This is the first study to investigate CCC with non-HDL-C in patients with stable coronary artery disease (CAD). The main finding of our study is that non-HDL-C negatively affects the coronary collateral development in patients with stable CAD.
Coronary collateral vessels are also present in normal hearts, and they provide an alternative way of providing blood flow to the ischemic area when coronary obstruction develops. In the collateral development process, the diameter of the collateral vessels can become up to four times larger [21]. Although CCC can supply enough blood to the heart during rest, it is often insufficient in cases of increased oxygen demand [22]. Coronary collaterals maintain myocardial functions in acute myocardial infarction, limit the infarct area and have a positive effect on remodelling [23,24,25]. The degree of CCC development shows marked heterogeneity in CAD. Numerous theories have been put forward regarding the mechanism underlying this heterogeneity, but the underlying mechanism has not been fully elucidated. It has been demonstrated in many clinical and in vivo studies that inflammation is closely related to the development of CCC and the presence of inflammation negatively affects coronary collateral development. Kerner et al. showed that elevated CRP levels in patients with chronic CAD are associated with decreased coronary collateral flow [26]. Similarly, it has been found in other studies that elevated CRP levels negatively affected the development of coronary collateral flow [14,27,28]. In our study, CRP levels were higher in patients with poor collateral circulation. This finding is compatible with the literature. In addition, there are publications indicating that the inflammatory markers tumor necrosis factor alpha and soluble adhesion molecules negatively affect coronary collateral circulation [29,30].
It has been reported in some studies that non-HDL-C is associated with inflammation. In a study conducted by Wang and Chang in a diabetic patient group, it was shown that non-HDL-C correlates with CRP levels and non-HDL-C is an independent predictor for inflammation in this patient group [15]. Hsu et al. found results which were similar to those in Wang’s work [31]. It has been suggested in a recent study that non-HDL-C may be superior to CRP in determining future cardiovascular events in children and adolescents with type 1 diabetes [32]. In fact, one study has shown that non-HDL-C has a high correlation with proinflammatory macrophages in adipose tissue [33]. Moreover, in an experimental study on apolipoprotein E-deficient mice, non-HDL-C reduction was reported to have a positive effect on the development of atherosclerosis by inhibiting leucocyte transmigration [34]. Evidence from these studies made it clear that there is a close relationship between non-HDL-C and inflammation. There are a limited number of studies investigating the relationship between HDL-C and CCC. In one of these studies, Kadi et al. showed that there was a positive relationship between high HDL-C levels and CCC in patients with at least one occluded coronary artery, and they suggested that the possible underlying cause may be related to the anti-inflammatory properties of HDL-C [35]. In addition, Hsu et al. claimed that there was no relationship between HDL-C and coronary collateral circulation in patients with coronary stenosis above 70% [36]. There are a limited number of studies investigating the relationship between LDL-C and coronary collateral flow. In a study of stable CAD patients with chronic total occlusion with type 2 diabetes mellitus, Shen et al. found LDL-C and non HDL-C as predictors for poor collateral development [37]. We did not include diabetic patients in our study group since in DM patients HDL-C is low and LDL-C and TG-rich lipoproteins are high [38,39]. There are no studies investigating the relationship between non-HDL-C and CCC. Our study is the first on this subject. In our study, we showed the relationship of non-HDL-C with CCC in both univariate and multivariate analyses. We also found that there is a close relationship between non-HDL-C and CRP levels, and CRP and non-HDL-C are independent predictors for CCC. Based on an analysis of our study findings, we can state that HDL-C is also an independent predictor for CCC because the p value was found within the limit of significance in logistic regression analysis. This may be related to the number of cases. This close relationship between non-HDL-C and CCC can be explained by increased inflammatory activity in patients with high non-HDL-C.
As a result, non-HDL-C, TC, elevated CRP and low HDL-C are independent predictors for poor coronary collateral development. TG level and LDL-C do not predict coronary collateral development.
Limitations of the study
First, coronary collateral flow was qualitatively evaluated with Rentrop scoring. The collateral flow index, which is a quantitative measurement and gives more accurate results, was not used. Second, patients with TG levels of 400 mg/dl were excluded from the study because LDL-C was calculated using the Friedewald formula. Finally, only the CRP of inflammation markers was evaluated, and no specific test for endothelial functions was performed.