Pathophysiology and Outcomes of Endothelium Function in Coronary Microvascular Diseases: A Systematic Review of Randomized Controlled Trials and Multicenter Study

Abstract

Background: Coronary macrovascular disease is a concept that has been well-studied within the literature and has long been the subject of debates surrounding coronary artery bypass grafting (CABG) vs. Percutaneous Coronary Intervention (PCI). ISCHEMIA trial reported no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management, while in the ORBITA trial PCI did not improve angina frequency score significantly more than placebo, albeit PCI resulted in more patient-reported freedom from angina than placebo. However, these results did not prove the superiority of the PCI against OMT, therefore do not indicate the benefit of PCI vs. the OMT. Please rephrase the sentence. We reviewed the role of different factors responsible for endothelial dysfunction from recent randomized clinical trials (RCTs) and multicentre studies. Methods: A detailed search strategy was performed using a dataset that has previously been published. Data of pooled analysis include research articles (human and animal models), CABG, and PCI randomized controlled trials (RCTs). Details of the search strategy and the methods used for data pooling have been published previously and registered with Open-Source Framework. Results: The roles of nitric oxide (NO), endothelium-derived contracting factors (EDCFs), and vasodilator prostaglandins (e.g., prostacyclin), as well as endothelium-dependent hyperpolarization (EDH) factors, are crucial for the maintenance of vasomotor tone within the coronary vasculature. These homeostatic mechanisms are affected by sheer forces and other several factors that are currently being studied, such as vaping. The role of intracoronary testing is crucial when determining the effects of therapeutic medications with further studies on the horizon. Conclusion: The true impact of coronary microvascular dysfunction (CMD) is perhaps underappreciated, which supports the role of medical therapy in determining outcomes. Ongoing trials are underway to further investigate the role of therapeutic agents in secondary prevention.

Coronary Microvascular Dysfunction and Hypertension: A Bond More Important than We Think

“…Numerous studies have shown that hypercholesterolemia leads to an inflammatory response within the microvasculature, decreased availability of nitric oxide, and increased production of reactive oxygen species (ROS) [51,52]. Endothelial dysfunction and capillary rarefaction are the two most important mechanisms, leading to severe microvascular impairment in different organs and provoking glomerulopathy-induced kidney dysfunction and hypertension, reduction in coronary flow reserve leading to coronary microvascular dysfunction, and hepatic dysfunction, as in non-alcoholic fatty liver disease [53]. It has been shown that the role of specific vasoactive substances is related to both hypercholesterolemia and hypertension, as well as the development of CMD, predominantly endothelium-dependent microvascular dysfunction.…”

Distinctive Signs of Disease as Deterrents for the Endothelial Function: A Systematic Review

“…Endothelial dysfunction, when detected by impaired brachial artery flow-mediated dilatation or digital reactive hyperemia index in peripheral arterial tonometry, may be the marker of prospective cardiovascular events in patients with coronary artery disease [ 6 , 7 , 8 ]. In patients revealing a 1-SD decrease in flow-mediated dilatation or index reactive hyperemia, a duplication of risk of cardiovascular events in patients with cardiovascular disease (CVD) is markedly superimposed [ 9 , 10 , 11 ]. These considerations support the determinant role that endothelial function exerts in peripheral vascular circulation that could forecast future cardiovascular events, to the point of being a potential predictor of future cardiovascular events [ 9 ].…”