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.     

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.     

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。     

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.     

Cardiac Troponin I in Non- Acute Coronary Syndrome Patients with Chronic Kidney Disease

Objective

The aim of this study was to assess the results of troponin I (cTnI) in non- acute Coronary Syndrome (ACS) patients with chronic kidney disease (CKD). We also examined the risk factors for elevated cTnI in non-ACS patients with CKD and whether stage 5 CKD modifies the associations of elevated cTnI and the risk factors in non-ACS patients with CKD.

Methods

A retrospective study was performed. Logistic regression models were used.

Results

293 non-ACS patients with CKD were included in the current study. 43.34% non-ACS patients with CKD have an elevated cTnI level and 5.12% have an elevated cTnT level in MI range. In CKD patients without ACS and heart failure, only 26.03% (38/146) patients have an elevated cTnT level. In adjusted analyses, age, diastolic blood pressure and congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD (OR 2.30, 95% CI 1.08,4.88, P=0.03). Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.

Conclusion

43.34% non-ACS patients with CKD and 26.03% CKD patients without ACS and congestive heart failure have an elevated cTnI level. Congestive heart failure is associated with an elevated cTnI level in non-ACS patients with CKD. Stage 5 CKD does not modify the association of congestive heart failure and an elevated cTnI level.     

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.     

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。     

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.     

Plasma Haptoglobin Concentrations Are Elevated in Patients with Coronary Artery Disease

Inflammation underlies the development and progression of coronary artery plaques. Haptoglobin (Hp) is an acute phase protein, the synthesis of which is increased during inflammation. The aim of this study was to investigate plasma Hp concentrations and phenotype in patients with coronary artery disease (CAD). We recruited 359 patients with fixed luminal stenosis ≥50% in at least one coronary artery (CAD group) and 83 patients with luminal stenosis ≤40%, normal ejection fraction, and normal regional wall motion (control group). Plasma Hp concentrations were measured using a phenotype-specific enzyme-linked immunosorbent assay. Hp phenotype was determined by native polyacrylamide gel electrophoresis. Plasma lipid concentrations were measured. Plasma Hp concentrations were significantly higher in the CAD compared with the control group (262.4±144.2 vs 176.0±86.7 ng/mL, P<0.001); however, there was no between group difference in the distribution of Hp phenotype (1-1 = 7.5% vs 7.2%; 2-1 = 40.4% vs 42.2%; 2-2 = 52.1% vs 50.6%). Stepwise multivariate logistic regression revealed that high Hp concentrations (odds ratio [OR] = 5.865), male sex (OR = 3.689), hypertension (OR = 2.632), diabetes mellitus (OR = 3.300), and low-density lipoprotein concentrations (OR = 1.480) were independently associated with CAD (all P<0.05). Hp phenotype was not associated with CAD. Plasma Hp concentrations were significantly correlated with the severity of luminal stenosis (r = 0.236, P<0.001). Our findings suggest that plasma Hp concentrations may be elevated in patients with CAD. There does not appear to be any relationship between Hp phenotype and CAD.     

冠心病患者体内瘦素与高敏C反应蛋白检测的临床意义

目的:研究血清瘦素(LP)与高敏C反应蛋白(hsCRP)水平在冠心病患者体内的变化,及临床检测意义。方法:入选住院确诊的冠心病住院患者168例,对照组62例。外周血白细胞(WBC)水平应用全自动血细胞计数仪检测,血清高敏C反应蛋白水平应用比浊法检测,并血清瘦素水平用酶联免疫吸附法检测,分析瘦素与高敏C反应蛋白和外周血白细胞的关系。结果:(1)冠心病稳定型心绞痛组、不稳定型心绞痛组及急性心肌梗死组血清瘦素、高敏C反应蛋白和外周血白细胞水平显著高于对照组(均P0.05)。(2)血浆瘦素、高敏C反应蛋白及外周血白细胞水平在稳定型心绞痛组、不稳定型心绞痛组及急性心肌梗死组三组间依次增高,差异有统计学意义(均P0.05)。(3)简单相关分析显示瘦素与高敏C反应蛋白和外周血白细胞相关,r值分别为5.241和4.025,均P0.05。结论:瘦素与高敏C反应蛋白和外周血白细胞关系密切,可能通过炎症反应参与冠心病的发生。     

Functional Analysis LRP6 Novel Mutations in Patients with Coronary Artery Disease

Background

Genetic architecture of coronary artery disease (CAD) is still to be defined. Since low density lipoprotein receptor-related protein 6 (LRP6) gene play critical roles in Wnt signal transduction which are important for vascular development and endodermis specification, we therefore resequenced it to search for mutations in CAD patients.

Methods

We systemically sequenced all the exons and promoter region of LRP6 gene in a sample of 380 early onset CAD patients and 380 control subjects in Chinese.

Results

In total, we identified 5 patient-specific mutations including K82N (two patients), S488Y (one patient), P1066T (two patients), P1206H (two patients) and I1264V (one patient) All these mutations located at the extracellular domain of LRP6 gene. In vitro functional analysis of patient-specific mutations demonstrated that these mutations resulted in a significant reduction in both protein level transporting to cell membrane and downstream Wnt signal activity. Furthermore, we found that LRP6 novel mutations attenuated proliferation and migration of human umbilical vein endothelial cells (HUVECs) when compared with wild type (WT) LRP6.

Conclusion

Our results demonstrated that these loss-of-function variants might contribute to disease liability in a subset of CAD and defects in Wnt signal activation might be important contributing factors for the onset of CAD.     

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.     

冠心病合并2型糖尿病的冠脉病变特征及危险因素分析

目的:探讨冠心病合并2型糖尿病的冠状动脉病变特征及其相关危险因素.方法:选择2010年1月至2012年1月我院经冠状动脉造影确诊为冠心病合并2型糖尿病的患者227例(DM组)和同期不合并2型糖尿病的冠心病患者229例(NDM组)为研究对象,回顾性分析其血脂、血糖及冠状动脉造影结果,比较两组患者冠状动脉病变的特点,探讨血糖水平对糖尿病合并冠心病患者冠状动脉病变的影响.结果:DM组患者总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)显著高于NDM组(P＜0.05),高密度脂蛋白胆固醇(HDL-C)显著低于NDM组(P＜0.05);DM组患者三支血管病变、弥漫性病变以及狭窄程度大于75％的血管的病例数百分率显著高于NDM组(P＜0.05);在DM患者中,血糖水平控制理想组(A组)的冠状动脉血管狭窄程度大于75％以及发生弥漫性病变的病例数百分率均显著低于血糖控制较差组(B组,P＜0.05).结论:2型糖尿病合并冠心病患者冠状动脉多表现为弥漫和多支病变,狭窄程度严重;血糖和血脂水平异常是其冠脉病变的危险因素;控制患者的血糖水平于正常范围可改善其冠状动脉病变程度并减小其病变范围.     

Obesity and Long-Term Clinical and Economic Outcomes in Coronary Artery Disease Patients

Objective: Obesity is an important risk factor for coronary artery disease (CAD); however, its effect on acute coronary syndrome (ACS) patients’ long-term clinical and economic outcomes has not been quantified. We assessed the impact of increasing body mass index (BMI) on 10-year outcomes for ACS patients. Research Methods and Procedures: ACS patients with significant CAD receiving an initial cardiac catheterization at Duke University Medical Center between 1986 and 1997 were included. Patients with a BMI < 18.5 kg/m² were excluded; the remaining patients were classified by BMI as normal, overweight, obese, or very obese. Medical costs were estimated from a prior ACS clinical trial with costs adjusted to 1997 dollars and discounted at 3% per annum. Results: There were 9405 patients with data available for analysis. Follow-up was complete on >95% of patients. Patients who were obese at baseline increased from 20% to 33% between 1986 and 1997. Increased BMI was associated with younger age, multi-morbidity, and less severe CAD at baseline. It was also associated with more clinical events, higher cumulative inpatient medical costs, and significant differences in unadjusted survival at 10 years. However, it was not associated with differences in 10-year survival after adjusting for baseline characteristic differences. Discussion: Obese ACS pateints are younger and are hospitalized more frequently during the first 10 years of their illness than are non-obese patients. They also incur higher cumulative inpatient medical costs, especially the very obese. These findings highlight the opportunities for therapeutic benefit that aggressive weight management and secondary prevention may provide this population.     

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.