Despite significant advancements in the treatment for acute myocardial infarction, there remains a subset of patients who fail to fully mitigate adverse prognosis resulting from ventricular remodeling, even when administered standardized therapeutic interventions 14, 15. Recently, the need for a practical long-term prognosis model has arisen for this subset of AMI patients. In this study, we constructed a prediction nomogram of the MACEs occurrence in 2 years, 3 years and 4 years of the patients who received emergency PCI treatments due to acute single-vessel myocardial infarction. Total cholesterol, CLR (a biomarker of lymphocyte count), along with several traditional clinical risk factors (age, diabetes, heart rate) were included in the model. According to the evaluation of the model efficiency, the validity of the nomogram built in the development cohort had been proved by the validation cohort, which suggested that our predictive model had good predictive ability and stability, and it could render new insights to the STEMI risk stratification thus to support the development of new strategies.
The CLR index is a crucial parameter, reflecting the dual aspects of the body's cholesterol accumulation and lymphocyte-mediated inflammatory response 9, 10. Central to the dynamic formation and progression of coronary atherosclerosis is the interplay between cholesterol accumulation and the involvement of lymphocytes in the inflammatory response 16. Serum total cholesterol, a well-established indicator of cholesterol accumulation, is recognized as an independent cardiovascular risk factor 17, 18. Cholesterol accumulation can lead to membrane injury, potentially contributing to cellular dysfunction and amplifying the body's response to external stressors 19, 20. Through this mechanism, cholesterol plays a role in modulating the immune response, especially the activation of lymphocytes, thereby impacting serum lymphocyte counts 21, 22. Prior research has highlighted a significant correlation between lymphocyte count and the prognosis of acute myocardial infarction patients. The process of lymphocyte antigen recognition, triggering their activation and interaction with antigen-presenting cells, is believed to be instrumental in this context 23. These activation pathways are closely linked to changes in lipoproteins and autoimmune reactions during atherosclerosis 24. Additionally, some studies have suggested that excessive cholesterol may intensify inflammation in atherosclerotic plaques by interacting with specific lymphocyte subsets 25. Our study emphasizes a marked association between the CLR index and poor prognosis in patients undergoing emergency PCI for acute myocardial infarction, thereby establishing it as a reliable indicator for long-term prognosis. Importantly, both serum cholesterol and lymphocyte levels are commonly measured in clinical practice. The CLR index, more easily obtainable and accessible than other indicators such as Osteopontin, trimethylamine N-oxide, and hyperuricemia, as noted in existing studies, offers valuable insights for the timely and effective personalized treatment of patients 26–28.
In our study, we noted that a history of diabetes emerged as a significant independent prognostic risk factor for patients, aligning with findings from previous research. Prior studies have consistently underlined the critical role of blood glucose levels in increasing the risk of stent restenosis, impacting both individuals with and without diabetes 29. Notably, recent studies have demonstrated a marked improvement in long-term cardiovascular outcomes in acute myocardial infarction patients treated with oral Sodium-glucose cotransporter 2 inhibitors, compared to those in a control group, highlighting the potential advantages of such treatments in cardiovascular risk management 30. Additionally, a growing body of evidence indicates that patients with diabetes experience an increase in mitochondrial reactive oxygen species (mtROS) production, significantly contributing to vascular endothelial cell dysfunction 31, 32. This dysfunction can lead to intimal damage, promote platelet aggregation, and ultimately worsen vascular stenosis 33, 34. Moreover, the increased production of reactive oxygen species, a consequence of elevated blood sugar levels, plays a crucial role in inducing oxidative stress, a fundamental element in the pathogenesis of cardiovascular diseases 35, 36. Therefore, it is essential to refine therapeutic strategies for diabetic patients presenting with acute myocardial infarction. Additionally, advocating for active, long-term blood sugar control management in all patients, regardless of their diabetes status, is paramount. These strategies are vital in improving the prognosis and overall outcomes for individuals afflicted with acute myocardial infarction.
This study's strengths are multifaceted. Foremost, the CLR index has been established as a validated prognostic tool for patients diagnosed with acute myocardial infarction. The rigorous internal validation process further enhances its credibility and applicability in clinical settings. Crucially, our inclusion of a large cohort comprising 1264 patients diagnosed with acute single-vessel myocardial infarction underscores the validity and robustness of our findings. In pursuit of precision, we meticulously excluded patients with severe multivessel lesions or significant left main coronary artery stenosis. Although complex lesions have the same pathophysiological mechanisms as single-vessel lesions in acute myocardial infarction, patients with complex lesions always need to implant stents for the second time, which led to data bias in the process of MACEs event statistics 37, 38. The survival prognosis of patients with this type of complex acute myocardial infarction is worse than that of patients with single-vessel disease 39. It is not practical for clinical guidance to analyze single-vessel lesions and complex lesions acute myocardial infarction, even if the results show significant statistical differences.
There are some limitations in this study. First, the urgent nature of PCI in patients with acute myocardial infarction necessitated the postponement of cholesterol measurements until after the procedure. It is important to consider that both the PCI treatment and subsequent statin use may introduce a bias in the CLR index. Additionally, this study did not explore the relationship between changes in cholesterol levels and inflammation. For a more comprehensive analysis of patient prognosis following acute myocardial infarction, future research could benefit from incorporating multiple samplings. This approach would allow for a dynamic observation of the interplay among cholesterol reduction, inflammation, and the CLR index. Secondly, it is pertinent to note that this study is a retrospective analysis conducted at a single center. Although internal validation was conducted, there is a need for multi-center and large-sample prospective studies. Such studies would enable external validation and facilitate a comparison of the efficacy of our findings with existing prognostic models, thus providing a more comprehensive evaluation. Third, the predicted results of the nomogram remain the same over time, but in reality, the disease outcomes can vary with improvements in treatment, early detection, or changes in the natural course of the disease, which may lead to the performance of a nomogram inaccurate.