## 4 Discussion  
The main findings of the present study enrolling 31 patients with first NSTE-ACS undergoing PCI are as follows: 1) thoracic DA inflammation as assessed using \({}^{18}\)F-FDG-PET/CT and expressed in terms of TBR was independently associated with low levels of serum cystatin C; 2) there was no relationship between cystatin C levels and either features of coronary plaque vulnerability as assessed using OCT or CAC score as assessed using a CT scan. During the past decade, cystatin C, a 13-kDa protein and member of a family of competitive inhibitors of lysosomal cysteine proteases, has gained great popularity because it has been consistently shown to be a more reliable marker of renal function than creatinine [2; 3]. Yet, high levels of cystatin C have been associated with an adverse cardiovascular outcome in several observational studies involving patients with a broad spectrum of clinical conditions [4; 5]. These findings, along with the observation that elastolytic cysteine proteases and their inhibitors, in particular cystatin C, are involved in the pathogenesis of atherosclerosis [8; 9], have led many researchers to thoroughly investigate the link between high levels of cystatin C and impaired cardiovascular outcome. At least partially, some studies have recently shed light on this topic. First, based on the fact that several single nucleotide polymorphisms are associated with circulating cystatin C level [22; 23], prospective observational studies [24; 25] and mendelian randomization studies [10; 11] have shown that high levels of cystatin C are not causally related to the incidence of coronary artery disease, ischemic stroke, and heart failure. In particular, mendelian randomization studies rely on a very large sample size and on the fact that genetic information, randomly distributed from parents to offspring, are not influenced by either disease status (reverse causality) or potential confounders. Secondly, it has been demonstrated that cystatin C is a more reliable marker of renal function than creatinine. It is  
Figure 3: Representative \({}^{18}\)F-FDG-PET/CT image of thoracic aorta showing a big focal calcification (_arrowhead_) not related to significant \({}^{18}\)F-FDG uptake (TBR\({}_{\text{max}}\) = 1.3). In the descending aorta, an active focal \({}^{18}\)F-FDG uptake (_arrow_) is also shown (TBR\({}_{\text{max}}\) = 1.8). Abbreviations: \({}^{18}\)F-FDG-PET/CT = \({}^{18}\)F-fluorodeoxyglucose-positron emission tomography/computed tomography; TBR = target to background ratio. able to detect a small reduction in renal function that may promote atherosclerosis and an adverse outcome [7]. However, whether high levels of cystatin C are independently related to the burden of atherosclerosis (reverse causality) is, on the contrary, still controversial, with some clinical studies using angiography showing a direct [26] relationship with the extent of coronary disease and others an inverse relationship [27]. In the present study, we used a multi-imaging approach to test in vivo the relationship between serum levels of cystatin C and different features of atherosclerosis in patients with NSTE-ACS and nearly normal renal function. First, FD-OCT is a recently developed optical imaging invasive technique that provides high-resolution and cross-sectional images of coronary tissue in situ [28]. The resolution of FD-OCT (about 10 \(\upmu\)m) is appropriate for measuring cap thickness and even plaque macrophage density. We showed that serum levels of cystatin C are not related to features of coronary plaque vulnerability, namely the number of lipid-rich plaques, lipid-rich plaques with macrophages, and TCFAs. Secondly, micro- and macro-calcification are a cardinal characteristic of atherosclerotic plaques and a hallmark of the inflammatory process [29]. CAC scoring by [PERSON] et al. [20] is associated with the extent of coronary plaque burden [30] and in clinical practice is considered a reliable marker of cardiovascular risk [31].