Short- versus long-term dual antiplatelet therapy after second-generation drug-eluting stent implantation in patients with diabetes mellitus: A meta-analysis of randomized controlled trials.

BACKGROUND: Diabetes is considered to be a high-risk factor for thromboembolic events. However, available data about the optimal dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) after second-generation drug-eluting stent (DES) implantation are scant. OBJECTIVE: The purpose of this study was to compare the impact of various DAPT durations on clinical outcomes in patients with DM after second-generation DES implantation. METHODS: We searched PubMed, Embase, and the Cochrane Library for studies that compared short-term (≤ 6 months) and long-term (≥ 12 months) DAPT in patients with DM. The primary endpoints were late (31-365 days) and very late (> 365 days) stent thrombosis (ST). The secondary endpoints included myocardial infarction (MI), target vessel recanalization (TVR), all-cause death, and major bleeding. RESULTS: Six randomized controlled trials, with a total of 3,657 patients with DM, were included in the study. In terms of the primary endpoint, there was no significant difference between the two groups in late (OR 1.15, 95% CI: 0.42-3.19, P = 0.79) or very late (OR 2.18, 95% CI: 0.20-24.18; P = 0.53) ST. Moreover, there was no significant difference in the secondary endpoints, including MI (OR 1.11, 95% CI: 0.72-1.71, P = 0.63), TVR (OR 1.31, 95% CI: 0.82-2.07, P = 0.26), all-cause death (OR 1.03, 95% CI: 0.61-1.75, P = 0.90) and major bleeding (OR 1.07, 95% CI: 0.34-3.40, P = 0.90) between the two groups. CONCLUSION: Our study demonstrated that compared with long-term DAPT, short-term DAPT had no significant difference in the clinical outcomes of patients with DM implanted with second-generation DES.

Association of Apolipoprotein E Gene Polymorphism with Ischemic Stroke in Coronary Heart Disease Patients Treated with Medium-intensity Statins.

OBJECTIVE: To study the association of apolipoprotein E(APOE) gene polymorphism with ischemic stroke (IS) in coronary heart disease (CHD) patients treated with medium-intensity statins. METHODS: The retrospective study was performed on 662 samples including 169 CHD subjects complicated with IS, 296 subjects with CHD, and 197 control subjects. The APOE gene was obtained from case files. Univariable and multivariable logistic regression analyses were utilized to recognize the possible risks of CHD and IS. RESULTS: The frequency of ε3-ε4 genotype was increased in the CHD group (p=0.013) and CHD-IS group (p=0.001), the frequency of ε4 allele was also increased in the CHD group (p=0.047) and the CHD-IS group (p=0.009) compared with control group. ε3-ε4 genotype was the independent risk for CHD and CHD-IS after adjusting for traditional risk factors with adjusted odds ratio (AOR) 2.210, 95%CI: 1.263-3.867, p=0.005) and (AOR 2.794, 95%CI: 1.539-5.072, p=0.002). The ε4 allele was also significantly associated with CHD (AOR 2.126, 95%CI: 1.265-3.575,=0.004) and CHD-IS (AOR 2.740, 95%CI: 1.569-4.784, p=0.001). CONCLUSION: These results demonstrated that ε4 allele influenced the development of CHD with or without IS, especially for the genotype of ε3-ε4. CHD patients carrying the ε3-ε4 genotype and the ε4 allele were significantly associated with the incidence of IS, even if medium-intensity statins had been used.

Three-year outcomes of bioresorbable vascular scaffolds versus second-generation drug-eluting stents: Meta-analysis of randomized trials.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) completely resorb within 3 years after placement into the coronary artery. The safety and effectiveness of bioabsorbable scaffolds are of critical importance during this 3-year period. OBJECTIVE: We performed a meta-analysis to compare the safety and efficacy of BVS and second-generation drug-eluting stents (DES) at 3 years after implantation. METHODS: Published randomized trials comparing BVS to second-generation DES for the treatment of coronary artery disease were identified within PubMed, EMBASE, Cochrane Library, Web of Science, and relevant Web sites with publication dates through June 2019. The primary efficacy endpoint was target lesion failure. The primary safety endpoint was definite/probable stent/scaffold thrombosis. Secondary outcomes were cardiac death, target vessel myocardial infarction, ischemia-driven target lesion revascularization, and a patient-oriented composite end point. RESULTS: Six randomized controlled trials, with a total of 5,412 patients (BVS n = 3,177; DES n = 2,235), were included. At 3 years, BVS was associated with higher rates of target lesion failure (OR = 1.33, 95%CI: 1.10-1.60, P = 0.003) and definite/probable stent/scaffold thrombosis (OR = 3.75, 95% CI: 2.22-6.35, P < .00001)compared with DES. The incidence of target vessel myocardial infarction (OR = 1.68, 95% CI: 1.30-2.17, P < .0001), ischemia-driven target lesion revascularization (OR = 1.46, 95% CI: 1.14-1.86, P = .003), and the patient-oriented composite end point(OR = 1.20, 95% CI: 1.04-1.39, P = .01) were higher for those treated with BVS compared with DES. However, there was no significant difference in risk of cardiac death (OR = 0.94, 95%CI: 0.61-1.45, P = .79) between treatment groups. CONCLUSIONS: At the 3-year follow-up, BVS was inferior to second-generation DES in both safety and efficacy.

GYY4137 exhibits anti-atherosclerosis effect in apolipoprotein E (-/-) mice via PI3K/Akt and TLR4 signalling.

Hydrogen sulphide (H2 S) had been suggested to be involved in the pathogenesis of atherosclerosis, but the underlying molecular mechanisms are poorly understood. In this study, we aimed to investigate the anti-atherosclerosis effect of morpholin-4-ium-methoxyphenyl-morpholino-phosphinodithioate (GYY4137) in RAW264.7 cell-derived foam cells formation and in the atherosclerotic plaque of ApoE-/- mice fed with a high-fat diet, and study the underlying mechanisms of phosphatidylinositol 3-kinase (PI3K), serine/ threonine kinase (Akt) and Toll-like receptor 4 (TLR4) signalling pathway. In the ApoE-/- mice fed with a high-fat diet, daily GYY4137 administration for 8 weeks effectively decreased carotid atherosclerotic plaque area and the volume of foam cells, regulated the lipid metabolism, down-regulated the pro-inflammatory cytokine levels and up-regulated the anti-inflammatory cytokines levels. Consistent with these findings, in the RAW264.7 cell-derived foam cells, GYY4137 ameliorated foam cell formation in vitro, and decreased the expression of pro-inflammatory cytokines. Furthermore, our studies showed that GYY4137 could activate the PI3K/Akt signalling pathway and consequently reduce the expression of TLR4 to be critical for foam cell formation, preventing atherosclerotic plaque formation and destabilization. LY294002, a PI3K inhibitor, could inhibit the phosphorylation of Akt and reduce the expression of TLR4, thus reduce the foam cell source and lipid volume in the unstable plaque tissue. Our results suggest that GYY4137 is an attractive novel therapeutic reagent for atherosclerosis diseases. This mechanism may be partially attributed to regulating the PI3K/Akt/TLR4 signalling pathway.

Mid-term outcomes of bioresorbable vascular scaffolds vs second-generation drug-eluting stents in patients with acute coronary syndromes: A systematic review and meta-analysis.

BACKGROUND: Everolimus-eluting bioresorbable vascular scaffolds (BVS), which have the characteristics of scaffold absorption and vascular function recovery, are the latest innovation in the treatment of coronary artery disease. This new concept has become a hot topic in the field of interventional cardiology. Data regarding mid-term clinical outcomes of BVS in acute coronary syndromes are currently scarce. The aim of this systematic review and meta-analysis is to compare mid-term outcome data for BVS and second-generation drug-eluting stents (DES) in the treatment of acute coronary syndromes. METHODS: We searched PubMed, Embase, the Cochrane Library, Web of Science, and relevant web sites for studies with a follow-up of ≥ 1 years that studied percutaneous coronary interventions with BVS vs second-generation DES in acute coronary syndromes. A meta-analysis was performed with the software RevMan following the standards of the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. RESULTS: Five studies, 2 randomized controlled trials, and 3 observational studies, with a total of 1758 patients (BVS n = 917; DES n = 841) and a median follow-up duration of 24 months, were included. BVS, when compared with DES, resulted in higher rates of target lesion revascularization (TLR) (OR, 2.20; 95% CI, 1.12-3.64; P = .02) and stent/scaffold thrombosis (ST/ScT) (OR = 2.35, 95% CI: 1.13-4.89, P = .02). When TLR due to device thrombosis were excluded, the difference in risk estimates between the 2 groups was no longer significant (OR: 1.67, 95% CI: 0.73-3.82, P = .22). The risk for all-cause death (OR = 1.32 95% CI: 0.61-2.88, P = .48), cardiac death (OR = 1.29, 95% CI: 0.58-2.86 P = .52), target vessel myocardial infarction (OR = 1.50, 95% CI: 0.86-2.61, P = .15), and target lesion failure (OR = 1.34, 95% CI: 0.76-2.35, P = .31) did not differ between BVS and DES groups. CONCLUSION: At mid-term follow-up, BVS had a higher risk of TLR and ST/ScT than the second-generation DES in patients with acute coronary syndromes. ST/ScT was the key factor indicating the decreased safety and effectiveness of BVS relative to DES.

The role of miR-328 in high glucose-induced endothelial-to-mesenchymal transition in human umbilical vein endothelial cells.

AIMS: Endothelial-to-mesenchymal transition (EndMT) contribute to diabetic cardiac fibrosis, the underlying mechanisms are poorly understood. In the study, we aimed to investigate the role of miR-328 in EndMT mediated by high glucose (HG) and the signaling pathways implicated in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS: EndMT of HUVECs was determined by immunofluorescent staining and western blot of the markers CD31 and α-SMA. Real-time polymerase chain reaction was used to detect mRNA expression of miR-328 and transforming growth factor ß1 (TGF-ß1). SB431542 was used to study the relation of miR-328 and TGF-ß1 during EndMT induced by HG. Over-expression and inhibition of miR-328 were achieved by transduction of miR-328 and antagomiR-328. The effects of miR-328 on expression of type I and III collagen, p-MEK1/2, p-ERK1/2 were examined by Western blot. KEY FINDINGS: The level of miR-328 was significantly up-regulated in HG-induced EndMT. MiR-328 showed the independent capability of inducing EndMT, which was not related to TGF-ß1, and this effect was abrogated by antagomiR-328. MiR-328 affected type I collagen in a time- and dose-dependent manner and enhanced protein expression of type I and III collagens. Further investigation displayed that a significantly higher expression of p-MEK1/2 and p-ERK1/2 in HUVECs transduced with miR-328, and a lower expression of p-MEK1/2 and p-ERK1/2 in cells transduced with antagomiR-328. SIGNIFICANCE: These results suggest a novel role for miR-328 in HG-induced EndMT, MEK1/2-ERK1/2 pathway is likely to be involved in the associated effects. Our findings may suggest antagomiR-328 as an alternative agent in prevention of HG-induced EndMT.