Accurate risk stratification for contrast-induced nephropathy (CIN) is important for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We aimed to compare the prognostic value of validated risk scores for CIN. We prospectively enrolled 422 consecutive patients with STEMI undergoing PPCI. Mehran; Gao; Chen; age, serum creatinine (SCr), or glomerular filtration rate, and ejection fraction (ACEF or AGEF); and Global Registry for Acute Coronary Events risk scores were calculated for each patient. The prognostic accuracy of the 6 scores for CIN, and in-hospital and 3-year all-cause mortality and major adverse clinical events (MACEs), was assessed using the c-statistic for discrimination and the Hosmer–Lemeshow test for calibration. CIN was defined as either CIN-narrow (increase in SCr ≥0.5 mg/dl) or CIN broad (≥0.5 mg/dl and/or a ≥25% increase in baseline SCr). All risk scores had relatively high predictive values for CIN-narrow (c-statistic: 0.746 to 0.873) and performed well for prediction of in-hospital death (0.784 to 0.936), MACEs (0.685 to 0.763), and 3-year all-cause mortality (0.655 to 0.871). The ACEF and AGEF risk scores had better discrimination and calibration for CIN-narrow and in-hospital outcomes. However, all risk score exhibited low predictive accuracy for CIN-broad (0.555 to 0.643) and 3-year MACEs (0.541 to 0.619). In conclusion, risk scores for predicting CIN perform well in stratifying the risk of CIN-narrow, in-hospital death or MACEs, and 3-year all-cause mortality in patients with STEMI undergoing PPCI. The ACEF and AGEF risk scores appear to have greater prognostic value.
Contrast-induced nephropathy (CIN) occurs more frequently after primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). CIN incidence has been reported to be as high as 28%. Furthermore, CIN is strongly associated with late renal and cardiovascular adverse events. However, excluding periprocedural hydration and the use of small amounts of low-osmolality contrast media, few agents have proved to be effective for CIN. Therefore, accurate identification of patients having the highest risk of CIN will facilitate closer monitoring and swift intervention. With the increasing adoption of PPCI as a primary method for achieving reperfusion and the increasing risk of CIN in patients with STEMI, a number of risk scores for evaluating CIN risk have been developed and validated. One of the earliest validated scores was the Mehran risk score, incorporating clinical and angiographic characteristics. Alternative risk scores include the age, serum creatinine (SCr), or estimated glomerular filtration rate (eGFR), and ejection fraction (ACEF or AGEF) ; the Global Registry for Acute Coronary Events (GRACE) ; and recent risk scores by Chen and Gao. However, limited data exist comparing the predictive value of various risk scores in patients with STEMI with PPCI. We aimed to compare the performance of different risk scores in risk stratification for CIN and long-term outcomes in these patients.
Methods
This study prospectively enrolled a series of consecutive patients with STEMI who underwent PPCI at Guangdong General Hospital, from March 2010 to October 2012. Acute STEMI was defined as the presence of typical chest pain and accompanying symptoms for ≥30 minutes but <12 hours in the presence of ST-segment elevation ≥1 mm in at least 2 continuous leads or a new or undetermined duration of left branch bundle block with ≥2 times increase in cardiac enzymes (troponin I or T). Patients were excluded if they were pregnant, had an allergy to the contrast medium (CM), had been exposed to CM within the previous 7 days, treated with nephroprotective drugs (e.g., N-acetylcysteine and sodium bicarbonate) or nephrotoxic drugs (e.g., steroid or nonsteroidal anti-inflammatory drugs), had severe hepatic insufficiency, or severe chronic disease.
The study protocol was approved by the Ethics Committee of Guangdong General Hospital and performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from most patients before the procedure; in some cases, next of kin were involved in the process of giving informed consent in patients undergoing PPCI, who were unable to sign an informed consent form themselves.
The level of SCr was measured at admission (before PPCI) and on days 1, 2, and 3 after the procedure. Serum blood urea nitrogen, plasma cardiac troponin I, creatine kinase-MB, and electrolyte levels were measured at admission. Serum levels of albumin, lipid profiles (total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein), and other standard clinical parameters were measured within 24 hours after the procedure. In addition, the eGFR was calculated using the 4-variable Modification of Diet in Renal Disease equation for Chinese patients. The left ventricular EF (LVEF) was evaluated by echocardiography in all patients within 24 hours after admission.
All patients were treated according to our institute’s protocol and the American Heart Association/American College of Cardiology guidelines. PPCI was performed by a 24-hour on-call interventional team, using standard clinical practice and techniques. Nonionic, low-osmolality CM (either Iopamiron, BRACCO, Guangzhou, China, or Ultravist Bayer, Guangzhou, China, both 370 mg I/ml) was used in all patients. Hydration with intravenous normal saline solution was initiated during the procedure and maintained until 6 to 12 hours after completion of the procedure. The hydration rate was 1 ml/kg/hour or 0.5 ml/kg/hour if the LVEF was <40%.
All eligible patients received aspirin (300 mg) and clopidogrel (300 or 600 mg) before PCI. After the procedure, dual antiplatelet therapy (aspirin, 100 mg/day; clopidogrel, 75 mg/day) was administered for at least 12 months after implantation of drug-eluting stents. Prescription of anticoagulants, glycoprotein IIb/IIIa inhibitors, β blockers, angiotensin-converting enzyme inhibitors, or inotropic drug support was given as appropriate by the coronary care unit cardiologists, in accordance with clinical protocols based on interventional guidelines.
Risk scores were calculated from the initial clinical history, laboratory values, and PCI procedure ( Table 1 ). For comparison of differences among risk scores, we classified patients into risk categories according to the tertiles from data presented in this study. Patients in tertiles I, II, and III were defined as low-, moderate- and high-risk patient populations, respectively.
| Scores | Variables | Score | Scores | Variables | Score |
|---|---|---|---|---|---|
| Mehran score | Age >75 years | 4 | GRACE score | Age | |
| Anemia ∗ | 3 | <30 | 0 | ||
| Diabetes mellitus | 3 | 30-39 | 8 | ||
| Chronic heart failure | 5 | 40-49 | 25 | ||
| Intra-aortic balloon pump | 5 | 50-59 60-69 | 41 58 | ||
| Hypotension | 5 | 70-79 | 75 | ||
| Contrast media volume | 1 | 80-89 ≥90 | 91 100 | ||
| Serum creatinine >1.5 mg/dL | 4 | Heart rate (beats/min) <50 | 0 | ||
| Chen score | Age ≥70 years | 4 | 50-69 | 3 | |
| History of myocardial infarction | 5 | 70-89 90-109 | 9 15 | ||
| Diabetes mellitus | 4 | 110-149 | 24 | ||
| Hypotension | 6 | 150-199 | 38 | ||
| Left ventricular ejection fraction ≤ 45% | 4 | >200 Systolic blood pressure(mm Hg) | 46 | ||
| Anemia ∗ | 3 | <80 | 58 | ||
| Estimated glomerular filtration rate <60 mL/min/1.73 m 2 | 7 | 80-99 100-119 120-139 | 53 43 34 | ||
| High density lipoprotein-cholesterol <1 mmol/L | 3 | 140-159 160-199 >200 Creatinine(mg/dl) | 24 10 0 | ||
| Urgent percutaneous coronary intervention | 3 | 0-0.39 0.4-0.79 | 1 4 | ||
| Gao score | Age > 60 years | 2 | 0.8-1.19 | 7 | |
| Hypertension | 2 | 1.2-1.59 | 10 | ||
| Acute myocardial infarction | 2 | 1.6-1.99 2-3.99 | 13 21 | ||
| Heart failure | 2 | >4 | 28 | ||
| Use of intra-aortic balloon pump | 4 | Killip’s classification I | 0 | ||
| Estimated glomerular filtration rate | II III | 20 39 | |||
| 89 to 70 | 1 | IV | 59 | ||
| 69 to 50 | 2 | Cardiac arrest at admission | 39 | ||
| 49 to 30 | 3 | Increased cardiac markers | 14 | ||
| <30 | 6 | ST-Segment deviation | 28 | ||
| Contrast media volume | AGEF score | Age/Left ventricular ejection fraction (%)+1, if Estimated glomerular filtration rate < 60 mL/min/1.73 m 2 | |||
| 100 to 300 | 1 | ||||
| 300 | 3 | ||||
| ACEF score | Age/Left ventricular ejection fraction (%)+1, if serum creatinine >2.0 mg/dl | ||||
∗ Anemia defined as baseline hematocrit 39% for men and 36% for women.
The primary study end point was the occurrence of CIN, defined as either CIN-narrow (increase in SCr ≥0.5 mg/dl) or CIN-broad (increase in SCr ≥0.5 mg/dl and/or a ≥25% increase in baseline SCr) occurring within 48 to 72 hours after CM exposure. The secondary end point was the occurrence of major adverse clinical events (MACEs), including all-cause of mortality, renal replacement therapy, nonfatal MI, target vessel revascularization, and cerebrovascular events during the observation period of hospitalization and follow-up. All patients included in the study were followed up by trained nurses through office visits or telephone interviews for at least 3 years.
Continuous variables are described as mean ± SD, and categorical variables are described as frequency and percentage. Incidences of CIN, and in-hospital death or MACEs were compared among risk categories, as previously described for each of the risk scores, using the chi-square tests. Score performances were evaluated based on discrimination and calibration. Discrimination, a measure of how well the model can separate cases from controls, was evaluated with receiver operating characteristic curves and expressed by the c-statistic. Differences in discrimination power between the 6 scores were compared using the MedCalc statistical software (MedCalc Software bvba, version 12.7.10, Ostend, Belgium). Calibration is a measure of how well predicted probabilities fit actual risks. The most widely used method for this analysis is the Hosmer–Lemeshow test. The cumulative mortality hazard and incidence of MACEs during follow-up was analyzed using the Kaplan–Meier method, and statistical assessment was performed using the log-rank test. SPSS software, version 16.0 (SPSS Inc, Chicago, Illinois) was used for all analyses. All statistical tests were 2-tailed, and statistical significance was accepted at p <0.05.
Results
A total of 422 consecutive patients (age: 62.48 ± 12.45 years) with STEMI were included in the present study. Baseline characteristics, medications, procedural variables, and the mean of all risk scores are presented in Table 2 . Of the entire cohort, 15.2% patients were women, 49.3% had hypertension, 22% had diabetes mellitus, and 35.1% had anemia. Complete follow-up was achieved in 91.6% of patients (35 patients were lost to follow-up). The overall incidence of CIN was 7.3% for CIN-narrow and 23.2% for CIN-broad. All-cause mortality was 4.0% in-hospital and 5.4% at 3 years, whereas the incidence of MACEs was 17.8% in-hospital and 23.7% at 3 years. When allocating patients to stratified risk groups (low, moderate, and high) according to the 6 risk scores, a significant positive correlation was observed between all in-hospital outcomes (CIN-narrow, in-hospital all-cause mortality, and MACEs) and increasing risk score; however, this relation did not hold true for CIN-broad ( Figure 1 ).
| Variables | |
|---|---|
| Age (years) | 62.5 ± 12.5 |
| Age>75 years | 71 (16.8%) |
| Female | 64 (15.2%) |
| Systolic blood pressure (mmHg) | 122.2 ± 19.8 |
| Diastolic blood pressure (mmHg) | 72.9 ± 11.6 |
| Heart rate (bpm) | 77.8 ± 14.3 |
| Diabetes Mellitus | 93 (22%) |
| Smoker | 213 (50.5%) |
| Hypertension | 208 (49.3%) |
| Prior myocardial infraction | 20 (4.7%) |
| Coronary artery bypass graft | 5 (1.2%) |
| Pre-procedural serum creatinine (μmol/L) | 94.5 ± 42.8 |
| Pre-procedural estimated glomerular filtration rate (mL/min/1.73m 2 ) | 83.4 ± 28.1 |
| Estimated glomerular filtration rate ≤ 60 | 65 (15.4%) |
| Total cholesterol (mmol/L, mg/dL) | 4.6 ± 1.1/176.4 ± 42.5 |
| Triglyceride (mmol/L, mg/dL) | 1.5 ± 1.3/130.0 ± 114.0 |
| Low density lipoprotein-cholesterol (mmol/L, mg/dL) | 2.9 ± 0.9/110.4 ± 36.0 |
| High density lipoprotein-cholesterol (mmol/L, mg/dL) | 0.9 ± 0.2/34.4 ± 8.5 |
| Hemoglobin A1c (%) | 6.7 ± 1.7 |
| Hemoglobin (g/L) | 133.6 ± 18.6 |
| Anemia ∗ | 148 (35.1%) |
| Serum albumin (g/L) | 33.5 ± 4.8 |
| Uric acid (μmol/L) | 366.6 ± 104.9 |
| Left ventricular ejection fraction (%) | 54.9 ± 10.4 |
| Left ventricular ejection fraction <45% | 84 (19.9%) |
| Medication during hospital stay | |
| Angiotensin- converting enzyme inhibitor/angiotensin receptor blocker | 380 (90%) |
| β-bloker | 331 (78.4%) |
| Calcium channel blocker | 41 (9.7%) |
| Statin | 417 (98.8%) |
| Procedural characteristic | |
| Contrast volume (mL) | 134.0 ± 50.6 |
| Contrast exposure time (min) | 80.6 ± 39.1 |
| Number of diseased vessels (n) | 2.1 ± 1.1 |
| Total length of stent (mm) | 35.2 ± 23.5 |
| Number of stents (n) | 1.5 ± 0.8 |
| Risk scores (Low, Moderate, High) | |
| Mehran | 10.8 ± 3.8 (≤7.8, 7.8-12, ≥12) |
| Age, Creatinine, and Ejection Fraction | 1.2 ± 0.5 (≤0.99, 0.99-1.30, ≥1.30) |
| Age, Glomerular filtration rate, and Ejection Fraction | 1.3 ± 0.6 (≤1.0, 1.0-1.37, ≥1.37) |
| Gao | 6.5 ± 2.6 (≤5, 5-8, ≥8) |
| Chen | 10.7 ± 6.3 (≤7, 7-13, ≥13) |
| Global Registry of Acute Coronary Events | 154.6 ± 29.1(≤141, 141-160, ≥160) |
∗ Anemia defined as baseline hematocrit 39% for men and 36% for women.
