Coronary Collateral Development Research Articles

Hypoxia-inducible factor-1α polymorphisms link to coronary artery collateral development and clinical presentation of coronary artery disease

This study aimed to investigate the association of Hypoxia-inducible factor-1α (HIF-1α) C1772T and G1790A single nucleotide polymorphisms (SNPs) with: incidence, clinical type, severity of coronary atherosclerosis and coronary collaterals of coronary artery disease (CAD). The clinical data and genomic DNA were gathered in 958 subjects, including 560 controls and 398 patients with CAD. CAD was confirmed with coronary angiography (CAG). The genotypes for two SNPs were determined by high resolution melting after PCR amplification. Neither the HIF-1α C1772T nor the G1790A genotype was significantly associated with CAD and, no gene-gene or gene-environmental interactions were identified. However, both HIF-1α C1772T and G1790A (P<0.05) alleles were associated with clinical type and formation of coronary collaterals (P<0.05). Patients carrying genotype CT (P=0.019, OR=4.905,91, 95% CI: 1.355-17.761) and GA (P=0.026, OR=3.052, 95% CI: 1.180-7.892) had significantly higher stable angina pectoris (SAP) than unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The presence of HIF-1 genotype CT (P=0.016, OR=13.373, 95% CI: 15.468-32.709) and GA (P=0.001, OR=19.741, 95% CI: 8.125-47.966) predicted lower collateral formation and severity of CAD secondary to the absence of collaterals (r=0.242, P<0.001). We conclude that functional polymorphisms in the HIF-1α gene do not modify CAD risk but they are associated with the formation of coronary collaterals and clinical presentation of CAD.

Effects of Serum Gamma Glutamyl Transferase Levels on Coronary Collateral Development in Patients with Coronary Chronic Total Occlusion

Effects of Serum Gamma Glutamyl Transferase Levels on Coronary Collateral Development in Patients with Coronary Chronic Total Occlusion

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.

The Assessment of Metformin Treatment on Coronary Collateral Development in Patients with Type 2 Diabetes Mellitus

The Assessment of Metformin Treatment on Coronary Collateral Development in Patients with Type 2 Diabetes Mellitus

Increased Neutrophile to Lymphocyte Ratio is Related with Poor Coronary Collateral Development in Patients with Stable Coronary Artery Disease

Increased Neutrophile to Lymphocyte Ratio is Related with Poor Coronary Collateral Development in Patients with Stable Coronary Artery Disease

The relationship between serum neuropeptide Y levels and coronary collateral development

Purpose: Neuropeptide Y (NPY) is a co-transmitter released from sympathetic nerve terminals. NPY stimulates endothelial cell activation, proliferation, migration, and tube formation. It has been demonstrated that NPY produces angiogenic activity in a variety of in vitro models. The aim of this study was to evaluate relationship of serum NPY levels with coronary collateral vessel development in patients with coronary artery disease (CAD). Methods: The study consisted of 81 patients with ≥1 coronary stenosis with ≥80% narrowing in coronary angiography. Collateral vessels were graded according to the Rentrop classification. The study patients were divided into two groups, namely, patients with well developed collaterals and patients with poorly developed collaterals. Well developed collaterals were defined as Rentrop collateral score 2. Serum levels of NPY, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and noradrenalin (NA) were measured. Results: Of the 81 patients included in the study, 33 (41%) had well developed collaterals. Patient profiles with respect to age, gender, diabetes, hypertension, hyperlipidemia, previous history of a myocardial infarction, and left ventricular ejection fraction are similar between groups. Extent of coronary artery disease (Gensini socre) was significantly higher in patients with well developed collaterals (65.4±24.4 vs 45.3±23.7, p<0.001). Mean level of serum NPY in patients with well developed collaterals was significantly higher than those patients with poorly developed collaterals (0.85±0.0.43 ng/mL versus 0.66±0.34 ng/mL, p=0.026). In contrast, NA was significantly lower in patients with well developed collaterals (4.34±2.58 ng/mL vs 6.60±5.1 ng/mL, p=0.022). There was no statistically significant difference in levels of VEGF and FGF between groups. The NPY level was negatively correlated with the level of the FGF (r=-0.232, p=0.037) and with the level of the LDL (r=-0.278, p=0.012), and positively correlated with the presence of diabetes (r=0.528, p<0.001). After confounding variables were controlled for, the NPY level in patients with well developed collaterals was significantly higher from those patients with poorly developed collaterals. Conclusions: We found that NPY levels are significantly higher in patients with well developed coronary collaterals compared to patients with poorly developed collaterals. New studies are needed to show whether this relationship is causal.

GW24-e3729 ERK5 Mediates advanced glycation end products-induced impairment of angiogenic capacity in cardiac endothelial cells under hypoxia condition through regulation of VEGF expression

ObjectivesDiabetes-induced impairment of collateral formation in ischaemic myocardium has been demonstrated both in experimental and clinical studies, which may contribute to unfavorableprognosis among diabetic individuals. However, the underlying mechanism remains...

Serum leptin has no effect on coronary collateral development in patients with non-ST- elevation acute coronary syndromes: an observational study

We attempted to investigate the potential association between leptin and coronary collateral vessel development in patients with non-ST elevation acute coronary syndromes (NSTE-ACS). One hundred and nineteen consecutive patients with NSTE-ACS with high-grade coronary stenosis or occlusion in at least one epicardial coronary artery were prospectively enrolled in a cross-sectional observational study. Serum leptin levels measured in all patients. Collateral circulation was graded according to the Rentrop classification. Firstly, we divided patients into two groups as good and poor collateral group. Patients with Rentrop 2.3 were regarded as good collateral group. Patients in Rentrop grades 0, 1 classified as poor collateral group. Secondly, patients were divided into collateral (+) group and collateral (-) group. Collateral (+) group included the patients with grade 1, 2, 3 collateral development. Collateral (-) group was composed of the patients with Rentrop 0. Statistical analysis was performed using Student t-test, Mann-Whitney U test, Chi-square test, Kruskal -Wallis test and Spearman's correlation. We did not find statistically significant difference between good and poor collateral groups with regard to leptin levels [4.2 (1.8-8.6) ng/mL and 6.4 (2.4-12.6) ng/mL, p=0.22, respectively]. There was no statistically significant difference in leptin levels between collateral (+) group and collateral (-) groups [4.7 (1.7-10.5) ng/mL and 6.8 (2.7-12.1) ng/mL, p=0.33, respectively]. We observed that there was lower leptin level at higher Rentrop grades [Rentrop 0; 6.8 (2.5-12.5) ng/mL, Rentrop 1; 5.9 (1.7-14.1) ng/mL, Rentrop 2; 4.3 (1.7-8.7) ng/mL, Rentrop 3; 3.9 (2.1-9.7) ng/mL]. However, this difference did not reach statistically significant level (p=0.54). In addition, we did not find statistically significant correlation between Rentrop grades and leptin levels (p=0.246, r=-0.107). The present study reveals no association between serum leptin level and coronary collateral development.

Coronary collateral development might be impaired by decreases in glomerular filtration rate

Coronary collateral development might be impaired by decreases in glomerular filtration rate

Coronary Collaterals Predict Improved Survival and Allograft Function in Patients With Coronary Allograft Vasculopathy

Despite improvements in the care of patients who have received cardiac transplants, coronary allograft vasculopathy (CAV) remains the most prevalent cause of late allograft failure and cardiac mortality. Few proven therapies are available for this important disease. The presence of coronary collaterals imparts a favorable prognosis in patients with native ischemic heart disease; however, the impact of collaterals in CAV is unknown. To determine whether the development of coronary collaterals is associated with improved outcomes in patients with CAV, we performed a retrospective analysis of patients followed in the heart transplant program at Barnes Jewish Hospital from 1994 to 2008. The primary end points included all cause mortality and the composite of all cause mortality, retransplantation, and inotrope dependence. We screened 485 patients and identified 59 (12%) subjects with moderate-to-severe CAV. Angiographically visible coronary collaterals were present in 34 (57%) subjects. Kaplan-Meier and Cox multivariable analyses revealed that patients with collaterals had reduced incidence of all cause mortality (hazard ratio, 0.20; P<0.001) and the composite end point (hazard ratio, 0.17; P<0.001). In addition, patients with collaterals had less severe heart failure symptoms as measured by New York Heart Association class. Immunostaining of biopsy specimens revealed that among patients with CAV, the presence of coronary collaterals correlated with increased microvascular density, reduced fibrosis, and decreased left ventricular end-diastolic pressure. Together, these data demonstrate that the presence of coronary collaterals predicts a favorable prognosis in patients with CAV and suggests that interventions aimed at promoting collateral and microvascular growth may serve as effective therapies for this disease.

Serum erythropoietin: a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis among the patients with coronary chronic total occlusion

The study was to investigate the association of endogenous erythropoietin (EPO) and coronary collateral development. Forty-nine patients (31 with chronic total occlusion (CTO), 18 with normal coronary artery) were consecutively enrolled. The serum EPO was positively related with Rentrop class. Increased serum EPO was one of the independent predictors of good collateral development (odds ratio 1.31; p = 0.025). A significantly positive correlation was seen between serum EPO and vascular endothelial growth factor (VEGF) levels (r = 0.96, p < 0.001). Circulatory EPO may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO.

Coronary Collaterals Predict Improved Survival and Allograft Function in Patients with Coronary Allograft Vasculopathy

Purpose Coronary allograft vasculopathy (CAV) remains the most prevalent cause of late allograft failure following transplantation. To date there are few proven therapies for this disease. The presence of coronary collaterals has been demonstrated to impart a favorable prognosis in patients with native ischemic heart disease, however the importance of coronary collaterals in CAV is unknown. Methods and Materials To determine whether the development of coronary collaterals is associated with improved outcomes in patients with CAV, we performed a retrospective analysis of patients followed at Barnes Jewish Hospital between 1994 and 2008. The primary endpoints included all cause mortality and the composite of all cause mortality, retransplantation, and inotrope dependence. Results We screened 493 patients and identified 59 (12%) subjects with moderate to severe CAV as defined by ISHLT guidelines. Angiographically visible coronary collaterals were present in 34 (57%) subjects. Kaplan-Meier and Cox multivariable analyses revealed that patients with collaterals were protected from death and allograft failure (all cause mortality HR 0.12, 95%CI 0.05-0.29, p Conclusions Together, these data demonstrate that the presence of coronary collaterals predicts a favorable prognosis in patients with CAV and suggests that interventions aimed at promoting collateral growth may serve as effective therapies for this disease. [ figure 1 ]

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.

Mechanistic, Technical, and Clinical Perspectives in Therapeutic Stimulation of Coronary Collateral Development by Angiogenic Growth Factors

Stimulation of collateral vessel development in the heart by angiogenic growth factor therapy has been tested in animals and humans for almost two decades. Discordance between the outcome of preclinical studies and clinical trials pointed to the difficulties of translation from animal models to patients. Lessons learned in this process identified specific mechanistic, technical, and clinical hurdles, which need to be overcome. This review summarizes current understanding of the mechanisms leading to the establishment of a functional coronary collateral network and the biological processes growth factor therapies should stimulate even under conditions of impaired natural adaptive vascular response. Vector delivery methods are recommended to maximize angiogenic gene therapy efficiency and reduce side effects. Optimization of clinical trial design should include the choice of clinical end points which provide mechanistic proof-of-concept and also reflect clinical benefits (e.g., surrogates to assess increased collateral flow reserve, such as myocardial perfusion imaging). Guidelines are proposed to select patients who may respond to the therapy with high(er) probability. Both short and longer term strategies are outlined which may help to make therapeutic angiogenesis (TA) work in the future.

Obstructive Sleep Apnea in the Acute Myocardial Infarction Setting - Should I Treat My Patient?

Obstructive Sleep Apnea in the Acute Myocardial Infarction Setting - Should I Treat My Patient? Obstructive sleep apnea is prevalent among patients with acute myocardial infarction. Epidemiological evidence supports an independent association between sleep apnea and myocardial infarction. Our current clinical practice is to recommend routine and immediate treatment for sleep apnea in patients with an acute myocardial infarction. However, emerging evidence from population based cohort studies does not support an independent role of sleep apnea in the development of incident coronary heart disease events. Furthermore, both animal and human studies suggest a potential cardioprotective role of intermittent hypoxia (as seen in sleep apnea) in the setting of an acute myocardial infarction. Routine treatment of withdrawing the intermittent hypoxia stimulus (such as positive airway pressure therapy for sleep apnea) may potentially adversely impact the myocardial recovery process post ischemic event. One potential mechanism may be due to hindrance of development of coronary collaterals due to reduced levels of vascular growth factors that are particularly sensitive and responsive to intermittent hypoxia stimulus. Treatment of sleep apnea in the immediate post-MI period appears to be debatable and clinical trials are needed to further delineate the role of sleep apnea and its associated intermittent hypoxemia in the myocardial recovery process post-acute myocardial infarction.

Central Diastolic Blood Pressure Is Associated With the Degree of Coronary Collateral Development

Coronary collaterals (CCs) serve as alternative conduits for blood flow in obstructive coronary artery disease. We investigated the association of various components of blood pressure (BP) parameters with the the degree of coronary collateralization. Patients (n = 245) who underwent coronary angiography were included. Intraarterial BP in the ascending aorta was determined using a standard fluid-filled system. Readings of the conventional peripheral pressure were measured using a manual sphygmomanometer. All blood samples were drawn at admission, before coronary angiography. A total of 65 patients were found to have adequate CC development. Central diastolic BP and peripheral diastolic BP were found to be lower in the group with adequate CC. In multivariate logistic regression model, central diastolic BP and Gensini score were found to be independent predictors of adequate CC. In conclusion, low central diastolic BP in the case of severe coronary stenosis may be an important stimulus for adequate CC development.

Predictor of poor coronary collaterals in chronic kidney disease population with significant coronary artery disease.

BackgroundCoronary collateral circulation plays an important role to protect myocardium from ischemia, preserve myocardial contractility and reduce cardiovascular events. Chronic kidney disease (CKD) is associated with poor coronary collateral development and cardiovascular outcome. However, limited research investigates the predictors for collateral development in the CKD population.MethodsWe evaluated 970 consecutive patients undergoing coronary angiography and 202 patients with CKD, defined as a glomerular filtration rate less than 60 ml/min/1.73 m2, were finally analyzed. The collateral scoring system developed by Rentrop was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.ResultsThe patients with poor collateral (n = 122) had a higher incidence of hypertension (82% vs 63.8%, p = 0.005), fewer diseased vessels numbers (2.1 ± 0.9 vs 2.6 ± 0.6, p < 0.001) and a trend to be diabetic (56.6% vs. 43.8%, p = 0.085) or female sex (37.7% vs. 25.0%, p = 0.067). Multivariate analysis showed hypertension (odd ratio (OR) 2.672, p = 0.006), diabetes (OR 1.956, p = 0.039) and diseased vessels numbers (OR 0.402, p < 0.001) were significant predictors of poor coronary collaterals development. Furthermore, hypertension and diabetes have a negative synergistic effect on collateral development (p = 0.004 for interaction).ConclusionsIn the CKD population hypertension and diabetes might negatively influence the coronary collaterals development.

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.

Mean platelet volume: An important predictor of coronary collateral development

Collaterals, which develop in response to ischemic stimuli derived from coronary artery disease (CAD), contribute to reduction of infarct size, left ventricular dysfunction, and mortality. However, there is considerable variation among patients with coronary heart disease regarding the extent of coronary collateral development (CCD). In this study, we aimed to investigate the association of the degree of platelet activation via mean platelet volume (MPV) with coronary collateral circulation. Therefore, 210 patients who underwent coronary angiography and had coronary stenosis ≥50 % in at least one coronary artery were included in the study. Clinical information and analyses of blood samples were obtained from a review of the patients’ chart. Blood samples for MPV were analyzed by K3 EDTA and collateral vessels were graded according to the Rentrop classification. In the study group, 150 of the 210 patients were found to have inadequate CCD. Although there was no difference between the two groups with regard to platelet count, MPV levels were significantly higher in the patients who had inadequate CCD (11.3 ± 1.0 fl vs. 9.5 ± 1.5 fl, p < 0.001). Furthermore, the Gensini score was significantly lower in patients who had inadequate CCD (45 ± 46 vs. 91 ± 35, p < 0.001). MPV, Gensini score, age, female gender, total cholesterol, red cell distribution width, triglyceride, and fasting glucose levels were found to have univariate association with poor CCD. In multivariate logistic regression model, MPV (OR = 2.45, p < 0.001) and Gensini score (OR = 0.98, p < 0.001) were found to be the independent predictors of impaired CCD. In receiver operator characteristic curve analysis, optimal cut-off value of MPV to predict inadequate CCD was found as >9.6 fl, with 96% sensitivity and 84.7% positive predictive value. In conclusion, we can say that MPV is an important, simple, effortless, and cost effective tool and can be useful in predicting the CCD in patients with significant CAD.