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ORIGINAL ARTICLE
Year : 2018  |  Volume : 6  |  Issue : 2  |  Page : 66-71

Evaluation of short-term outcomes of impaired creatinine clearance in patients with acute coronary syndromes: A prospective cohort study at tertiary care center


1 Department of Cardiology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Division of Cardiology, Christchurch Hospital, Christchurch, New Zealand
3 Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication19-Jun-2018

Correspondence Address:
Pravesh Vishwakarma
Department of Cardiology, King George's Medical University, Lucknow - 226 007, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_9_18

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  Abstract 


Background: Chronic kidney disease is commonly seen in patients presenting with acute coronary syndrome (ACS), and it has been shown to have poor outcomes. We evaluated the prevalence of impaired creatinine clearance and its impact on short-term clinical outcomes in patients admitted with ACS without prior documented chronic renal disease.
Materials and Methods: The present study was an observational, prospective cohort study conducted at a tertiary care center in North India. In patients admitted with a diagnosis of ACS, glomerular filtration rate was estimated (eGFR) by the Modification of Diet in Renal Disease Study Equation. Patients with eGFR <90 mL/min were taken as study group and those with values >90 mL/min comprised control group. The study group was further categorized into three subgroups on the basis of eGFR (<30 mL/min; 30–59 mL/min; 60–89 ml/min). The primary outcomes compared between study and control group were major adverse cardiac event (MACE) (composite of death, reinfarction, congestive heart failure, cardiogenic shock, and arrhythmia). The secondary outcome measures were individual components of primary outcome.
Results: Among the 200 enrolled patients with ACS, the prevalence of impaired creatinine clearance was 29.5%. The study cohort had higher rates of MACE (28.8 vs. 9.2%, P ≤≤ 0.0001), in-hospital mortality (13.6 vs. 3.5%, P = 0.009), and overall mortality (15.3 vs. 5.1%, P = 0.014) as compared to control group. However, the 30-day mortality was not significantly different. The MACE in the study subgroups was higher in eGFR 30–60 mL/min (odds ratio [OR] 3.97) subgroup followed by eGFR <30 mL/min (OR 3.04) and eGFR 60–90 mL/min (OR 1.38). Using eGFR <90 mL/min as cutoff (as compared to serum creatinine [SCr] >1.5 mg/dl) enhances the ability to predict death by 33% and MACE events by 143%. The OR for predicting death with various cutoff of eGFR was as follows: eGFR <30 ml/min – 3.61, eGFR: 30–60 ml/min – 4.2 and eGFR: 60–90 ml/min – 0.5.
Conclusion: Almost one-third of the patients presenting with ACS have impaired creatinine clearance. Patients with impaired creatinine clearance have worse outcome in hospital vis-a-vis their contemporary groups with normal eGFR. eGFR is a better risk assessment parameter than SCr for predicting MACE and overall mortality in ACS patients.

Keywords: Acute coronary syndrome, estimated glomerular filtration rate, impaired renal function, major adverse cardiac event, serum creatinine


How to cite this article:
Pradhan A, Jain N, Vishwakarma P, Sethi R, Narain VS, Dwivedi SK, Saran R K, Yadav SC, Puri A, Bajpai J. Evaluation of short-term outcomes of impaired creatinine clearance in patients with acute coronary syndromes: A prospective cohort study at tertiary care center. Heart India 2018;6:66-71

How to cite this URL:
Pradhan A, Jain N, Vishwakarma P, Sethi R, Narain VS, Dwivedi SK, Saran R K, Yadav SC, Puri A, Bajpai J. Evaluation of short-term outcomes of impaired creatinine clearance in patients with acute coronary syndromes: A prospective cohort study at tertiary care center. Heart India [serial online] 2018 [cited 2018 Jul 20];6:66-71. Available from: http://www.heartindia.net/text.asp?2018/6/2/66/234665




  Introduction Top


Chronic kidney disease (CKD) is strongly associated with very high mortality rates and accelerated cardiovascular disease (CVD).[1] The main concern for individuals with CKD is the incidence of cardiovascular events, including coronary heart disease, CVD, and peripheral vascular disease. Today, it is well established that in patients receiving renal replacement therapy, the relative risk of dying from cardiac causes increases by a factor of 10–100, depending on age.[2] A recent meta-analysis provided strong evidence that individuals with renal insufficiency experience a 1.4 to 3.7-fold increased risk for CVD mortality compared with their counterparts without renal insufficiency. Despite strong evidence linking CKD to worse outcomes, however, the impact of CKD on mortality and morbidity in patients with acute coronary syndrome (ACS) is probably underappreciated, and patients with CKD receiving acute cardiac care may not be treated as aggressively or with evidence-based therapies as frequently as those with normal renal function.

It has only recently been recognized, however, that even minor renal dysfunction, as reflected by an increase in urinary albumin excretion or a decrease in glomerular filtration rate, is an independent CV risk factor in addition to the known risk factors assessed by the Framingham score.[3],[4],[5] Because of the high prevalence of minor renal dysfunction in the general population, such recent insights have enormous public health relevance.

The present study was undertaken to evaluate the prevalence of impaired creatinine clearance and its impact on short-term clinical outcomes that include death and major adverse cardiac event (MACE) in patients with ACS. In addition, we intend to explore prognostic factors of ACS in relation to severity of impaired creatinine clearance.


  Materials and Methods Top


A total of 200 patients of ACS admitted to the cardiology department of a tertiary care center enrolled after written as well as informed consent [Figure 1]. ACS was defined by the WHO [3] and was classified as related or not related to ST-segment elevation on the basis of the presence or absence of at least 1 mm of ST-segment elevation in two or more contiguous leads on initial electrocardiography. Location of acute myocardial infarction (AMI) was classified as anterior, inferior, or other. Since patients often develop multiple symptoms before seeking care, we defined AMI onset as the time at which care was sought. The use of adjunctive therapy during hospitalization was recorded. Killip's classification was defined at admission.[4] Left ventricular ejection fraction (LVEF) was recorded by echocardiography (modified Simpson's). The presence of conventional CV risk factors namely diabetes, hypertension, smoking, and tobacco intake was also determined.
Figure 1: The distribution of patients according to estimated glomerular filtration rate

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Renal function was assessed by the estimated glomerular filtration rate (eGFR) using the abbreviated Modification of Diet in Renal Disease Study Equation:[5]

eGFR = 186 × SCr −1.154 × age −0.203 × (0.742 if female)

Patients with eGFR >90 ml/min were taken as control group (Group II) and those with eGFR <90 ml/min were enrolled for analysis in the study group (Group I). Following the National Kidney Foundation Guidelines,[6] we stratified the study population into three groups according to eGFR as follows: group IA – eGFR: 60–89 mL/min; Group IB – eGFR: 30–59 mL/min; and Group IC – eGFR <30 mL/min.

Primary outcome was defined as occurrence of MACE i.e. composite of death from any cause, reinfarction, congestive heart failure, cardiogenic shock, and arrhythmia at 30 days. Deaths were categorized as In-hospital mortality (deaths during the course of hospital stay) and 30-day mortality (deaths within 30 days of discharge). Congestive heart failure was defined as the development of heart failure during hospitalization or follow up requiring intravenous diuretics and ventilatory support. Hemodynamically significant arrhythmias were considered those requiring DC cardioversion or temporary transvenous pacing. Cardiogenic shock was defined according to standard criteria (Ref). The secondary outcome measures were individual components of primary outcome. Clinical and/or telephonic follow-up were scheduled at 30 days for adverse clinical events. Parameters were compared between the study and control groups, and further comparison was made between different subgroups of the study group. In the last, sensitivity analysis for the prediction of outcome with eGFR and serum creatinine (SCr) was performed. Patients with documented CKD, sepsis, active systemic infections and malignancy were excluded from the study.

Statistical analysis

The statistical analysis was done using Statistical Package for the Social Sciences Version 18.0 (SPSS Inc., Chicago, IL, USA). The data were represented in number, percentages, and mean ± standard deviation. Chi-square test was used for nonparametric variables. The test for significance used for parametric variables was the Student's t-test and ANOVA. A P< 0.05 was considered statistically significant.


  Results Top


Baseline profile

Of 200 patients of ACS, 59 (29.5%) had impaired creatinine clearance (eGFR <90 ml/min); hence, the prevalence of impaired creatinine clearance in our study was 29.5%. [Table 1] shows a comparison of clinical, demographic, and angiographic characteristics in both groups according to the eGFR. There was a significant difference between both groups with respect to age, diabetes, hypertension, thrombolysis in myocardial infarction (TIMI) score, and LVEF. Rest of the parameters were similar in both the groups. The mean age of subjects in Group I (study group) was higher as compared to Group II (64.56 ± 9.94 vs. 53.84 ± 11.01 years, P < 0.001). Diabetes and hypertension were significantly higher in the study group. Among non-ST-segment elevation myocardial infarction (NSTEMI)/USA patients, mean TIMI scores were found to be significantly higher in study group as compared to control group (P = 0.030). More patients were in higher Killip's class (II–IV) at presentation to the hospital in study group compared to ACS patients with normal eGFR (42%/7%, P < 0.001). The mean LVEF was significantly lower in patients of impaired creatinine clearance than in control group (44.96 ± 8.82, 52.40 ± 9.59, P < 0.001). Among angiographic characteristics compared between two groups, left anterior descending artery was the most commonly involved artery in both the groups, but the proportion of right coronary artery involvement was significantly higher in the study group as compared to control group (P = 0.010).
Table 1: Demographic, clinical characteristics and angiographic profile in between study group and control group

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Outcome analysis

The primary outcome event defined by MACE was significantly higher in the study group (28.8% vs 9.2%, P < 0.0001). All individual secondary outcomes were also significantly higher in the study group, except 30-day mortality which was not significant among groups [Table 2].
Table 2: The primary and secondary outcomes compared between study and control group

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Subgroup analysis

The study group was further stratified into three subgroups based upon eGFR values. Majority of patients (n = 29, 49.1%) had eGFR in the range of 30–60 ml/min (Group IB) followed by Group IA (n = 21, 35.5%), and Group IC (n = 9, 15.2%). There was no significant difference found in terms of baseline characteristics. The primary and secondary outcomes were also not different in various subgroups of low eGFR. A nonsignificant higher incidence of in-hospital deaths in Group IB (eGFR: 30–60 mL/min) was seen. The MACE rates were similar in Group IC and IB but were higher in comparison to Group IA although the values did not reach statistical significance.

Predictive efficacy of estimated glomerular filtration rate

This study also tried to find out the predictive efficacy of abnormal eGFR (<90 ml/min) as well as abnormal SCr (>1.5 mg/ml) for MACE and overall mortality, as shown in [Table 3] and [Figure 2]. eGFR had better sensitivity albeit at the cost of lower specificity compared to SCr for the prediction of MACE and death. For prediction of death using the eGFR <90 mL/min criteria, the ability to locate true-positive cases for poor outcome enhances by 33% (SCr >1.5 mg/dl detects only 6 cases, while eGFR <90 mL/min detects 9 cases). Using eGFR <90 ml/min, the ability to predict MACE enhances by 143% (an abnormal SCr predicted 7 cases where 17 events occurred with abnormal eGFR).
Table 3: The predictive efficacy of following variables for major adverse cardiac event and overall death

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Figure 2: Predictive value of abnormal estimated glomerular filtration rate and abnormal serum creatinine for adverse cardiovascular events at 30 days

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  Discussion Top


Our study revealed that around 30% patients admitted with ACS had impaired creatinine clearance (defined by an eGFR <90 ml/min). Further characterizing the study group into subgroups, most of the patients had eGFR between 30 and 60 mL/min (49.1%), comprising 14.5% of the total patients. Around 4.5% patients of ACS had eGFR <30 mL/min. These were patients without any documented evidence of abnormal renal function in the past as such patients were excluded from the study.

The data are in concordance with the study by Goldenberg et al.[7] where the prevalence of renal dysfunction measured by eGFR was 31.8%. Mehran et al.[8] in their substudy of ACUITY trial found the prevalence to be 19.1%. El-Menyar et al.[9] found higher prevalence of renal dysfunction as calculated by measuring eGFR. In their study, the prevalence of various grades of renal dysfunction was 5%, 20%, and 43%. Kang et al.[10] also found a higher prevalence of renal dysfunction and the prevalence of various grades of renal dysfunction was 8.7%, 27.7%, and 40.5%, respectively.

The most striking as well as alarming observation was that the study cohort had higher rates of in-hospital mortality (13.6% vs. 3.5%), MACE (28.8% vs 9.2%), and 30-day overall mortality (15.3 vs. 5.1%). All these comparisons were statistically significant. Goldenberg et al.[7] also had found similar significantly higher rates of in-hospital (5.4%) and 30-day (7.2%) case fatality compared with patients without CKD (1.1% and 1.7%, respectively; P < 0.001 for both). Age difference between the study and control group was significant (64.56 ± 9.94 vs. 53.78 ± 11.1; P < 0.001), and its contribution in higher mortality and MACE in the study group could not be underestimated. In other words, higher age is related to decrease eGFR and higher event rates. With regard to the type of ACS at presentation, STEMI was the major type of presentation in both the groups being about two-third in each case. Within the STEMI cohort anterior wall MI was again the predominant type. Hence, the study population was a high-risk cohort with predominant anterior STEMI. Within the NSTEMI/USA group almost in all but two patients, biomarker-positive NSTEMI was the predominant form of presentation. Again, biomarker positivity has also consistently been shown to be associated with worse outcomes in NSTEMI/USA.

The Killip's class on admission was also significantly higher in the study group, with two-third of patients in Killip's Class ≥2 whereas less than 10% of control group were in Killip's Class ≥2. Interestingly, within the STEMI cohort, more nonthrombolyzed patients presented with impaired creatinine clearance (80% vs. 70%) although the difference was not statistically significant. It is well known that STEMI patients who are nonthrombolyzed or thrombolyzed late are at increased risk of CV events as compared to those in whom patency of culprit vessel is promptly restored by early fibrinolysis. Within the NSTEMI cohort, the TIMI score at presentation was significantly higher in the study group vis-a-vis the controls. With regard to prevalence of risk factors, the study cohort had significantly higher rates of diabetes and hypertension, both of which are well-known predictors and perpetuators of renal dysfunction. Beattie et al.,[11] in their study, found that the comorbidities of patients with STEMI and CKD (mean creatinine = 2.7 mg/dl) included older age (mean 70.2 years), diabetes (38.1%), and prior heart failure (23.2%). Santopinto et al.,[12] who analyzed data of Global Registry of Acute Coronary Events (GRACE) study, also reported that patients with moderate or severe renal dysfunction were older, were more likely to be women, and presented to participating hospitals with more comorbidities than those with normal or minimally impaired renal function.

The mean LVEF was significantly lower in the study cohort as compared to control group (44.9% ± 8.8% vs. 52.4% ± 9.6%). Angiographic data showed higher likelihood of finding at least one totally occluded major epicardial coronary artery in the study group.

With the study group, the subgroup of eGFR <30 mL/min had higher mean age and greater proportion of females. STEMI was the predominant form of presentation with anterior wall MI tending to predominate with declining eGFR. With declining eGFR, the thrombolysis rates also went down with almost none of patients of STEMI with eGFR <30 ml/min being thrombolyzed. Prevalence of diabetes and hypertension was also higher in tertiles of lowest eGFR. With declining eGFR, there was also a trend toward lower LVEF, higher TIMI score, and Killip's class though not statistically significant. There was also a trend toward higher in-hospital mortality, MACE, 30-day overall mortality in lower two subgroups of eGFR as compared to subgroup of eGFR of higher one.

When various clinical and demographic variables were compared for association with adverse outcomes in terms of death only, eGFR <90 ml/min and SCr were statistically significant predictors. The odds ratio (OR) for predicting death with various cutoff of eGFR was as follows: eGFR <30 ml/min – 3.61, eGFR: 30–60 ml/min – 4.2 and eGFR: 60–90 ml/min – 0.5. Santopinto et al. analyzed the data of the prospective, multicenter, observational GRACE study and found that patients with moderate renal dysfunction were twice as likely to die (OR 2.09, 95% confidence interval [CI] 1.55–2.81) and those with severe renal dysfunction almost four times more likely to die (OR 3.71, 95% CI 2.57–5.37) after adjustment for other potentially confounding variables.

In our study, eGFR <90 mL/min had sensitivity of 56.3%, specificity of 73%, positive predictive value (PPV) of 15.3%, and negative predictive value (NPV) of 95% for predicting overall death in the study population. Similarly, eGFR <60 mL/min had sensitivity of 50%, specificity of 84%, PPV of 21%, and NPV of 95%. SCr >1.5 mg/dl had sensitivity of 37.5%, specificity of 87.5%, PPV of 20.7, and NPV of 94%. Using eGFR <90 mL/min, the ability to predict poor outcomes of overall death enhances by 33% (as compared with SCr >1.5 mg/dl).

Analysis of various clinical and demographic parameters for the association with MACE events revealed that age, female sex, and eGFR were the only significant predictors. The MACE in the subgroup of the study group was higher in eGFR – 30–60 mL/min (OR 3.97) subgroup followed by eGFR – <30 mL/min (OR 3.04) and eGFR – 60–90 mL/min (OR 1.38). The present study showed that eGFR <90 ml/min for the prediction MACE in study group had a sensitivity, specificity, PPV, and NPV of 56.7%, of 75.3%, 28.8%, and 91%, respectively. Similarly, eGFR <60 ml/min had sensitivity of 43.3%, specificity of 85.3%, PPV of 34%, and NPV of 89.5%. SCr >1.5 had sensitivity of 23.3%, specificity of 87%, PPV of 24, and NPV of 86.5%. Using eGFR <90 ml/min, the ability to predict MACE enhances by 143% (as compared with SCr >1.5 mg/dl). The study is limited by a small number of the subjects and confounding variables such as age, patients with impaired renal functions had less chance to get revascularisation therapy, and more commonly had other risk factors associated with it. Nevertheless, the study showed poor short-term outcome in ACS with renal function.


  Conclusions Top


We conclude that given the high prevalence of impaired creatinine clearance in ACS and adverse short-term outcomes in the cohort with eGFR <90 ml/min, the measurement of eGFR needs to compulsorily be incorporated into risk prediction scores used for prognostication. The widely used and recommended TIMI score and GRACE scores do not incorporate eGFR as one of their variables. To identify and risk stratify high-risk patients who are at increased risk of events and hence would logically benefit from an early invasive therapy, eGFR needs to be incorporated into routine assessment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. Kidney disease as a risk factor for development of cardiovascular disease: A statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation 2003;108:2154-69.  Back to cited text no. 1
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Killip T 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 1967;20:457-64.  Back to cited text no. 4
    
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Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function – Measured and estimated glomerular filtration rate. N Engl J Med 2006;354:2473-83.  Back to cited text no. 5
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National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-266.  Back to cited text no. 6
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Goldenberg I, Subirana I, Boyko V, Vila J, Elosua R, Permanyer-Miralda G, et al. Relation between renal function and outcomes in patients with non-ST-segment elevation acute coronary syndrome: Real-world data from the European public health outcome research and indicators collection project. Arch Intern Med 2010;170:888-95.  Back to cited text no. 7
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Mehran R, Nikolsky E, Lansky AJ, Kirtane AJ, Kim YH, Feit F, et al. Impact of chronic kidney disease on early (30-day) and late (1-year) outcomes of patients with acute coronary syndromes treated with alternative antithrombotic treatment strategies: An ACUITY (Acute catheterization and urgent intervention triage strategy) substudy. JACC Cardiovasc Interv 2009;2:748-57.  Back to cited text no. 8
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El-Menyar A, Zubaid M, Sulaiman K, Singh R, Al Thani H, Akbar M, et al. In-hospital major clinical outcomes in patients with chronic renal insufficiency presenting with acute coronary syndrome: Data from a registry of 8176 patients. Mayo Clin Proc 2010;85:332-40.  Back to cited text no. 9
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Kang YU, Jeong MH, Kim SW. Impact of renal dysfunction on clinical outcomes of acute coronary syndrome. Yonsei Med J 2009;50:537-45.  Back to cited text no. 10
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Beattie JN, Soman SS, Sandberg KR, Yee J, Borzak S, Garg M, et al. Determinants of mortality after myocardial infarction in patients with advanced renal dysfunction. Am J Kidney Dis 2001;37:1191-200.  Back to cited text no. 11
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Santopinto JJ, Fox KA, Goldberg RJ, Budaj A, Piñero G, Avezum A, et al. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: Findings from the global registry of acute coronary events (GRACE). Heart 2003;89:1003-8.  Back to cited text no. 12
    


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