Journals | Policy | Permission

Journal of Clinical Medicine Research

Original Article

Volume 8, Number 4, April 2016, pages 325-330

The Impact of Admission Serum Creatinine Derived Estimated Glomerular Filtration Rate on Major Adverse Cardiac Events in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Chronic kidney disease (CKD) is a significant and independent cause of cardiovascular adverse events and mortality in general population and patients with cardiovascular diseases [1-4]. Additionally, in many studies, it has shown that any degree of renal impairment assessed by estimated glomerular filtration rate (eGFR) is related to increased adverse cardiovascular outcomes and predicts in-hospital, short- and long-term mortality in acute coronary syndrome (ACS) and general population [5-8]. Decreased renal function assessed by eGFR predicts prognosis in both genders in ST-segment elevation myocardial infarction (STEMI) [9]. In STEMI patients undergoing primary percutaneous coronary intervention (PCI), poor myocardial perfusion and increased no-reflow phenomenon were detected in patients with decreased eGFR [10, 11]. Two recent studies have shown relation between decreased eGFR and increased burden of atherosclerosis and decreased left ventricular ejection fraction (EF) in various forms of ACSs [12, 13]. Renal dysfunction is associated with female gender, older age, hypertension (HT), and diabetes mellitus (DM) [7]. These factors are linked with worse clinical outcomes.

In the present study, we investigated the relation between admission serum creatine (Cr) derived eGFR and in-hospital and long-term adverse cardiac events in STEMI patients undergoing primary PCI.

This retrospective observational single-centered study was conducted between May 2009 and 2011. Patients presenting with STEMI undergoing primary PCI were enrolled. Patients with unstable angina, non-STEMI and STEMI that did not undergo primary PCI were excluded. The European Society Cardiology/American College of Cardiology Foundation/American Heart Association (ESC/ACCF/AHA) committee advisement of ECG criteria was used for diagnosis of STEMI [14, 15]. These were definitive new bundle branch block or > 0.1 mV new ST elevation in two contiguous leads. The procedures were conducted by a highly experienced staff (performing > 75 PCIs/year), in a high volume center (> 3,000 PCIs/year).

Following the diagnosis of STEMI, the blood samples were obtained from the patients at the emergency department. The eGFR was calculated from these initial blood samples.

Cockroft-Gault (C-G) equation: C-G = ((140 - age) × weight (kg))/((72 × creatinine) × (0.85 if female)) was used for eGFR [16]. Patients were classified into four categories according to the eGFR (< 60, 60 - < 90, 90 - < 120, and ≥ 120 mL/min/1.73 m²).

Baseline demographic data were collected from the medical records. The left ventricular EF was measured just before discharge. The modified Simpson’s method was used for measurement via a System V (Vingmed, GE, Horten, Norway) [17].

The written informed consent was obtained from all patients and hospital local ethic committee approved the study protocol.

All coronary angiographies and primary PCIs were performed via the femoral approach. The infarct related artery was graded by using thrombolysis in myocardial infarction (TIMI) classification [18]. The coronary artery stenosis was assumed as significant if stenosis was > 50% of diameter. The primary PCI was applied just to the infarct related artery. Following the diagnosis of STEMI, prior to primary PCI, all patients were loaded with 300 mg clopidogrel and 300 mg aspirin (unless contraindicated). Due to payment strategy of the Minister of Health, ticagrelor and prasugrel were not used. No statin loading was applied before primary PCI. After the revealing of the coronary anatomy, all patients were administered 100 U/kg heparin. Following the procedure, patients were transferred to the coronary care unit. Intravenous heparin (500 U/h) or subcutaneous low molecular heparin (enoxaparin) (1 mg/kg/day) was maintained in coronary care unit. Certain medications, e.g. aspirin 100 mg/day, clopidogrel 75 mg/day, rosuvastatin 20 mg/day or atorvastatin 40 mg/day, angiotensin converting enzyme inhibitor or angiotensin receptor blocker, and beta-blockers were administered according to the hemodynamic status of the patients. Glycoprotein IIb/IIIa receptor blocker (e.g. tirofiban) was used according to the burden of the thrombus on visual assessment.

The Killip clinical examination was used for definition of patient clinical condition at presentation. HT was defined if a patient was on an antihypertensive treatment or requiring an antihypertensive drug in hospital. Any patient on an oral anti-diabetic drug and/or insulin was assumed to be diabetic. Major adverse cardiac events (MACEs) consisted of cardiovascular mortality, re-infarction and target vessel revascularization (TVR). Re-infarction was defined by ST-segment elevation along with at least two-fold increase in serum creatine kinase-myocardial band (CK-MB) fraction activity.

All quantitative variables were expressed as mean ± standard deviation (SD), and qualitative variables were expressed as percent (%). Comparison of parametric values between four groups was performed using the one-way ANOVA test. Non-parametric values between four groups were analyzed using the Mann-Whitney U test. Categorical variables were compared by the Chi-square test or Fisher’s exact test. Stepwise, multivariate Cox regression analysis, which included variables with a P value of less than 0.1, was performed to identify independent predictors. Age, gender, history, duration of hospitalization, left ventricular EF, volume, CK-MB, potassium, percent of stenosis, diameter and length of the stent, HT, and admission Cr were included in the model. A two-sided P value of less than 0.05 was considered statistically significant. All statistical studies were carried out with SPSS program (version 15.0, SPSS, Chicago, IL, USA).

A total of 884 patients (113 female) undergoing primary PCI were enrolled to the study. Patients with renal dysfunction were often more female and older (P < 0.001 and P < 0.001) (Table 1). Even though patients with eGFR < 60 mL/min/1.73 m² were more diabetic and hypertensive, this did not reach statistical significance (P = 0.137 and P = 0.072). The history of coronary artery disease and smoking did not differ between groups. With respect to laboratory findings, leucocyte count, CK-MB, admission glucose, and potassium levels were higher in the eGFR < 60 mL/min/1.73 m² group (P = 0.004, P < 0.001, P < 0.001, and P < 0.001, respectively). The left ventricular EF significantly differed between groups (P < 0.001). Patients with eGFR < 60 mL/min/1.73 m² group hospitalized longer (P = 0.004).

Click to view

Table 1. Demographics of All Patients by Estimated Glomerular Filtration Rate

In-hospital complications, including shock, ventricular arrhythmias, inotropic usage, atrial fibrillation, and intra-aortic balloon pump (IABP) usage were significantly different between groups (P < 0.001, P = 0.012, P < 0.001, P < 0.001, and P < 0.001, respectively) (Table 2). In-hospital MACE majorly driven by in-hospital mortality was significantly higher in eGFR < 60 mL/min/1.73 m² group (P < 0.001 and P < 0.001, respectively). Even though the number was small, in-hospital stroke occurred more frequently in eGFR < 60 mL/min/1.73 m² group (P = 0.07). Short- and long-term stent thrombosis and TVR were similar between groups (P = 0.133, P = 0.369, P = 0.464, and P = 0.247, respectively). Long-term MACE was higher in eGFR < 60 mL/min/1.73 m² group and was driven by mortality and re-infarction (P = 0.028, P = 0.046, and P = 0.026, respectively).

Click to view

Table 2. In-Hospital and Long-Term Events of All Patients by Glomerular Filtration Rate

The unadjusted and adjusted models of logistic regression analysis for mortality according to eGFR are listed in Table 3. The mortality had the highest rates at eGFR < 60 mL/min/1.73 m² level and had 7.78 times higher mortality rates (95% CI: 0.91 - 66.8) than eGFR > 120 mL/min/1.73 m², which had the lowest rates as reference. After adjusted regression analysis, eGFR < 60 mL/min/1.73 m² still had a 2.92 times higher mortality rate (95% CI: 0.23 - 36.8).

Click to view

Table 3. Logistic Regression Models for In-Hospital Mortality by Estimated Glomerular Filtration Rate

The present study demonstrated that any degree of renal impairment is associated with increased in-hospital and long-term mortality and MACE in patients presenting with STEMI undergoing primary PCI. Also, patients with renal impairment had lower left ventricular EF and higher cardiac enzyme. On the other hand, no relation was found between stent thrombosis and renal impairment for short- and long-term period.

Serum Cr level solely did not predict the severity of renal function. Even serum Cr level could stay in normal range until moderate and severe renal impairment developed [2, 7]. That is why eGFR was used for prediction of renal dysfunction. Generally, modification of diet in renal disease (MDRD) formula was used for prediction of eGFR in previous studies and in clinical practice [2, 7]. In our previous study, we found that C-G derived eGFR predicts worse prognosis better than MDRD in STEMI [19]. This was a major difference between present and previous studies.

It was demonstrated that renal impairment is more frequently associated with HT and DM in addition to older age and female gender [7]. These clinical factors are associated with poor prognosis in acute MI [7]. Even though in the present study patients with renal impairment are mostly female, older and more frequently had HT and DM, after multivariate regression analysis, eGFR derived renal impairment is still prognostic in STEMI patients undergoing primary PCI.

The relation between CKD and cardiovascular mortality is well known [1-3]. Several different studies have shown that even mild degree of renal impairment is related with increased adverse outcomes in normal population and patients with cardiac disease. A similarly designed study with the present one shows that an eGFR < 30 mL/min/1.73 m² is associated with increased in-hospital and 1-year mortality [20]. In the present study, we show that long-term mortality and adverse events are sustained beyond 2 years. And also regression analysis showed that mild degree of renal impairment is related with adverse events. There are some potential explanations why renal impairment is associated with worse outcomes. Firstly, it has shown that as eGFR decreased, fibroblast and parathyroid hormone levels increased. As a result, vitamin D and phosphate metabolisms are deteriorated which leads to vascular dysfunction and coronary artery disease [6, 21, 22]. Secondly, potential explanation is that renal impairment is associated with enhanced pro-coagulant state, increased homocysteine levels, and endothelial dysfunction that eventually lead to atherosclerotic plaque formation and destabilization [2, 23]. A recent study by Duran et al showed that mild and moderate renal impairment is associated with increased atherosclerosis burden [13].

Another important finding of our study was that as left ventricular EF decreased, eGFR also decreased. Also, CK-MB level was highest in the eGFR < 60 mL/min/1.73 m² group. In a recent study, Sonmez et al found that in patients with STEMI undergoing primary PCI, an eGFR < 60 mL/min/1.73 m² is associated with lower left ventricular EF and larger myocardial infarct size [12].

Some other findings of the present study were in accordance with the previous studies. The hospitalization duration was longer in lowest eGFR group as in Alfaleh et al’s study, probably as a result of increased in-hospital adverse events [24]. Previous reports indicated that the risk of stroke increases with renal impairment [24, 25]. Even though the number of stroke was low, in the present study, there was a significant inverse relation with eGFR and stroke.

In the present study, the rate of stent thrombosis did not differ significantly between groups. There are different results in previous studies in regard of different types of stents. In a study performed by Miao et al, CKD, in elective DES implantation patients, was associated with increased stent thrombosis [26]. Another study that excluded STEMI patients showed that in patients with eGFR < 60 mL/min/1.73 m², DES usage is not associated with stent thrombosis but reduced myocardial infarction and rate of repeat revascularization [27]. Similar to Wang et al’s study, Toutouzas et al showed that new generation DES did not increase the rate of stent thrombosis in CKD patients [28]. Another study performed with bare metal stents showed an inverse relation between renal dysfunction and neo-intima formation after BMS deployment. In that study the neo-intima intravascular ultrasound showed greater lipid volume, suggesting atherosclerosis development [29]. In the present study, BMS was deployed for stent implantation. For BMS, restenosis rather than thrombosis is a concern [30]. Probably this could be the explanation why no difference of stent thrombosis was found between groups.

The present study had several limitations. Firstly, this study was retrospective and single-centered. Secondly, just the effect of admission Cr derived eGFR was used for assessment. Thirdly, the impact of in-hospital medication on prognosis and eGFR was not assessed. Fourthly, the standard method of renal function assessment, 24 h Cr clearance, was not performed.

In conclusion, the present study demonstrated that any degree of renal impairment and especially eGFR < 60 mL/min/1.73 m² was associated with increased in-hospital and long-term mortality and MACE and decreased left ventricular EF. C-G derived eGFR is a simple, easily bedside applicable method of renal impairment for risk stratification in STEMI patients undergoing primary PCI.

Conflict of Interest

The authors declare no conflicts of interest with respect to the research, authorship, and/or publication of this article.

1. Akkaya E, Ayhan E, Uyarel H, Ergelen M, Turer A, Demirci D, Cicek G, et al. [The impact of chronic kidney disease on in-hospital clinical outcomes in patients undergoing primary percutaneous angioplasty for ST-segment elevation myocardial infarction]. Turk Kardiyol Dern Ars. 2011;39(4):276-282.
   doi pubmed
2. Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285-1295.
   doi pubmed
3. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073-2081.
   doi
4. Blasco L, Sanjuan R, Carbonell N, Solis MA, Puchades MJ, Torregrosa I, Miguel JA. Estimated Glomerular Filtration Rate in Short-Risk Stratification in Acute Myocardial Infarction. Cardiorenal Med. 2011;1(2):131-138.
   doi pubmed
5. Campbell NG, Varagunam M, Sawhney V, Ahuja KR, Salahuddin N, De Palma R, Rothman MT, et al. Mild chronic kidney disease is an independent predictor of long-term mortality after emergency angiography and primary percutaneous intervention in patients with ST-elevation myocardial infarction. Heart. 2012;98(1):42-47.
   doi pubmed
6. Oh SW, Baek SH, Kim YC, Goo HS, Heo NJ, Na KY, Chae DW, et al. Mild decrease in estimated glomerular filtration rate and proteinuria are associated with all-cause and cardiovascular mortality in the general population. Nephrol Dial Transplant. 2012;27(6):2284-2290.
   doi pubmed
7. Kim JY, Jeong MH, Ahn YK, Moon JH, Chae SC, Hur SH, Hong TJ, et al. Decreased Glomerular Filtration Rate is an Independent Predictor of In-Hospital Mortality in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention. Korean Circ J. 2011;41(4):184-190.
   doi pubmed
8. Donfrancesco C, Palleschi S, Palmieri L, Rossi B, Lo Noce C, Pannozzo F, Spoto B, et al. Estimated glomerular filtration rate, all-cause mortality and cardiovascular diseases incidence in a low risk population: the MATISS study. PLoS One. 2013;8(10):e78475.
   doi pubmed
9. Damman P, Kikkert WJ, Woudstra P, Kuijt WJ, Grundeken MJ, Harskamp RE, Baan J, et al. Gender difference in the prognostic value of estimated glomerular filtration rate at admission in ST-segment elevation myocardial infarction: a prospective cohort study. BMJ Open. 2012;2(2):e000322.
   doi pubmed
10. Celik T, Iyisoy A, Yuksel CU, Kilic S, Yilmaz MI, Akgul EO, Jata B, et al. Impact of admission glomerular filtration rate on the development of poor myocardial perfusion after primary percutaneous intervention in patients with acute myocardial infarction. Coron Artery Dis. 2008;19(8):543-549.
    doi pubmed
11. Kurtul A, Murat SN, Yarlioglues M, Duran M, Celik IE, Kilic A. Mild to Moderate Renal Impairment Is Associated With No-Reflow Phenomenon After Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction. Angiology. 2015;66(7):644-651.
    doi pubmed
12. Sonmez O, Vatankulu MA, Tasal A, Bacaksiz A, Ayhan S, Yazici HU, Karakaya E, et al. Does estimated glomerular filtration rate have an effect on left ventricular function after ST-elevation myocardial infarction? Echocardiography. 2014;31(3):318-324.
    doi pubmed
13. Duran M, Uysal OK, Gunebakmaz O, Baran O, Turfan M, Ornek E, Cetin M, et al. Glomerular filtration rate is associated with burden of coronary atherosclerosis in patients with acute coronary syndrome. Angiology. 2014;65(4):350-356.
    doi pubmed
14. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Katus HA, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012;33(20):2551-2567.
    doi pubmed
15. Colaco R, Reay P, Beckett C, Aitchison TC, McFarlane PW. False positive ECG reports of anterior myocardial infarction in women. J Electrocardiol. 2000;33(Suppl):239-244.
    doi pubmed
16. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
    doi
17. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2(5):358-367.
    doi
18. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation. 1987;76(1):142-154.
    doi pubmed
19. Ekmekci A, Uluganyan M, Gungor B, Tufan F, Cekirdekci EI, Ozcan KS, Erer HB, et al. Comparison of Cockcroft-Gault and modification of diet in renal disease formulas as predictors of cardiovascular outcomes in patients with myocardial infarction treated with primary percutaneous coronary intervention. Angiology. 2014;65(9):838-843.
    doi pubmed
20. Tsai TH, Yeh KH, Sun CK, Yang CH, Chen SM, Hang CL, Chen CJ, et al. Estimated glomerular filtration rate as a useful predictor of mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. Am J Med Sci. 2013;345(2):104-111.
    doi pubmed
21. Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Demirkaya E, Eyileten T, et al. FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int. 2010;78(7):679-685.
    doi pubmed
22. Naito K, Anzai T, Yoshikawa T, Anzai A, Kaneko H, Kohno T, Takahashi T, et al. Impact of chronic kidney disease on postinfarction inflammation, oxidative stress, and left ventricular remodeling. J Card Fail. 2008;14(10):831-838.
    doi pubmed
23. Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA, Tracy RP, Furberg CD, et al. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation. 2003;107(1):87-92.
    doi pubmed
24. AlFaleh HF, Alsuwaida AO, Ullah A, Hersi A, AlHabib KF, AlShahrani A, AlNemer K, et al. Glomerular filtration rate estimated by the CKD-EPI formula is a powerful predictor of in-hospital adverse clinical outcomes after an acute coronary syndrome. Angiology. 2012;63(2):119-126.
    doi pubmed
25. Wannamethee SG, Shaper AG, Perry IJ. Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke. Stroke. 1997;28(3):557-563.
    doi pubmed
26. Miao Y, Yu-Jie Z, Zhi-Jian W, Dong-Mei S, Yu-Yang L, Ying-Xin Z, Fei G, et al. Chronic kidney disease and the risk of stent thrombosis after percutaneous coronary intervention with drug-eluting stents. Catheter Cardiovasc Interv. 2012;80(3):361-367.
    doi pubmed
27. Wang ZJ, Harjai KJ, Shenoy C, Gao F, Shi DM, Liu YY, Zhao YX, et al. Drug-eluting stents versus bare-metal stents in patients with decreased GFR: a meta-analysis. Am J Kidney Dis. 2013;62(4):711-721.
    doi pubmed
28. Toutouzas K, Patsa C, Synetos A, Karanasos A, Karampelas J, Tsiamis E, Spanos A, et al. The impact of new generation drug-eluting stent implantation on patients with chronic kidney disease and a single lesion in the proximal segment of the left anterior descending artery. Hellenic J Cardiol. 2011;52(2):103-110.
    pubmed
29. Hayano S, Ishii H, Ichimiya S, Kanashiro M, Watanabe J, Suzuki S, Yoshikawa D, et al. Renal dysfunction and atherosclerosis of the neointima following bare metal stent implantation. Am J Nephrol. 2013;38(1):58-65.
    doi pubmed
30. Yoshida T, Sakata K, Nitta Y, Taguchi T, Kaku B, Katsuda S, Shimojima M, et al. Short- and long-term benefits of drug-eluting stents compared to bare metal stents even in treatment for large coronary arteries. Heart Vessels. 2015.
    doi

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Clinical Medicine Research is published by Elmer Press Inc.