Plasma level of homocysteine is inversely-associated with the development of collateral circulation in patients with single-vessel coronary artery disease.

Homocysteine induces endothelial injury and inhibits endothelial cell proliferation, which is a key role in angiogenesis. The purpose of this study was to investigate whether the plasma level of homocysteine is associated with the development of collaterals in patients with single-vessel coronary artery disease (CAD). Among a series of 105 male patients with angiographic estimation, 49 with single-vessel CAD were intensively investigated. Development of collaterals was classified by Rentrop's method. Univariate and multivariate analyses revealed that hyperhomocysteinemia negatively affected the development of collaterals (p=0.0015 and 0.0011, odds ratio 0.69, 95% confidence interval 0.52-0.90), whereas the duration of angina and percent stenosis evaluated by quantitative coronary angiography had a positive affect. Moreover, the level of homocysteine in the group with poorly developed collaterals (n=7, Rentrop class 0 and 1) was significantly higher than that in the group with well-developed collaterals (n=12, Rentrop class 2 and 3) of the patients with single-vessel disease showing total occlusion (p=0.034). This study clearly demonstrates that the plasma level of homocysteine is independently and inversely associated with the development of collateral circulation in CAD patients. Homocysteine might be a new undesirable aspect of ischemic heart disease through its inhibition of collateral development.     

冠心病患者可溶性细胞粘附分子的检测及其临床意义

目的 :检测冠心病 (CHD)患者可溶性细胞间粘附分子 1(sICAM 1)及P 选择素的变化 ,探讨其在CHD发病机制中的意义。方法 :用ELISA法和酶法分别检测 6 8例CHD患者和 5 5例对照者的血清sICAM 1、P 选择素、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯 (TG)、总胆固醇水平 ,Gensini积分法评价冠状动脉病变程度 ,进行统计学分析。结果 :CHD患者血清sICAM 1和P 选择素水平均较对照组高 ,且差异有非常显著性意义 (均P <0 .0 0 1) ;sICAM 1水平与冠状动脉病变程度显著相关 (r =0 .6 6 2 ,P <0 .0 0 1) ;TG与sICAM 1水平呈正相关 (r =0 .4 0 3,P <0 .0 1) ;P 选择素与冠状动脉病变程度无明显关系。结论 :sICAM 1及P 选择素可能参与了CHD的发病过程 ,血清sICAM 1的检测有助于临床病情分析 ,TG是影响sICAM 1水平的因素之一。     

Mildly decreased glomerular filtration rate is associated with poor coronary collateral circulation in patients with coronary artery disease

Background:

The aim of this study was to evaluate the association between mildly decreased glomerular filtration rate (GFR) and coronary collateral circulation (CCC).

Hypothesis:

There would be an association between mildly decreased GFR and CCC.

Methods:

Patients who had an occlusion in at least 1 major coronary artery were included in this study. Patients with severely and moderately decreased GFR were excluded. Patient data were obtained from their files. To classify CCC, we used the Rentrop classification. Patients were classified as having poor CCC (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). We used the Modification of Diet in Renal Disease (MDRD) equation to calculate GFR. Mildly decreased GFR was defined as 60 mL/min per 1.73 m² ≥ eGFR ≤89 mL/min per 1.73 m² according to the MDRD definition. Multivariate logistic regression analysis was performed to determine independent variables.

Results:

The study group consisted of 299 patients. Ninety‐three patients had poor CCC and 206 patients had good CCC. The frequency of mildly decreased GFR was higher in the poor CCC group than in the good CCC group (P<0.001). Also, the frequency of diabetes and dyslipidemia, and the plasma high sensitive C‐reactive protein levels, were higher in the poor CCC group (P = 0.003, P = 0.018, P<0.001, respectively). Logistic regression analysis revealed that eGFR is an independent predictor of CCC (B = 1.68; odds ratio = 5.4; P<0.001; 95% confidence interval, 3.1–9.4).

Conclusions:

We found that CCC was worse in patients with mildly decreased GFR compared to patients with normal GFR in patients with coronary artery disease. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Pravastatin promotes coronary collateral circulation in patients with coronary artery disease

BACKGROUND: Previous studies suggested that hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) promotes collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with pravastatin and the development of coronary collateral circulation as assessed by the Rentrop Score in patients with coronary artery disease (CAD) in a case-control study. DESIGN: The study included patients who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels. Patients who did and did not receive pravastatin were defined as case participants (n = 42) and control participants (n = 100), respectively. RESULTS: The case participants included a higher percentage of 3-V patients with a Rentrop Score 1 compared to the control participants but there was no difference among 1-V and 2-V patients, suggesting that pravastatin was associated with coronary collateral circulation independent of the number of stenosed vessels. Patients with 3-V disease who were treated with pravastatin were most likely [odds ratio (confidence interval), 17.4 (4.4-115)] to develop collateral circulation, as assessed by multiple logistic regression analysis. CONCLUSIONS: Treatment with pravastatin was associated with the development of collateral circulation in patients with CAD, suggesting that such action constitutes part of the pleiotropic effects of statin.     

冠状动脉侧支循环影响因素的探讨

目的探讨冠状动脉侧支循环形成的相关影响因素。方法选择冠状动脉闭塞病变的患者106例,用单因素和多因素回归分析方法分析了患者年龄、性别、体重指数、血压、血脂、尿酸、血糖、胰岛素水平以及冠状动脉闭塞程度、病变特点等与侧支循环的关系。结果血糖水平和冠状动脉闭塞程度与冠状动脉侧支循环形成之间的回归系数达显著水平(P<0.01)。结论血糖水平和冠状动脉闭塞程度是影响冠状动脉侧支循环形成的重要因素。     

冠心病患者冠状动脉侧支循环形成的相关因素

目的:探讨冠状动脉侧支循环形成的意义及影响侧支循环形成的相关因素。方法:冠状动脉造影中发现有侧支循环形成者47例作为研究组,以病变程度相同但无侧支循环形成者58例作为对照组;同时超声心动图检查病变局部室壁运动情况。结果:侧支循环形成与糖尿病、吸烟呈负相关,与服用他汀类药物呈正相关,而与性别、年龄、胸痛时间、有无高血压病、有无高脂血症、家族史、冠状动脉病变支数、服用ACEI类、硝酸酯类药物无关。结论:侧支循环多出现在病变严重的冠心病患者,糖尿病、吸烟是侧支循环形成的不利因素,服用他汀类药物能促进侧支循环形成;糖尿病患者即使形成侧支循环,对心功能的保护作用也较差。     

Hematological parameters and coronary collateral circulation in patients with stable coronary artery disease

BACKGROUND:

Although hematological parameters have been associated with prognosis in patients with various cardiovascular diseases, their relationship with coronary collateral (CC) circulation in patients with stable coronary artery disease (CAD) is unknown.

OBJECTIVE:

To investigate the relationship between hematological parameters and CC vessel development in patients with stable CAD.

METHODS:

A total of 96 patients who underwent coronary angiography were retrospectively enrolled. All study participants had at least one occluded major coronary artery. Development of CCs was classified using the method of Rentrop. Rentrop grades of 0 and 1 indicate poor CCs, whereas grades 2 and 3 indicate good CCs. Hematological parameters, including mean platelet volume (MPV) and neutrophil/lymphocyte (N/L) ratio, were measured. Multivariate logistic regression analysis was performed to identify independent variables.

RESULTS:

The MPV and N/L ratio were significantly higher in the poor CC group compared with the good CC group. Negative correlations were found in the analyses comparing Rentrop score with MPV and N/L ratio (r=−0.274; P=0.012 and r=−0.339; P=0.001, respectively). In multivariate analysis, the N/L ratio was independently related to CC circulation (OR 0.762 [95% CI 0.587 to 0.988]; P=0.04).

CONCLUSION:

The results suggest that N/L ratio and MPV are associated with poor CCs, and a high N/L ratio is a significant predictor of poor CC development in patients with stable CAD.     

Markers of low-grade inflammation and soluble cell adhesion molecules in Chinese patients with coronary artery disease

BACKGROUND: Inflammation plays an important role in atherosclerosis. Markers of low-grade chronic inflammation, such as C-reactive protein (CRP) and soluble cell adhesion molecules (sCAMs), have been associated with coronary artery disease (CAD). OBJECTIVE: To evaluate the significance of inflammatory markers as novel risk factors for CAD in the Chinese population. METHODS: High-sensitivity CRP (hs-CRP); sCAMs, including vascular cell adhesion molecule-1 (sVCAM-1), intercellular cell adhesion molecule-1 (sICAM-1), P-selectin (sP-selectin) and E-selectin (sE-selectin); and white blood cell (WBC) count were measured in 170 angiographically defined CAD patients (70% or greater stenosis affecting at least one vessel) and 177 healthy control subjects in the Chinese population in Singapore. RESULTS: The levels of hs-CRP, sVCAM-1 and sP-selectin, and the WBC count were higher in CAD patients than in control subjects (P<0.001, P<0.05, P<0.05 and P<0.001, respectively). There were no significant differences in the levels of sICAM-1 and sE-selectin between the two groups. Patients with unstable angina or myocardial infarction had higher levels of hs-CRP, and higher WBC and monocyte counts than those with stable angina or atypical chest pain (all P<0.05). The level of sP-selectin in patients with multivessel disease was higher than in those with single-vessel disease (P<0.05). Overall, the levels of hs-CRP and sCAMs showed a significant correlation with the lipid profile and the WBC count. CONCLUSIONS: The present study suggests that inflammatory markers, including hs-CRP and WBC count, together with sP-selectin and sVCAM-1, could serve as markers of atherogenesis in Chinese patients with CAD, with potential diagnostic and therapeutic implications.     

Impact of coronary collateral circulation on QT dispersion in patients with coronary artery disease

OBJECTIVE: The aim of this study was to assess the effect of coronary collateral circulation (CCC) on QT dispersion (QTD) in coronary artery disease. BACKGROUND: A prolonged QTD has been linked to increased heterogeneity of ventricular repolarization implicated in the genesis of ventricular arrhythmias and has been associated with an adverse prognosis in patients with coronary artery disease. METHOD: CCC and corrected QTD (QTcD) were established in patients who had at least 85% stenosis in the left anterior descending coronary artery or in proximal part or in the body of the right coronary artery. Furthermore, left ventricular function score was determined for all the patients. RESULTS: While CCC was not present (CCC grade 0) in 32 patients, 68 patients were observed with CCC (CCC grade > or =1). Mean QTcD was higher in patients who had CCC grade > or =1 than in patients with grade 0 (64.3+/-3.5 and 46.8+/-2.7, respectively, P=0.002). We detected a significant correlation between the collateral score and QTcD (r=0.354, P=0.001). CCC grade > or =1 patients had higher mean left ventricular function scores than grade 0 patients (P=0.048). Left ventricular function score and QTcD were observed to be correlated (r=0.200, P=0.046). CONCLUSION: CCC in chronic coronary artery disease was not established to have a positive decreasing effect on QTcD. On the contrary, QTcD values were observed to be even higher in patients with well developed CCC. Further research including larger series and long-term follow-up is required to investigate this issue.     

Significance of collateral circulation in patients with left main coronary artery disease

Fifty patients with left main coronary artery disease were studied to evaluate the functional role of collateral circulation. The left main was narrowed 50-70% in 22 patients (group I), and more than 70% in 28 patients (group II). Significant disease in the other vessels was equally common in each group. There was no significant difference in the incidence of inter- and intracoronary collaterals in the two groups. Fifteen patients with no collaterals were compared with 35 patients with collaterals, and to a subset of 11 patients with very rich right-to-left collaterals, and there was no significant difference in historic or ECG evidence of old infarction, duration of angina, incidence of unstable angina, left ventricular end-diastolic pressure, cardiac index, ejection fraction, or segmental contraction abnormalities. We conclude that there is no evidence of protective effect of collateral vessels in patients with left main disease.     

Angiotensin-converting enzyme inhibitor promotes coronary collateral circulation in patients with coronary artery disease.

Previous studies have suggested that angiotensin-converting enzyme inhibitors (ACEI) promote collateral circulation in ischemic limbs of rabbits. The present study was designed to determine the association between treatment with ACEI and the development of coronary collateral circulation, as assessed by the Rentrop Score, in patients with coronary artery disease (CAD) in a case - control study. Subjects included 456 patients with angina who underwent coronary angiography. Those who had one (1-V), two (2-V) or three (3-V) significantly stenosed vessels, and who received only ACEI without any other anti-hypertensive medication were defined as cases (n=33), and age, sex and body mass index-matched subjects (n=56) were selected as controls. Among 1-V patients, but not 2-V or 3-V patients, the cases included a higher percentage of patients with Rentrop Score of at least 1 than the controls, suggesting that ACEI was associated with coronary collateral circulation. Patients with 1-V disease who were treated with ACEI were most likely [odds ratio (confidence interval): 6.1 (1.4-30.1)] to develop collateral circulation, as assessed by a multiple logistic regression analysis. Therefore, treatment with ACEI was associated with the development of collateral circulation in patients with CAD, suggesting that such an action is associated with bradykinin production by ACEI.     

Circulating adhesion molecules in patients with stable coronary artery disease

To evaluate platelet and endothelial function in patients with stable coronary artery disease (CAD), we investigated levels of the plasma-soluble (s) adhesion molecules E-selectin (sE-selectin), P-selectin (sP-selectin), and intercellular adhesion molecule-1 (sICAM-1) in 74 patients (mean age, 53 +/- 8 years) with angiographically documented coronary artery disease. Levels were compared to 27 matched healthy control subjects. Patients were excluded if they had recent cardiovascular events or any illness that might influence platelet and endothelial cell function. Concentrations of sP-selectin were significantly higher in patients with stable CAD (276 +/- 61 ng/mL) compared with control subjects (188 +/- 32 ng/mL) (P = .0001), whereas sE-selectin and sICAM-1 levels were similar between the 2 groups. Pooling both groups showed that sICAM-1 correlated weakly with triglycerides (r = 0.240, P = .01) and sP-selectin correlated weakly with low-density lipoprotein cholesterol (r = 0.204, P = .04). Although plasma sICAM-1 concentrations were significantly increased in hypercholesterolemic patients compared with those of normocholesterolemic patients (P = .04), sP-selectin and sE-selectin levels were similar between the 2 groups. In conclusion, significantly increased sP-selectin levels, indicating platelet activation, were found in patients with stable CAD. No other sign of endothelial cell activation in these patients could be detected. Moreover, sP-selectin levels seem to reflect the activation of platelets rather than of endothelial cells.     

Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.     

冠心病预后与冠状动脉侧支循环的关系

目的：研究冠心病（CHD）预后与冠状动脉侧支循环的关系。方法：依据冠状动脉造影结果98例患者被分为CHD无侧支循环组（62例）、CHD有侧支循环组（20例）、正常对照组（16例）,分析各组患者的临床资料。结果：CHD组（无论有无侧支循环）与正常对照组相比,除糖尿病发病率较高外（P〈0.01）,其他CHD易患因素差异均无显著性（P〉0.05）;有侧支循环与无侧支循环CHD患者相比,主要CHD易患因素、不稳定型心绞痛的发生率差异均无显著性（P〉0.05）;但无侧支循环患者左室射血分数〈50%患者比率（29.0%比10.0%）,心肌梗死（61.3%比30.0%）、室壁瘤（22.6%比0）的发生率较有侧支循环患者显著增加（P〈0.01）。结论：侧支循环存在与否与冠心病患者预后有关。     

Leukocyte counts and concentrations of soluble adhesion molecules as predictors of coronary atherosclerosis

BACKGROUND: Authors of recent studies have reported that there is a relationship between level of adhesion molecules and atherosclerosis. In an animal study it was demonstrated that there is an interaction between adhesion molecules and leukocytes in atherosclerotic tissue. OBJECTIVE: To study the relationships between coronary-artery atherosclerosis and both differential blood-leukocyte count and concentrations of soluble adhesion molecules in patients with and without coronary artery disease (CAD). METHODS: Our subjects were 168 patients who underwent diagnostic coronary angiography. Forty-eight patients had normal coronary angiograms (control group), and 120 patients had significant coronary-artery stenoses (diameter stenosis > 70%) in at least one major coronary-artery branch (CAD group). Total and differential blood-leukocyte counts, and concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were assayed prior to angiography. RESULTS: Monocyte counts for patients in the CAD group were significantly greater than those for patients in the control group (366 +/- 99 versus 258 +/- 44/microl, P < 0.0001), as were the sICAM-1 concentrations (272 +/- 52 versus 203 +/- 24 ng/ml, P < 0.0001). The mean concentrations of sVCAM-1 in members of the two groups were the same (671 +/- 138 versus 668 +/- 97 ng/ml, P=0.4). There was a higher incidence of significant coronary-artery stenosis among patients with both a high monocyte count and a high concentration of sICAM-1 (> or = mean + SD) than there was among patients with a low monocyte count and a low concentration of sICAM-1 (> or = mean - SD; 100 versus 25%, P < 0.0001). CONCLUSIONS: Higher levels both of monocyte counts and of serum concentrations of ICAM-1 may serve as markers for coronary atherosclerosis.     

Relation of coronary collateral circulation with epicardial fat volume in patients with stable coronary artery disease

Objective

To investigated the relationship between epicardial fat volume (EFV) and coronary collateral circulation (CCC) in patients with stable coronary artery disease (CAD).

Methods

The study population consisted of 152 consecutive patients with CAD who underwent coronary angiography and were found to have at least 95% significiant lesion in at least one major coronary artery. EFV was assessed utilizing 64-multislice computed tomography. The patients were classifield into impaired CCC group (Group 1, Rentrop grades 0−1, n = 58), or adequate CCC (Group 2, Rentrop grades 2−3, n = 94).

Results

The EFV values were significantly higher in paitients with adequate CCC than in those with impaired CCC. In multivariate logistic regression analysis, EFV (OR = 1.059; 95% CI: 1.035−1.085; P = 0.001); and presence of angina were independent predictors of adequate CCC. In receiver-operating characteristic curve analysis, the EFV value > 106.5 mL yielded an area under the curve value of 0.84, with the test sensitivity of 49.3%, and with 98.3% specifity.

Conclusions

High EFV, and the presence of angina independently predict adequate CCC in patients with stable coronary artery disease. This association offers new diagnostic opportinities to assess collateral flow by conventional ultrasound techniques.     

Significance of soluble thrombomodulin in the coronary circulation of patients with coronary artery disease

OBJECTIVES: The relationship between plasma levels of soluble thrombomodulin, a probable marker for endothelial damage, and the severity of coronary atherosclerosis was investigated. METHODS: Plasma soluble thrombomodulin levels were evaluated in 160 patients(mean age 62 +/- 11 years) who underwent coronary angiography. Blood samples were obtained from the peripheral vein, ostium of the left coronary artery and coronary sinus. The levels of plasma thrombomodulin were measured by enzyme-linked immunosorbent assay. The change of thrombomodulin level in the coronary circulation (delta TM) was calculated as the coronary sino-arterial difference. Patients were classified into four groups according to the number of diseased vessels, and the severity of coronary atherosclerosis was evaluated with the modified Gensini score. RESULTS: Coronary sinus levels of thrombomodulin were significantly higher in the two or more vessel disease(VD) groups than in the no or one VD groups(p < 0.05). delta TM were significantly higher in the 2VD than in the 0VD groups(p < 0.05), and higher in the 3VD than in the 0VD or 1VD groups(p < 0.05). delta TM showed positive correlation with Gensini score for left coronary arteries(r = 0.347, p < 0.0001). CONCLUSIONS: The increment of thrombomodulin across the coronary circulation was significantly correlated with the severity of coronary atherosclerosis, suggesting a close association between the progression of coronary atherosclerotic stenosis and damage to the endothelial surface.