Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Prognostic Value of Combining Apelin-12 and Estimated Glomerular Filtration Rate in Patients with ST-Segment Elevation Myocardial Infarction

Prognostic Value of Combining Apelin-12 and Estimated Glomerular Filtration Rate in Patients with... Hindawi Journal of Interventional Cardiology Volume 2022, Article ID 2272928, 9 pages https://doi.org/10.1155/2022/2272928 Research Article Prognostic Value of Combining Apelin-12 and Estimated Glomerular Filtration Rate in Patients with ST-Segment Elevation Myocardial Infarction Yue Liu , Huasong Xia, Meng Li, Yi Chen, and Yanqing Wu Department of Cardiology, Second Affiliated Hospital of Nanchang University, No. 1 Mingde Road, Nanchang 330006, Jiangxi, China Correspondence should be addressed to Yanqing Wu; wuyanqing01@sina.com Received 25 January 2022; Revised 25 April 2022; Accepted 27 April 2022; Published 24 June 2022 Academic Editor: Jacek Bil Copyright © 2022 Yue Liu et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Apelin-12 and estimated glomerular filtration rate (eGFR) are considered prognostic factors for ST-segment el- evation myocardial infarction (STEMI). However, little is known about whether the combined use of these two biomarkers could enhance the prognostic value. *is study aimed to investigate the utility of combining apelin-12 and eGFR for STEMI. Methods. Patients were divided into four groups based on median apelin-12 level and eGFR level: A: low apelin-12, low eGFR; B: low apelin- 12, high eGFR; C: high apelin-12, low eGFR; and D: high apelin-12, high eGFR. *e Cox regression was used to identify prognostic factors. *e Kaplan–Meier and the receiver operating characteristic (ROC) curves were generated to evaluate the prognostic value of apelin-12 combined with eGFR in patients with STEMI. Results. Among 460 patients, 118 (25.7%) experienced major adverse cardiac events (MACEs) during the entire follow-up of 30 months. *e Kaplan–Meier curve analysis revealed that group D had the best prognosis compared with the other three groups. *e combination of apelin-12 and eGFR (area under the ROC curve (AUC), 0.699) enhanced the predictive value for MACE compared with either apelin-12 (AUC, 0.617) or eGFR (AUC, 0.596) alone. *ere was a negative association between apelin-12 and eGFR (r � −0.32, p< 0.001), while no association was observed between the Gensini score and apelin-12 or eGFR. Conclusions. *is study suggests that both low apelin-12 (<0.76 ng/ml) and low eGFR (<94.06 mL/min/1.73 m ) are associated with poor prognosis in STEMI, indicating that the combination of apelin-12 and eGFR could enhance the prognostic value of patients with STEMI. major adverse cardiac events (MACEs) after STEMI [4]. 1. Introduction *erefore, it is necessary to identify risk factors associated ST-segment elevation myocardial infarction (STEMI), with the prognosis of patients with STEMI. characterized by cardiomyocyte death due to persistent is- Apelin-12, a member of the apelin family, is a ligand of chemia and hypoxia, is one of the most common and fatal the human orphan G protein-coupled receptor (APJ). It has diseases. Despite the decline in mortality rates in recent years been suggested that the apelin/APJ system plays a critical [1], STEMI remains a significant threat to global health. role in various diseases, including respiratory [5], gastro- According to the Jakarta Acute Coronary Syndrome Registry intestinal [6], and hepatic diseases [7]. Recently, apelin-12 database [2], STEMI accounts for approximately 37% of has also been investigated in cardiovascular diseases. Liu and acute coronary syndrome cases in developing countries, his teammates enrolled 120 patients with STEMI who un- consistent with that reported in a previous study [3]. Al- derwent primary percutaneous coronary intervention (PCI) though considerable advances have been achieved in and were followed up for 12 months. *e authors found that reperfusion therapies and drug treatments, the prognosis of the incidence of MACE was significantly higher in patients patients with STEMI remains far from satisfactory because with low apelin-12 levels than in those with high apelin-12 many patients continue to experience complications and (p< 0.001) [8]. Another observational study suggested that 2 Journal of Interventional Cardiology Patients with initial symptoms of STEMI N = 464 Excluded patients with miss data N = 4 Patients included in the study N = 460 Median apelin and GFR Group A Group B Group C Group D Low apelin Low apelin High apelin High apelin Low GFR High GFR Low GFR High GFR N = 70 N = 154 N = 158 N = 78 Figure 1: Flow chart of the study. patients, and apelin-12 detection have been described pre- the MACE rate was much lower in patients with an apelin-12 level >2.2 ng/mL [9]. *e underlying cardioprotective viously [12]. *e Gensini score was used to assess the severity mechanisms may be that the apelin system promotes va- and extent of coronary artery stenosis, and detailed infor- sodilation, reduces blood pressure in a nitric oxide-de- mation can be referred in the literature [13]. To compare pendent way, increases cardiac contractility, and improves prognosis, patients were initially divided into two groups angiogenesis after myocardial infarction [10]. according to the median levels of apelin-12 or eGFR. Fur- *e estimated glomerular filtration (eGFR) is a useful ther, patients were divided into four groups according to the indicator of quantifying renal function in clinical settings. median apelin-12 level and eGFR level: A (low apelin-12, low *e relationship between lower eGFR and poor outcomes in eGFR (n � 70)); B (low apelin-12, high eGFR (n � 154)); C patients with STEMI has long been established. According to (high apelin-12, low eGFR (n � 158)); and D (high apelin-12, a study by Anavekar, for each reduction in eGFR by 10 units high eGFR (n � 78)). *e flow chart is shown in Figure 1. Because all patient data were anonymized and data analysis below 81.0 mL/min/1.73 m , the risk of death and nonfatal cardiovascular outcomes is increased by 10% [11]. A pre- adhered to the Dryad database rules, neither ethics approval nor patient consent was required for this study. We verified vious study has suggested that apelin-12 has prognostic value in predicting short-term (during hospitalization) and that the sample size is sufficient using PASS software with an long-term (2.5 years) MACE, especially in those with normal alpha of 0.05 and a power of 80%. We estimated a sample eGFR [12]. However, little is known about whether the size of 308 patients, and our study included 460 patients. combination of apelin-12 and eGFR has a better prognostic *e primary endpoint was the occurrence of MACE, value than each biomarker alone. defined as a composite of cardiac death, recurrent target Accordingly, this study aimed to determine whether the vessel-related myocardial infarction, ischemia-driven target combination of apelin-12 and eGFR served as a better lesion revascularization, cardiogenic shock, or congestive prognostic biomarker in patients with STEMI than either heart failure. *e eGFR was calculated using the equation published in the Modification of Diet in Renal Disease study one individually. equation [14]. More specifically, 2. Methods ∧ ∧ GFR � 186.3 × (Scr) − 1.154 × (age) (1) Clinical data of 464 patients with STEMI were downloaded − 0.203 × 0.742(if female). from Dryad (https://doi.org/10.5061/dryad.pf56m), a pub- licly available database that houses a large quantity of Hypertension was defined as blood pressure ≥140/ datasets from published articles. After removing the data of 90 mmHg and/or using antihypertensive drugs. T2DM was four patients with missing information, this study ultimately defined as FPG ≥7.0 mmol/L and/or on medication for included 460 patients with STEMI from the First People’s T2DM. Hospital of Taizhou, Zhejiang, China, who were admitted All patients were followed up for 30 months or until the with STEMI symptoms between January 2010 and October occurrence of MACE. Survival time was calculated from the 2014. *e inclusion and exclusion criteria, therapy process of date of PCI until an adverse event occurred. Journal of Interventional Cardiology 3 Table 1: Characteristics of patients. All patients (N � 460) A (N � 70) B (N � 154) C (N � 158) D (N � 78) p value Age 62.9± 11.9 66.3± 11.1 59.3± 12.1 66.4± 11.1 59.9± 11.1 <0.001 Sex <0.001 Male 353 (76.7%) 48 (68.6%) 137 (89.0%) 99 (62.7%) 69 (88.5%) Female 107 (23.3%) 22 (31.4%) 17 (11.0%) 59 (37.3%) 9 (11.5%) HR 76.9± 17.2 78.7± 18.2 77.4± 16.0 75.9± 18.6 76.6± 15.3 0.694 SBP 132± 27.2 134± 28.8 131± 27.8 131± 27.0 134± 24.7 0.693 Anterior wall MI 0.129 No 231 (50.2%) 29 (41.4%) 74 (48.1%) 81 (51.3%) 47 (60.3%) Yes 229 (49.8%) 41 (58.6%) 80 (51.9%) 77 (48.7%) 31 (39.7%) Killip grade 0.165 I 348 (75.7%) 46 (65.7%) 122 (79.2%) 122 (77.2%) 58 (74.4%) ≥II 112 (24.3%) 24 (34.3%) 32 (20.8%) 36 (22.8%) 20 (25.6%) DM 0.913 No 312 (67.8%) 48 (68.6%) 103 (66.9%) 110 (69.6%) 51 (65.4%) Yes 148 (32.2%) 22 (31.4%) 51 (33.1%) 48 (30.4%) 27 (34.6%) HTN 0.754 No 196 (42.6%) 33 (47.1%) 61 (39.6%) 68 (43.0%) 34 (43.6%) Yes 264 (57.4%) 37 (52.9%) 93 (60.4%) 90 (57.0%) 44 (56.4%) Previous MI 0.904 No 405 (88.0%) 61 (87.1%) 137 (89.0%) 140 (88.6%) 67 (85.9%) Yes 55 (12.0%) 9 (12.9%) 17 (11.0%) 18 (11.4%) 11 (14.1%) Apelin-12 0.76 (0.60–1.00) 0.64 (0.56–0.71) 0.58 (0.48–0.66) 1.03 (0.90–1.22) 0.88 (0.82–1.06) <0.001 WBC 10.1± 3.65 9.96± 4.19 10.3± 3.74 9.68± 3.45 10.5± 3.27 0.265 Neutrophils 75.7± 11.5 77.4± 11.2 74.8± 11.8 76.3± 11.7 74.7± 11.0 0.310 Hemoglobin 144± 17.2 145± 17.7 144± 17.1 143± 17.9 143± 15.7 0.848 Platelet 232± 56.3 239± 57.2 230± 56.1 230± 55.4 234± 58.0 0.642 Albumin 38.0 (35.0–41.0) 39.0 (35.0–41.2) 38.0 (35.0–40.9) 38.0 (35.1–40.6) 38.0 (34.0–40.8) 0.636 TC 5.66± 1.09 5.91± 1.22 5.67± 0.99 5.58± 1.13 5.62± 1.08 0.186 TG 0.99 (0.55–1.54) 0.98 (0.52–1.54) 1.10 (0.55–1.75) 0.90 (0.55–1.39) 0.93 (0.58–1.55) 0.441 HDL 1.20± 0.27 1.24± 0.30 1.20± 0.26 1.19± 0.28 1.21± 0.24 0.532 LDL 3.00 (2.49–3.60) 3.22 (2.59–3.84) 3.01 (2.50–3.63) 2.81 (2.40–3.38) 3.18 (2.41–3.89) 0.009 FBG 7.67± 2.54 7.36± 2.38 8.02± 2.66 7.51± 2.49 7.59± 2.47 0.196 Urea nitrogen 6.73± 2.07 6.58± 2.08 6.65± 2.04 6.96± 2.00 6.54± 2.26 0.378 Creatinine 75.0 (62.0–86.0) 86.0 (79.2–90.2) 59.0 (52.0–69.0) 85.6 (80.0–92.5) 65.9 (58.2–71.8) <0.001 Uric acid 337± 73.9 355± 81.6 330± 76.2 342± 69.7 325± 67.4 0.044 eGFR 94.1 (77.8–119) 79.2 (72.4–85.3) 125 (106–145) 76.9 (65.3–84.0) 110 (101–125) <0.001 CK-MB 106 (45.8–195) 94.5 (42.0–172) 106 (48.0–212) 108 (50.0–190) 132 (38.2–194) 0.668 cTnI 13.9 (4.36–29.0) 13.3 (6.04–29.5) 15.5 (5.01–30.0) 13.9 (3.50–27.3) 12.7 (2.98–27.4) 0.701 Pathological Q wave 0.080 No 239 (52.0%) 34 (48.6%) 75 (48.7%) 95 (60.1%) 35 (44.9%) Yes 221 (48.0%) 36 (51.4%) 79 (51.3%) 63 (39.9%) 43 (55.1%) Gensini score 72.1± 32.2 73.0± 33.7 74.5± 32.0 66.9± 31.4 77.2± 31.8 0.069 Culprit vessels 0.029 LAD 230 (50.0%) 42 (60.0%) 76 (49.4%) 80 (50.6%) 32 (41.0%) LCX 72 (15.7%) 9 (12.9%) 30 (19.5%) 15 (9.49%) 18 (23.1%) RCA 158 (34.3%) 19 (27.1%) 48 (31.2%) 63 (39.9%) 28 (35.9%) Stent number 1.38± 0.54 1.37± 0.62 1.32± 0.50 1.43± 0.57 1.38 (0.52) 0.399 For continuous variables, data are expressed as mean and group into the multivariate Cox regression will yield a standard deviation (SD) or median and interquartile range. collinearity effect. For survival analysis, the Kaplan–Meier curves were plotted, and the log-rank test was used for Categorical variables are expressed as frequency (percent- age). Differences between groups were compared using the statistical analysis. To compare the discriminatory power one-way analysis of variance or the chi-square test. between the combination of apelin-12 and eGFR and ei- *e univariate Cox regression analysis was performed ther apelin-12 or eGFR alone, receiver operating charac- to identify potential prognostic factors. Variables with teristic (ROC) curves were constructed. All analyses were p< 0.05 except apelin-12 and eGFR were entered into the performed using R software version 4.0.4 (R Foundation multivariate Cox regression analysis to identify the final for Statistical Computing, Vienna, Austria). Differences factors. Because the variable “Group” was created by the with two-sided p< 0.05 were considered to be statistically levels of apelin and eGFR, putting them along with the significant. 4 Journal of Interventional Cardiology 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 p =0.026 p=0.0095 0.00 0.00 0 10 20 30 0 10 20 30 Number at risk Number at risk Apelin low 224 204 198 156 eGFR low 228 206 197 158 Apelin high 236 221 216 186 eGFR high 232 219 217 184 010 20 30 010 20 30 Follow up time (month) Follow up time (month) Apelin low eGFR low Apelin high eGFR high (a) (b) 1.00 0.75 0.50 0.25 p = 0.00018 0.00 0 10 20 30 Number at risk Group A 70 60 55 40 Group B 154 144 143 116 Group C 158 146 142 118 Group D 78 75 74 68 10 20 30 Follow up time (month) Group A Group C Group B Group D (c) Figure 2: Kaplan–Meier curves for MACE. Kaplan–Meier curves for MACE based on apelin-12 (a), or eGFR (b), or the combination of apelin-12 and eGFR (c). eGFR: estimated glomerular filtration rate; MACE: major adverse cardiac events. these results prompted us to ask whether the combination of 3. Results apelin-12 and eGFR could serve as a better prognostic factor *is study included 460 patients, 118 (25.7%) of whom for patients with STMEI. *erefore, patients were divided experienced MACE during the follow-up period. As shown into four groups based on the median apelin-12 level and in Table 1, the mean (±SD) age of the patients was 62.9± 11.9 eGFR. As shown in Figure 2(c), group D (high apelin-12, years, and the mean (±SD) systolic blood pressure was high eGFR) had the highest survival probability compared 132± 27.2 mmHg. *e majority of patients (76.7%) were with group A (low apelin-12, low eGFR), suggesting that the male. Except for creatinine level, no significant differences combined use of apelin-12 and eGFR served as a better were observed among the four groups in terms of demo- prognostic factor for patients with STEMI than the use of graphic information, medical history, and laboratory test either biomarker alone. results. *e prognostic value of combining apelin-12 and eGFR Patients were divided into two groups according to the was evaluated according to the area under the ROC curve median apelin-12 level or eGFR. As shown in Figure 2(a), (AUC). As shown in Figure 3, the combination of apelin-12 patients with lower apelin-12 levels (<0.76 ng/mL) experi- and eGFR (AUC 0.699) yielded a better predictive value for enced a significantly higher occurrence of MACE than those MACE than either apelin-12 (AUC: 0.617) or eGFR (AUC: with higher levels (p � 0.026). Meanwhile, patients with low 0.596) alone. eGFR (<94.06 mL/min/1.73 m ) had a poorer prognosis than In univariate analyses, age, heart rate, anterior wall myo- those with high eGFR (p � 0.0095) (Figure 2(b)). As such, cardial infarction (MI) history, Killip grade> I, apelin-12, Survival probability Survival probability Survival probability Journal of Interventional Cardiology 5 1.0 0.8 0.6 0.4 Apelin-12 AUC: 0.617 0.2 eGFR AUC: 0.596 Apelin-12& eGFR AUC: 0.699 0.0 0.0 0.5 1.0 1 – Specificity Figure 3: ROC curves for the combination of apelin-12 and eGFR, and either apelin-12 or eGFR alone. eGFR: estimated glomerular filtration rate; ROC: receiver operating characteristic. hemoglobin, total cholesterol, high-density lipoprotein, eGFR, Apelin-12, one of the most potent active forms of apelin, and pathological Q wave were identified as potential prognostic has been widely studied in the cardiovascular system. It has risk factors for MACE (Table 2). Multivariate analyses revealed been reported that the plasma concentration of apelin-12 that age (hazard ratio (HR): 1.03, 95% confidence interval (CI): after acute myocardial infarction (AMI) is significantly lower 1.01 to 1.05; p � 0.0008), anterior wall MI history (HR: 1.57, than that in the control population [15, 16]. Apelin-12 is 95% CI: 1.06 to 2.32; p � 0.0243), TC (HR: 1.23, 95% CI:1.05 to negatively associated with troponin I levels, high-sensitivity 1.44; p � 0.0121), and pathological Q wave (HR: 1.73, 95% CI: C-reactive protein, neutrophil/lymphocyte ratio, and the 1.18 to 2.53; p � 0.0047) were associated with an increased risk rate of MACE, indicating that apelin-12 can serve as a of MACE. Compared with patients in group A, those in group prognostic biomarker for STEMI patients [9, 17]. *is is B (HR: 0.6, 95% CI: 0.37 to 0.98; p � 0.0399), group C (HR: consistent with the results of our study. As shown by the 0.55, 95% CI: 0.34 to 0.89; p � 0.0151), and group D (HR: 0.27, Kaplan–Meier curves, patients with lower apelin-12 levels 95% CI: 0.13 to 0.57; p � 0.0005) had better prognoses (<0.76 ng/mL) exhibited a lower survival probability than those with higher apelin-12 levels. In addition, apelin-12 has (Table 2). *e Gensini score is widely used as an indicator of been confirmed to exert cardioprotective effects in animal coronary artery stenosis degree in clinical settings. models. Pisarenko and his colleagues explored the efficacy of *erefore, scatter plots were generated and Pearson’s apelin-12 in an ischemia/reperfusion model using hearts correlation coefficients were calculated to explore corre- isolated from rats. It was suggested that apelin-12 increased lations between apelin-12, eGFR, and Gensini score. *ere coronary flow and contractile and pump function during was a significant negative correlation between apelin-12 reperfusion in a dose-dependent manner [18]. *e same levels and eGFR (r � −0.32, p< 0.001). *ere was a weak investigator also reported that injection of apelin-12 led to a correlation between the Gensini score and eGFR (r � 0.14, reduction in systolic blood pressure and necrosis markers, p � 0.0021). However, there was no significant correlation including creatinine kinase-MB and lactose dehydrogenase between the Gensini score and apelin-12 (r � -0.028, [19]. p � 0.55) (Figure 4). eGFR is a useful indicator of renal function in clinical practice. It is known that AMI patients with renal impair- ment experience higher MACE rates and have poorer 4. Discussion prognoses [20]. *erefore, eGFR is considered to be an STEMI is a major threat to human health worldwide, and independent predictor of short- and long-term outcomes in prognostic factors have long been explored. In this study, we patients with AMI [21–24]. *e results of our study, in found that both apelin-12 and eGFR were significant factors accordance with those from previous research, indicated that influencing STEMI prognosis. More importantly, the a lower eGFR was associated with a poorer prognosis. More combination of apelin-12 and eGFR could efficiently en- importantly, the additive prognostic value of apelin-12 in hance the predictive power of long-term MACEs in patients combination with eGFR was confirmed in our study. As with STEMI. shown by the Kaplan–Meier curves, patients with both low Sensitivity 6 Journal of Interventional Cardiology Table 2: Univariate and multivariate Cox regression. Univariate Cox Multivariate Cox Variables HR 95% CI p HR 95% CI p Age 1.04 1.02–1.06 <0.001 1.03 1.01–1.05 8.00E-04 Sex Female vs. male 1.27 0.85–1.90 0.240 HR 1.01 1.00–1.02 0.043 1.00 0.99–1.01 0.4481 SBP 1.00 0.99–1.01 0.809 Anterior wall MI Yes vs. no 1.71 1.18–2.47 0.005 1.57 1.06–2.32 0.0243 Killip grade II vs. I 1.89 1.29–2.76 0.001 1.49 0.99–2.24 0.0557 DM Yes vs. no 1.12 0.77–1.63 0.562 HTN Yes vs. no 1.18 0.81–1.70 0.391 Previous MI Yes vs. no 1.53 0.93–2.49 0.091 Apelin-12 0.22 0.11–0.44 <0.001 WBC 1.03 0.98–1.09 0.183 Neutrophils 1.01 0.99–1.03 0.203 Hemoglobin 0.98 0.97–0.99 0.001 0.99 0.98–1.00 0.0944 Platelet 1.00 1.00–1.01 0.080 Albumin 1.00 0.95–1.04 0.853 TC 1.20 1.04–1.40 0.014 1.23 1.05–1.44 0.0121 TG 0.92 0.73–1.16 0.467 HDL 2.11 1.07–4.17 0.031 1.06 0.53–2.11 0.8639 LDL 1.06 0.83–1.35 0.659 FBG 1.00 0.93–1.07 0.922 Urea nitrogen 1.01 0.93–1.10 0.832 Creatinine 1.00 1.00–1.01 0.31 Uric acid 1.00 1.00–1.02 0.647 eGFR 0.99 0.98–1.00 0.004 CK-MB 1.00 1.00–1.03 0.475 cTnI 1.01 1.00–1.03 0.092 Pathological Q wave Yes vs. no 1.72 1.19–2.48 0.004 1.73 1.18–2.53 0.0047 Gensini score 1.00 1.00–1.01 0.141 Culprit vessels LAD ref ref ref LCX 0.88 0.52–1.48 0.621 RCA 0.80 0.53–1.20 0.281 Stent number 0.88 0.62–1.25 0.472 Group Group A Ref Ref Ref Ref Ref Ref Group B 0.49 0.30–0.79 0.003 0.6 0.37–0.98 0.0399 Group C 0.51 0.32–0.83 0.006 0.55 0.34–0.89 0.0151 Group D 0.24 0.12–0.49 <0.001 0.27 0.13–0.57 5.00E-04 eGFR and apelin-12 experienced the worst outcomes. ROC ventricular hypertrophy [25]. *ird, apelin can directly curve analysis revealed that the combination of apelin-12 protect the heart against ischemia/reperfusion injury by and eGFR significantly enhanced the discriminative ability enhancing the expression of endothelial nitric oxide syn- for survival compared with either apelin-12 or eGFR alone. thase and the phosphorylation of ERK1/2 and Akt [26]. *e Potential explanations for the positive prognostic value of pro-angiogenic effects of apelin may also explain its asso- apelin-12 are as follows. First, apelin can reduce mean ar- ciation with better prognosis in patients who experience terial pressure and mean circulatory filling pressure via a STEMI [27]. nitric oxide-dependent mechanism, thus alleviating cardiac Our study showed that there was no correlation between afterload and preload. Second, apelin has been shown to apelin-12 and the degree of coronary artery stenosis indi- increase myocardial contractility by enhancing the sensi- cated by the Gensini score. However, a study by Topuz 2+ tivity of myofilaments to activator Ca , leading to aug- suggested that apelin-12 was negatively correlated with the mentation of cardiac output but without developing left angiographic severity, as assessed according to the SYNTAX Journal of Interventional Cardiology 7 r = -0.028 p = 0.55 200 r = -0.32 p < 0.001 0.0 0.5 1.0 1.5 2.0 0.0 0.5 1.0 1.5 2.0 Apelin-12 (ng/ml) Apelin-12 (ng/ml) (a) (b) r = 0.14 p = 0.0021 50 100 150 200 eGFR (ml/min/1.73m ) (c) Figure 4: Relationships between apelin-12 or eGFR and Gensini score. (a) Relationship between apelin-12 and eGFR. (b) Relationship between apelin-12 and Gensini score. (c) Relationship between eGFR and Gensini score. eGFR: estimated glomerular filtration rate. score [16]. *is discrepancy may be due to the different these two markers can better predict prognosis and guide sample sizes and methods used to assess the degree of personalized treatment for STEMI patients. coronary stenosis. In addition, another study reported that apelin-12 levels were not related to duration or anterior Abbreviations location of ischemia [28]; however, further studies are warranted to confirm these results. AMI: Acute myocardial infarction *is study has several limitations. First, the sample size AUC: Area under the ROC curve of this study was relatively small, especially when the sample CI: Confidence interval was divided into four separate groups. *erefore, the gen- eGFR: Estimated glomerular filtration rate eralization of our conclusions needs further studies. Second, HR: Hazard ratio the outcome of our study only included MACE; other MACEs: Major adverse cardiac events endpoints, such as all-cause mortality or cardiac mortality, PCI: Percutaneous coronary intervention were not analyzed because detailed information was not ROC: Receiver operating characteristic provided in the public database. *ird, many previous STEMI: ST-segment elevation myocardial infarction. studies grouped patients according to the tertile or quartile of eGFR; however, we only divided patients into high and Data Availability low GFR groups based on the median eGFR values. *erefore, we were unable to analyze the relationship be- *e data used in this study can be downloaded from the tween the severity of renal impairment and long-term Dryad database (https://datadryad.org/) using the reference outcomes. number doi.org/10.5061/dryad.pf56m. Clinical data of 464 patients with STEMI were downloaded from Dryad (https:// doi.org/10.5061/dryad.pf56m), a publicly available database 5. Conclusions that houses a large quantity of datasets from published In summary, our study is the first to suggest that both low articles. After removing the data of four patients with apelin-12 levels and low eGFR are associated with poor missing information, this study ultimately included 460 prognosis in patients with STEMI. *e combined use of patients with STEMI from the First People’s Hospital of eGFR(ml/min/1.73m ) GENSINI score GENSINI score 8 Journal of Interventional Cardiology [8] H.-T. Liu, M. Chen, J. Yu, and W. Li, “Serum apelin level Taizhou, Zhejiang, China, who were admitted with STEMI predicts the major adverse cardiac events in patients with ST symptoms between January 2010 and October 2014. elevation myocardial infarction receiving percutaneous cor- onary intervention,” Medicine (Baltimore), vol. 94, no. 4, Ethical Approval Article ID e449, 2015. [9] X. Krasniqi, B. Berisha, M. Gashi, D. Koçinaj, F. Jashari, and *is study was approved by the Second Affiliated Hospital of J. Vincelj, “Influence of apelin-12 on troponin levels and the Nanchang University Medical Research Ethics Committee. rate of MACE in STEMI patients,” BMC Cardiovascular Disorders, vol. 17, no. 1, p. 195, 2017. Conflicts of Interest [10] F. A. Chapman, D. Nyimanu, J. J. Maguire, A. P. Davenport, D. E. Newby, and N. Dhaun, “*e therapeutic potential of *e authors declare that there are no conflicts of interest. apelin in kidney disease,” Nature Reviews Nephrology, vol. 17, no. 12, pp. 840–853, 2021. [11] N. S. Anavekar, J. J. V. McMurray, E. J. Velazquez, and Authors’ Contributions S. D. Solomon, “Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction,” New LY and XHS proposed the concept/design. XHS and CY England Journal of Medicine, vol. 351, no. 13, pp. 1285–1295, analyzed and interpreted the data. LY and LM drafted the manuscript. WYQ critically revised and approved the study. [12] L. Yang, T. Zheng, H. Wu, and W. Xin, “Predictive value of All authors have read and approved the manuscript. Yue Liu apelin-12 in patients with ST-elevation myocardial infarction and Huasong Xia contributed to this work equally. with different renal function: a prospective observational study,” BMJ Open, vol. 7, no. 11, Article ID e018595, 2017. Acknowledgments [13] G. G. Gensini, “A more meaningful scoring system for de- termining the severity of coronary heart disease,” +e *e authors acknowledge Xiaoyu Wu’s team for collecting American Journal of Cardiology, vol. 51, no. 3, p. 606, 1983. and sharing the data and the Dryad database for repositing [14] G. Manjunath, M. J. Sarnak, and A. S. Levey, “Prediction the high-quality data for researchers. *is study was sup- equations to estimate glomerular filtration rate: an update,” ported by the National Natural Science Foundation of China Current Opinion in Nephrology and Hypertension, vol. 10, (No. 82160085) and Jiangxi Provincial Department of Sci- no. 6, pp. 785–792, 2001. [15] R. A. P. Weir, K. S. Chong, J. R. Dalzell, and C. J. Petrie, ence and Technology Foundation (No. 20181BCB24013). “Plasma apelin concentration is depressed following acute myocardial infarction in man,” European Journal of Heart References Failure, vol. 11, no. 6, pp. 551–558, 2009. [16] Y. Wei and B. Wang, “*e expression levels of plasma [1] C. Garc´ıa-Garc´ıa, T. Oliveras, N. El Ouaddi et al., “Short- and dimethylglycine (DMG), human maternally expressed gene 3 long-term mortality trends in STEMI-cardiogenic shock over (MEG3), and Apelin-12 in patients with acute myocardial three decades (1989-2018): the ruti-STEMI-shock Registry,” infarction and their clinical significance,” Annals of Palliative Journal of Clinical Medicine, vol. 9, no. 8, Article ID 2398, Medicine, vol. 10, no. 2, pp. 2175–2183, 2021. [17] M. Topuz, F. Oz, O. Akkus, and O. Sen, “Plasma apelin-12 [2] S. Dharma, H. Andriantoro, I. Dakota, and I. Purnawan, levels may predict in-hospital major adverse cardiac events in “Organisation of reperfusion therapy for STEMI in a devel- ST-elevation myocardial infarction and the relationship be- oping country,” Open Heart, vol. 2, no. 1, Article ID e000240, tween apelin-12 and the neutrophil/lymphocyte ratio in pa- tients undergoing primary coronary intervention,” Perfusion, [3] P. G. Steg, R. J. Goldberg, J. M. Gore et al., “Baseline char- vol. 32, no. 3, pp. 206–213, 2017. acteristics, management practices, and in-hospital outcomes [18] O. I. Pisarenko, V. S. Shulzhenko, Y. A. Pelogeykina, of patients hospitalized with acute coronary syndromes in the I. M. Studneva, and D. N. Khatri, “Apelin-12 improves Global Registry of Acute Coronary Events (GRACE),” +e metabolic and functional recovery of rat heart after global American Journal of Cardiology, vol. 90, no. 4, pp. 358–363, ischemia,” Health, vol. 02, no. 08, pp. 927–934, 2010. [19] O. I. Pisarenko, L. I. Serebryakova, Y. A. Pelogeykina, and [4] T. Jernberg, P. Hasvold, M. Henriksson, H. Hjelm, I. M. Studneva, “In vivo reduction of reperfusion injury to the M. *uresson, and M. Janzon, “Cardiovascular risk in post- heart with apelin-12 peptide in rats,” Bulletin of Experimental myocardial infarction patients: nationwide real world data Biology and Medicine, vol. 152, no. 1, pp. 79–82, 2011. demonstrate the importance of a long-term perspective,” [20] Y. Hashimoto, Y. Ozaki, S. Kan, and K. Nakao, “Impact of European Heart Journal, vol. 36, no. 19, pp. 1163–1170, 2015. chronic kidney disease on in-hospital and 3-year clinical [5] X.-F. Fan, F. Xue, Y.-Q. Zhang, and X.-P Xing, “*e Apelin- outcomes in patients with acute myocardial infarction treated APJ axis is an endogenous counterinjury mechanism in ex- perimental acute lung injury,” Chest, vol. 147, no. 4, by contemporary percutaneous coronary intervention and optimal medical therapy ― insights from the J-MINUET pp. 969–978, 2015. [6] S. Han, E. W. Englander, G. A. Gomez, and G. H. Greeley, study,” Circulation Journal, vol. 85, no. 10, pp. 1710–1718, “Apelin regulates nuclear factor-κB’s involvement in the in- flammatory response of pancreatitis,” Pancreas, vol. 46, no. 1, [21] J.-p. Li, M. Momin, Y. Huo, and C.-Y. Wang, “Renal insuf- ficiency is an independent predictor of in-hospital mortality pp. 64–70, 2017. [7] H. Yasuzaki, S.-I. Yoshida, T. Hashimoto, and W. M. Shibata, for patients with acute myocardial infarction receiving pri- mary percutaneous coronary intervention,” Journal of Zhe- “Involvement of the apelin receptor APJ in Fas-induced liver injury,” Liver International, vol. 33, no. 1, pp. 118–126, 2013. jiang University–Science B, vol. 13, no. 8, pp. 638–644, 2012. Journal of Interventional Cardiology 9 [22] J. E. Sabroe, P. *ayssen, L. Antonsen, M. Hougaard, K. N. Hansen, and L. O. Jensen, “Impact of renal insufficiency on mortality in patients with ST-segment elevation myo- cardial infarction treated with primary percutaneous coronary intervention,” BMC Cardiovascular Disorders, vol. 14, no. 1, p. 15, 2014. [23] C.-h. Wang, S.-y. Zhang, Q. Fang, and Z.-J. Shen, “Renal dysfunction and hsCRP predict long-term outcomes of per- cutaneous coronary intervention in acute myocardial in- farction,” +e American Journal of the Medical Sciences, vol. 349, no. 5, pp. 413–420, 2015. [24] G. Li, G. Qi, B. Zhang, and B. Zhou, “*e dose-response association between estimated glomerular filtration rate and prognosis of patients with ST-segment elevation myocardial infarction from rural areas of China’s Liaoning province,” Medicine (Baltimore), vol. 96, no. 52, Article ID e9508, 2017. [25] E. Ashley, J. Powers, M. Chen, and R. Kundu, “*e endog- enous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo,” Cardiovascular Research, vol. 65, no. 1, pp. 73–82, 2005. [26] X. J. Zeng, L. K. Zhang, H. X. Wang, L. Q. Lu, L. Q. Ma, and C. S. Tang, “Apelin protects heart against ischemia/reperfu- sion injury in rat,” Peptides, vol. 30, no. 6, pp. 1144–1152, [27] D. Tempel, M. de Boer, E. D. van Deel, and R. A Haasdijk, “Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells,” Circulation Research, vol. 111, no. 5, pp. 585–598, 2012. [28] F. Tatin, E. Renaud-Gabardos, A.-C. Godet, and F. Hantelys, “Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction,” JCI Insight, vol. 2, no. 12, p. 2, 2017. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Interventional Cardiology Hindawi Publishing Corporation

Prognostic Value of Combining Apelin-12 and Estimated Glomerular Filtration Rate in Patients with ST-Segment Elevation Myocardial Infarction

Download PDF
9 pages

Loading next page...
 
/lp/hindawi-publishing-corporation/prognostic-value-of-combining-apelin-12-and-estimated-glomerular-RnoTfnOR0g

References (29)

Publisher
Hindawi Publishing Corporation
Copyright
Copyright © 2022 Yue Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN
1540-8183
eISSN
0896-4327
DOI
10.1155/2022/2272928
Publisher site
See Article on Publisher Site

Abstract

Hindawi Journal of Interventional Cardiology Volume 2022, Article ID 2272928, 9 pages https://doi.org/10.1155/2022/2272928 Research Article Prognostic Value of Combining Apelin-12 and Estimated Glomerular Filtration Rate in Patients with ST-Segment Elevation Myocardial Infarction Yue Liu , Huasong Xia, Meng Li, Yi Chen, and Yanqing Wu Department of Cardiology, Second Affiliated Hospital of Nanchang University, No. 1 Mingde Road, Nanchang 330006, Jiangxi, China Correspondence should be addressed to Yanqing Wu; wuyanqing01@sina.com Received 25 January 2022; Revised 25 April 2022; Accepted 27 April 2022; Published 24 June 2022 Academic Editor: Jacek Bil Copyright © 2022 Yue Liu et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Apelin-12 and estimated glomerular filtration rate (eGFR) are considered prognostic factors for ST-segment el- evation myocardial infarction (STEMI). However, little is known about whether the combined use of these two biomarkers could enhance the prognostic value. *is study aimed to investigate the utility of combining apelin-12 and eGFR for STEMI. Methods. Patients were divided into four groups based on median apelin-12 level and eGFR level: A: low apelin-12, low eGFR; B: low apelin- 12, high eGFR; C: high apelin-12, low eGFR; and D: high apelin-12, high eGFR. *e Cox regression was used to identify prognostic factors. *e Kaplan–Meier and the receiver operating characteristic (ROC) curves were generated to evaluate the prognostic value of apelin-12 combined with eGFR in patients with STEMI. Results. Among 460 patients, 118 (25.7%) experienced major adverse cardiac events (MACEs) during the entire follow-up of 30 months. *e Kaplan–Meier curve analysis revealed that group D had the best prognosis compared with the other three groups. *e combination of apelin-12 and eGFR (area under the ROC curve (AUC), 0.699) enhanced the predictive value for MACE compared with either apelin-12 (AUC, 0.617) or eGFR (AUC, 0.596) alone. *ere was a negative association between apelin-12 and eGFR (r � −0.32, p< 0.001), while no association was observed between the Gensini score and apelin-12 or eGFR. Conclusions. *is study suggests that both low apelin-12 (<0.76 ng/ml) and low eGFR (<94.06 mL/min/1.73 m ) are associated with poor prognosis in STEMI, indicating that the combination of apelin-12 and eGFR could enhance the prognostic value of patients with STEMI. major adverse cardiac events (MACEs) after STEMI [4]. 1. Introduction *erefore, it is necessary to identify risk factors associated ST-segment elevation myocardial infarction (STEMI), with the prognosis of patients with STEMI. characterized by cardiomyocyte death due to persistent is- Apelin-12, a member of the apelin family, is a ligand of chemia and hypoxia, is one of the most common and fatal the human orphan G protein-coupled receptor (APJ). It has diseases. Despite the decline in mortality rates in recent years been suggested that the apelin/APJ system plays a critical [1], STEMI remains a significant threat to global health. role in various diseases, including respiratory [5], gastro- According to the Jakarta Acute Coronary Syndrome Registry intestinal [6], and hepatic diseases [7]. Recently, apelin-12 database [2], STEMI accounts for approximately 37% of has also been investigated in cardiovascular diseases. Liu and acute coronary syndrome cases in developing countries, his teammates enrolled 120 patients with STEMI who un- consistent with that reported in a previous study [3]. Al- derwent primary percutaneous coronary intervention (PCI) though considerable advances have been achieved in and were followed up for 12 months. *e authors found that reperfusion therapies and drug treatments, the prognosis of the incidence of MACE was significantly higher in patients patients with STEMI remains far from satisfactory because with low apelin-12 levels than in those with high apelin-12 many patients continue to experience complications and (p< 0.001) [8]. Another observational study suggested that 2 Journal of Interventional Cardiology Patients with initial symptoms of STEMI N = 464 Excluded patients with miss data N = 4 Patients included in the study N = 460 Median apelin and GFR Group A Group B Group C Group D Low apelin Low apelin High apelin High apelin Low GFR High GFR Low GFR High GFR N = 70 N = 154 N = 158 N = 78 Figure 1: Flow chart of the study. patients, and apelin-12 detection have been described pre- the MACE rate was much lower in patients with an apelin-12 level >2.2 ng/mL [9]. *e underlying cardioprotective viously [12]. *e Gensini score was used to assess the severity mechanisms may be that the apelin system promotes va- and extent of coronary artery stenosis, and detailed infor- sodilation, reduces blood pressure in a nitric oxide-de- mation can be referred in the literature [13]. To compare pendent way, increases cardiac contractility, and improves prognosis, patients were initially divided into two groups angiogenesis after myocardial infarction [10]. according to the median levels of apelin-12 or eGFR. Fur- *e estimated glomerular filtration (eGFR) is a useful ther, patients were divided into four groups according to the indicator of quantifying renal function in clinical settings. median apelin-12 level and eGFR level: A (low apelin-12, low *e relationship between lower eGFR and poor outcomes in eGFR (n � 70)); B (low apelin-12, high eGFR (n � 154)); C patients with STEMI has long been established. According to (high apelin-12, low eGFR (n � 158)); and D (high apelin-12, a study by Anavekar, for each reduction in eGFR by 10 units high eGFR (n � 78)). *e flow chart is shown in Figure 1. Because all patient data were anonymized and data analysis below 81.0 mL/min/1.73 m , the risk of death and nonfatal cardiovascular outcomes is increased by 10% [11]. A pre- adhered to the Dryad database rules, neither ethics approval nor patient consent was required for this study. We verified vious study has suggested that apelin-12 has prognostic value in predicting short-term (during hospitalization) and that the sample size is sufficient using PASS software with an long-term (2.5 years) MACE, especially in those with normal alpha of 0.05 and a power of 80%. We estimated a sample eGFR [12]. However, little is known about whether the size of 308 patients, and our study included 460 patients. combination of apelin-12 and eGFR has a better prognostic *e primary endpoint was the occurrence of MACE, value than each biomarker alone. defined as a composite of cardiac death, recurrent target Accordingly, this study aimed to determine whether the vessel-related myocardial infarction, ischemia-driven target combination of apelin-12 and eGFR served as a better lesion revascularization, cardiogenic shock, or congestive prognostic biomarker in patients with STEMI than either heart failure. *e eGFR was calculated using the equation published in the Modification of Diet in Renal Disease study one individually. equation [14]. More specifically, 2. Methods ∧ ∧ GFR � 186.3 × (Scr) − 1.154 × (age) (1) Clinical data of 464 patients with STEMI were downloaded − 0.203 × 0.742(if female). from Dryad (https://doi.org/10.5061/dryad.pf56m), a pub- licly available database that houses a large quantity of Hypertension was defined as blood pressure ≥140/ datasets from published articles. After removing the data of 90 mmHg and/or using antihypertensive drugs. T2DM was four patients with missing information, this study ultimately defined as FPG ≥7.0 mmol/L and/or on medication for included 460 patients with STEMI from the First People’s T2DM. Hospital of Taizhou, Zhejiang, China, who were admitted All patients were followed up for 30 months or until the with STEMI symptoms between January 2010 and October occurrence of MACE. Survival time was calculated from the 2014. *e inclusion and exclusion criteria, therapy process of date of PCI until an adverse event occurred. Journal of Interventional Cardiology 3 Table 1: Characteristics of patients. All patients (N � 460) A (N � 70) B (N � 154) C (N � 158) D (N � 78) p value Age 62.9± 11.9 66.3± 11.1 59.3± 12.1 66.4± 11.1 59.9± 11.1 <0.001 Sex <0.001 Male 353 (76.7%) 48 (68.6%) 137 (89.0%) 99 (62.7%) 69 (88.5%) Female 107 (23.3%) 22 (31.4%) 17 (11.0%) 59 (37.3%) 9 (11.5%) HR 76.9± 17.2 78.7± 18.2 77.4± 16.0 75.9± 18.6 76.6± 15.3 0.694 SBP 132± 27.2 134± 28.8 131± 27.8 131± 27.0 134± 24.7 0.693 Anterior wall MI 0.129 No 231 (50.2%) 29 (41.4%) 74 (48.1%) 81 (51.3%) 47 (60.3%) Yes 229 (49.8%) 41 (58.6%) 80 (51.9%) 77 (48.7%) 31 (39.7%) Killip grade 0.165 I 348 (75.7%) 46 (65.7%) 122 (79.2%) 122 (77.2%) 58 (74.4%) ≥II 112 (24.3%) 24 (34.3%) 32 (20.8%) 36 (22.8%) 20 (25.6%) DM 0.913 No 312 (67.8%) 48 (68.6%) 103 (66.9%) 110 (69.6%) 51 (65.4%) Yes 148 (32.2%) 22 (31.4%) 51 (33.1%) 48 (30.4%) 27 (34.6%) HTN 0.754 No 196 (42.6%) 33 (47.1%) 61 (39.6%) 68 (43.0%) 34 (43.6%) Yes 264 (57.4%) 37 (52.9%) 93 (60.4%) 90 (57.0%) 44 (56.4%) Previous MI 0.904 No 405 (88.0%) 61 (87.1%) 137 (89.0%) 140 (88.6%) 67 (85.9%) Yes 55 (12.0%) 9 (12.9%) 17 (11.0%) 18 (11.4%) 11 (14.1%) Apelin-12 0.76 (0.60–1.00) 0.64 (0.56–0.71) 0.58 (0.48–0.66) 1.03 (0.90–1.22) 0.88 (0.82–1.06) <0.001 WBC 10.1± 3.65 9.96± 4.19 10.3± 3.74 9.68± 3.45 10.5± 3.27 0.265 Neutrophils 75.7± 11.5 77.4± 11.2 74.8± 11.8 76.3± 11.7 74.7± 11.0 0.310 Hemoglobin 144± 17.2 145± 17.7 144± 17.1 143± 17.9 143± 15.7 0.848 Platelet 232± 56.3 239± 57.2 230± 56.1 230± 55.4 234± 58.0 0.642 Albumin 38.0 (35.0–41.0) 39.0 (35.0–41.2) 38.0 (35.0–40.9) 38.0 (35.1–40.6) 38.0 (34.0–40.8) 0.636 TC 5.66± 1.09 5.91± 1.22 5.67± 0.99 5.58± 1.13 5.62± 1.08 0.186 TG 0.99 (0.55–1.54) 0.98 (0.52–1.54) 1.10 (0.55–1.75) 0.90 (0.55–1.39) 0.93 (0.58–1.55) 0.441 HDL 1.20± 0.27 1.24± 0.30 1.20± 0.26 1.19± 0.28 1.21± 0.24 0.532 LDL 3.00 (2.49–3.60) 3.22 (2.59–3.84) 3.01 (2.50–3.63) 2.81 (2.40–3.38) 3.18 (2.41–3.89) 0.009 FBG 7.67± 2.54 7.36± 2.38 8.02± 2.66 7.51± 2.49 7.59± 2.47 0.196 Urea nitrogen 6.73± 2.07 6.58± 2.08 6.65± 2.04 6.96± 2.00 6.54± 2.26 0.378 Creatinine 75.0 (62.0–86.0) 86.0 (79.2–90.2) 59.0 (52.0–69.0) 85.6 (80.0–92.5) 65.9 (58.2–71.8) <0.001 Uric acid 337± 73.9 355± 81.6 330± 76.2 342± 69.7 325± 67.4 0.044 eGFR 94.1 (77.8–119) 79.2 (72.4–85.3) 125 (106–145) 76.9 (65.3–84.0) 110 (101–125) <0.001 CK-MB 106 (45.8–195) 94.5 (42.0–172) 106 (48.0–212) 108 (50.0–190) 132 (38.2–194) 0.668 cTnI 13.9 (4.36–29.0) 13.3 (6.04–29.5) 15.5 (5.01–30.0) 13.9 (3.50–27.3) 12.7 (2.98–27.4) 0.701 Pathological Q wave 0.080 No 239 (52.0%) 34 (48.6%) 75 (48.7%) 95 (60.1%) 35 (44.9%) Yes 221 (48.0%) 36 (51.4%) 79 (51.3%) 63 (39.9%) 43 (55.1%) Gensini score 72.1± 32.2 73.0± 33.7 74.5± 32.0 66.9± 31.4 77.2± 31.8 0.069 Culprit vessels 0.029 LAD 230 (50.0%) 42 (60.0%) 76 (49.4%) 80 (50.6%) 32 (41.0%) LCX 72 (15.7%) 9 (12.9%) 30 (19.5%) 15 (9.49%) 18 (23.1%) RCA 158 (34.3%) 19 (27.1%) 48 (31.2%) 63 (39.9%) 28 (35.9%) Stent number 1.38± 0.54 1.37± 0.62 1.32± 0.50 1.43± 0.57 1.38 (0.52) 0.399 For continuous variables, data are expressed as mean and group into the multivariate Cox regression will yield a standard deviation (SD) or median and interquartile range. collinearity effect. For survival analysis, the Kaplan–Meier curves were plotted, and the log-rank test was used for Categorical variables are expressed as frequency (percent- age). Differences between groups were compared using the statistical analysis. To compare the discriminatory power one-way analysis of variance or the chi-square test. between the combination of apelin-12 and eGFR and ei- *e univariate Cox regression analysis was performed ther apelin-12 or eGFR alone, receiver operating charac- to identify potential prognostic factors. Variables with teristic (ROC) curves were constructed. All analyses were p< 0.05 except apelin-12 and eGFR were entered into the performed using R software version 4.0.4 (R Foundation multivariate Cox regression analysis to identify the final for Statistical Computing, Vienna, Austria). Differences factors. Because the variable “Group” was created by the with two-sided p< 0.05 were considered to be statistically levels of apelin and eGFR, putting them along with the significant. 4 Journal of Interventional Cardiology 1.00 1.00 0.75 0.75 0.50 0.50 0.25 0.25 p =0.026 p=0.0095 0.00 0.00 0 10 20 30 0 10 20 30 Number at risk Number at risk Apelin low 224 204 198 156 eGFR low 228 206 197 158 Apelin high 236 221 216 186 eGFR high 232 219 217 184 010 20 30 010 20 30 Follow up time (month) Follow up time (month) Apelin low eGFR low Apelin high eGFR high (a) (b) 1.00 0.75 0.50 0.25 p = 0.00018 0.00 0 10 20 30 Number at risk Group A 70 60 55 40 Group B 154 144 143 116 Group C 158 146 142 118 Group D 78 75 74 68 10 20 30 Follow up time (month) Group A Group C Group B Group D (c) Figure 2: Kaplan–Meier curves for MACE. Kaplan–Meier curves for MACE based on apelin-12 (a), or eGFR (b), or the combination of apelin-12 and eGFR (c). eGFR: estimated glomerular filtration rate; MACE: major adverse cardiac events. these results prompted us to ask whether the combination of 3. Results apelin-12 and eGFR could serve as a better prognostic factor *is study included 460 patients, 118 (25.7%) of whom for patients with STMEI. *erefore, patients were divided experienced MACE during the follow-up period. As shown into four groups based on the median apelin-12 level and in Table 1, the mean (±SD) age of the patients was 62.9± 11.9 eGFR. As shown in Figure 2(c), group D (high apelin-12, years, and the mean (±SD) systolic blood pressure was high eGFR) had the highest survival probability compared 132± 27.2 mmHg. *e majority of patients (76.7%) were with group A (low apelin-12, low eGFR), suggesting that the male. Except for creatinine level, no significant differences combined use of apelin-12 and eGFR served as a better were observed among the four groups in terms of demo- prognostic factor for patients with STEMI than the use of graphic information, medical history, and laboratory test either biomarker alone. results. *e prognostic value of combining apelin-12 and eGFR Patients were divided into two groups according to the was evaluated according to the area under the ROC curve median apelin-12 level or eGFR. As shown in Figure 2(a), (AUC). As shown in Figure 3, the combination of apelin-12 patients with lower apelin-12 levels (<0.76 ng/mL) experi- and eGFR (AUC 0.699) yielded a better predictive value for enced a significantly higher occurrence of MACE than those MACE than either apelin-12 (AUC: 0.617) or eGFR (AUC: with higher levels (p � 0.026). Meanwhile, patients with low 0.596) alone. eGFR (<94.06 mL/min/1.73 m ) had a poorer prognosis than In univariate analyses, age, heart rate, anterior wall myo- those with high eGFR (p � 0.0095) (Figure 2(b)). As such, cardial infarction (MI) history, Killip grade> I, apelin-12, Survival probability Survival probability Survival probability Journal of Interventional Cardiology 5 1.0 0.8 0.6 0.4 Apelin-12 AUC: 0.617 0.2 eGFR AUC: 0.596 Apelin-12& eGFR AUC: 0.699 0.0 0.0 0.5 1.0 1 – Specificity Figure 3: ROC curves for the combination of apelin-12 and eGFR, and either apelin-12 or eGFR alone. eGFR: estimated glomerular filtration rate; ROC: receiver operating characteristic. hemoglobin, total cholesterol, high-density lipoprotein, eGFR, Apelin-12, one of the most potent active forms of apelin, and pathological Q wave were identified as potential prognostic has been widely studied in the cardiovascular system. It has risk factors for MACE (Table 2). Multivariate analyses revealed been reported that the plasma concentration of apelin-12 that age (hazard ratio (HR): 1.03, 95% confidence interval (CI): after acute myocardial infarction (AMI) is significantly lower 1.01 to 1.05; p � 0.0008), anterior wall MI history (HR: 1.57, than that in the control population [15, 16]. Apelin-12 is 95% CI: 1.06 to 2.32; p � 0.0243), TC (HR: 1.23, 95% CI:1.05 to negatively associated with troponin I levels, high-sensitivity 1.44; p � 0.0121), and pathological Q wave (HR: 1.73, 95% CI: C-reactive protein, neutrophil/lymphocyte ratio, and the 1.18 to 2.53; p � 0.0047) were associated with an increased risk rate of MACE, indicating that apelin-12 can serve as a of MACE. Compared with patients in group A, those in group prognostic biomarker for STEMI patients [9, 17]. *is is B (HR: 0.6, 95% CI: 0.37 to 0.98; p � 0.0399), group C (HR: consistent with the results of our study. As shown by the 0.55, 95% CI: 0.34 to 0.89; p � 0.0151), and group D (HR: 0.27, Kaplan–Meier curves, patients with lower apelin-12 levels 95% CI: 0.13 to 0.57; p � 0.0005) had better prognoses (<0.76 ng/mL) exhibited a lower survival probability than those with higher apelin-12 levels. In addition, apelin-12 has (Table 2). *e Gensini score is widely used as an indicator of been confirmed to exert cardioprotective effects in animal coronary artery stenosis degree in clinical settings. models. Pisarenko and his colleagues explored the efficacy of *erefore, scatter plots were generated and Pearson’s apelin-12 in an ischemia/reperfusion model using hearts correlation coefficients were calculated to explore corre- isolated from rats. It was suggested that apelin-12 increased lations between apelin-12, eGFR, and Gensini score. *ere coronary flow and contractile and pump function during was a significant negative correlation between apelin-12 reperfusion in a dose-dependent manner [18]. *e same levels and eGFR (r � −0.32, p< 0.001). *ere was a weak investigator also reported that injection of apelin-12 led to a correlation between the Gensini score and eGFR (r � 0.14, reduction in systolic blood pressure and necrosis markers, p � 0.0021). However, there was no significant correlation including creatinine kinase-MB and lactose dehydrogenase between the Gensini score and apelin-12 (r � -0.028, [19]. p � 0.55) (Figure 4). eGFR is a useful indicator of renal function in clinical practice. It is known that AMI patients with renal impair- ment experience higher MACE rates and have poorer 4. Discussion prognoses [20]. *erefore, eGFR is considered to be an STEMI is a major threat to human health worldwide, and independent predictor of short- and long-term outcomes in prognostic factors have long been explored. In this study, we patients with AMI [21–24]. *e results of our study, in found that both apelin-12 and eGFR were significant factors accordance with those from previous research, indicated that influencing STEMI prognosis. More importantly, the a lower eGFR was associated with a poorer prognosis. More combination of apelin-12 and eGFR could efficiently en- importantly, the additive prognostic value of apelin-12 in hance the predictive power of long-term MACEs in patients combination with eGFR was confirmed in our study. As with STEMI. shown by the Kaplan–Meier curves, patients with both low Sensitivity 6 Journal of Interventional Cardiology Table 2: Univariate and multivariate Cox regression. Univariate Cox Multivariate Cox Variables HR 95% CI p HR 95% CI p Age 1.04 1.02–1.06 <0.001 1.03 1.01–1.05 8.00E-04 Sex Female vs. male 1.27 0.85–1.90 0.240 HR 1.01 1.00–1.02 0.043 1.00 0.99–1.01 0.4481 SBP 1.00 0.99–1.01 0.809 Anterior wall MI Yes vs. no 1.71 1.18–2.47 0.005 1.57 1.06–2.32 0.0243 Killip grade II vs. I 1.89 1.29–2.76 0.001 1.49 0.99–2.24 0.0557 DM Yes vs. no 1.12 0.77–1.63 0.562 HTN Yes vs. no 1.18 0.81–1.70 0.391 Previous MI Yes vs. no 1.53 0.93–2.49 0.091 Apelin-12 0.22 0.11–0.44 <0.001 WBC 1.03 0.98–1.09 0.183 Neutrophils 1.01 0.99–1.03 0.203 Hemoglobin 0.98 0.97–0.99 0.001 0.99 0.98–1.00 0.0944 Platelet 1.00 1.00–1.01 0.080 Albumin 1.00 0.95–1.04 0.853 TC 1.20 1.04–1.40 0.014 1.23 1.05–1.44 0.0121 TG 0.92 0.73–1.16 0.467 HDL 2.11 1.07–4.17 0.031 1.06 0.53–2.11 0.8639 LDL 1.06 0.83–1.35 0.659 FBG 1.00 0.93–1.07 0.922 Urea nitrogen 1.01 0.93–1.10 0.832 Creatinine 1.00 1.00–1.01 0.31 Uric acid 1.00 1.00–1.02 0.647 eGFR 0.99 0.98–1.00 0.004 CK-MB 1.00 1.00–1.03 0.475 cTnI 1.01 1.00–1.03 0.092 Pathological Q wave Yes vs. no 1.72 1.19–2.48 0.004 1.73 1.18–2.53 0.0047 Gensini score 1.00 1.00–1.01 0.141 Culprit vessels LAD ref ref ref LCX 0.88 0.52–1.48 0.621 RCA 0.80 0.53–1.20 0.281 Stent number 0.88 0.62–1.25 0.472 Group Group A Ref Ref Ref Ref Ref Ref Group B 0.49 0.30–0.79 0.003 0.6 0.37–0.98 0.0399 Group C 0.51 0.32–0.83 0.006 0.55 0.34–0.89 0.0151 Group D 0.24 0.12–0.49 <0.001 0.27 0.13–0.57 5.00E-04 eGFR and apelin-12 experienced the worst outcomes. ROC ventricular hypertrophy [25]. *ird, apelin can directly curve analysis revealed that the combination of apelin-12 protect the heart against ischemia/reperfusion injury by and eGFR significantly enhanced the discriminative ability enhancing the expression of endothelial nitric oxide syn- for survival compared with either apelin-12 or eGFR alone. thase and the phosphorylation of ERK1/2 and Akt [26]. *e Potential explanations for the positive prognostic value of pro-angiogenic effects of apelin may also explain its asso- apelin-12 are as follows. First, apelin can reduce mean ar- ciation with better prognosis in patients who experience terial pressure and mean circulatory filling pressure via a STEMI [27]. nitric oxide-dependent mechanism, thus alleviating cardiac Our study showed that there was no correlation between afterload and preload. Second, apelin has been shown to apelin-12 and the degree of coronary artery stenosis indi- increase myocardial contractility by enhancing the sensi- cated by the Gensini score. However, a study by Topuz 2+ tivity of myofilaments to activator Ca , leading to aug- suggested that apelin-12 was negatively correlated with the mentation of cardiac output but without developing left angiographic severity, as assessed according to the SYNTAX Journal of Interventional Cardiology 7 r = -0.028 p = 0.55 200 r = -0.32 p < 0.001 0.0 0.5 1.0 1.5 2.0 0.0 0.5 1.0 1.5 2.0 Apelin-12 (ng/ml) Apelin-12 (ng/ml) (a) (b) r = 0.14 p = 0.0021 50 100 150 200 eGFR (ml/min/1.73m ) (c) Figure 4: Relationships between apelin-12 or eGFR and Gensini score. (a) Relationship between apelin-12 and eGFR. (b) Relationship between apelin-12 and Gensini score. (c) Relationship between eGFR and Gensini score. eGFR: estimated glomerular filtration rate. score [16]. *is discrepancy may be due to the different these two markers can better predict prognosis and guide sample sizes and methods used to assess the degree of personalized treatment for STEMI patients. coronary stenosis. In addition, another study reported that apelin-12 levels were not related to duration or anterior Abbreviations location of ischemia [28]; however, further studies are warranted to confirm these results. AMI: Acute myocardial infarction *is study has several limitations. First, the sample size AUC: Area under the ROC curve of this study was relatively small, especially when the sample CI: Confidence interval was divided into four separate groups. *erefore, the gen- eGFR: Estimated glomerular filtration rate eralization of our conclusions needs further studies. Second, HR: Hazard ratio the outcome of our study only included MACE; other MACEs: Major adverse cardiac events endpoints, such as all-cause mortality or cardiac mortality, PCI: Percutaneous coronary intervention were not analyzed because detailed information was not ROC: Receiver operating characteristic provided in the public database. *ird, many previous STEMI: ST-segment elevation myocardial infarction. studies grouped patients according to the tertile or quartile of eGFR; however, we only divided patients into high and Data Availability low GFR groups based on the median eGFR values. *erefore, we were unable to analyze the relationship be- *e data used in this study can be downloaded from the tween the severity of renal impairment and long-term Dryad database (https://datadryad.org/) using the reference outcomes. number doi.org/10.5061/dryad.pf56m. Clinical data of 464 patients with STEMI were downloaded from Dryad (https:// doi.org/10.5061/dryad.pf56m), a publicly available database 5. Conclusions that houses a large quantity of datasets from published In summary, our study is the first to suggest that both low articles. After removing the data of four patients with apelin-12 levels and low eGFR are associated with poor missing information, this study ultimately included 460 prognosis in patients with STEMI. *e combined use of patients with STEMI from the First People’s Hospital of eGFR(ml/min/1.73m ) GENSINI score GENSINI score 8 Journal of Interventional Cardiology [8] H.-T. Liu, M. Chen, J. Yu, and W. Li, “Serum apelin level Taizhou, Zhejiang, China, who were admitted with STEMI predicts the major adverse cardiac events in patients with ST symptoms between January 2010 and October 2014. elevation myocardial infarction receiving percutaneous cor- onary intervention,” Medicine (Baltimore), vol. 94, no. 4, Ethical Approval Article ID e449, 2015. [9] X. Krasniqi, B. Berisha, M. Gashi, D. Koçinaj, F. Jashari, and *is study was approved by the Second Affiliated Hospital of J. Vincelj, “Influence of apelin-12 on troponin levels and the Nanchang University Medical Research Ethics Committee. rate of MACE in STEMI patients,” BMC Cardiovascular Disorders, vol. 17, no. 1, p. 195, 2017. Conflicts of Interest [10] F. A. Chapman, D. Nyimanu, J. J. Maguire, A. P. Davenport, D. E. Newby, and N. Dhaun, “*e therapeutic potential of *e authors declare that there are no conflicts of interest. apelin in kidney disease,” Nature Reviews Nephrology, vol. 17, no. 12, pp. 840–853, 2021. [11] N. S. Anavekar, J. J. V. McMurray, E. J. Velazquez, and Authors’ Contributions S. D. Solomon, “Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction,” New LY and XHS proposed the concept/design. XHS and CY England Journal of Medicine, vol. 351, no. 13, pp. 1285–1295, analyzed and interpreted the data. LY and LM drafted the manuscript. WYQ critically revised and approved the study. [12] L. Yang, T. Zheng, H. Wu, and W. Xin, “Predictive value of All authors have read and approved the manuscript. Yue Liu apelin-12 in patients with ST-elevation myocardial infarction and Huasong Xia contributed to this work equally. with different renal function: a prospective observational study,” BMJ Open, vol. 7, no. 11, Article ID e018595, 2017. Acknowledgments [13] G. G. Gensini, “A more meaningful scoring system for de- termining the severity of coronary heart disease,” +e *e authors acknowledge Xiaoyu Wu’s team for collecting American Journal of Cardiology, vol. 51, no. 3, p. 606, 1983. and sharing the data and the Dryad database for repositing [14] G. Manjunath, M. J. Sarnak, and A. S. Levey, “Prediction the high-quality data for researchers. *is study was sup- equations to estimate glomerular filtration rate: an update,” ported by the National Natural Science Foundation of China Current Opinion in Nephrology and Hypertension, vol. 10, (No. 82160085) and Jiangxi Provincial Department of Sci- no. 6, pp. 785–792, 2001. [15] R. A. P. Weir, K. S. Chong, J. R. Dalzell, and C. J. Petrie, ence and Technology Foundation (No. 20181BCB24013). “Plasma apelin concentration is depressed following acute myocardial infarction in man,” European Journal of Heart References Failure, vol. 11, no. 6, pp. 551–558, 2009. [16] Y. Wei and B. Wang, “*e expression levels of plasma [1] C. Garc´ıa-Garc´ıa, T. Oliveras, N. El Ouaddi et al., “Short- and dimethylglycine (DMG), human maternally expressed gene 3 long-term mortality trends in STEMI-cardiogenic shock over (MEG3), and Apelin-12 in patients with acute myocardial three decades (1989-2018): the ruti-STEMI-shock Registry,” infarction and their clinical significance,” Annals of Palliative Journal of Clinical Medicine, vol. 9, no. 8, Article ID 2398, Medicine, vol. 10, no. 2, pp. 2175–2183, 2021. [17] M. Topuz, F. Oz, O. Akkus, and O. Sen, “Plasma apelin-12 [2] S. Dharma, H. Andriantoro, I. Dakota, and I. Purnawan, levels may predict in-hospital major adverse cardiac events in “Organisation of reperfusion therapy for STEMI in a devel- ST-elevation myocardial infarction and the relationship be- oping country,” Open Heart, vol. 2, no. 1, Article ID e000240, tween apelin-12 and the neutrophil/lymphocyte ratio in pa- tients undergoing primary coronary intervention,” Perfusion, [3] P. G. Steg, R. J. Goldberg, J. M. Gore et al., “Baseline char- vol. 32, no. 3, pp. 206–213, 2017. acteristics, management practices, and in-hospital outcomes [18] O. I. Pisarenko, V. S. Shulzhenko, Y. A. Pelogeykina, of patients hospitalized with acute coronary syndromes in the I. M. Studneva, and D. N. Khatri, “Apelin-12 improves Global Registry of Acute Coronary Events (GRACE),” +e metabolic and functional recovery of rat heart after global American Journal of Cardiology, vol. 90, no. 4, pp. 358–363, ischemia,” Health, vol. 02, no. 08, pp. 927–934, 2010. [19] O. I. Pisarenko, L. I. Serebryakova, Y. A. Pelogeykina, and [4] T. Jernberg, P. Hasvold, M. Henriksson, H. Hjelm, I. M. Studneva, “In vivo reduction of reperfusion injury to the M. *uresson, and M. Janzon, “Cardiovascular risk in post- heart with apelin-12 peptide in rats,” Bulletin of Experimental myocardial infarction patients: nationwide real world data Biology and Medicine, vol. 152, no. 1, pp. 79–82, 2011. demonstrate the importance of a long-term perspective,” [20] Y. Hashimoto, Y. Ozaki, S. Kan, and K. Nakao, “Impact of European Heart Journal, vol. 36, no. 19, pp. 1163–1170, 2015. chronic kidney disease on in-hospital and 3-year clinical [5] X.-F. Fan, F. Xue, Y.-Q. Zhang, and X.-P Xing, “*e Apelin- outcomes in patients with acute myocardial infarction treated APJ axis is an endogenous counterinjury mechanism in ex- perimental acute lung injury,” Chest, vol. 147, no. 4, by contemporary percutaneous coronary intervention and optimal medical therapy ― insights from the J-MINUET pp. 969–978, 2015. [6] S. Han, E. W. Englander, G. A. Gomez, and G. H. Greeley, study,” Circulation Journal, vol. 85, no. 10, pp. 1710–1718, “Apelin regulates nuclear factor-κB’s involvement in the in- flammatory response of pancreatitis,” Pancreas, vol. 46, no. 1, [21] J.-p. Li, M. Momin, Y. Huo, and C.-Y. Wang, “Renal insuf- ficiency is an independent predictor of in-hospital mortality pp. 64–70, 2017. [7] H. Yasuzaki, S.-I. Yoshida, T. Hashimoto, and W. M. Shibata, for patients with acute myocardial infarction receiving pri- mary percutaneous coronary intervention,” Journal of Zhe- “Involvement of the apelin receptor APJ in Fas-induced liver injury,” Liver International, vol. 33, no. 1, pp. 118–126, 2013. jiang University–Science B, vol. 13, no. 8, pp. 638–644, 2012. Journal of Interventional Cardiology 9 [22] J. E. Sabroe, P. *ayssen, L. Antonsen, M. Hougaard, K. N. Hansen, and L. O. Jensen, “Impact of renal insufficiency on mortality in patients with ST-segment elevation myo- cardial infarction treated with primary percutaneous coronary intervention,” BMC Cardiovascular Disorders, vol. 14, no. 1, p. 15, 2014. [23] C.-h. Wang, S.-y. Zhang, Q. Fang, and Z.-J. Shen, “Renal dysfunction and hsCRP predict long-term outcomes of per- cutaneous coronary intervention in acute myocardial in- farction,” +e American Journal of the Medical Sciences, vol. 349, no. 5, pp. 413–420, 2015. [24] G. Li, G. Qi, B. Zhang, and B. Zhou, “*e dose-response association between estimated glomerular filtration rate and prognosis of patients with ST-segment elevation myocardial infarction from rural areas of China’s Liaoning province,” Medicine (Baltimore), vol. 96, no. 52, Article ID e9508, 2017. [25] E. Ashley, J. Powers, M. Chen, and R. Kundu, “*e endog- enous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo,” Cardiovascular Research, vol. 65, no. 1, pp. 73–82, 2005. [26] X. J. Zeng, L. K. Zhang, H. X. Wang, L. Q. Lu, L. Q. Ma, and C. S. Tang, “Apelin protects heart against ischemia/reperfu- sion injury in rat,” Peptides, vol. 30, no. 6, pp. 1144–1152, [27] D. Tempel, M. de Boer, E. D. van Deel, and R. A Haasdijk, “Apelin enhances cardiac neovascularization after myocardial infarction by recruiting aplnr+ circulating cells,” Circulation Research, vol. 111, no. 5, pp. 585–598, 2012. [28] F. Tatin, E. Renaud-Gabardos, A.-C. Godet, and F. Hantelys, “Apelin modulates pathological remodeling of lymphatic endothelium after myocardial infarction,” JCI Insight, vol. 2, no. 12, p. 2, 2017.

Journal

Journal of Interventional Cardiology – Hindawi Publishing Corporation

Published: Jun 24, 2022

There are no references for this article.