Dyslipidemia is a well-recognized, major risk factor for atherosclerosis [13, 14]. The increased serum lipids, especially LDL-C, will deposit in the arterial wall, and gradually form atherosclerotic plaques, which can consequently block the native artery and cause cardiovascular diseases such as coronary heart disease [15]. Increased inflammation is the core process in all stages of atherosclerosis. With the application and development of many techniques such as anti-inflammatory therapy, antithrombotics, thrombolysis drugs, and catheter treatment in recent decades, the incidence and mortality of atherosclerosis or obstructive vascular diseases have been significantly reduced [16, 17]. CAE is a multifactorial disease and the pathogenic mechanism has not yet been fully elucidated. CAE was considered a variation of atherosclerosis, mainly resulting from the thinning and/or destruction of the myocardial membrane. However, the dilatation process may be independent from the atherosclerotic process because it can be found as an isolated lesion in coronary arteries and other vascular systems [18]. It has been found that elevated inflammatory markers, such as plasma IL-6, and plasma soluble adhesion molecules are closely linked to the presence of coronary artery dilation [19–21]. Long-term exposure to nitrites, herbicide sprays, acetylcholine inhibitors, cocaine, and smoking can also lead to degeneration of the endometrium of the coronary arteries through oxidative stress-induced inflammation, which can eventually cause CAE [10]. Research on inflammation and CAE has characterized CAE-related inflammation, which includes elevated Hs-CRP and IL-6 levels [22]. Accumulation of excess circulating LDL-C was associated with an overproduction of reactive oxygen species and an increase in pro-inflammatory cytokines in the coronary endothelium, linking elevated cholesterol with cardiovascular inflammation [23].
Rosuvastatin is a selective hydroxy methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor widely used in the field of coronary atherosclerotic heart disease [24]. The liver is the main target organ of rosuvastatin, where it can lower cholesterol levels and increase the number of LDL receptors on the surface of liver cells, thereby improving lipid metabolism by promoting LDL absorption and inhibiting hepatic synthesis of very-low-density lipoprotein (VLDL) [25]. Statin therapy can exert pleiotropic effects in atherosclerotic processes such as regulating inflammatory responses, endothelial function, and thrombus formation based on the reduction in LDL-C levels [26]. Rosuvastatin can also stabilize or reverse atherosclerotic plaque through suppressing MMP expression and protect the vascular endothelium against inflammation [27, 28].
There are limited studies focused on the inflammatory status of different age groups of CAE patients. In this study, the cholesterol, LDL-C, Hs-CRP, and IL-6 levels were significantly higher in the total CAE groups than in the NC Group (Table 1). The total cholesterol and LDL-C levels are important for the risk evaluation of coronary heart disease, which benefits from statin therapy through the reduction of LDL-C, Hs-CRP, and IL-6 [29]. Moreover, comparisons between CAE groups of different ages revealed that the highest serum levels of Hs-CRP and IL-6 were found in younger CAE patients (CAE-A), suggesting that cardiovascular inflammation related to CAE may occur at a comparatively younger age (Table 4). There are some potential explanations for this result. First, younger patients are more likely to be stressed resulting in a more primed or activated inflammatory status [30]. In addition, younger patients responded more strongly to physical and emotional stimulation [31] which can lead to increased levels of inflammatory markers. There are other life factors that can also lead to inflammation, such as cocaine abuse and trauma [8].
Previous retrospective studies have also found that statins could efficiently slow down the growth rate of an abdominal aortic aneurysm compared with controls [32]. In the present study, the efficacy of rosuvastatin in CAE patients among different age groups was investigated and compared. The results of follow-up found that younger patients had a greater reduction in the serum levels of Hs-CRP and IL-6, suggesting that rosuvastatin had a greater anti-inflammatory effect in younger patients (Table 4, Fig. 3, Fig. 4). This may be explained by higher levels of inflammatory markers in younger patients compared to older patients, thus the same dose of rosuvastatin could be more likely to produce a greater anti-inflammatory effect. Moreover, a smaller percentage of younger people have never taken rosuvastatin before. Older patients had a higher proportion of rosuvastatin history because of arteriosclerosis, hyperlipidemia, stroke, among other health complications. Therefore, the lipid-lowering effect of rosuvastatin may be more potent, which boosts its anti-inflammatory effects in young patients. The Cholesterol Treatment Trialists' Collaboration reported that the efficacy of statin therapy in older patients was lower than that in younger patients [33]. Furthermore, younger individuals have a higher basal metabolism level in lipid synthesis and degradation [34], therefore, younger CAE patients could be more sensitive to rosuvastatin treatment. After rosuvastatin treatment, the Hs-CRP and IL-6 levels of the CAE-A group reduced to comparable levels with the NC Group, while those in the CAE-C group were only partially reversed, indicating that the inflammatory status of younger CAE patients was more severe but reversible, while inflammation in older CAE patients was comparatively mild, persistent, and irreversible.