The present study demonstrated that pre-procedural MHR levels are higher in patients with ISR compared to patients without ISR, and that MHR correlates with UA and CRP levels. Moreover, the MHR was an independent predictor of ISR on top of high CRP, UA levels, stent diameter and time between two coronary angiographic studies. The pre-procedural MHR >14.1 predicted ISR with a sensitivity of 66 % and specificity of 61 %. This might reportedly be the first study demonstrating the link between MHR and bare-metal restenosis in stable or unstable angina pectoris patients.

The patients with ISR had a higher risk of cardiac death and MI and that a prolonged regiment of DAPT may reduce this risk [14]. Despite new medications and techniques, however, ISR still remains an unresolved problem. After stent implantation, several processes play roles in the coronary wall [15]. During stent implantation, mechanical vascular damage occurs and triggers inflammation, followed by smooth muscle cell migration and proliferation. After that neo-intimal proliferation occurs and finally this process end with ISR by promoting neo-intimal proliferation through the stent struts [16, 17], particularly in patients with persistent systemic inflammation or autoimmune disease. Indeed, the inflammation is associated with many different diseases or disorders such as diabetes-associated nephropathy and retinopathy, infectious diseases, rheumatoid arthritis, systemic lupus erythematosus; chronic obstructive pulmonary disease (COPD); metabolic syndrome, end stage renal disease (ESRD) as well as various cardiovascular diseases or disorders including atherosclerosis. Moreover, it is well established that diabetes, ESRD or COPD are comorbidities related to higher ISR risk [18]. Therefore; several inflammatory markers have been studied in the prediction of ISR [19‐21]. It has been demonstrated in a metaanalysis that pre-procedural CRP levels were a significant predictor of ISR after BMS implantation [22]. The count of circulating monocytes, as the source of tissue macrophages and foam cells, interact with platelets and endothelial cells and leading to aggravated inflammation [4]. Monocyte count has been shown as a predictor of coronary events [23] and monocyte activation is a very important step in the beginning of the atherosclerotic process [24]. HDL cholesterol has antiinflammatory, antioxidant, and antithrombotic effects [25]. HDL is highly effective at inhibiting endothelial expression of adhesion molecules and preventing monocyte recruitment to the artery wall [26]. HDL-cholesterol has a close interaction with monocytes through suppressing monocyte activities, interrupting differentiation of monocytes to macrophages which result in a restricted inflammatory response [27]. Therefore, it is possible to combine these two parameters into a single ratio as an MHR, which can reflect the underlying inflammation process. Indeed, it has been demonstrated that higher MHR related to worse cardiovascular events in chronic kidney disease [28] or the isolated coronary ectasia patients [29]. Canbolat et al. showed that pre-procedural MHR levels are associated with atrial fibrillation recurrence after ablation procedure [8]. In a recent study by Cetin et al., MHR was shown as an independent predictor of stent thrombosis in STEMI patients [9]. In all studies, the MHR was associated systemic inflammation and endothelial dysfunction and defined as a novel inflammation-based prognostic marker in cardiovascular diseases.

It is well known that another important role in the pathogenesis of ISR is oxidative stress. High levels of reactive oxygen species produced after PCI and they have been related to migration and proliferation of smooth muscle cells and resulted to ISR [30]. The UA is a well-known oxidative biomarker. Turak et al. demonstrated that the UA levels are related with ISR after BMS implantation and our findings are consistent with this [31]. Indeed, the oxidative stress and inflammation are closely related pathophysiological processes, one of which can be easily induced by another [32]. Since the role of inflammation as both a cause and a result of oxidative stress is supported by a considerable body of evidence, both processes are simultaneously found in many pathological conditions. On the other side, while the oxidative stress pathway is closely related to inflammation, most studies of biomarkers of oxidative stress do not consider markers of inflammation. Therefore, the combining this new MHR parameter as a “inflammatory marker” with the UA levels as an “oxidative stress marker” might be used in predicting of the ISR as a composite measure of oxidative stress- and inflammation-related restenosis process.