9), F1 (−455 G>A) rs1800790 (OR 11.4; 95% CI 3.6–35.9), GP IIb–IIIa (1565 T>C) rs5918 (OR 10.5; 95% CI 3.5–30.8), and PAI-I (−675 5G>4G) rs1799889 (OR 12.9; 95% CI 4.2–39.7). We evaluated long-term outcomes (case fatality rate, recurrent MI, and stroke) over a period of 12 months in both groups. The variables associated with these outcomes were laboratory parameters, such as protein C deficiency, hyperhomocysteinemia, and a content of LP (a) > 30 mg/dL. However, we did not reveal the prognostic value of polymorphisms of the studied genes representing the blood coagulation system and the folate pathway. (4) Conclusion. We established no statistically significant differences between the MINOCA and MIOCA groups in the prevalence of congenital thrombophilias and the prevalence of folate pathway enzyme genes and blood coagulation system genes. The MTHFR 1298 A>C (rs1801131) and F1 (−455 G>A) rs1800790 genes were associated with in-hospital mortality in both groups. More significant prognostic factors in both groups during the one-year period were protein C deficiency, hyperhomocysteinemia, and LP (a) > 30 mg/dL.

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MINOCA患者凝血系统和叶酸代谢相关基因多态性的患病率及其对血栓形成的预测价值：近期和长期预后

（1）背景。非阻塞性冠状动脉（MINOCA）心肌梗死（MI）的原因之一是原位血栓形成，然后溶解，导致血管造影形态正常，但潜在的血栓前状态可能容易复发。最近的研究表明，MINOCA患者的一个子集在筛查时可能存在血栓形成性疾病。目的：通过检测已知的先天性血栓形成倾向和凝血激活标志物，比较MINOCA患者与MI和阻塞性冠状动脉（MIOCA）患者的凝血酶原趋势。（2）材料和方法。筛查包括先天性血栓形成倾向症（因子V Leiden；蛋白C、蛋白S和抗凝血酶III的评估）和8个基因。其中，四个基因代表叶酸途径酶：MTHFR 677 C>T（rs1801133）、MTHFR 1298 A>C（rs18011.31）、MTR 2756 A>G（rs1805087）和MTRR 66 A>G。其他四个基因代表凝血系统：F13（163 G>T）rs5985、F1（−455 G>A）rs1800790、GP IIb–IIIa（1565 T>C）rs5918和PAI-I（−675 5G>4G）rs1799889。此外，我们还检测了同型半胱氨酸和脂蛋白（LP）（a）的水平。（3）结果。我们的研究包括269名患者：114名MINOCA患者和155名MIOCA患者，其中一条冠状动脉有病变。凝血系统和叶酸途径基因多态性的频率在各组之间没有差异。以下基因与MINOCA组的住院死亡率相关：MTHFR 1298 A>C rs1801131（OR 8.5；95%CI 1.67–43.1）和F1（−455 G>A）rs1800790（OR 5.8；95%CI 1.1–27.8），GP IIb–IIIa（1565 T>C）rs5918（OR 10.5；95%CI 3.5–30.8）和PAI-I（−675 5G>4G）rs1799889（OR 12.9；95%CI 4.2–39.7）。我们评估了两组在12个月内的长期结果（病死率、复发性MI和中风）。与这些结果相关的变量是实验室参数，如蛋白质C缺乏、高同型半胱氨酸血症和LP（a）含量>30 mg/dL。然而，我们没有揭示所研究的代表凝血系统和叶酸途径的基因多态性的预后价值。（4）结论。我们确定MINOCA和MIOCA组在先天性血栓形成倾向的患病率、叶酸途径酶基因和凝血系统基因的患病率方面没有统计学上的显著差异。MTHFR 1298 A>C（rs1801131）和F1（−455 G>A）rs1800790基因与两组患者的住院死亡率相关。在一年期间，两组中更重要的预后因素是蛋白质C缺乏、高同型半胱氨酸血症和LP（a）>30 mg/dL。

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Cardiogenetics CARDIAC & CARDIOVASCULAR SYSTEMS-

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11 weeks