In this study, we demonstrated that NHR is an independent risk factor for the development of ACS in the T2DM population. Our result showed that NHR had a significant positive correlation with some biochemical markers of myocardial ischemia, necrosis, and remodeling in T2DM patients combined with ACS. It has strongly suggested the potential importance of NHR in the progression of ACS in T2DM patients. Furthermore, our study showed that NHR≧4.32 has good discriminatory power in diagnosing ACS patients in the T2DM population, although the accuracy may need to be demonstrated by more patients and data. NHR may help predict ACS patients in T2DM patients.
With further analysis, we found the correlation of NHR with biochemical marks of myocardial ischemia, necrosis, and remodeling (cardiac ultrasound indices) in T2DM patients combined with ACS. The results revealed that NHR levels were significantly and positively correlated with cTnI, CK, CK-Mb, LDH, and MB, which are indicators of myocardial ischemia and injury. In addition, NHR levels also showed a significant positive correlation with left atria (LA) and left ventricle (LV) levels, suggesting a relationship between NHR and cardiac remodeling aspects. NHR levels were significantly and negatively correlated with EF and FS, indicators of cardiac function. It has been shown that neutrophils are a critical contributor to LV infarct wall thinning due to cardiac remodeling and that higher neutrophils correspond to lower EF and FS20. The correlation of these markers may explain their diagnostic value in T2DM patients combined with ACS.
To evaluate the diagnostic and predictive value of NHR level for ACS in T2DM patients, we performed ROC analysis to determine the cut-off value, sensitivity, specificity, AUC, and Youden’s index of NHR for diagnosing acute coronary syndrome in T2DM patients. Further, we examined the discriminatory ability of the cut-off value of NHR in T2DM patients combined with STE-ACS and NSTE-ACS. Our results showed that NHR had higher discriminatory accuracy and diagnostic value in T2DM patients combined with STE-ACS, which is of higher severity than NSTE-ACS. This suggests that NHR may correlate with the severity of ACS in T2DM patients. Traditionally, the diagnosis of ACS has been made by clinical symptoms, ECG changes, cardiac biomarkers, and, in some cases, cardiac imaging. However, the search for new biomarkers is increasing, which will help to improve the diagnosis and prognosis of patients with ACS. Our study suggests that NHR levels could be potentially used as a new complementary marker, with the traditional cardiac markers together, for diagnosing ACS patients in the T2DM population.
Recently, an increasing number of studies have used composite predictors of hematological parameters as novel potential risk markers. The ratios of different parameters can provide more comprehensive information than traditional single parameters and have considerable diagnostic and predictive power16,17,18,21,22,23. For example, neutrophil to HDL-C ratio (NHR)16,17,18,23, platelet to lymphocyte ratio (PLR)24, monocyte to HDL-C ratio (MHR)21,22, lymphocyte to HDL-C ratio (LHR)25, platelet to HDL-C ratio (PHR)26, and triglyceride to HDL-C ratio (THR)27. These markers from routine blood tests have a good future due to their affordability and accessibility.
Many previous studies have found that NHR has a better application in the above-mentioned indices due to its unique advantages16,17,18,23. Firstly, T2DM and ACS involve complex pathological processes of inflammatory response and abnormal lipid metabolism9,10,28. NHR can not only present both inflammatory state and lipid metabolism, but also indicate the interaction between neutrophils and HDL-C. Advanced atherosclerotic plaques have a high number of neutrophils and their counts are positively correlated with the histopathological features of rupture-prone atherosclerotic lesions29. It has also been demonstrated that low HDL-C is an important factor in accelerating atherosclerosis in diabetic patients30. Neutrophils and HDL-C play a mutually regulating role in ACS. Activated neutrophils can also mediate HDL oxidation and impair cholesterol efflux by possessing enzymes that produce oxidants31. In contrast, HDL-C can inhibit neutrophil activation, adhesion, proliferation and migration15. Secondly, neutrophils make up the major part of leukocytes and therefore they can better reflect cardiovascular risk than monocytes and lymphocytes11,12,32,33. On the other hand, neutrophils are considered to be the primary players in the acute inflammatory response and play an important role in the subsequent activation of monocytes and lymphocytes34,35,36. These key roles of neutrophils allow NHR to provide better diagnostic and predictive value for cardiovascular disease.
However, our study still has some limitations that should be noted. First, the NHR was measured only once at baseline, which may not reflect the time-dependent association of dynamic changes in NHR with clinical performance. Therefore, our study can only demonstrate that NHR is helpful in the diagnosis and prediction of ACS in patients with T2DM, and more data and more diverse studies are needed to support our view. Second, although the study process was adjusted for covariates as much as possible, we cannot exclude possible residual confounding effects of unmeasured or unincluded variables, such as the different disease duration and different treatments for each T2DM patient. Third, variables such as lifestyle factors and medical history were self-reported, which could lead to recall bias. Finally, this was a cross-sectional study, so a causal relationship between NHR and the development of ACS in T2DM patients could not be demonstrated. Further prospective studies are needed to analyze whether lowering NHR reduces the occurrence and progression of ACS.