Reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion

Abstract

BackgroundThe extent of coronary collateral formation is a primary determinant of the severity of myocardial damage and mortality after coronary artery occlusion. Type 2 diabetes mellitus (T2DM) represents an important risk factor for impaired collateral vessel growth. However, the mechanism of reduced coronary collateralization in type 2 diabetic patients remains unclear.MethodsWith the reference to the recent researches, this review article describes the pathogenic effects of T2DM on collateral development and outlines possible clinical and biochemical markers associated with reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion (CTO).ResultsDiffuse coronary atherosclerosis in T2DM reduces pressure gradient between collateral donor artery and collateral recipient one, limiting collateral vessel growth and function. An interaction between advanced glycation end-products and their receptor activates several intracellular signaling pathways, enhances oxidative stress and aggravates inflammatory process. Diabetic condition decreases pro-angiogenic factors especially vascular endothelial growth factor and other collateral vessel growth related parameters. Numerous clinical and biochemical factors that could possibly attenuate the development of coronary collaterals have been reported. Increased serum levels of glycated albumin, cystatin C, and adipokine C1q tumor necrosis factor related protein 1 were associated with poor coronary collateralization in type 2 diabetic patients with stable coronary artery disease and CTO. Diastolic blood pressure and stenosis severity of the predominant collateral donor artery also play a role in coronary collateral formation.ConclusionsT2DM impairs collateral vessel growth through multiple mechanisms involving arteriogenesis and angiogenesis, and coronary collateral formation in patients with T2DM and CTO is influenced by various clinical, biochemical and angiographic factors. This information provides insights into the understanding of coronary pathophysiology and searching for potential new therapeutic targets in T2DM.

Impact of coronary collateralization on long-term clinical outcomes in type 2 diabetic patients after successful recanalization of chronic total occlusion

“…Abundant evidence has demonstrated that T2DM exerts a detrimental effect on glucose and lipid metabolism and vascular endothelial function, leading to development and progression of coronary atherosclerosis and unfavorable clinical outcomes [32][33][34][35] . In this study, T2DM was the only independent risk factor for poor coronary collateralization, suggesting that presence of T2DM is correlated negatively with the development of functional collateral arteries 22,23 , and may contribute partially to adverse prognosis of CTO patients 36 . Although presence of a chronic totally occluded lesion has been considered as a prerequisite for spontaneous collateral recruitment, the mechanism of collateral vessel growth is complex in situations where atherosclerosis affects large conductance arteries 37 , and even become more complicated by the presence of T2DM in which multiple biochemical and cellular components are involved 23,38,39 .…”

Non-infarct related chronically occluded coronary arteries and its association with diabetes and prediabetes

“…11,26,27 DM adversely affects coronary collateral development through multiple cellular mechanisms on arteriogenesis and angiogenesis, and the formation of coronary collaterals in patients with DM and CTO is infl uenced by various clinical, biochemical and angiographic factors. 28 The diabetic pathophysiology promotes an anti-angiogenic process and meanwhile mitigates pro-angiogenic factors in coronary vasculature during ischemia, jointly leading to impaired collateral growth. 28,29 Although the influence of the DM on collateral development is debatable, 11,[30][31][32][33][34] it has been reported that diabetics and prediabetics generally have a poor acute collateral response because of the diffusely impaired endothelial function, [35][36][37] particularly in the presence of active smoking.…”

“…28 The diabetic pathophysiology promotes an anti-angiogenic process and meanwhile mitigates pro-angiogenic factors in coronary vasculature during ischemia, jointly leading to impaired collateral growth. 28,29 Although the influence of the DM on collateral development is debatable, 11,[30][31][32][33][34] it has been reported that diabetics and prediabetics generally have a poor acute collateral response because of the diffusely impaired endothelial function, [35][36][37] particularly in the presence of active smoking. 5,38,39 Whereas the DM and prediabetes aggressively induces atherosclerosis and may be more susceptible to infarction; they can also activate some endogenous cardioprotective mechanisms protecting the left ventricular contractile function.…”

“…23 The revascularization decision of a CTO should be based not only on clinical manifestation of the patients but also on the morphology of occluded coronary lesions, the quality of collaterals, and myocardial viability. 28 Current evidence favors coronary artery bypass grafting as the preferred revascularization modality for diabetic patients with MVD/CTO, which is likely to refl ect the more complete revascularization and global protection provided by arterial conduits against rapid atherosclerosis progression in percutaneous coronary intervention and untreated segment. 28 In the current study, we found that the prediabetes beyond the DM was also associated with non-IRA CTO.…”

“…28 Current evidence favors coronary artery bypass grafting as the preferred revascularization modality for diabetic patients with MVD/CTO, which is likely to refl ect the more complete revascularization and global protection provided by arterial conduits against rapid atherosclerosis progression in percutaneous coronary intervention and untreated segment. 28 In the current study, we found that the prediabetes beyond the DM was also associated with non-IRA CTO. The present defi nition of DM is based on the level of glucose at which retinopathy occurs, but macrovascular complications such as coronary artery disease appear earlier and, using current glycemic criteria are often present at the time when DM is diagnosed.…”