Impacts of Established Cardiovascular Risk Factors on the Development of Collateral Circulation in Chronic Total Occlusion of Coronary Arteries

Research Article

J Dis Markers. 2014;1(3): 1011.

Impacts of Established Cardiovascular Risk Factors on the Development of Collateral Circulation in Chronic Total Occlusion of Coronary Arteries

Zahra Ansari Aval1, Mahnoosh Foroughi2*

1Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITlD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

2Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

*Corresponding author: Mahnoosh Foroughi, Cardiovascular Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Received: September 19, 2014; Accepted: September 24, 2014; Published: September 25, 2014


Background: Presence and magnitude of coronary collateral circulation, as an adaptive mechanism has been shown to affect prognosis in patients with ischemic coronary artery disease. Thus far, the clinical determinants of the coronary collateral circulation were not well-established.

Objective: The objective of the study is to determine possible relationship between medical history, clinical findings and angiographic evidences of collateral coronary blood flow.

Methods: In an observational study, all patients who underwent coronary angiography for the first time with total occlusion in at least one coronary artery were participated in the study from February 2012 to February 2013. To determine the status of collateral flow, patients were divided into 4 groups according to Rentrop classification to detect possible factors that may influence collateral formation.

Results: A total of 52 patients met the inclusion criteria and entered the study. Statin therapy (67%), smoking (58%) and a positive family history (19%) were the most frequent findings. According to Rentrop classification, 7 (13.5%) patients were in grade 0, 17(32.7%) in grade 1, 21(40.4%) in grade 2, and 7(13.5%) were classified in grade 3 (Table1). There was significant association between myocardial performance and angiographic findings. There was no statistically significant difference between the grades for any of the risk factors (p value >0.05).

Conclusion: Although large epicardial or septal col ateral vessels has been stated to become visible within two weeks after a complete occlusion of a major coronary vessel, our findings suggest that this vessel formation could not be related to medical history and clinical findings of patients.

Keywords: Collateral circulation; Coronary artery disease; Myocardial infarction; Angiogenesis


Coronary artery disease (CAD) is the leading cause of death in the current century. Development of coronary collaterals in patients with CAD as an alternative source of blood supply has been hypothesized to decrease the infarct size, increase electrical stability, increase myocardial viability and ventricular function after acute and chronic coronary artery occlusion for future ischemic events. In fact, presence and extent of coronary collateral circulation have been shown to affect outcome of patients with CAD by reducing cardiovascular events [1-7].

There is a considerable variation of collateral formation in CAD patients. Thus , certain variables have been proposed to be related to the development of coronary collateral circulation such as patient's age, body mass index, gender, smoking status, history of diabetes mellitus, hypertension, hyperlipidemia, pre- infarction angina, use of beta-blockers, nitrates, antioxidants, angiotensin-converting enzyme inhibitors, serotonin blockers and alcohol consumption. This may explain considerable variability between the studies. There are few studies to report the same set of variables as predictors of collateral circulation [3-9]. Since the underlying molecular mechanism for collateral coronary vessel formation are not directly related to the clinical risk factors, there is still a need for well-designed studies with homogenous participants to show possible predictors of collateral circulation formation.

This prospective study tends to investigate impacts of established CAD risk factors as well as the effect of two common prescribed drugs on formation of coronary collateral circulation in patients with chronic total occlusion of the coronary artery.


Study participants

After approval of Ethics Committee of Shahid Beheshti University of Medical Sciences, this cross -sectional study was performed from February 2012 to February 2013 in the cardiac ward of Modarres hospital_ a training tertiary hospital, Tehran, Iran. All participants gave written informed consent. Study population consisted of patients being admitted with both elective and emergency condition for the first time coronary angiography. Coronary angiography was performed in the presence of acute coronary syndrome and in stable patients when non invasive tests were in favor of myocardial ischemia.

Chronic total occlusion in at least one of the three main coronary arteries was considered as an inclusion criterion. Chronic total occlusion was defined as 100% luminal diameter stenosis without a visible lumen and lack of antegrade flow. Patients with subtotal coronary occlusion and those who had acute occlusion were excluded.

Study variables

In this study positive history of smoking was limited to the current smokers. Patients would be assumed as hypertensive if their blood pressure was =140/90 mmHg on two separate readings, or if they were taking any antihypertensive medications. Obesity was defined as a body mass index of > 30 kg/m2. Diabetes mellitus was defined as the presence of history of antidiabetic medication, or a fasting glucose level above 126 mg/dL. Patients were considered to have hyperlipidemia if their total cholesterol was =200 mg/dL, or if they were taking lipid-lowering medication. Previous history of documented myocardial infarction (MI) in patients and a positive family history of the premature CAD in their family members were carefully obtained. History of receiving two widely prescribed drugs including beta-blockers and statins was recorded.

Coronary angiography and grading of coronary collaterals

All patients underwent selective coronary angiography in multiple orthogonal projections by the Judkins technique. Angiograms were reviewed by an experienced cardiologist who was blinded to the study objectives. Presence and extent of the coronary collateral vessels were graded according to a visual assessment, the Rentrop scoring system: 0= no filling; 1= filling of the small side branches; 2 =partial filling of the epicardial artery by collateral vessels; 3= complete filling of the epicardial artery by collateral vessels [9, 10]. The same physician performed echocardiographic evaluation of the patients, while their angiographic data were masked.

Statistical analysis

Continuous data were expressed as mean± standard deviation and categorical data was given in number and percentage. Comparison of the continuous data between the two collateral groups (presence and absence of collateral circulation) was evaluated by independent samples t-test, if there was no normal distribution, via the Mann- Whitney U test. Categorical data were evaluated by a Chi-square or Fisher's exact test as appropriate. In this study p value < 0.05 was accepted as significant. All statistical analyses were carried out via SPSS version 20.0 for Mac OS (SPSS, Inc., Chicago, Ill, USA).


Study subjects

A total of 52 patients met the inclusion criteria and were included in statistical analysis. Eighty-five percent of the participants were male with the mean age of 62.6 ± 9.9 years (39 - 84). Descriptive analysis of the clinical and demographic data in recruited patients revealed that positive history of previous treatment with beta-blockers (71%) and Statins (67%) were the most prevalent findings. Of the established risk factors of CAD, presence of smoking (58%), previous MI (52%), hypertension (50%), hyperlipidemia (42.5%), obesity (29%), diabetes mellitus (25%) and positive family history of CAD (19%) were shown to be present in our patients. The interval between MI and coronary angiography was from 3 months to 5 years. Results of the study indicated there was no statistically significant difference between males and females in terms of the presence of any studied risk factors (chi-square p>0.05 for all variables). Moreover, age distribution between the presence and absence of the risk factors was not statistically significant for any of the variables (Mann-Whitney U test p>0.05 for all risk factors).

Presence of collateral circulation according to rentrop classification

Results showed that in 7 patients (13.5%), there was no collateral flow (grade 0). Seventeen patients (32.7%) were classified as grade one, 21 patients (40.4%) had partial collateral flow (grade 2) and in 7 patients (13.5%), complete collateral perfusion was noted (grade 3). To understand possible association between the studied variables and collateral circulation formation, at the first stage of our analysis, coronary collateral were treated as a four-level variable. Table 1 summarizes status of each variable according to Rentrop classification. Left anterior descending artery was the most occluded artery in this population (Table 2). There was significant association between echocardiographic left ventricular ejection fraction (EF) and angiographic findings mean EF in grade 0:28%, grade1:46%, geade 2:51% and grade 3:53%, p value= 0.01.