Vulnerable plaques are clinically defined as atherosclerotic plaques that are susceptible to rupture, thrombus formation and rapid progression, and are likely to develop into "criminal plaques", or more likely to cause "clinical events" atherosclerotic plaques to occur. The morphological changes of vulnerable plaques mainly include: rupture of the plaque surface, components calcification and changes, thinning of the fibrous cap, formation of huge lipid cores, formation of neovascularization, plaque hemorrhage and secondary thrombosis. The changes of cellular molecular level of vulnerable plaques mainly include smooth muscle cell proliferation, macrophage aggregation, extracellular lipid aggregation, T lymphocyte aggregation, etc. Vulnerable plaque is the basis for the occurrence of angina pectoris, myocardial infarction and stroke, but atherosclerosis is usually clinically silent before the acute events caused by narrowing of arterial lumen or plaque rupture. Up to 60% of acute myocardial infarction (AMI), sudden cardiac death and stroke are the first manifestations of the disease. Therefore, it is of great significance for early accurate assessment and effective intervention of vulnerable plaques.
In addition to the previously studied risk factors for unstable plaque formation such as hypertension, diabetes, and lipids, this study find that serum markers MMP-9, LOX-1, and YKL-40 are also independent risks of unstable plaque formation. CPS is an independent predictor of vulnerable plaque formation. Atherosclerotic plaques are composed of a lipid core covered with a fibrous cap, which is mainly composed of an extracellular matrix containing a large amount of collagen fibers, smooth muscle cells, and a small number of macrophages. The lipid core is composed of macrophages, smooth muscle cells, and ECM composition. The weakening of the fibrous cap due to the net degradation of the extracellular matrix is considered to be an important cause of plaque rupture. MMP-9, also known as gelatinase B, is highly expressed in macrophage-rich atheromatous plaque regions, and its main function is to mediate the degradation and remodeling of ECM, as well as the degradation of all components of the vascular wall, so it plays an important role in the degradation of the fibrous cap in arterial plaque. Laura found that MMP-9 can promote the transformation of plaque from stable to vulnerable state, increase plaque instability, and MMP-9 has certain value for the prediction, diagnosis and prognosis of acute coronary syndrome. The results of this study support the view that MMP-9 predicts vulnerable plaques, but the average value of the plaque-free group is greater than 0 ng/ml. Therefore, MMP-9 may be involved in other stages besides atherosclerotic plaque progression, such as tissue remodeling , inflammation , tumor invasion, wound healingc and other physiological processes can increase its serum value. LOX-1 is a class E scavenger receptor, which accelerates the instability of arterial plaques by promoting lipid accumulation, inducing endothelial cell activation and dysfunction, and indirectly degrading the extracellular matrix . Multivariate regression analysis in this study showed that LOX-1 is an independent risk factor for vulnerable plaque in the carotid artery, which is basically consistent with the previous research results. Serum LOX-1 level can serve as an index to evaluate the properties of arterial plaque. YKL-40 is an inflammatory glycoprotein without chitinase activity. It is mainly expressed by macrophages at the late stage of differentiation. It not only participates in angiogenesis, cell migration and tissue remodeling, but also aggravates plaque instability by affecting the synthesis of hyaluronic acid as well as the expression and activation of MMP-9. Li studied the relationship between serum inflammatory markers and plaque properties in patients with h-type hypertension and carotid atherosclerosis confirmed that YKL-40 level was positively correlated with plaque properties. As plaque instability increased, serum YKL-40 is on the rise. Our study found that YKL-40 may exist as a potential biomarker of vulnerable plaque circulation, and it is of great significance for the evaluation of atherosclerotic plaque properties.
In 1986, J R. Crouse first proposed the concept of "plaque score" to quantitatively analyze the degree of arteriosclerosis, also known as "Crouse score". The Crouse Score defines IMT > 1.2 mm as plaques. Regardless of the length of a single plaque, the maximum thickness (mm) of each isolated plaque on both sides of the carotid artery measured by the cross-section of the probe is added to obtain the bilateral carotid artery. The sum of plaque thickness is the carotid plaque score (CPS). Many previous studies[5, 23, 24]confirmed that CPS is an independent predictor of ASCCVD, and unstable plaque is the basis of the onset of ASCCVD, in other words, both high CPS and unstable plaques can easily lead to the onset of cardiovascular and cerebrovascular diseases. The CPS reflects the instability of plaques from the side. The relationship between CPS and carotid plaque stability has not been reported at home and abroad. The results of this study find that the CPS has a strong correlation with plaque stability. The average CPS of the unstable plaque group is significantly higher than that of the stable plaque group. Multivariate regression analysis showed that the CPS is an independent predictor of vulnerable plaque (OR = 1.334; 95% CI: 1.087–1.637; P = 0.006). This result validates the opinions of previous literature. CPS is obtained by carotid ultrasound, which has the characteristics of easy to operation, cheap price, and no radiation. Therefore, it can be used as a screening for high-risk ASCCVD population. However, it should be noted that the subjective factors of operators and the plaque definition criteria in clinical practice may affect. There are some errors in the measurement results.
In order to predict the incidence of cardiovascular and cerebrovascular diseases early, many standards and indicators have been developed. These tools can help identify high-risk populations, thereby raising people's awareness, improving lifestyles, and even reducing morbidity and mortality. One of the simplest and most practical methods is the Framingham risk score (FRS). Since the release of FRS by Wilson et al in 1998, FRS has become the basis for calculating the risk of adult treatment in the United States. This model can estimate the risk of cardiovascular disease in ordinary people for 10 years, and provides a convenient method for classification of low, middle and high risk groups of coronary heart disease. The 10-year ICVD calculation in this study applied the improved Chinese "Ischemic Cardiovascular Disease (ICVD) 10-year Onset Risk Assessment Method", and based on the sum of the scores of various risk factors, the absolute 10-year ICVD risk of the individual was obtained. The univariate analysis in this study showed that the average 10-year ICVD in the plaque group was significantly larger than that in the non-plaque group (P = 0.000). Compared with the stable plaque group, the 10-year ICVD was higher in the unstable plaque group, and we also found that vulnerable plaques have a good correlation with the 10-year ICVD trend (P = 0.003). Multivariate analysis found that 10-year ICVD is not an independent factor for vulnerable plaques. If very few special samples are excluded (such as older but not smoking, hypertension, hypertension, diabetes, etc, it will also calculate a larger 10-year ICVD value), calculation found that 10-year ICVD is an independent predictor of vulnerable plaque. The combined detection method in this study made up for the shortcomings of 10 years of inaccurate prediction of ICVD for special cases.
In order to further screen high-risk ASCCVD patients early with more accuracy and to avoid the shortcomings of inaccurate prediction of special cases, we took patients in the vulnerable plaque group as the research object and explored the combination of serum markers and 10-year ICVD in predicting high-risk patients with ASCCVD, as shown in Table 4. It is recommended to combine 10-year ICVD and serum markers to guide early intervention. If the 10-year ICVD risk is < 5%, early intervention is not recommended regardless of the amount of serum markers; The risk of ICVD in 10 years is 5%-7.5%, and any marker of MMP-9, LOX-1 and YKL-40 is higher than the critical value, it is suggested to intervene; When MMP-9, LOX-1, YKL-40 < critical value, considering intervention; The 10-year ICVD risk is 7.5%-20% and any marker of MMP-9, LOX-1 and YKL-40 is higher than the critical value ,it is recommended for intervention; MMP-9, LOX-1, YKL-40 < critical value, considering intervention; The 10-year ICVD risk > 20%, and early intervention is recommended regardless of serum markers.