In our study, the results showed that increased CHR levels were closely related to the degree of coronary artery stenosis. And we also found that CHR was an independent predictor of CAD.As far as we know, our study is the first research to investigate whether CHR is associated with CAD severity of coronary artery disease. A total of 360 patients were included in our work, and the results showed that CHR (OR: 0.904, 95%CI: 0.819–0.998), NHR, age, male, and history of diabetes were independent risk factors for CAD. we also demonstrate that elevated CHR levels are a predictor of severity of coronary artery disease and perform better than NHR in terms of diagnostic efficacy.
In recent years, with the rapid economic development, the change of lifestyle and the adoption of unhealthy diet cardiovascular disease has been the "first killer" of human health6, seriously threatening the life expectancy and quality of life of people all over the world7. In Europe, more than 4 million people die each year from cardiovascular disease (CVD)8. The incidence of cardiovascular disease (CVD) in China is also on the rise. At present, there are about 290 million people with cardiovascular diseases in China, including 11 million patients with coronary heart disease9. Therefore, for patients with chest pain, assessing the severity of coronary artery stenosis is a necessary prerequisite for preventing and controlling cardiovascular disease progression, and helps clinicians develop individualized, comprehensive treatment strategies to improve patients' quality of life10.
In fact, the pathophysiological process of CAD is mainly atherosclerosis, in which dyslipidemia and chronic inflammation of the arteries as well as various inflammatory factors play a central role11. Studies have shown that hs-CRP levels and dyslipidemia have a synergistic effect in the pathogenesis of CAD, and the association between dyslipidemia and CAD seems to be strengthened by the increased hs-CRP levels. Mediation analysis showed that the effect of dyslipidemia on CHD is 8.27% mediated by hs-CRP levels, and the direct effect is 0.6214. To our knowledge, however, no study has directly combined HDL-C and hs-CRP, two biological indicators, to explore the degree of coronary artery stenosis. In ou work, we assumed that CHR is a biomarker composed of inflammation marker and lipid cholesterol marker. through univariate and multivariate analysis, we explored many factors related to CAD. the results show that CHR is positively correlated with Gensini score. after adjusting for confounding factors, we find that CHR is an independent predictor of CAD disease.In addition, our study also found that THE specificity of CHR cut-1.17 for predicting CAD was 83.9%.
Based on our analysis, we attempted to interpret the results associated with increased CHR and severity of coronary artery stenosis.hs-CRP is a blood biomarker produced by the liver, representing acute systemic inflammation, and is considered a perfect marker for assessing systemic inflammation because its serum level does not change with circadian rhythm within 24 hours and does not change with food intake12. hs-CRP is widely used in clinical practice, especially in cerebrovascular and cardiovascular diseases13. hs-CRP is considered as a risk factor of cardiovascular diseases and can increase the mortality of cardiovascular diseases14,15. CRP is involved in the pathogenesis and development of vascular inflammation and coronary atherosclerosis16.It directly affects complement activation, apoptosis, vascular cell activation, monocyte recruitment, lipid accumulation, and thrombosis and other atherosclerotic processes17,18. Epidemiological meta-analysis showed that hs-CRP > 3.0 mg/dL compared to < 1.0 mg/dL increased the risk of CAD by 1.6 times, and the hs-CRP levels were positively associated with the severity of coronary heart disease, which increase with the increase of lesion count19. Therefore, plasma hs-CRP has become a sensitive biomarker of inflammation2,which is of great significance to predict the stability of coronary plaque in coronary heart disease, the severity of vascular disease, restenosis of coronary arteries after coronary angioplasty, and the incidence of cardiovascular events9. Our results showed that the levels of hs-CRP in the CAD+ group were significantly higher than those of the CAD− group and control group, and Gensini score was positively related to hs-CRP, which was also consistent with previous studies20.
Dyslipidemia is viewed as a necessary condition for atherosclerosis, and studies have shown that dyslipidemia may account for 50% of the attributable risk in patients with CAD. Therefore, recent studies on the correlation between lipid biomarkers and coronary heart disease have become the focus21. HDL-C, as a typical lipid related biomarker, plays an important protective role in the process of atherosclerosis and inflammation due to its anti-oxidant, anti-inflammatory, anti-apoptotic and anti-thrombotic properties22–24. HDL-C has been shown to regulate cholesterol efflux, protect vascular endothelium, stabilize plaque, and prevent rupture25–27. In addition, HDL reduces inflammation by inhibiting the expression of adhesion molecules in endothelial cells and reduces coronary atherosclerosis by inhibiting the oxidation of low-density lipoprotein28,29. Therefore, HDL-C, on the one hand, inhibits the progression of atherosclerosis and on the other hand promotes plaque regression30. It had been estimated that for each increment of 1 mg/dL in HDL-C, the CAD risk was reduced by 2% in males and by 3% in females31,32. Current evidence suggested an inverse correlation between HDL-C levels and CAD, myocardial infarction, carotid atherosclerosis, and stroke.Increased HDL levels can prevent coronary heart disease24,33.
In conclusion, due to the interaction between decreased HDL-C and increased CRP in CAD, increased CHR may be associated with inflammatory activity and dyslipidemia. In addition, a comprehensive CHR indicator may be more effective and reliable than a single indicator in explaining the complex interactions between CRP and HDL-C. As far as we know, there was no study to discuss the relationship between CHR and the degree of coronary artery disease. In our work, we directly explored the correlation between the severity of coronary artery disease and conducted regression analysis on the predictors of multiple indicators, which was our advantage. Studies have shown that NHR was correlated with the degree of coronary artery disease34. In our work, CHR, as a new predictor for patients with coronary heart disease, has more diagnostic advantages than NHR in evaluating the severity of coronary artery stenosis. This may be because hs-CRP is more sensitive than neutrophils in detecting low-grade inflammation.
The modified Gensini score is an reliable marker for assessing the severity of coronary artery disease. Some experts found that patients with severe CAD were grouped according to the modified Gensini score, and the results indicated that there were significant differences between the highly rated groups and other groups35,36. In our work, CHR was positively correlated with the modified Gensini score, suggesting that patients with relatively high CHR may have more severe coronary stenosis, and that CHR may be useful in predicting the severity of the lesion.
In conclusion, we believe that CHR may preliminarily reflect the severity of coronary artery, so as to better guide clincal practice. However, our work had some limitations. First, this was a single-center retrospective design, and the type of study had determined its limitations; In addition, we did not apply a China-PAR(prediction for ASCVD risk in China) model to explore the correlation between CHR and MACE events. In future work, we will expand the sample size for multi-center discussion.