Obesity is associated with impaired coronary collateral vessel development

BACKGROUND: Chronic myocardial ischaemia due to coronary artery stenosis or occlusion has been shown to increase the growth of coronary collateral circulation. Collateralization leads to increased oxygen delivery to the area at risk and hence may reduce ischaemia, prevent infarction and preserve contractile function. However, there is considerable variation among patient subsets in terms of the presence or degree of collateralization. We aimed to evaluate the relationship between obesity and coronary collateral development in patients with ischaemic heart disease. METHODS AND RESULTS: In all, 215 patients (mean age, 57.8+/-8.9 y) with body mass index (BMI)> or =30 kg/m(2) were enrolled into our study. A total of 90 age- and sex-matched patients (mean age, 58.7+/-10 y) with BMI<25 kg/m(2) and significant coronary artery disease were selected as a control group. The mean age and distribution of risk factors for coronary heart disease were not significantly different between two groups other than poorer HDL cholesterol and triglyceride profile in obese patients. The mean BMI was significantly higher in the patient group (33.3+/-2.4 vs 22.8+/-1.7, P<0.001). The mean number of diseased vessels and maximum lesion severity were not significantly different between the two groups. The mean Rentrop collateral score of the patient group was significantly worse than the control group (1.08+/-0.68 vs 2.10+/-0.72, P<0.001). CONCLUSIONS: Our findings suggest that collateral vessel development is poorer in obese patients (defined as BMI> or =30 kg/m(2)) with ischemic heart disease compared to normal range BMI, and the risk of having poor collateral vessel development is significantly increased. However, this might be reflecting the cluster of risk factors, associated with metabolic syndrome, in which insulin resistance plays a major role.     

Asymmetric dimethylarginine and coronary collateral vessel development

INTRODUCTION: Nitric oxide (NO) plays a major role in collateral vessel development. Asymmetric dimethylarginine (ADMA) that is an endogenous inhibitor of NO synthesis may impair the effective coronary collateral vessel development. The aim of this study was to evaluate the relationship between plasma ADMA level and coronary collateral vessel development. METHODS: The patients with a greater than or equal to 95% obstruction in at least one epicardial coronary artery were included in the study. Degree of coronary collateral development was determined according to Rentrop method. Patients with grade 2-3 collateral development were regarded as good collateral group and formed group I. The patients with grade 0-1 collateral development were regarded as poor collateral group and were included in group II. Group III that had been formed as a control group included the patients with a normal coronary angiogram. We compared the plasma ADMA, symmetric dimethylarginine, L-arginine/ADMA ratio among three groups. RESULTS: Seventy-four patients have been included in the study. Patients with good collateral development had lower plasma ADMA level in comparison with patients with poor collateral development (0.41+/-0.25 micromol/l vs. 0.70+/-0.23 micromol/l, P=0.001) and had similar plasma ADMA levels with the patients who have normal coronary arteries. When we compared L-arginine/ADMA ratio between good and poor collateral groups, we found that the patients with higher L-arginine/ADMA ratio have significantly better collateral development (270.8+/-168.0 vs. 120.9+/-92.1, P<0.001). In the analyses comparing Rentrop score with ADMA level and L-arginine/ADMA ratio, there were significant correlations (r=-0.444, P=0.008 and r=0.553, P=0.001, respectively). In multivariate analysis, ADMA level (odds ratio, 0.009; 95% confidence interval, 0.000-0.466, P=0.020) and L-arginine/ADMA ratio (odds ratio, 1.010; 95% confidence interval, 1.001-1.020, P=0.032) were independent predictors of collateral development. CONCLUSION: Increased plasma ADMA levels are related with poor coronary collateral development. ADMA may be responsible for the difference in coronary collateral vessel development among different patients with coronary artery disease. NO inhibitors that have a determinative relation with endothelial cell functions may be integral prerequisite in all steps of collateral development.     

Impaired coronary collateral vessel development in patients with metabolic syndrome

BACKGROUND: The development of coronary collateral vessels is the physiological response of myocardial tissue to hypoxia or ischemia, which results in an increase in blood supply to the tissue. However, a lack of collateral vessels or the presence of poor collateralization in some patients despite the presence of significant coronary stenosis or obstruction and evidence of myocardial ischemia suggest that some other factors may affect the development of collateral circulation. In the present study we aimed to evaluate coronary collateral circulation in patients with metabolic syndrome with advanced coronary artery disease and compare the results with those of patients without metabolic syndrome. METHOD: The study population comprised 102 patients with metabolic syndrome and advanced coronary artery disease (>or=90% diameter stenosis in at least one major epicardial coronary artery) and 102 control participants without metabolic syndrome who also had >or=90% diameter stenosis in at least one major epicardial coronary artery. The diagnosis of metabolic syndrome was based on the National Cholesterol Education Program Adult Treatment Panel III clinical definition. Coronary collateral vessels were analysed according to the Cohen and Rentrop grading system. Both groups were also divided into two additional groups according to the Rentrop collateral score as patients with poor collateral circulation (Rentrop score 0-1) and good collateral circulation (Rentrop score 2-3). RESULTS: The mean Rentrop collateral score for patients with metabolic syndrome was significantly lower than for those without metabolic syndrome (1.38+/-0.79 compared with 1.99+/-1.08, respectively, P<0.001). When two groups were compared with respect to poor and good collateral circulation, poor collateral circulation was found to be significantly higher in the metabolic syndrome group (70% compared with 32%, respectively, P<0.001). Moreover, multivariate logistic regression analysis revealed a significant relationship between poor collateral circulation and metabolic syndrome (odds ratio=4.29, 95% confidence interval=1.73-10.69, P=0.002). CONCLUSION: We have shown for the first time that the development of coronary collateral vessels is poorer in patients with metabolic syndrome with advanced ischemic heart disease than in control participants without metabolic syndrome. Thus, it can be suggested that metabolic syndrome is one of the significant factors affecting the development of coronary collateral vessels adversely.     

Effect of obesity on coronary collateral vessel development in patients with coronary artery disease

The purpose of this study was to compare coronary collateral circulation and with other risk factors in patients with coronary artery disease and different body mass index. Between January 1999 and December 2001, of 867 patients who underwent angiography for the first time, 90 patients (24 women and 66 men), with occlusion in only 1 coronary artery participated in the study. Information regarding age, body mass index, sex, smoking, hypertension, diabetes mellitus, hyperlipidemia, preinfarction angina, and use of oral beta blockers and nitrates were recorded for all patients. The patients were separated into 2 groups in accordance with development of their coronary collateral circulation; those with insufficient (Rentrop 0, 1, and 2) and those with sufficient coronary collateral circulation. They were also divided into 3 groups on the basis of body mass index as follows: (I) 18.0-24.9 kg/m(2), (II) 25.0-29.9 kg/m(2), and (III) more than 30 kg/m(2). In the obesity and overweight groups, hyperlipidemia, diabetes mellitus, and nitrate use were identified more frequently than in the other groups (p < 0.05). Use of oral nitrates more than 6 months before the myocardial infarction and existence of preinfarction angina affected collateral coronary vessel development in the positive direction (p = 0.01, p = 0.03, respectively). There was no correlation between coronary artery disease and coronary collateral vessel development in the obese patients (p = 0.6). Although it has been shown that coronary collateral vessel development was affected negatively in obese patients with coronary artery disease, no statistical significance was identified.     

Impaired coronary collateral vessel development in patients with proliferative diabetic retinopathy

BACKGROUND: Diabetic patients have been reported to have impaired coronary collateral vessel growth, although they have excessive neovascularization in the retina. HYPOTHESIS: This study was designed to compare coronary collateral circulation (CCC) in patients with proliferative diabetic retinopathy (PDR) with that in patients without DR. METHODS: Ninety diabetic patients with chronic total occlusion in at least one major epicardial coronary artery were enrolled in the study. Groups 1 and 2 consisted of 48 patients without DR and 42 patients with PDR, respectively. Coronary collateral circulation (CCC) was analyzed according to the Rentrop system. Each group was also divided into two subgroups according to poor and good CCC. Serum vascular endothelial growth factor (VEGF) levels were measured using the enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The mean Rentrop collateral score was higher in Group 1 than in Group 2 (2.39 +/- 1.07 vs. 1.76 +/- 0.76, respectively, p < 0.001). When the two groups were compared with respect to poor and good CCC, poor CCC was higher in patients with PDR (64 vs. 36%, respectively, p = 0.01). Serum VEGF levels were higher in patients with PDR than in those without DR (219 +/- 99 vs. 139 +/- 98 pg/ml, p < 0.001); however, patients with poor and good CCC had similar VEGF levels. CONCLUSIONS: We have shown that patients with PDR have a lower coronary collateral score than patients without DR. Also, serum VEGF was significantly higher in patients with PDR than in those without DR. These findings have suggested that diabetes mellitus may have a different action on retinal and coronary circulation.     

Relationship of vessel reactive substances with coronary collateral circulation in patients with severe coronary artery stenosis

目的探讨冠状动脉高度狭窄老年冠心病患者冠状动脉侧支循环（CCC）的形成与血管活性物质血管紧张素转换酶（ACE）、血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）,内皮素（ET）和一氧化氮（NO）之间的关系。方法收集成都军区昆明总医院2007年6月至2009年1月行冠状动脉造影,三支主要冠状动脉中至少有一支狭窄程度在95%以上的80例老年冠心病患者,年龄（70.23±7.86）岁。根据侧支循环形成情况,分为2组：CCC形成良好组和CCC形成不良组,并同时测定2组血中以下血管活性物质的活性及浓度：ACE,Ang Ⅱ,ALD,ET和NO。结果 CCC形成不良组患者血中ACE活性[（38.07±6.25） vs （27.02±4.15）U/L],AngⅡ浓度[（90.27±10.31） vs （70.13±7.30）ng/L], ALD浓度[（170.75±23.46） vs （130.34±11.23）ng/L],ET浓度[（74.78±7.35） vs （57.23±6.04）ng/L]明显高于CCC形成良好组（P＜0.05）,而NO浓度则相反[（34.8±6.24） vs （49.34±6.67）μmol/L;P＜0.05]。结论冠状动脉高度狭窄病变的老年患者中ACE,AngⅡ,ALD和ET不利于CCC的形成,而NO有利于CCC的形成。     

Relation of coronary collateral vessel development in patients with a totally occluded right coronary artery to the metabolic syndrome

Development of coronary collaterals (CCs) is triggered by the gradient between arteries due to obstruction and myocardial ischemia. Presence of CCs that feed the jeopardized myocardial area may limit the infarct size after coronary occlusion and may even provide a survival benefit. However, some patients develop good CCs, whereas others do not. The metabolic syndrome (MS) has been identified as a secondary target to decrease cardiovascular risk, although the effect of MS on development of CCs has not been investigated. We prospectively enrolled 596 consecutive patients (337 men and 259 women; mean age 56 +/- 8 years) who underwent coronary angiography at our center and were found to have total occlusion of the right coronary artery. Patients were then classified as having good CCs (Rentrop's grades 2 to 3) or poor CCs (Rentrop's grades 0 to 1). There were significant differences in terms of body mass index (kilograms of body weight divided by square meters of height), glucose levels, triglyceride levels, and years with angina pectoris between those with good and poor CCs. Prevalences of diabetes mellitus were 27.1% among patients with good CCs and 44% among those with poor CCs (p <0.001). Presence of MS was significantly higher in patients with poor CCs than in those with good CCs (78.4% vs 49.2%, p <0.001). In regression analysis, duration of angina pectoris (beta = 0.347, 95% confidence interval [CI] 0.266 to 0.453, p <0.001), presence of diabetes mellitus (beta = 1.829, 95% CI 1.021 to 3.279, p = 0.042), wall score (beta = 2.379, 95% CI 1.356 to 4.173, p = 0.003), and presence of MS (beta = 2.993, 95% CI 1.541 to 5.813, p = 0.001) were independent predictors of angiographically determined poor CCs. In conclusion, MS seems to be independently associated with poor CCs in patients with an occluded right coronary artery.     

Reactivity of canine isolated epicardial collateral coronary arteries. Relation to vessel structure

To study the relation between structure and vascular reactivity in mature coronary collateral arteries, we prepared 17 dogs with a casein occluder near the origin of the circumflex coronary artery. At least 24 weeks later, we examined the reactivity of surface collateral arteries (approximately 500 micron i.d.) to a range of constrictor and dilator agents and compared them with normal left anterior descending coronary arteries of similar size branching away from the collateral zone. Pairs of normal and collateral arteries 2 mm long were mounted in a double-vessel myograph for isometric force recording. Arteries were contracted by K+ (124 mM) or by cumulative addition of endothelin-1 (1-100 nM) or U46619 (1-300 nM), a thromboxane A2 mimetic drug. In each case, the collateral vessels contracted to approximately half the force generated by the normal arteries. When partially contracted by K+ (25-30 mM), the collateral vessels had a greater range of relaxation and similar sensitivity to acetylcholine, sodium nitroprusside, and cromakalim compared with normal arteries. Morphological and morphometric analyses revealed that the collateral arteries had thickened adventitia, thinner media, ruptured internal elastic laminae, and a thick neointima lined by endothelium. Theoretical calculations of luminal area were made for isotonic conditions in response to constrictor stimuli. Despite the poor contractility of the collateral arteries, the neointimal luminal encroachment further reduced the lumen to zero, an exaggerated response compared with normal arteries. Coronary collateral arteries are thus compromised flow conduits that may play a role in vasospastic angina.     

The relationship of chronic angiotensin converting enzyme inhibitor use and coronary collateral vessel development

BACKGROUND: Angiotensin II induces various growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor, and recent studies suggest that the expression of these growth factors promotes collateral growth. We hypothesized that the blockage of angiotensin II production by ACE inhibitors might interfere with collateral development in patients with coronary occlusion. METHODS: The study group consisted of 187 patients (114 males, mean ages, 62 +/- 11 years) who had chronic (> 1 month) coronary occlusion (TIMI flow grade < or = 1) in one of 3 epicardial coronary arteries. Collaterals were graded using the Rentrop classification, and the patients were divided into 2 groups according to having good (grade 2 and 3) or poor (grade 0 and 1) collaterals (n = 127 and 60, respectively). Clinical and angiographic characteristics were compared in the 2 groups. RESULTS: ACE inhibitor use (52% versus 35%, P = 0.04) and the prevalence of diabetes mellitus (DM) (43% versus 27%, P = 0.02) was higher in patients with poor collaterals. Patients with poor collaterals had a higher frequency of circumflex artery (Cx) occlusion, worse wall motion, and lower ejection fraction. In multivariate analysis, ACE inhibitor use (OR: 2.4; 95% CI = 1.23-4.68, P = 0.01) and the occlusion of Cx (OR: 3.3, 95% CI; 1.33-8.12, P = 0.01) were found to be independent predictors for poor collateral development, whereas there was a trend for DM as a predictor for poor collaterals (OR: 1.9, 95% CI = 0.97-3.8, P = 0.06). CONCLUSION: The findings suggest that ACE inhibitor therapy may contribute to poor collateral development in patients with coronary occlusion.     

Lipid management among coronary artery disease patients with diabetes mellitus or advanced age

Aggressive lipid management is likely beneficial for coronary artery disease patients with diabetes mellitus or of advanced age. Nevertheless, a study of a large national sample of patients seen in ambulatory medical practices suggests pharmacologic undertreatment in these high-risk groups.     

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.     

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation. The influence of collateral function and coronary hemodynamics

OBJECTIVES: The goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO). BACKGROUND: Collaterals may have an adverse effect on TVF. METHODS: In 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured. RESULTS: Angiographic follow-up after 5 +/- 4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR >or= 2.0, and only 18% a CFVR >or=2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 +/- 07 vs. 0.86 +/- 08, p < 0.05) but not with restenosis (0.87 +/- 0.06). CONCLUSIONS: This study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion.