ST-elevation myocardial infarction (STEMI) is a significant cause of morbidity and mortality in patients with coronary heart disease. Patients with STEMI are at high risk for complications and poor outcome, including death. All patients with STEMI should undergo early risk stratification soon after admission. Multiple methods have been developed for risk stratification in STEMI. Complicated multivariable models developed for predicting mortality in patients with STEMI identify independent clinical predictors and quantify their relative contribution to mortality risk.1 One widely used and easily accessible model is the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI, which is readily applied in routine clinical practice and is able to predict both early (30-day) and one-year mortality.2

The TIMI score was created and validated in a sample of patients with ST-segment elevation myocardial infarction. It is based on ten rapidly calculated clinical indices to provide a score between 0 and 14 points. The parameters included in the score are age, systolic blood pressure <100 mmHg, diabetes, angina, history of hypertension, heart rate >100 bpm, weight <67 kg, Killip class II-IV, anterior STEMI or left bundle branch block (LBBB), and time to treatment >4 hours. Time to treatment is defined as time from symptom onset to first balloon inflation.

The monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) has emerged as a novel prognostic marker that has been reported to be related to cardiovascular outcomes in various cardiovascular diseases.3–5 Monocytes are a source of various cytokines associated with inflammatory processes. It has been found that monocytes and differentiated macrophages can modulate inflammatory cytokines and tissue remodeling in the pathophysiology of coronary artery disease (CAD).6 By contrast, the major function of HDL-C is to protect peripheral tissues through the removal of cholesterol and to suppress monocyte activation and the proliferation and differentiation of monocyte progenitor cells.7,8

To the best of our knowledge, there have been no studies investigating the relationship between MHR and TIMI risk score in STEMI patients. In this study, we aimed to investigate this relationship and its possible prognostic value for clinical risk stratification in STEMI patients.

A total of 161 patients (118 male [73.3%]; mean age 51.8±6.9 years) were enrolled in the study. The baseline characteristics of the two groups according to clinical presentation are listed in Table 1. There were 50 patients (32 male [64%]; mean age 52.0±8.05 years) with normal coronary arteries and 111 patients (86 male [77.5%]; mean age 51.7±6.43 years) with acute STEMI. The control and STEMI groups were similar in terms of gender, smoking, family history, hypertension, diabetes, and age (Table 1). There were no significant differences between the two groups with respect to the serum biochemical parameters of glucose, creatinine, total cholesterol, triglycerides, LDL-C, total protein, albumin, AST, ALT, Na, and K (p>0.05 for all) except for HDL-C, which was significantly lower in the STEMI group (37.4±7.2 vs. 34.6±7.8 mg/dl, p=0.027). Regarding hematological parameters, there were significant differences between the groups: monocyte count (0.62±0.15 vs. 0.71±0.24×103/μl, p=0.003), MHR (1.71±0.47 vs. 2.21±0.98, p=0.001), WBC (8.6±1.7 vs. 9.9±2.7×103/μl, p=0.035) and neutrophil count (5.34±1.8 vs. 6.5±2.64×103/μl, p=0.004) were significantly higher in the STEMI group than in controls (Table 1).

Multivariate logistic regression analysis including male gender, smoking, MHR, WBC, and neutrophil count demonstrated that MHR was the only independent predictor of STEMI (Table 2).

In the subgroup analysis, the 111 patients with STEMI treated by pPCI were divided into two groups according to TIMI score. There were 39 patients (31 male [79.5%]; mean age 50.8±5.3 years) in the low TIMI score group and 72 patients (55 male [76.4%]; mean age 52.1±6.9 years) in the high TIMI score group. SYNTAX scores and TIMI score parameters of the low and high TIMI score groups are shown in Table 3 and the baseline clinical and demographic characteristics of the study population based on TIMI score are shown in Table 4. The groups were similar in terms of age, gender, smoking, family history of CAD, and diabetes (p>0.05 for all) but not hypertension (p=0.028). The biochemical and hematological parameters were similar between the low and high TIMI score groups (p>0.05 for all) except for HDL-C, monocyte count, MHR, WBC and neutrophil count: HDL-C levels were significantly lower (37.1±7.5 vs. 33.2±7.61 mg/dl, p=0.011), and monocyte count (0.64±0.17 vs. 0.75±0.26×103/μl, p=0.019), MHR (1.80±0.59 vs. 2.42±1.09, p=0.001), WBC (8.9±1.82 vs. 10.5±2.9×103/μl, p=0.004) and neutrophil count (5.7±1.7 vs. 6.99±2.93×103/μl, p=0.014) were significantly higher in the high than in the low TIMI score group.

Multivariate logistic regression analysis including hypertension, MHR, WBC, and neutrophil count demonstrated that MHR was the only independent predictor of high TIMI score in patients with STEMI (Table 5). In correlation analysis, there was a significant positive correlation between MHR and TIMI score (r=0.479, p<0.001). The cutoff value of MHR for high TIMI score was 2.409, with a sensitivity of 43.06% and a specificity of 87.18% (area under the curve 0.669; 95% confidence interval 0.569-0.8769; p=0.003) on ROC curve analysis (Figure 1).

Figure 1.

Receiver operating characteristic curve analysis of MHR for high TIMI score in patients with ST-segment elevation myocardial infarction. AUC: area under the curve; CI: confidence interval; MHR: monocyte to high-density lipoprotein cholesterol ratio.

(0,11MB).

There were some important findings in our study. First, MHR was significantly higher in patients with STEMI and was associated with higher TIMI risk score. Second, MHR was an independent predictor of STEMI and of high TIMI score in patients with STEMI.

The TIMI score predicts mortality in STEMI patients, a TIMI score of 9 having particular short-term prognostic value. According to Walsh et al.,9 pPCI can be performed in an elderly population who have a high-risk TIMI score with low mortality and marked symptomatic benefit. The TIMI risk score is based on clinical information that is available at the time of hospital arrival and is suitable for early risk stratification at the bedside, but in the Intravenous nPA for Treatment of Infarcting Myocardium Early (InTIME II) trial, the TIMI score was not the best predictor of poor outcome because of the small sample size.10 Gonzalez-Pacheco et al. found a C-statistic of 0.80 for the predictive value of the TIMI risk score for in-hospital mortality. Also in a meta-analysis, the pooled C-statistic value for the TIMI score from 15 validation studies including 134557 patients with STEMI was 0.77.11 Intense secondary prevention improves outcomes in STEMI patients, and the RESPONSE (Randomized Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists) trial showed that usual care plus six-month nursing through outpatient visits improved risk factor prevalence and reduced estimated long-term mortality risk.12 Popovic et al.13 found that the TIMI risk score has a poor discriminatory prognostic value in patients with effective early revascularization. Morrow et al.14 demonstrated C-statistic values ranging from 0.76 to 0.81 across time points. In a large American registry the accuracy of the TIMI risk score was as high as 0.80 in patients treated with pPCI. Morrow et al.15 also demonstrated that high TIMI risk scores for STEMI predict high 30-day mortality.

The inflammatory response plays an important role in the progression of atherosclerosis. Various studies have shown the association of CAD and white blood cell counts. Bath et al.16 reported that monocytes from hypercholesterolemic patients, as opposed to controls, were more sensitive to stimulation by chemoattractant agents with respect to chemokinesis. This may explain the increased involvement of monocytes in hypercholesterolemia-related atherogenesis. Murphy et al.17 reported that HDL-C and its major protein component apolipoprotein A-I exert anti-inflammatory effects on human monocytes by inhibiting the activation of CD11b. HDL-C inhibits LDL-C oxidation by reducing monocyte chemotaxis and monocyte chemoattractant protein 1 expression, and HDL-C thereby influences the inflammatory index. Kalantar-Zadeh et al.18 examined the role of HDL-C in promoting the proinflammatory potential of LDL-C in 189 patients with chronic kidney disease followed for 30 months and found a higher adjusted hazard ratio for death in patients with a higher HDL-C proinflammatory index. Besides its anti-inflammatory properties, HDL-C is also an important marker for the prognosis of cardiovascular disease.19 Kanbay et al.20 reported that MHR increased with decreasing estimated glomerular filtration rate in predialytic chronic kidney disease patients and that a higher MHR was associated with a worse cardiovascular profile and was an independent predictor of major cardiovascular events during follow-up. Recently, MHR has been described as a novel marker for major adverse outcomes with prognostic importance for predicting in-hospital and long-term major adverse cardiovascular events in STEMI patients.11,21

This is the first study in the literature focusing on the relationship between MHR and TIMI risk score in STEMI patients. The fact that a significant relation was found between TIMI score and MHR in this study is important. Our study added a new observation, that MHR may be valuable for prediction of in-hospital and short-term major adverse cardiovascular events in patients with STEMI.

The authors have no conflicts of interest to declare.