Neutrophils to high-density lipoprotein cholesterol ratio as a new prognostic marker in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a retrospective study

Acute myocardial infarction (AMI) is a major cause of global morbidity and mortality. Despite the improvements in reperfusion strategies, the outcome of patients with AMI remains unsatisfactory. Early risk stratification and timely interventions are significant in improving the prognosis of these patients.

Atherosclerosis and atherosclerotic plaque rupture are the main causes of STEMI. Atherosclerosis is characterized by inflammation and abnormal lipid metabolism and may cause plaque rupture in patients with certain risk factors [1‐4]. Also, previous study showed that baseline inflammation status was an important factor in stent restenosis in STMI patient [5]. Neutrophils play an important role in innate immunity and atherosclerosis, particularly, the inflammatory responses in the pathogenesis of atherosclerosis [6]. In contrast, high-density lipoprotein cholesterol (HDL-c) has been associated with anti-inflammatory, antioxidant and antithrombotic effects [7]. Previous studies indicated that HDL-c was strongly associated with neutrophils in the pathogenesis of atherosclerosis, suggesting that HDL-c may regulate the function of activated neutrophils [8]. Activated neutrophils also affected the composition and function of HDL-c [9]. In a recent study, neutrophils count to high-density lipoprotein ratio (NHR) was identified as a novel factor in predicting poor long-term clinical outcomes in elderly patients with AMI [10]. However, the short-term prognostic ability of NHR has not been studied in ST-segment elevation myocardial infarction (STEMI) patients. Therefore, the present study aimed to investigate the association between NHR levels on admission with in-hospital major adverse cardiac events (MACE) in STEMI patients underwent primary percutaneous coronary intervention (PPCI).

The main finding of the study were that ALT, presence of Killip class III-IV and NHR value was independently associated with in-hospital MACE in STEMI patients treated with PPCI. In addition, increased NHR was significantly associated with worse Killip classification. To the best of our knowledge, this was the first study focused on the prognostic value of NHR in predicting MACE in STEMI patients.

Inflammation plays a critical role in formation of atherosclerosis. In the presence of serval risk factors, inflammation may lead plaque rupture, which is the main cause of STEMI. Also, inflammation is correlated with adverse event and life threating complications in these patients. Various inflammatory indexes, such as blood platelet count, CRP, neutrophil to lymphocyte ratio, and so on, have been investigated in patients with cardiovascular disease and demonstrated to be short or long term prognostic factors [12‐14]. In the current study, admission WBC, neutrophil count, monocyte count, hs-CRP level were significantly higher in the MACE group compared with the MACE-free.

Neutrophils, as a component of immune cell, have attracted the attention of researchers in the past decade, emerging studies have suggested that neutrophils play an important role in different stages of atherosclerosis, including atherogenesis, plaque destabilization, plaque erosion, as well as repair processes in myocardial infarction[15‐17]. When arterial plaque ruptured, neutrophils and platelets aggregated rapidly at the lesion site, where the neutrophils may induce and amplify platelet activation and blood coagulation [18‐20].Neutrophil extracellular trap, a protein synthesized by neutrophils, has been considered to be a key component of pathological thrombi and drive cardiovascular disease [21, 22]. Neutrophil-derived micro-vesicles represented another mechanism by which neutrophils amplify inflammatory processes [23]. In addition, Clinical studies have shown that the increase in neutrophils was independently correlated with the infarct size, left cardiac function and adverse events in patients with AMI [24, 25].

HDL-c is a well-known antioxidant, anti-inflammatory, antiapoptotic, antithrombotic, anti-atherosclerotic agent that also has reverse-cholesterol transport effects [26]. Reduced HDL-c is common in patients with AMI and is associated with the severe coronary artery disease. Clinical studies showed HDL-c was negatively correlated with the risk of coronary heart disease, and lower levels of HDL-c were an independent predictor of adverse cardiovascular events [27]. In our study, admission HDL-c levels were lower in the MACE group but did not show statistical significance and it did not correlate with in-hospital MACE in multivariate analysis.

Recent studies on HDL-c have focused on its immunomodulatory effects [28]. Neutrophils can be activated in hyperlipidemia. HDL-c has been shown to stimulate the biogenesis of microRNA-223-3p which regulates neutrophil development, hyperactivity and recruitment during infection [29]. Another study indicated that HDL may contribute to the neutrophil activation by decreasing neutrophil membrane lipid rafts [30]. In in vitro and in vivo studies of myocardial ischemia/reperfusion injury, HDL-c administration prior to ischemia or reperfusion had a multidimensional protective effect on cardiac function, and involved the ability of HDL-c to restrict endothelial permeability, as well as promote vasodilation and neovascularization in coronary endothelial cells [31, 32].

As mentioned above, NHR was considered as a valuable biomarker of inflammatory status and may be a predictor for adverse cardiovascular events in myocardial infarction patient. A recent clinical study on elderly patients with AMI by Huang et al. [10] reported that high NHR was a predictor of the long-term clinical outcomes including mortality and recurrence of myocardial infraction, and was superior to pre-existing biomarker called monocyte to High-density Lipoprotein Cholesterol ratio (MHR) and low-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol ratio (LDL-C/HDL-C). The present study was conducted to further verify the short-term prognostic value of NHR in STEMI patients. In the study, NHR was higher in patients with in-hospital MACE than those patients who were MACE-free. ROC curve analysis revealed that NHR greater than 11.28 as a cutoff value for in-hospital MACE. A high NHR value was independently associated with increased incidence of in-hospital MACE in STEMI patients treated with PPCI. Patients with NHR greater than 11.28 groups had a 2.211 (95% CI: 1.092–4.479)-fold increased risk of occurrence of in-hospital MACE, compared with NHR less than 11.28.

Interestingly, patients with increased NHR in our study were associated with worse Killip classification and SBP, which indicated that NHR may be a new biomarker of cardiac function. This funding was consistent with a previous report which suggested that excessive infiltration or delayed regression of neutrophils aggravated myocardium injury via the abundant release of inflammatory mediators and proteinases [33].

There were some limitations in this study. First, the retrospective design of the study set a limit to the convincement of our study. The second limitation was this research was based in a single center and the study population size was small, so multicenter and large-scale studies are needed to verify this conclusion.

In conclusion, NHR is an easily calculated and universally available marker that may be useful in in-hospital risk classification of STEMI patients undergoing PPCI. Given the interactions and significant roles played by neutrophils and HDL-c in the pathogenesis of atherosclerosis and myocardial infraction, strategies aimed at reducing the NHR have potential therapeutic effects for STEMI patients undergoing PPCI.