In this study, we analyzed the predictive value of preoperative peripheral blood NLR and PLR counts and the ALB level for ISR in patients who underwent cerebrovascular bare-metal stent implantation. We noted that higher preoperative NLR (> 2.28), PLR (> 140.25), and lower ALB level (≤ 42.32) were associated with the development of ISR, and hence these parameters could help predict the occurrence of ISR. The incidence rate of ISR after cerebrovascular stenting was recorded to be 20–30%16, and the ISR rate was found to vary according to the clinical centers and locations. The occurrence of ISR increases the risk of cerebrovascular accidents, increase costs, and reduces the quality of life17. Therefore, the etiology of stent restenosis has become a research hotspot. At present, the pathophysiological mechanism of ISR is considered to mainly involve: immune inflammatory response, vascular remodeling, new atherosclerosis, and thrombosis, among others.18–20
The relationship between NLR, as a sensitive indicator of inflammation, and ISR was confirmed in previous studies. NLR has been suggested as a predictor of cerebrovascular ISR9 and coronary ISR21. Mechanical damage and blood flow changes during stent placement leads to the deposition of platelets and fibrin22. The interaction between white blood cells and platelets leads to the recruitment of white blood cells, including neutrophils, into the scaffold segment, which in turn triggers an inflammatory response, in which the involved inflammatory factors lead to the formation of neointima. The neointima is dysfunctional and does not inhibit platelet aggregation. Some subtypes of lymphocytes, such as regulatory T-cells (Tregs), suppress autoimmune inflammation and maintain homeostasis23. Therefore, increased NLR counts indicate an active inflammatory response and promotes the occurrence of ISR.
PLR is a new indicator that reflects platelet activation and inflammation status, and it is widely used to predict adverse outcomes of cardiovascular and cerebrovascular disease, such as stroke24, myocardial infarction25, and heart failure26. S Y et al. confirmed that high PLR is associated with the incidence of coronary ISR12. The possible mechanism may be as follows: inflammatory mediators stimulate megakaryocytes to proliferate and produce relatively greater higher number of platelets, which play an important role in the pathogenesis of atherosclerosis27. Platelets participate in both the formation of plaques and the formation of fibrin plugs as a result of the rupture of unstable plaques. They can also release thrombin and other substances, thus exacerbating the inflammatory response28. Thus, increased platelet count increases the risk of thrombosis, while lymphocytes achieve an inflammation-anti-inflammatory balance by suppressing their own inflammatory response23. Therefore, inflammation and high platelet activation increases with an increase in the PLR count.
The two new types of inflammatory indicators PLR and NLR are closely related to the progression of atherosclerosis29. Shah et al30 found that low lymphocyte count is an independent risk factor for coronary heart disease, which will not be affected by the absolute counts of blood cells under different physiological conditions, such as dehydration or exercise. Thus, they may have good predictive value for ISR.
ALB exerts physiological effects such as the regulation of inflammation, anti-oxidation, anti-coagulation, and inhibition of platelet aggregation, which has been confirmed to be related to stroke, cardiovascular disease, and coronary ISR11, 31. It can be reversibly combined with nitric oxide (NO) and prostaglandin through oxidation and glycosylation in order to achieve anti-oxidation and regulation of inflammation32. ALB also possesses heparin-like activity, probably due to the similarity in their structures and electrostatic charges33. M P et al. compared the low ALB group, physiological albumin group, and high ALB group using platelet function analyzer and found that the low ALB group was more likely to demonstrate thrombosis34. Therefore, hypoalbuminemia can aggravate inflammation, promote platelet aggregation, and aggravate the occurrence of ISR.
Based on our analysis, the most important method that helps reduce the incidence of ISR is monitoring and prevention, which makes standardization of long-term medication and regular review essential. Whole blood cell test is a non-invasive, economical, and simple test method. The identification of blood markers can help predict ISR to facilitate effective patient follow-up study. Once ISR is detected, active intervention is needed to reduce the occurrence of cerebrovascular events. Balloon dilatation or repeated stenting should be considered when anti-platelet drugs or statins are ineffective35. There continues to be a risk of ISR after repeated stent placement. Because of the high mutation rate of anti-platelet drug resistance genes in the Chinese population, conducting genetic screening for drug resistance, if the conditions permits, is recommended for guide drug selection36.