Poor Collateral Development Research Articles

The Effect of CD31 on Coronary Collateral Development.

Coronary collaterals are the feeding bridges between the main epicardial arteries, and research has shown that this collateral development plays a crucial role in myocardial performance, especially in patients with coronary artery disease. However, the evolution of these collaterals has not been fully explained. In this study, we aimed to reveal the effect of CD31 on coronary collateral development. As a result of coronary angiography performed in our clinic, 89 patients with coronary artery disease and 90 patients with normal coronary arteries were included in the study. Collateral development degrees were recorded from the angiographic images of the subjects. CD31 values were compared between the group with coronary artery disease and the control group. In addition, the coronary artery disease group was divided into subgroups according to the collateral development in terms of good collateral development and poor collateral development, and the factors that may affect the collateral development were tried to be determined. CD31 levels were significantly higher in the group with coronary artery disease compared to the control group (p <0.001). In addition, CD31 levels in the subgroup with good collateral were significantly higher than in the group with weak collateral (p <0.001). In the correlation analysis, a significant positive correlation was found between serum CD31 level and SYNTAX score, age, glucose, and rentrop grade. Multivariate logistic regression analysis showed CD31 to be an independent predictor of good coronary collateral development. CD31, a marker of angiogenesis, may be involved in coronary collateral development.

The association of new atherosclerosis markers with coronary collaterals in chronic total occlusion patients

Objectives: In the present study, we investigated the relationship between mentioned markers and chronic total occlusion collateral development. Patients and methods: A total of 243 patients (210 males, 33 females; mean age: 63.3±11.5; range, 51 to 76 years) who underwent coronary angiography due to typical chest pain or myocardial ischemia detected in noninvasive stress tests and diagnosed with ≥1 major coronary artery occlusion between January and September 2020 were included in the cross-sectional observational study. The angiographic collateral index was determined according to the Cohen-Rentrop classification. The patients were divided into two groups according to the sufficiency of collateral development: the well-developed collaterals group (n=155) and the poor-developed collaterals group (n=88). Results: Statistically significant parameters in univariate logistic regression analysis were evaluated with multivariate (stepwise) logistic regression analysis; as a result, presence of chronic total occlusion in left anterior descending artery (odds ratio [OR]=2.447; 95% confidence interval [CI], 1.160-5.162; p=0.019), total number of occlusions (OR=3.503; 95% CI, 1.445-8.494; p=0.006), left ventricular ejection fraction (OR=1.056; 95% CI, 1.022-1.091; p=0.001), and the atherogenic index of plasma (OR=0.017; 95% CI, 1.022-1.091; p&lt;0.001) were independently associated with well-developed collaterals. Although the triglyceride-glucose index had statistical significance in the univariate analysis, it was not detected as an independent variable in the multivariate analysis. The monocyte-lymphocyte ratio was not significant in the univariate analysis. Conclusion: Of the new atherosclerosis markers, only the atherogenic index of plasma had an independent association with poor collateral development.

Hemoglobin A1c, Koroner Kronik Total Oklüzyonu Olan Diyabetik Olmayan Hastalarda Zayıf Kollateral Gelişiminin Bir Prediktörüdür: Retrospektif Klinik Çalışma

Objective: Collateral circulation plays an important role for the nutrition of the myocardium in the region of chronic total occlusion (CTO), and affects clinical prognosis. It has been accepted that increased hemoglobin A1c (HbA1c) is a risk factor for cardiovascular events and subclinical atherosclerosis in individuals without diabetes mellitus. In this study, we aimed to reveal the effect of HbA1c level on coronary collateral development in the non-diabetic adult population with CTO. Material and Methods: The study included 208 non-diabetic patients out of 487 patients diagnosed with CTO on coronary angiography between March 2014 and January 2019. The patients were classified into two groups based on the Rentrop classification. Group 1 (Rentrop 0-1) (poor collateral) (90 patients) and Group 2 (Rentrop 2-3) (good collateral) (118 patients). This is a retrospective analysis. Results: The two groups were similar in terms of male gender, age, hypertension and previous history of myocardial infarction (78.9% vs. 75.4%, p=0.557; 58.9±9.9 vs. 60.8±11.2, p=0.194; 26.7% vs. 33.0%, p=0.321; and 18.9% vs. 12.7%, p=0.221; respectively). HbA1c value was statistically higher in Group 1 (5.85±0.45) than in Group 2 (5.22±0.84) (p<0.001). The ideal HbA1c cut-off value was 5.65 that was calculated by the Youden index had 77% sensitivity, and 75% specificity (Receiver operating characteristic area under curve: 0.780, 95% confidence interval: 0.717-0.844, p<0.001) for poor collateral development of CTO. Conclusion: HbA1c is a parameter that affects coronary collateral development even in non-diabetic patients. In non-diabetic patients with CTO, high HbA1c levels correlate with poor collateral development.

The relationship between serum homocysteine levels and development of coronary collateral circulation in patients with acute coronary syndrome

Aim: Homocysteine is an amino acid that plays a role in folate metabolism and inhibits endothelial cell proliferation which is important for angiogenesis. In this study, we aimed to investigate the relationship between serum homocysteine levels and coronary collateral development. Material and Method: 176 consecutive patients, with acute coronary syndrome and chronic total occlusion, were divided into two groups according to coronary collateral development. Rentrop 0 and 1 were regarded as group I and Rentrop 2 and 3 as group II. Results: Plasma homocysteine levels were 18,2 ± 7,0 μmol/L in the group I and 15,7 ± 5,1 μmol/L in the group II. Univariate logistic regression analysis showed that mean platelet volume and homocysteine were associated with poor coronary collateral. Multivariate logistic regression analysis showed that homocysteine level was independently associated with poor coronary collateral circulation (OR 1,069 [95% CI 1,012-1,130]; P=0,018). Conclusion: In this study clearly demonstrates that high serum homocysteine level is associated with poor collateral development in patients with acute coronary syndrome.

Impact of Admission Blood Glucose on Coronary Collateral Flow in Patients with ST-Elevation Myocardial Infarction.

In patients with acute myocardial infarction, glucose metabolism is altered and acute hyperglycemia on admission is common regardless of diabetes status. The development of coronary collateral is heterogeneous among individuals with coronary artery disease. In this study, we aimed to investigate whether glucose value on admission is associated with collateral flow in ST-elevation myocardial infarction (STEMI) patients. We retrospectively evaluated 190 consecutive patients with a diagnosis of first STEMI within 12 hours of onset of chest pain. Coronary collateral development was graded according to Rentrop classification. Rentrop 0-1 was graded as poor collateral development, and Rentrop 2-3 was graded as good collateral development. Admission glucose was measured and compared between two groups. Mean admission glucose level was 173.0 ± 80.1 mg/dl in study population. Forty-five (23.7%) patients had good collateral development, and 145 (76.3%) patients had poor collateral development. There were no statistically significant differences in demographic characteristics between two groups. Three-vessel disease was more common in patients with good collateral development (p=0.026). Mean admission glucose level was higher in patients with poor collateral than good collateral (180.6 ± 84.9 mg/dl versus 148.7 ± 56.6 mg/dl, resp., p=0.008). In univariate analysis, higher admission glucose was associated with poor collateral development, but multivariate logistic regression analysis revealed a borderline result (odds ratio 0.994, 95% CI 0.989–1.000, p=0.049). Our results suggest that elevated glucose on admission may have a role in the attenuation of coronary collateral blood flow in acute myocardial infarction. Further studies are needed to validate our results.

Effect of serum YKL-40 on coronary collateral development and SYNTAX score in stable coronary artery disease

ObjectiveMany studies have revealed a role of YKL-40 as a new inflammatory biomarker in angiogenesis, inflammation, atherosclerosis and cardiovascular events. Thus, the aim of this study was to investigate the association of serum YKL-40 level with coronary collateral development and SYNTAX score in patients with stable coronary artery disease. MethodsA total of 165 patients who had ≥90% stenosis in at least one major coronary artery were prospectively enrolled in the study. Collateral degree was graded according to Rentrop–Cohen classification. Patients with grade 2 or 3 collateral degree were included in good collateral group and patients with grade 0 or 1 collateral degree were included in poor collateral group. The patients were also classified according to SYNTAX criteria, those with low (≤22) and those with high (>22) SYNTAX score. ResultsSerum YKL-40 and hs-CRP levels were significantly lower in good collateral group. Furthermore, YKL-40 level showed significant positive correlations with SYNTAX score (r=0.486, p<0.001) and hs-CRP level (r=0.340, p<0.001). In multivariate regression analysis, serum YKL-40 (odds ratio: 0.928; 95% confidence interval: 0.917–0.940; p<0.001), duration of ischemic symptom and total occlusion were independent predictors of good collateral development. In ROC curve analysis, a YKL-40 value cut-off point of ≥168.5 predicted the high SYNTAX score with a sensitivity of 81.0% and specificity of 72.4%. ConclusionsIncreased serum YKL-40 level was related with poor collateral development and high SYNTAX score. According to these findings YKL-40 can be used as a predictor of good collateral development and high SYNTAX score.

Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion.

ObjectiveErythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.MethodsA total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).ResultsThere was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = −0.210, p = 0.006).ConclusionsSerum EPO is a useful biomarker for coronary collateral development in patients with CTO.

Plasma Catestatin: A Useful Biomarker for Coronary Collateral Development with Chronic Myocardial Ischemia.

BackgroundsCatestatin is an endogenous multifunctional neuroendocrinepeptide. Recently, catestatin was discovered as a novel angiogenic cytokine. The study was to investigate the associations between endogenous catestatin and coronary collateral development among the patients with chronic myocardial ischemia.MethodsThirty-eight patients with coronary artery chronic total occlusions (CTO) (CTO group) and 38 patients with normal coronary arteries (normal group) were enrolled in the series. Among the patients with CTO, coronary collateral development was graded according to the Rentrop score method. Rentrop score 0–1 collateral development was regarded as poor collateral group and 2–3 collateral development was regarded as good collateral group. Plasma catestatin level and vascular endothelial growth factor (VEGF) were measured by ELISA kits.ResultsThe plasma catestatin levels in CTO group were significantly higher than that in normal group (1.97±1.01 vs 1.36±0.97ng/ml, p = 0.009). In the CTO group, the patients with good collateral development had significantly higher catestatin and VEGF levels than those with poor collateral development (2.36±0.73 vs 1.61±1.12 ng/ml, p = 0.018; 425.23±140.10 vs 238.48±101.00pg/mL, p<0.001). There is a positive correlation between plasma catestatin levels and Rentrop scores (r = 0.40, p = 0.013) among the patients with CTO. However, there is no correlations between plasma catestatin levels and VEGF (r = -0.06, p = 0.744). In the multiple linear regression models, plasma catestatin level was one of the independent factors of coronary collateral development after adjustment for confounders.ConclusionsPlasma catestatin was associated with coronary collateral developments. It may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO.

Diabetes mellitus and female gender are the strongest predictors of poor collateral vessel development in patients with severe coronary artery stenosis.

Coronary collateral vessel development (CVD), i.e., arteriogenesis, is regarded as one of the most important mechanisms—along with angiogenesis—to result in protection of the myocardium. Coronary CVD is associated with a reduction in infarct size, future cardiovascular events and improved survival in patients with occlusive coronary artery disease by enhancing regional perfusion in the chronically ischemic myocardium. In the present study, we aimed to investigate the relation of cardiovascular risk factors and hematological parameters with collateral development in patients with severely stenotic (≥95%) and totally occluded coronary artery disease including at least one major coronary artery. The study population was selected from the patients who underwent coronary angiography between January 2008 and March 2009. Five hundred and two patients who had at least one coronary artery stenosis ≥95% (368 men; mean age 59 ± 10 years) comprised the study population. Of the 502 patients, 228 had total occlusion in at least one major epicardial coronary artery. Collateral artery grading was performed by using Cohen-Rentrop method to the vessel with coronary artery stenosis of ≥95% and patients with chronic total occlusions (CTO). Patients with grade 0-1 collateral development were regarded as the poor collateral group, and patients with grade 2-3 collateral development were regarded as the good collateral group. Two hundred and fifty-eight (51%) of 502 patients had poor collateral development, and 244 (49%) had good collateral development. Logistic regression analysis revealed that DM was independently associated with poor CVD in patients with ≥95% stenosis (p < 0.001). Additionally, female gender and DM were found to be independently associated with poor CVD in patients with CTO (p = 0.005 and p < 0.001, respectively). Monocyte count was found to be independent of CVD neither in patients with ≥95% stenosis nor in patients with CTO. Our data show that DM is an independent factor for poor coronary CVD both in patients with severe coronary artery stenosis and in patients with CTO. Female gender or being in post-menopausal period is another negative risk factor for poor CVD in addition to DM in patients with CTO.

Lower vitamin D level is associated with poor coronary collateral circulation

Objectives. Vitamin D regulates calcium and bone homeostasis, and parathyroid hormone (PTH) secretion. Cross-sectional associations between lower vitamin D levels and cardiovascular diseases have been reported, but the relationship between vitamin D levels and collateral arteries in stable coronary artery disease (CAD) has not been reported before. Design. Two hundred and fourteen patients with above 95% stenosis in at least one epicardial coronary artery were consecutively recruited after coronary angiography (CAG) during the winter season. The coronary collateral circulation (CCC) was graded using Rentrop classification. Poor CCC group included patients with Rentrop Grade 0–1 CCC and control group included patients with Rentrop Grade 2–3 CCC. Vitamin D and PTH levels were measured on the day of CAG. Results. In the poor CCC group, vitamin D levels were lower (34 ± 25 pmol/L vs. 49 ± 33 pmol/L; p = 0.01) and the prevalence of vitamin D deficiency (< 37 pmol/L) was higher (67% vs. 43%; p = 0.01) compared to the controls. PTH levels, calcium, and phosphate levels were not significantly different between the groups. Female gender, lower HDL cholesterol, and lower vitamin D levels were independently correlated with poor CCC in the study population. Conclusion. Lower vitamin D levels may be associated with poor collateral development in patients with stable CAD.

Predictor of Poor Coronary Collaterals in Elderly Population With Significant Coronary Artery Disease

BackgroundCoronary collateral circulation plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. Advanced age might be associated with poor coronary collateral development and cardiovascular outcome. However, limited studies investigate the predictors for collateral development in the elderly population. MethodsThe authors evaluated 950 consecutive patients undergoing coronary angiography and finally analyzed 207 patients of 65 years or more. The collateral scoring system developed by Rentrop was used to classify patients into those with poor or good collateral formation. ResultsThe patients with poor collateral were older age, had lower incidence of smoking, more male sex, had fewer diseased vessels and had a trend to be diabetic. Multivariate analysis showed age (odds ratio (OR)=1.068; P=0.019), diabetes (OR=2.681; P=0.003) and diseased vessels numbers (OR=0.337; P<0.001) were significant predictors of poor collaterals development. Furthermore, age and diabetes have a synergistic effect on poor collateral development (P=0.041 for interaction). ConclusionsEven in the elderly population, age and diabetes might negatively influence the coronary collaterals development.

Influence of high-density lipoprotein cholesterol on coronary collateral formation in a population with significant coronary artery disease

BackgroundCoronary collateral circulation plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. Low High-density lipoprotein cholesterol (HDL-C) level is a strong risk factor for coronary artery disease (CAD) and is associated with poor cardiovascular outcome. It was recently reported to be associated with poor coronary collateral development in Turkish population. Hence, we investigated the influence of HDL-C on coronary collateral formation in Chinese population.MethodsWe evaluated 970 consecutive patients undergoing coronary angiography, and 501 patients with significant coronary artery disease (SCAD) were finally analyzed. The collateral scoring system developed by Rentrop was used to classify patient groups as those with poor or good collaterals.ResultsThe patients with poor collaterals had fewer diseased vessels (1.97 ± 0.84 vs 2.47 ± 0.68, p < 0.001) and lower diffuse score (2.65 ± 1.63 vs 3.76 ± 1.78, p < 0.001). There was no significant difference in HDL-C and other variables between good and poor collaterals. Multivariate analysis showed only number of diseased vessels (odd ratio 0.411, p < 0.001) was a significant predictor of poor collateral development.ConclusionsThe extent of CAD severity but not HDL-C level was the most powerful predictor of coronary collateral formation in our Chinese population with SCAD.

Relationship of fragmented QRS complexes with inadequate coronary collaterals in patients with chronic total occlusion

Fragmented QRS (fQRS) complexes are defined as various RSR' patterns (≥1 R' or notching of S wave or R wave) in two contiguous leads corresponding to a major coronary artery territory. In previous studies, fQRS has been associated with increased morbidity and mortality, sudden cardiac death and recurrent cardiovascular events (CVEs). The causative relationship between fQRS and cardiac fibrosis has been shown in prior studies. The association between inadequate (poor) coronary collaterals and presence of fQRS has not comprehensively been studied in patients with chronic total occlusion (CTO) until now. We tested the hypothesis that the presence of fQRS is associated with inadequate coronary collateral growth. This study had a cross-sectional observational design. The study population consisted of patients who underwent coronary angiography with the suspicion of coronary artery disease at our institution in an outpatient manner. Patients who had CTO in at least one major epicardial coronary artery were included. Coronary angiograms of 148 eligible patients from our database were analyzed again. Ninety-three patients had good and 55 had poor collateral development according to the Cohen-Rentrop method. Patients with poor collateral development had higher plasma glucose (130 ± 54 vs. 116 ± 33 mg/dl, P = 0.047) and an older age (65 ± 10 vs. 61 ± 10 years, P = 0.042) in comparison to patients with good collateral growth. The presence and number of fQRS were higher in the poor collateral group than the good collateral group (64 vs. 32%, P < 0.001 and 2.3 ± 2.4 vs. 1.2 ± 2.0, P = 0.002, respectively). Left ventricular ejection fraction was significantly lower in the poor collateral group than the good collateral group (45 ± 11 vs. 51 ± 13, P = 0.014). There was a significant correlation between number of fQRSs and the echocardiographic wall-motion abnormality score (r = 0.662, P < 0.001). In multivariate analysis, only the presence of fQRS was independently related to poor collateral development (odds ratio, 3.559; 95% confidence interval, 1.708-7.415, P = 0.001). We found that fQRS was independently related to inadequate coronary collaterals in patients with CTO. fQRS, which may be derived from the effects of myocardial ischemia or scar on myocardial electricity at the cellular level, can represent inadequate coronary collateral development in patients with CTO.

The association between impaired collateral circulation and non-alcoholic fatty liver in patients with severe coronary artery disease

Background and purposeCoronary collateral circulation (CCC) has been demonstrated to be impaired in patients with type 2 diabetes mellitus which is characterized by insulin resistance. In this study, our purpose was to find out a possible relationship between CCC and non-alcoholic fatty liver disease (NAFLD), which is also characterized by insulin resistance, in non-diabetic patients with severe coronary artery disease. MethodsOne hundred and fifty-one consecutive non-diabetic patients with stable angina pectoris who were found to have >95% stenosis of at least one major coronary artery were enrolled. Abdominal ultrasonography (USG) was performed after coronary angiography to determine the presence or absence of NAFLD. ResultsAccording to Cohen–Rentrop method, 81 (53.7%) patients had good and 70 (46.3%) patients had poor collateral development. NAFLD was present in 98 patients (64.9% of study population) and more prevalent in patients with poor collateral development [58 of 70 patients (82.9%) vs. 40 of 81 patients (49.4%), p<0.001]. Mean Rentrop collateral score was significantly lower in patients with NAFLD (1.2±1.2 vs. 2.1±0.9, p<0.001). Shorter angina time, metabolic syndrome, presence of insulin resistance, less severe coronary artery disease, and female sex were also associated with poor collateral development. When the logistic regression analysis was performed using these factors, NAFLD was still significantly related to poor collateral development. ConclusionsPresence of NAFLD is associated with poor coronary collateral development in non-diabetic patients with severe coronary artery disease independent from other variables, especially metabolic syndrome and insulin resistance. Which mechanisms play role in this association is needed to be cleared with further studies.

Increased Serum Bilirubin Level is Related to Good Collateral Development in Patients with Chronic Total Coronary Occlusion

Bilirubin is a bile pigment with potent anti-oxidant properties; in previous studies it has been reported to be negatively associated with coronary artery disease (CAD). Although elevated serum bilirubin concentrations may protect against endothelial dysfunction, it is not clear whether higher serum bilirubin levels (SBLs) in physiological ranges may work in favor of good collateral development in patients with chronic total coronary occlusion (CTO). The study population consisted of patients who underwent coronary angiography with a suspicion of CAD. Patients who had CTO in at least one major coronary artery were included. Coronary angiograms of 179 eligible patients from our database were reanalyzed and 110 of them had good collateral development and 69 had poor collateral development according to the Cohen-Rentrop method. Patients with good collateral development had a lower fasting plasma glucose level (FPG) (p=0.024) and higher SBLs in comparison to patients with poor collateral development (p<0.001). The number of CTO vessels (p=0.013) and left ventricular ejection fraction (EF%) were higher in good collateral group than poor collateral group (p=0.017). In multivariate analysis, FPG negatively (odds ratio [OR]: 0.981, p=0.003) and SBL (OR for per 0.1-mg/dL increase: 1.832, p<0.001) and the number of CTO vessels (OR: 5.642, p=0.007) were positively related to coronary collateral development. This study suggests that higher bilirubin levels within relatively normal ranges were related with favorable coronary collateral growth in patients with CTO. SBL may be responsible for the difference in coronary collateral vessel development among different patients with coronary artery disease. The anti-inflammatory and anti-oxidant properties of bilirubin may mediate this effect.

Thymosin beta 4 is associated with collateral development in coronary artery disease

Objectives: Thymosin beta 4 (Tβ4) plays an essential role in cardiac vessel development and is currently being developed as a therapeutic agent for the treatment of coronary artery disease (CAD) in some experimental studies. Thus, we aimed to investigate the association of serum Tβ4 levels and collateral formation in patients presenting with severely stenotic CAD. Methods: Thirteen patients with poor collateral development and 16 age- and sex-matched patients with good collateral development who had ≥ 95% stenosis in at least one major coronary artery on coronary angiogram (CAG) were enrolled in the study. The Gensini score was calculated for each patient by using CAG results. Collateral development was classified according to the Cohen-Rentrop method. Serum Tβ4 levels were measured with enzyme-linked immune sorbent assay. Results: There were no statistically significant differences between the two groups in regard to clinical and laboratory characteristics of the patients except for Tβ4 levels. The Tβ4 levels in the well-collateralized study group were found to be significantly higher than those of the poorly collateralized study group and serum Tβ4 levels were positively correlated with the collateral development. Conclusions: Our findings suggest that serum Tβ4 levels are significantly associated with the collateral development in severe CAD.

Asymmetric dimethylarginine and coronary collateral vessel development

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. 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. 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. 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.

Glu298Asp polymorphism of the eNOS gene is associated with coronary collateral development

Objective We examined the endothelial nitric oxide (eNOS) gene Glu298Asp polymorphism to assess its possible association with the extent of coronary collaterals. Methods A total of 473 consecutive patients who had high grade coronary stenosis or occlusion were evaluated for the extent of coronary collaterals by using Rentrop classification. Patients with grade 0 or 1 collaterals were identified as having poor collaterals. The relation between collateral status and eNOS Glu298Asp polymorphism was studied by multivariate logistic regression analysis. Results Subjects with poor collaterals were more likely to have diabetes mellitus ( p < 0.001) and unstable angina pectoris as clinical presentation ( p = 0.014) and more likely to carry Asp298 variant ( p = 0.02) but they were less likely to have received statins ( p = 0.031). Multivariate analysis demonstrated that Asp298 allele carriers were 1.7 times more likely to have poor collaterals than patients with GluGlu genotype (95% CI: 1.09–2.69, p = 0.024). There was a significant interaction between diabetes mellitus and eNOS Glu298Asp polymorphism in the analysis of collateral development. Among 145 diabetic patients Asp298 allele was the only predictor of poor collateral development with OR of 5.38 (95% CI: 2.41–11.98, p < 0.001). Once diabetic patients were excluded from the analysis Asp298 allele was no longer a significant correlate of poor collateral formation. Conclusions The present study suggests that the Asp298 allele of the eNOS gene is significantly associated with impaired collateral development, especially in patients with diabetes mellitus. Treatment strategies that modulate eNOS activity and/or NO production may improve coronary collateral development.

Increased circulating monocyte count is related to good collateral development in coronary artery disease

Monocytes have been shown to take an important role in collateral growth in animal studies. The aim of the study was to investigate the relation of circulating monocyte count with collateral development in patients with severely stenotic CAD. Patients who had ≥95% stenosis in at least one major coronary artery were included in the study. Coronary angiograms of 210 eligible patients from our database were analyzed again and 103 of them had good and 107 had poor collateral development according to Cohen-Rentrop method. Only the monocyte count was found to be significantly different between two groups (671±218mm−3 versus 522±195mm−3, p<0.001) when multivariate analysis was performed and an increased monocyte count was observed in the good collateral group (Odds ration [OR], 2.918; 95% confidence interval [CI], 1.281–6.648, p=0.011). This study in which the relationship between monocyte count in blood and collateral development was disclosed has a potential importance in clinical and basic cardiovascular medicine.

The Relationship of Chronic Angiotensin Converting Enzyme Inhibitor Use and Coronary Collateral Vessel Development

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. 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. 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). The findings suggest that ACE inhibitor therapy may contribute to poor collateral development in patients with coronary occlusion.