Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus.

BACKGROUND: The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. PATIENTS AND METHODS: A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems. RESULTS: The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis). CONCLUSIONS: We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.

Novel Biomarkers for Coronary Restenosis Occurrence After Drug-Eluting Stent Implantation in Patients With Diabetes Having Stable Coronary Artery Disease.

The purpose of the study was to assess whether the occurrence of restenosis is associated with CD45+ platelet count and neutrophil to lymphocyte ratio in patients with type 2 diabetes mellitus (DM) after drug-eluting stent (DES) implantation for stable coronary artery disease (CAD). The study comprised 126 patients, including 55 patients with type 2 DM and stable CAD who underwent elective coronary artery stenting with DES and follow-up angiography within 6 to 12 months. Blood samples were collected from each patient on the morning of the coronary angiography procedure. The variables related to in-stent restenosis were selected by logistic regression analysis. The logistic regression analysis showed that 2 inflammatory factors, CD45+ platelet count (odds ratio [OR] = 4.51, 95% confidence interval [CI]: 1.50-13.50, P = .007) and neutrophil to lymphocyte ratio (OR = 3.09, 95% CI: 1.05-9.10, P = .04), were significantly associated with the risk of in-stent restenosis after stenting with DES in patients with stable CAD and type 2 DM. A receiver operator characteristic curve analysis indicated that the area under the curve was 0.83% (0.05%; P < .001), which showed that the logistic model had good predictive accuracy (based on CD45+ platelet count and neutrophil to lymphocyte ratio) for the risk of in-stent restenosis development in DES in patients with CAD and type 2 DM. Two novel biomarkers of restenosis, CD45+ platelet count and neutrophil to lymphocyte ratio, may be effectively used to predict in-stent restenosis after DES implantation in patients with CAD and type 2 DM.

Blood level of CD45+ platelets and development of restenosis after drug-eluting stent implantation in patients with stable coronary artery disease.

OBJECTIVE: The aim of this study was to assess CD45-positive platelets (CD45+ platelets) involvement in restenosis development after drug-eluting stent (DES) implantation in patients with stable coronary artery disease (CAD). METHODS: The study comprised 126 male and female patients with stable angina pectoris, who underwent elective coronary stenting with DES and follow-up angiography within 6-12 months. The patients were assigned to the group with restenosis (n = 53) or group without restenosis (n = 73) according to the follow-up angiograms. In both groups we compared the level in blood of CD45+ platelets, the clinical, laboratory and angiographic variables, which may affect the development of restenosis. We have also constructed a logit regression model for prognosis of restenosis occurrence after DES implantation. RESULTS: The blood count of CD45+ platelets was higher in patients with restenosis than in patients without: 0.82 % (0.58; 1.12) vs. 0.34 % (0.20; 0.68), p < 0.001, data are expressed as median (lower quartile; upper quartile). By binary comparisons of more than 35 different clinical, laboratory and angiographic variables we identified 8 significant risk factors for the development of stent restenosis after DES. In order to define the risk of the development of restenosis, we have built a logit regression model. The resulting logit regression equation included the level of CD45+ platelets, the neutrophil to lymphocyte ratio (NLR), small diameter arteries stenting and the number of simultaneously implanted stents in one patient. Receiver operating characteristic (ROC) curve analysis has demonstrated the high prognostic value of the resulting logit regression equation with an area under the curve (AUC) of 0.91 % (p < 0.001). CONCLUSIONS: The acquired data indicate the presence of a close relationship between circulating CD45+ platelets and restenosis development after DES implantation in patients with stable CAD.