IL-31 Associated with Coronary Artery Lesion Formation in Kawasaki Disease

Background

Kawasaki disease (KD) is known to be associated with T help (Th) 2 reaction and subsequently allergic diseases. Interleukin-31 (IL-31) has also been reported to be involved in Th2 mediated diseases such as allergic diseases. However, the role of IL-31 in KD has not been previously reported. The aim of this study is to investigate whether IL-31 is associated with KD and its clinical outcome.

Material

A total of 78 KD patients who met the criteria of KD were enrolled in this study as well as 20 age-matched controls. Plasma samples were conducted to measure IL-31 before intravenous immunoglobulin (IVIG) treatment (KD1), within 3 days after IVIG treatment (KD2) and at least 3 weeks after IVIG treatment (KD3) by utilizing enzyme-linked immunosorbent assay (ELISA).

Result

Our findings showed that IL-31 expression was higher in KD patients after IVIG treatment significantly (KD2>KD1: 1265.0±199.3 vs. 840.2±152.5 pg/ml, p<0.0001). Further analysis revealed that IL-31 level was significantly higher in KD patients with coronary artery lesion (CAL) (656.6±139.5 vs. 1373.0±422.0 pg/ml, p = 0.04) before IVIG treatment (KD1). There were no significant differences between the IVIG resistance and IVIG responsiveness groups.

Conclusion

IL-31 was increased after IVIG treatment in patients with KD and was significantly associated with CAL formation. The results from this study may help to identify a novel risk factor for predicting KD and CAL formation.     

Correlation of Chronic Renal Dysfunction and Albuminuria with Severity of Coronary Artery Lesions in Patients with Coronary Artery Disease

This study was conducted to investigate the possible correlation of chronic renal dysfunction and albuminuria with the severity of coronary artery lesions in patients with coronary artery disease (CAD). Two-hundred and ninety-nine patients who had undergone coronary angiography for suspected CAD were stratified into three groups according to the glomerular filtration rate (GFR): group I included 144 patients with normal renal function GFR >90 ml/(min × 1.73 m²), group II included 97 patients with mild renal impairment GFR 60–89 ml/(min × 1.73 m²), and group III included 58 patients with moderate renal impairment GFR <60 ml/(min × 1.73 m²). Patients were then stratified into two groups according to the albuminuria level (0; minimal, 1+, 2+, 3+): the albuminuria negative group (negative = 0) included 171 patients and the albuminuria positive group (positive = minimal, 1+, 2+, 3+) included 128 patients. Clinical features and coronary lesion characteristics were compared among these groups. Patients with more severe renal dysfunction and positive albuminuria had a higher incidence of CAD (66.7 vs. 70.1 vs. 72.4 %, p = 0.025 and 64.2 vs. 75.0 %, p = 0.032), more multi-vessel disease (31.2 vs. 41.2 vs. 53.4 %, p = 0.004 and 33.3 vs. 46.1 %, p = 0.015), more left anterior descending branch lesions (50.7 vs. 56.7 vs. 60.3 %, p = 0.012 and 49.1 vs. 61.7 %, p = 0.009), and a higher Gensini score (42.3 ± 14.7 vs. 46.1 ± 19.9 vs. 52.8 ± 21.2, p = 0.026 and 44.0 ± 16.0 vs. 50.5 ± 20.2, p = 0.017). In conclusion, chronic renal dysfunction and albuminuria may be important factors determining the occurrence and the severity of CAD. Albuminuria was an especially significant indicator at the early stage of renal dysfunction.     

Coronary Artery Disease with Single Coronary Artery

The authors have reviewed the literature in search of the coexistence of single coronary artery with significant coronary artery disease. Two cases of single right coronary artery are described. In both, the anomalies were unsuspected and diagnosed roentgenographically in life. Both patients had angina pectoris, positive graded-exercise stress tests, and hemodynamically significant obstruction or occlusion to the coronary arteries. In neither case was the stenosis proximal or amenable to bypass surgery.     

Analysis of Gene-Gene Interactions among Common Variants in Candidate Cardiovascular Genes in Coronary Artery Disease

ObjectiveOnly a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD.ConclusionsModerately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated.     

女性冠心病患者的危险因素分析及与冠脉病变严重程度的关系

目的:了解女性冠心病患者的危险因素及与冠脉病变严重程度的关系。方法:随机选取本院2012年至2014年心血管科住院治疗的疑似冠心病女性患者150例,经冠脉造影确诊冠心病患者105例,非冠心病患者45例。对患者的临床资料和冠脉病变严重程度进行单因素和多因素分析。结果:冠心病患者高血压与糖尿病百分比、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)及纤维蛋白原水平均高于非冠心病患者,而高密度脂蛋白(HDL-C)和血红蛋白水平均低于非冠心病患者(P0.05);年龄、高血压与糖尿病百分比、血脂上升百分比(高TC、高TG、低HDL-C、高LDL-C)、高尿酸百分比和纤维蛋白原水平均随冠状动脉病变支数及Gensini积分的增加而增加(P0.05);多因素分析发现女性冠心病的影响因素分别为高LDL-C、糖尿病、低HDL-C、TG和高血压,其中高LDL-C的影响最为显著(P0.05)。结论:高血压、糖尿病史、血脂水平为女性冠心病的影响因素,其中高LDL-C的影响最显著,各影响因素均与冠脉病变程度紧密相关。     

超声在完全与不完全川崎病患儿冠状动脉病变评估中的应用价值

摘要 目的：探讨超声在完全与不完全川崎病（Kawasaki Disease,KD）患儿冠状动脉病变（Coronary artery lesions,CAL）评估中的应用价值。方法：2019年6月到2021年5月选择在西安医学院第二附属医院住院诊治的83例川崎病患儿,其中完全川崎病患儿43例（完全组）,不完全川崎病患儿40例（不完全组）。所有患儿都给予超声检查,评估两组的临床表现、血液学指标、冠状动脉病变情况以及超声的诊断价值。结果：完全组的球结膜充血、皮疹、口唇破裂、手足硬肿、颈部淋巴结肿大等发生率高于不完全组（P>0.05）。两组的白细胞计数、血红蛋白对比差异有统计学意义（P<0.05）,C反应蛋白、血小板、白蛋白对比差异无统计学意义（P>0.05）。完全组的冠状动脉病变发生率为60.5 %,高于不完全组的27.5 %（P<0.05）。在83例患儿中,超声诊断为完全川崎病42例,不完全川崎病41例,超声对完全与不完全川崎病患儿的鉴别诊断敏感性与特异性为97.7 %（42/43）和100.0 %（40/40）。结论：完全与不完全川崎病患儿在临床表现、冠状动脉病变与实验室检测指标上都存在一定的差异,超声能鉴别诊断完全与不完全川崎病患儿的敏感性与特异性都比较好。     

Gender-Specific Associations between Circulating T-Cadherin and High Molecular Weight-Adiponectin in Patients with Stable Coronary Artery Disease

Close relationships exist between presence of adiponectin (APN) within vascular tissue and expression of T-cadherin (T-cad) on vascular cells. APN and T-cad are also present in the circulation but here their relationships are unknown. This study investigates associations between circulating levels of high molecular weight APN (HMW-APN) and T-cad in a population comprising 66 women and 181 men with angiographically proven stable coronary artery disease (CAD). Plasma HMW-APN and T-cad were measured by ELISA and analysed for associations with baseline clinical characteristics and with each other. In multivariable analysis BMI and HDL were independently associated with HMW-APN in both genders, while diabetes and extent of coronary stenosis were independently associated with T-cad in males only. Regression analysis showed no significant association between HMW-APN and T-cad in the overall study population. However, there was a negative association between HMW-APN and T-cad (P=0.037) in a subgroup of young men (age <60 years, had no diabetes and no or 1-vessel CAD) which persisted after multivariable analysis with adjustment for all potentially influential variables (P=0.021). In the corresponding subgroup of women there was a positive association between HMW-APN and T-cad (P=0.013) which disappeared after adjustment for HDL. After exclusion of the young men, a positive association (P=0.008) between HMW-APN and T-cad was found for the remaining participants of the overall population which disappeared after adjustment for HDL and BMI. The existence of opposing correlations between circulating HMW-APN and T-cad in male and female patient populations underscores the necessity to consider gender as a confounding variable when evaluating biomarker potentials of APN and T-cad.     

Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

Background

Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD.

Methods

A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis.

Results

Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses.

Conclusion

CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.     

川崎病患儿肠道菌群构成及分布与其冠状动脉病变的相关性分析

摘要 目的：分析川崎病患儿肠道菌群构成及分布与其冠状动脉病变的相关性。方法：选择我院自2020年1月至2023年2月接诊的86例川崎病患儿作为研究对象,根据是否出现冠状动脉病变,分为冠状动脉病变组（35例）和非冠状动脉病变组（51例）。检测所有患儿的肠道菌群多样性[肠道菌群丰度（Ace指数）、肠道菌群多样性（Shannon指数）]、肠道菌群构成比例[门水平（变形菌门、厚壁菌门、拟杆菌门）、属水平（乳杆菌属、拟杆菌属、韦荣球菌属）],使用多因素Logistic回归分析肠道菌群构成及分布与冠状动脉病变的关系。结果：冠状动脉病变组Ace指数大于非冠状动脉病变组（P＜0.05）;冠状动脉病变组与非冠状动脉病变组的Shannon指数比较无差异（P＞0.05）;冠状动脉病变组肠道厚壁菌门占比低于非冠状动脉病变组,拟杆菌门占比高于非冠状动脉病变组（P＜0.05）;冠状动脉病变组与非冠状动脉病变组的肠道变形菌门占比比较无差异（P＞0.05）;冠状动脉病变组肠道乳杆菌属占比、韦荣球菌属占比均低于非冠状动脉病变组（P＜0.05）;冠状动脉病变组与非冠状动脉病变组的肠道拟杆菌属占比比较无差异（P＞0.05）;经多因素Logistic回归分析,肠道Ace指数、厚壁菌门、拟杆菌门、乳杆菌属、韦荣球菌属均是川崎病患儿发生冠状动脉病变的独立影响因素（P＜0.05）。结论：川崎病患儿肠道菌群构成及分布与其冠状动脉病变密切相关,为改善肠道菌群失调、增加患儿的临床获益提供依据,应引起临床重视。     

Association of CCR2-CCR5 Haplotypes and CCL3L1 Copy Number with Kawasaki Disease,Coronary Artery Lesions,and IVIG Responses in Japanese Children

Background

The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown.

Methodology/Principal Findings

We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., < or > four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR)  = 2.25, p = 0.004 and OR = 6.26, p = 0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR = 0.21, p = 0.026) and CAL development (OR = 0.44, p = 0.071).

Conclusions/Significance

The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG.     

川崎病患儿并发冠状动脉损伤的危险因素及风险预测指标模型的评价与构建

摘要 目的：分析川崎病（KD）患儿并发冠状动脉损伤（CALs）的危险因素,并评价风险预测指标构建的模型价值。方法：选取2019年1月～2022年5月我院收治的100例KD患儿,根据是否合并CALs分为CALs组33例和非CALs组67例。采用单因素和多因素Logistic回归分析KD患儿并发CALs的影响因素。以多因素Logistic回归所保留的变量构建KD患儿并发CALs的预测模型。采用受试者工作特征（ROC）曲线分析构建的预测模型对KD患儿并发CALs的预测价值。结果：CALs组发热持续时间≥10 d、丙种球蛋白（IVIG）治疗延迟、IVIG无反应比例、中性粒细胞计数、红细胞沉降率（ESR）、C反应蛋白（CRP）、降钙素原（PCT）、N端脑利钠肽前体（NT-proBNP）、肌酸激酶MB（CK-MB）水平高于非CALs组（均P＜0.05）。多因素Logistic回归分析分析显示,发热持续时间≥10 d、IVIG治疗延迟、IVIG无反应、ESR、CRP、PCT、NT-proBNP、CK-MB为KD患儿并发CALs的危险因素（均P＜0.05）。以上述指标所构建KD患儿并发CALs的联合预测模型评估效能较高,其ROC-AUC（0.95CI）为0.891（0.813～0.950）。结论：发热持续时间、IVIG治疗延迟、IVIG无反应和ESR、CRP、PCT、NT-proBNP、CK-MB升高是KD患儿并发CALs的危险因素,根据风险预测指标构建的预测模型对KD患儿并发CALs的预测能效较好。     

冠心病相关循环miRNA

冠心病诊断中最主要的挑战就是从常规的血液样本中鉴定出可靠的临床生物标志物.循环miRNA是一种可以稳定存在于体液中的小分子RNA,具有较高的组织、疾病特异性及敏感性,具有作为新的冠心病非侵入性生物标志物的潜力.通过综述血液样本（全血、血浆、血清、外周血单核细胞（PBMC）、内皮祖细胞（EPC）及血小板）中冠心病相关循环miRNA,及探讨循环miRNA研究中存在的一些问题,为未来筛选出真正具有临床应用价值的循环miRNA生物标志物奠定基础.     

川崎病患儿并发冠状动脉损伤的危险因素及预测模型的构建与评价

摘要 目的：分析川崎病患儿并发冠状动脉损伤（CAL）的危险因素,并构建和评价川崎病患儿并发CAL的预测模型。方法：选取2019年1月～2022年5月我院收治的342例川崎病患儿,根据是否并发CAL分为CAL组和非CAL组。收集所有患儿临床资料,采用单因素和多因素Logistic回归分析川崎病患儿并发CAL的影响因素,并构建预测模型,H-L检验和受试者工作特征（ROC）曲线检验预测模型拟合优度和对川崎病患儿并发CAL的预测价值。结果：342例川崎病患儿CAL发生率为16.67％（57/342）。单因素分析显示,CAL组发热持续时间≥10 d、静脉注射免疫球蛋白（IVIG）治疗延迟、IVIG无反应比例和单核细胞比例（MO％）、嗜酸性粒细胞比例（EO％）、C反应蛋白（CRP）、红细胞沉降率（ESR）、降钙素原（PCT）、心肌肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK-MB）水平高于非CAL组（P均＜0.05）。多因素Logistic回归分析显示,发热持续时间≥10 d、IVIG治疗延迟、IVIG无反应和MO％、CRP、ESR、PCT、cTnI升高为川崎病患儿并发CAL的独立危险因素（P均＜0.05）。H-L检验川崎病患儿并发CAL的预测模型拟合效果良好。ROC曲线分析显示,该模型预测川崎病患儿并发CAL的曲线下面积（AUC）为0.911（95％CI：0.876～0.939）。结论：发热持续时间≥10 d、IVIG治疗延迟、IVIG无反应和MO％、CRP、ESR、PCT、cTnI升高为川崎病患儿并发CAL的危险因素,根据危险因素构建的川崎病患儿并发CAL预测模型价值较高。     

冠心病合并代谢综合征患者的冠状动脉病变特点及与 代谢综合征组分的相关性研究

目的:探讨冠心病合并代谢综合征(metabolic syndrome,MS)患者的冠脉病变特点及冠心病与MS各组分的相关性。方法:选取540例冠心病患者为研究对象,其中合并MS患者164例,非合并MS患者376例,并将所有患者根据MS的组分个数进行分组,比较冠心病合并MS的病变特点、MS组分个数对冠状动脉病变程度的影响及冠状动脉病变程度与代谢综合症各组分的相关性;结果:①冠心病合并MS组BMI、FBG、TG、LDL-C、TC、UA、FIB、高血压分级等指标较非MS组高,差异有统计学意义(P<0.01),HDL-C、LVEF较非MS组低,差异有显著性(P<0.01);②MS组冠脉Gensini积分较高,三支病变、主干病变发生率高,差异有显著性(P<0.01);③随着合并MS组分个数的增加,冠脉Gensini积分也逐渐增加,各组间比较有显著性差异(P<0.01);④冠脉Gensini积分与MS组分BMI、高血压分级、TG、TC、LDL-C、UA等指标存在正相关(P<0.05),与性别、HDL-C存在负相关(p<0.01);调整传统危险因素后,Gensini积分与MS的组分数显著相关(r=0.739、P<0.01)。结论:冠心病患者有较高的MS患病率,冠心病合并MS患者冠脉病变程度更重,且以多支病变、主干病变为主;随着合并MS组分个数的增加,冠脉病变程度也呈加重趋势;MS的各个组分均与冠状动脉病变程度显著相关,可以作为冠心病严重程度的预测指标。     

Impact of Coexisting Coronary Artery Disease on the Occurrence of Cerebral Ischemic Lesions after Carotid Stenting

Background

Coronary artery disease (CAD) may coexist with extracranial carotid artery stenosis (ECAS), but the influence of CAD on procedure-related complications after carotid artery stenting (CAS) has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI) scanning.

Methods

Coronary angiography was performed within six months before CAS. DWI scanning was repetitively done within 1 week before and after CAS. Clinical outcome measures were stroke, angina, myocardial infarction and death within 30 days.

Results

Among 126 patients (69.5±9.0 years) recruited for unilateral protected CAS, 33 (26%) patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33) and 48% (45 in 93) of patients with and without peri-CAS DWI-positive lesions (OR, 4.0; 95% CI, 1.6–10.0; P = .0018), and the number of concomitant CAD on coronary angiography was positively correlated with the risk for peri-CAS DWI-positive lesions (P = .0032). In patients with no CAD (n = 55), asymptomatic CAD (n = 41) and symptomatic CAD (n = 30), the occurrence rates of peri-CAS DWI-positive lesions were 13%, 41% and 30% (P = .0048), and the peri-CAS stroke rates were 2%, 7% and 0% (P = .2120).

Conclusions

The severity of morphological CAD and the presence of either symptomatic or asymptomatic CAD are associated with the occurrence of peri-CAS cerebral ischemic lesions.     

早发冠心病患者的危险因素及冠脉病变特点研究

目的:探讨早发冠心病(PCAD)患者的危险因素及冠脉病变特点。方法:收集2014年8月至2015年2月北京安贞医院急诊科行冠状动脉造影的1000例患者为研究对象,根据冠状动脉造影结果和临床资料分为早发冠心病(PCAD)组(男55岁,女65岁,n=340)、晚发冠心病组(n=300)和对照组(非冠心病者,n=360)。对三组患者的临床资料进行统计学分析,采用logistic回归分析PCAD患者的危险因素,并比较PCAD组与晚发冠心病组的冠状动脉病变特点。结果:Logistic回归分析结果提示:吸烟、早发冠心病家族史、高血压病及2型糖尿病是PCAD的独立危险因素(P0.001)。PCAD组单支病变比例显著高于晚发冠心病组(P0.05);回旋支、右冠状动脉病变比例低于晚发冠心病组(P0.05)。结论:吸烟、早发冠心病家族史、高血压病及2型糖尿病是PCAD的独立危险因素。早发冠心病患者冠脉病变主要累及前降支,单支病变多于晚发冠心病患者。