MiR-486 and miR-92a Identified in Circulating HDL Discriminate between Stable and Vulnerable Coronary Artery Disease Patients

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL₂, while miR-92a prevailed in HDL₃, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.     

Calprotectin and Platelet Aggregation in Patients with Stable Coronary Artery Disease

BackgroundRecent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD). However, the impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated.ObjectivesWe investigated the association between calprotectin levels and platelet aggregation in stable, high-risk CAD patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to investigate independent clinical and laboratory determinants of calprotectin levels.MethodsWe performed a cross-sectional study including 581 stable, high-risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet aggregation was assessed by 1) impedance aggregometry (Multiplate Analyzer) using arachidonic acid (AA) and collagen as agonists and by 2) the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by calprotectin, high-sensitive C-reactive-protein (hs-CRP) and interleukin-6. Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1 inhibition was evaluated by serum thromboxane B₂, both measured by ELISA.ResultsCalprotectin levels correlated positively with platelet aggregation according to Multiplate Analyzer (r=0.12, p=0.01). Additionally, calprotectin was positively associated with leukocytes (r=0.33, p<0.0001), hs-CRP (r=0.31, p<0.0001), interleukin-6 (r=0.28, p<0.0001), soluble P-selectin (r=0.10, p=0.02) and serum thromboxane B₂ (r=0.10, p=0.02). Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004), and trends were seen for body mass index (p=0.06) and smoking (p=0.07). Compliance with aspirin was confirmed by low serum thromboxane B₂ levels in all patients (median [25%;75%]: 1.07 [0.52;1.87] ng/mL).ConclusionCalprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B₂ in high-risk, stable CAD patients treated with aspirin.     

G-CSF Predicts Cardiovascular Events in Patients with Stable Coronary Artery Disease

Granulocyte-colony-stimulating-factor (G-CSF) induces mobilization of progenitor cells but may also exert pro-inflammatory and pro-thrombotic effects. Treatment with recombinant G-CSF after acute myocardial infarction is currently under examination and has been associated with in-stent restenosis. However, it is not known whether plasma levels of endogenous G-CSF are also associated with an increased cardiovascular risk. Therefore we included 280 patients with angiographically proven stable coronary artery disease. G-CSF was measured by specific ELISA and patients were followed for a median of 30 months for the occurrence of major adverse cardiovascular events (MACE: death, myocardial infarction, re-hospitalization). Those with cardiac events during follow-up showed significant higher G-CSF levels (32.3 pg/mL IQR 21.4–40.5 pg/mL vs. 24.6 pg/mL IQR 16.4–34.9 pg/mL; p<0.05) at baseline. Patients with G-CSF plasma levels above the median had a 2-fold increased risk for MACE (p<0.05). This was independent from established cardiovascular risk factors. In addition, G-CSF above the median was a predictor of clinical in-stent restenosis after implantation of bare-metal stents (6.6% vs. 19.4%; p<0.05) but not of drug-eluting stents (7.7% vs. 7.6%; p = 0.98). This data suggests that endogenous plasma levels of G-CSF predict cardiovascular events independently from established cardiac risk factors and are associated with increased in-stent restenosis rates after implantation of bare metal stents.     

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.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low–28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Shared Decision Making in Patients with Stable Coronary Artery Disease: PCI Choice

Background

Percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) are comparable, alternative therapies for many patients with stable angina; however, patients may have misconceptions regarding the impact of PCI on risk of death and myocardial infarction (MI) in stable coronary artery disease (CAD).

Methods and Results

We designed and developed a patient-centered decision aid (PCI Choice) to promote shared decision making for patients with stable CAD. The estimated benefits and risks of PCI+OMT as compared to OMT were displayed in a decision aid using pictographs with natural frequencies and text. We engaged patients, clinicians, health service researchers, and designers with over 20 successive iterations of the decision aid, which were field tested during real-world clinical encounters involving clinicians and patients. The decision aid is intended to facilitate knowledge transfer, deliberation based on patient values and preferences, and shared decision making.

Conclusions

We describe the methods and outcomes of the design and development of a decision aid (PCI Choice) to promote shared decision making between clinicians and patients regarding the choice of PCI+OMT vs. OMT for treatment of stable CAD. We will evaluate the impact of PCI Choice on patient knowledge, decisional conflict, participation in decision-making, and treatment choice in an upcoming randomized trial.     

Determinants of Reduced Antiplatelet Effect of Aspirin in Patients with Stable Coronary Artery Disease

BackgroundAspirin is a cornerstone in management of coronary artery disease (CAD). However, considerable variability in the antiplatelet effect of aspirin has been reported.AimTo investigate independent determinants of reduced antiplatelet effect of aspirin in stable CAD patients.MethodsWe performed a cross-sectional study including 900 stable, high-risk CAD patients. Among these, 795 (88%) had prior myocardial infarction, 250 (28%) had type 2 diabetes, and 170 (19%) had both. All patients received 75 mg aspirin daily as mono antiplatelet therapy. The antiplatelet effect of aspirin was assessed by measurement of platelet aggregation employing 1) multiple electrode aggregometry (MEA, Multiplate Analyzer) in whole blood anticoagulated with citrate or hirudin using arachidonic acid (AA) or collagen as agonists, and 2) VerifyNow Aspirin Assay. Compliance was assessed by measurement of serum thromboxane B₂.ResultsPlatelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased AA-induced MEA platelet aggregation in citrate and hirudin anticoagulated blood (p-values ≤ 0.045). Similar results were found with VerifyNow. Prior coronary artery bypass grafting, age, smoking (MEA, AA/citrate) and female gender (MEA, AA/hirudin) were also independent determinants of increased platelet aggregation (p-values ≤ 0.038). Compliance was confirmed by low serum thromboxane B₂ levels in all patients (median [25%;75%]: 0.97 [0.52;1.97], range 0.02-26.44 ng/ml).ConclusionPlatelet count, prior myocardial infarction, type 2 diabetes and body mass index were independent determinants of increased platelet aggregation, indicating that these characteristics may be key factors in reduced antiplatelet effect of aspirin in stable CAD patients.     

NT-proBNP与急性冠脉综合征患者冠脉病变程度及预后的关系

目的:探讨N末端脑钠肽原(NT-pro BNP)与急性冠脉综合征(ACS)患者冠脉病变程度及预后的关系。方法:选择2012年1月至2015年6月我院收治的ACS患者400例为研究对象,根据病情症状的不同将患者分为不稳定心绞痛(UA)组和急性心肌梗死(AMI)组,各200例,另选同期200例非ACS患者作为对照组,比较各组患者的NT-pro BNP水平及ACS患者的心功能情况,并比较ACS患者的冠脉造影结果,通过Syntax评分系统评价冠脉病变,随访6-12个月,对比各组患者的主要心血管不良事件(MACE)发生率,通过上述比较及分析,研究ACS患者NT-pro BNP与冠脉病变程度及预后的关系。结果:AMI组及UA组患者的NT-pro BNP水平明显高于对照组,且AMI组患者的NT-pro BNP水平明显高于UA组,差异有统计学意义(P0.05);AMI组患者的冠脉病变Syntax积分高于UA组,差异有统计学意义(P0.05);冠脉病变Syntax积分≥33分的ACS患者的NT-pro BNP水平高于Syntax积分0-22分的患者,差异有统计学意义(P0.05);同时双支病变和三支病变患者的Syntax积分及NT-pro BNP水平高于单支病变患者,差异有统计学意义(P0.05);随访6-12个月发生MACE患者的NT-pro BNP水平明显高于未发生MACE者,差异有统计学意义(P0.05)。Pearson相关性分析显示,患者的冠脉病变程度与NT-pro BNP及Syntas积分均呈正相关(r=0.667,0.842;P0.05)。患者随访6-12个月MACE发生率与NT-pro BNP及Syntas积分也呈正相关(r=0.708,0.821;P0.05)。结论:ACS患者的冠脉病变程度及预后与其NT-pro BNP水平具有较好的相关性,值得临床关注。     

Serum Cystatin C Reflects Angiographic Coronary Collateralization in Stable Coronary Artery Disease Patients with Chronic Total Occlusion

Objective

We investigated whether and to what extent cystatin C was associated with angiographic coronary collateralization in patients with stable coronary artery disease and chronic total occlusion.

Methods

Serum levels of cystatin C and high-sensitive C-reactive protein (hsCRP) and glomerular filtration rate (GFR) were determined in 866 patients with stable angina and angiographic total occlusion of at least one major coronary artery. The degree of collaterals supplying the distal aspect of a total occlusion from the contra-lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary collateralization (Rentrop score of 2 or 3).

Results

In total, serum cystatin C was higher in patients with poor collateralization than in those with good collateralization (1.08 ± 0.32 mg/L vs. 0.90 ± 0.34 mg/L, P < 0.001), and correlated inversely with Rentrop score (adjusted Spearmen’s r = -0.145, P < 0.001). The prevalence of poor coronary collateralization increased stepwise with increasing cystatin C quartiles (P for trend < 0.001). After adjusting for age, gender, risk factors for coronary artery disease, GFR and hsCRP, serum cystatin C ≥ 0.97 mg/L remained independently associated with poor collateralization (OR 2.374, 95% CI 1.660 ~ 3.396, P < 0.001). The diagnostic value of cystatin C levels for detecting poor coronary collateralization persisted regardless of age, gender, presence or absence of diabetes, hypertension or renal dysfunction.

Conclusions

Serum cystatin C reflects angiographic coronary collateralization in patients with stable coronary artery disease, and cystatin C ≥ 0.97 mg/L indicates a great risk of poor coronary collaterals.     

Small-Size Circulating Endothelial Microparticles in Coronary Artery Disease

Objectives

Several recent lines of evidence indicate that endothelial microparticles are a new biomarker that can be used to monitor endothelial dysfunction in coronary artery disease (CAD). However, data concerning the detection of small microparticles (diameter <0.5 µm) are lacking. The aim of this study was to detect small-size endothelial microparticles (SEMPs) in CAD patients to monitor endothelial dysfunction.

Methods

In total, 19 CAD patients and 14 healthy subjects were recruited. The absolute numbers and percentages of CD31⁺/CD42b⁻ SEMPs and CD62E⁺ SEMPs were determined by flow cytometry. Clinical parameters were also recorded.

Results

The mean percentage of CD62E⁺ SEMPs was higher in the CAD patient group than in the healthy subject group. The area under the receiver operating characteristic curve of the percentage of CD62E⁺ SEMPs was 0.795, and the cut-off value was 1.35. There was no correlation between the percentage of CD62E⁺ SEMPs and various clinical parameters.

Conclusion

The percentage of CD62E⁺ SEMPs is a potential biomarker for monitoring endothelial function in CAD.     

Statin Intensity and Clinical Outcome in Patients with Stable Coronary Artery Disease and Very Low LDL-Cholesterol

BackgroundAlthough intensive statin therapy is recommended for high risk patients, evidence of its benefit in patients with stable coronary artery disease (CAD) and very low low-density lipoprotein-cholesterol (LDL-C) has been very rare. In this study, we investigated whether higher statin intensity reduces cardiovascular risks in this population.MethodsIn this retrospective study, a total of 5234 patients with stable CAD were screened at three tertiary hospitals in Korea; 449 patients (mean age: 65 years, male: 69%) with LDL-C <80 mg/dL were finally analyzed. The statin intensities were classified according to the 2013 American College of Cardiology/American Heart Association guidelines. Patients who received statins equivalent to or weaker than atorvastatin 10 mg (group 1) were compared with those who took statins equivalent to or stronger than atorvastatin 20 mg (group 2). The impact of statin intensity on major adverse cardiac events (MACE) was evaluated during follow-up.ResultsGroup 1 and group 2 consisted of 181 patients (40.3%) and 268 patients (59.7%), respectively. The mean LDL-C level decreased to 52 and 57 mg/dL in group 1 and group 2, respectively, during follow-up. In a median follow-up of 4.5 years, patients of group 2 had a lower incidence of MACE (30 [16.6%] vs. 12 [4.5%], p <0.001), which were mostly related to a lower incidence of coronary revascularization. Cox proportional hazard analyses identified the statin intensity of group 2 (adjusted hazard ratio: 0.25, confidence interval: 0.11–0.55, p <0.001) and the baseline high-density lipoprotein-cholesterol level as independent determinants of MACE.ConclusionThis study provides evidence that higher intensity statins are beneficial for cardiovascular outcomes in patients with stable CAD and very low LDL-C. Statins equivalent to or stronger than atorvastatin 20 mg are more effective than lower intensity statins.     

Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Objective

Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.

Methods

We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.

Results

Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.

Conclusion

The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.     

Fractional Flow Reserve Is Not Associated with Inflammatory Markers in Patients with Stable Coronary Artery Disease

Background

Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR), is associated with increased levels of blood based inflammatory biomarkers.

Methods

Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions.We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation.Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS), an extension of the Syntax Score.

Results

For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization.We found no difference for any of the selected biomarkers between patients with a positive FFR (≤0.75) and negative FFR (>0.80). We observed no relationship between the investigated biomarkers and FSS.

Conclusion

The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.     

Renal Artery Stenosis Predicts Coronary Artery Disease in Patients with Hypertension

In hypertensive patients with indication of renal arteriography to investigate renal artery stenosis (RAS) there are no recommendations regarding when to investigate coronary artery disease (CAD). Moreover, the predictors of CAD in patients with RAS are not clear. We aimed to evaluate the frequency and the determinants of CAD in hypertensive patients referred to renal angiography. Eighty-two consecutive patients with high clinical risk suggesting the presence of RAS systematically underwent renal angiography and coronary angiography during the same procedure. Significant arterial stenosis was defined by an obstruction≥70% to both renal and coronary territories. Significant CAD was present in 32/82 (39%) and significant RAS in 32/82 (39%) patients. Both CAD and RAS were present in 25.6% from the 82 patients. Patients with severe CAD were older (63±12 vs. 56±13 years; p = 0.03) and had more angina (41 vs. 16%; p = 0.013) compared to patients without severe CAD. Significant RAS was associated with an increased frequency of severe CAD compared to patients without significant RAS (66% vs. 22%, respectively; p<0.001). Myocardial scintigraphy showed ischemia in 21.8% of the patients with CAD. Binary logistic regression analysis showed that RAS≥70% was independently associated with CAD≥70% (OR: 11.48; 95% CI 3.2–40.2; p<0.001), even in patients without angina (OR: 13.48; 95%CI 2.6–12.1; p<0.001). Even considering a small number of patients with significant RAS, we conclude that in hypertensive patients referred to renal angiography, RAS≥70% may be a strong predictor of severe CAD, independently of angina, and dual investigation should be considered.     

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.     

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

Objectives

Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.

Methods

We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results

73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.

Conclusion

The presence of CE was associated with poorer coronary collateral development in patients with SCAD.     

Gene-Gene Associations with the Susceptibility of Kawasaki Disease and Coronary Artery Lesions

Kawasaki disease (KD) is a systemic vasculitis primarily affecting children < 5 years old. Genes significantly associated with KD mostly involve cardiovascular, immune, and inflammatory responses. Recent studies have observed stronger associations for KD risk with multiple genes compared to individual genes. Therefore, we investigated whether gene combinations influenced KD susceptibility or coronary artery lesion (CAL) formation. We examined 384 single-nucleotide polymorphisms (SNPs) for 159 immune-related candidate genes in DNA samples from KD patients with CAL (n = 73), KD patients without CAL (n = 153), and cohort controls (n = 575). Individual SNPs were first assessed by univariate analysis (UVA) and multivariate analysis (MVA). We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models. UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05). Significant associations in MDR analysis were only observed for the two-locus models after permutation testing (p ≤ 0.05). In logistic regression, combined possession of PDE2A (rs341058) and CYFIP2 (rs767007) significantly increased KD susceptibility (OR = 3.54; p = 4.14 x 10⁻⁷), while combinations of LOC100133214 (rs2517892) and IL2RA (rs3118470) significantly increased the risk of CAL in KD patients (OR = 5.35; p = 7.46 x 10⁻⁵). Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.     

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。