Combined and independent impact of coronary artery calcification and inflammation on risk for adverse cardiovascular events after percutaneous coronary intervention: Results from a large single-center registry.
- 作者列表："Aoi S","Baber U","Kovacic JC","Mehran R","Aquino M","Dangas G","Sweeny J","Vijay P","Shah S","Barman N","Moreno P","Kini AS","Sharma SK
PURPOSE:Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI). BACKGROUND:CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events. METHODS:A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year. RESULTS:Within the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1-year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p-trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP. CONCLUSIONS:The presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.
目的: 我们的研究调查了冠状动脉钙化 (CAC) 和全身炎症对经皮冠状动脉介入治疗 (PCI) 后主要不良心血管事件 (MACE) 风险的影响。 背景: 已知 CAC 和全身性炎症与心血管事件风险增加有关。 方法: 根据 CAC 程度 (中度/重度 vs.无/轻度) 对 2009年1月1日至 2015年12月31日在我院连续行 PCI 的 17,711 例患者进行分组。和高敏 C 反应蛋白 (hsCRP) 水平 (≥ 2 vs. <2 mg/L)。MACE 定义为 1 年以上发生的死亡、心肌梗死 (MI) 或靶血管血运重建 (TVR)。 结果: 在四组中，同时存在中度/重度 CAC 和 hsCRP 升高的患者 (n = 1,814 [10.2%]) 与单独使用中度/重度 CAC (n = 1,687 [9.5%]) 、单独使用 hsCRP 升高 (n = 7,597 [42.9%]) 相比，合并危险因素更多或无异常 (n = 6,613 [37.3%])。类似的 1 年 MACE 率分别为 21.2 、 14.9 、 11.5 和 7.8% (p 趋势 <.001)。多变量校正后结果无变化，提示 CAC 和 hsCRP 升高患者存在协同不良反应。 结论: 中度/重度 CAC 和全身性炎症的存在对 PCI 术后 MACE 的风险具有协同作用。表明需要新型或更强烈的治疗干预措施来减轻此类患者的风险。
METHODS:Aims : We sought to investigate the thrombogenicity of different DES and BMS in an in vitro system of stent perfusion. Material and Methods: The experimental model consisted of a peristaltic pump connected to 4 parallel silicone tubes in which different stents were deployed. Blood was drawn from healthy volunteers and the amount of stent surfaced -induced thrombus deposition was determined using 125 I -fibrinogen. Results: Compared to Resolute, Biomatrix and Vision, Xience was associated with the lowest amount of stent surface -induced thrombus formation, with a significant difference compared to Vision (125 I -fibrinogen median value deposition [IQ range]: 50 ng [25 -98] versus 560 ng [320 - 1,520], respectively, p<0.05), but not to other DES. In the second set of experiments Fluoropolymer -coated BMS not eluting drug was associated with a significant 3 -fold reduction in 125 I -fibrinogen deposition (245 ng [80 -300]) compared to Vision (625 ng [320 -760], p<0.05), but a 7 -fold increase compared to Xience (35 ng [20 -60], p<0.05). Finally Xience was associated with a significantly greater absorption of albumin compared to BMS. Conclusions: In an in vitro system of stent perfusion, Xience was associated with the lowest amount of stent surface -induced thrombus formation compared with Resolute, Biomatrix and Vision, with a noted synergistic effect between the fluoropolymer and the drug.
METHODS::Fibronectin-splice variant containing extra domain A (Fn-EDA) is associated with smooth muscle cells (SMCs) following vascular injury. The role of SMC-derived Fn-EDA in SMC phenotypic switching or its implication in neointimal hyperplasia remains unclear. Herein, using human coronary artery sections with a bare metal stent, we demonstrate the expression of Fn-EDA in the vicinity of SMC-rich neointima and peri-strut areas. In mice, Fn-EDA colocalizes with SMCs in the neointima of injured carotid arteries and promotes neointima formation in the comorbid condition of hyperlipidemia by potentiating SMC proliferation and migration. No sex-based differences were observed. Mechanistic studies suggested that Fn-EDA mediates integrin- and TLR4-dependent proliferation and migration through activation of FAK/Src and Akt1/mTOR signaling, respectively. Specific deletion of Fn-EDA in SMCs, but not in endothelial cells, reduced intimal hyperplasia and suppressed the SMC synthetic phenotype concomitant with decreased Akt1/mTOR signaling. Targeting Fn-EDA in human aortic SMCs suppressed the synthetic phenotype and downregulated Akt1/mTOR signaling. These results reveal that SMC-derived Fn-EDA potentiates phenotypic switching in human and mouse aortic SMCs and neointimal hyperplasia in the mouse. We suggest that targeting Fn-EDA could be explored as a potential therapeutic strategy to reduce neointimal hyperplasia.
METHODS:OBJECTIVE:The goal of this study was to determine the impact of late-acquired stent malapposition (LASM) on long-term clinical outcomes in patients treated with coronary stent implantation. Approach and Results: We investigated major adverse cardiac event during 10 years after 6-month intravascular ultrasound examination using our previous studies database. A total of 732 patients treated with bare-metal stent (54 LASM versus 678 non-LASM) and 529 patients treated with first-generation drug-eluting stent (82 LASM versus 447 non-LASM), who did not have clinical event or censoring at the time of follow-up intravascular ultrasound, were included for the present analysis. major adverse cardiac event was defined as the composite of cardiac death, target vessel-related myocardial infarction, target lesion revascularization and stent thrombosis. Multivariable adjustment and inverse probability weight were performed to consider baseline differences. After multivariable adjustment, LASM was related to a greater risk of major adverse cardiac event (hazard ratio, 1.666 [95% CI, 1.041-2.665]; P=0.0333) and very-late stent thrombosis (hazard ratio, 3.529 [95% CI, 1.153-10.798]; P=0.0271) than non-LASM in patients treated with first-generation drug-eluting stent, but not in those treated with bare-metal stent. Results were consistent after inverse probability weight. Among patients with LASM of first-generation drug-eluting stent, no late stent thrombosis occurred in patients who continued to receive dual antiplatelet therapy. CONCLUSIONS:The relationship between LASM and major adverse cardiac event might depend on the type of implanted stents during the long-term follow-up, highlighting the clinical significance of polymers and drugs in drug-eluting stent system.