Abstract
Background:
Microalbuminuria (MA) is considered a major risk factor predisposing to cardiovascular morbidity and mortality. Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by MA have been well described. However, data regarding admission MA and coronary and myocardial flow are scant. The aims of this study were to evaluate the effects of admission MA on coronary blood flow and prognosis in ST‐segment elevation myocardial infarction (STEMI) patients undergoing primary PCI.
Hypothesis:
Did elevated admission microalbuminuria predict poor myocardial blood flow and 6‐month mortality in ST‐segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention?
Methods:
A total of 247 patients undergoing primary PCI for STEMI within 12 hours after symptom onset were studied. Patients were divided into 2 groups according to admission urinary albumin extraction rate (UAER): (1) an MA group (UAER 20–200 µg/min), and (2) a normoalbuminuria (NA) group (UAER < 20 µg/min).
Results:
Microalbuminuria was observed in 108 patients. Univariate analyses showed statistical differences between the NA and MA groups in serum creatine level, plasma glucose level, and peak creatine kinase level on presentation. Thrombolysis In Myocardial Infarction (TIMI) flow grades (TFGs) 0–2 in the MA group were more frequent (9.4% vs 21.2%, P < 0.05) than in the NA group, and corrected TIMI frame count was higher (23.9 ± 18.5 vs 29.8 ± 23.5, P < 0.05). Admission MA was an independent predictor of poor myocardial perfusion (adjusted relative risk: 3.14, 95% confidence interval: 0.99–6.78) and a higher rate of 6‐month mortality in STEMI patients undergoing primary PCI (adjusted relative risk: 1.58, 95% confidence interval: 0.74–3.39).
Conclusions:
Admission MA levels are associated with impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI. © 2012 Wiley Periodicals, Inc.
The authors have no funding, financial relationships, or conflicts of interest to disclose.
Introduction
Several factors, such as age, diabetes mellitus (DM), prior angina, heart failure, and depressed left ventricular function, can adversely affect prognosis in subjects with acute myocardial infarction (AMI).1, 2, 3, 4 Microalbuminuria (MA) has been reported to occur in patients with AMI and it has been associated with increased risk for in‐hospital mortality.5, 6, 7 Several studies have shown that microalbuminuria can predict all‐cause mortality in the general population and in patients with DM.8, 9, 10
Although immediate restoration of normal blood flow in the infarct‐related artery (IRA) is the primary aim of primary percutaneous coronary intervention (PCI), it has been recognized that preservation of the microcirculation is highly critical to clinical outcome.11 In addition, it has been shown that it is extremely important to maintain epicardial artery patency in AMI; however, recent attention has been shifted from epicardial artery patency to the status of the microvasculature.11 Now, it is well known that achievement of Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow cannot be sufficient to ensure myocardial salvage.11, 12 Studies have shown that echocontrast “no‐reflow,” despite TIMI grade 3 flow, occurred in one‐third of patients after reperfusion therapy and is associated with a higher incidence of congestive heart failure and left ventricular dysfunction.13, 14 Earlier clinical studies have clearly delineated that no‐reflow predicts short‐ and long‐term adverse clinical outcome in patients presenting with AMI.15, 16
Accordingly, we aimed to investigate the impact of admission MA on the development of poor myocardial perfusion after primary PCI in patients presenting with AMI.
Methods
Patients
The study population consisted of 247 patients (180 were men, mean age 58.03 ± 11.67 years) with acute ST‐segment elevation myocardial infarction (STEMI) at Beijing Friendship Hospital who were treated by primary PCI within 12 hours of the onset of symptoms, retrospectively collected between July 2009 and December 2010. The diagnosis of STEMI was based on the following: >30 minutes of continuous chest pain; ST elevation >2.0 mm in ≥2 contiguous electrocardiographic (ECG) leads; and creatine kinase (CK) level equivalent to >2× the upper limit of normal. This study excluded patients with a history of recent surgery or trauma within the preceding 2 months, renal insufficiency (creatinine > 106 µmol/L), nephrotic proteinuria, dialytic treatment, malignancy or liver cirrhosis, febrile disorders, acute or chronic inflammatory disease on study entry, history of recent infection, previous MI, those with AMI onset >12 hours, those patients in whom antiplatelet agents had been used for >3 days before AMI, and cardiogenic shock patients. The study protocol was reviewed and approved by the ethical committee at Beijing Friendship Hospital. Informed consent to participate in this study was obtained from all patients.
All participants were asked to collect a timed overnight urine sample (10 p.m.–6 a.m.; 8 hours) on the first day after admission. The urinary albumin concentration was measured by chemiluminescence. Urinary albumin extraction rate (UAER) was expressed as µg/minute. Intra‐ and interassay coefficients of variation were <5% for the urine albumin measurements. A UAER <20 µg/min was defined as normoalbuminuria (NA), 20–200 µg/minute as microalbuminuria (MA), and ≥200 µg/minute as macroalbuminuria.
Coronary Angiography
All patients received an intravenous (IV) bolus injection of 2000 U of heparin prior to angiography. Diagnostic coronary angiography was performed via the femoral or radial approach using the Judkins technique. After an additional IV or intra‐arterial bolus injection of 6000 U of heparin, PCI was performed. Primary PCI was done using the conventional technique, and coronary stents were used without restrictions. The IRA was the only target of the procedure. Intra‐aortic balloon counter pulsation was performed in cases of hemodynamic instability. TIMI grade 3 coronary flow in the treated vessel with a residual stenosis <20% was considered successful PCI. Serum CK was measured serially every 2 hours after revascularization until the peak value was achieved. Patients received conventional drug treatment according to individual need, which was determined by the attending physician. The patients with stents received dual antiplatelet therapy with a clopidogrel and aspirin regimen (clopidogrel 75 mg once a day and aspirin 100 mg once a day).
Angiographic Analysis
Angiographic images were acquired using a GE INNOVA‐2000 single‐plane system (GE Healthcare, Wauwatosa, WI) at a cine rate of 30 frames per second. Angiographic TIMI flow grade was evaluated using the initial coronary angiography procedure, as described previously. TIMI grade 0 (no perfusion) denoted absent antegrade flow beyond the point of obstruction; TIMI grade 1 (penetration without perfusion) denoted flow beyond the point of obstruction but incomplete filling of the distal vessel; TIMI grade 2 (partial perfusion) represented patent vessels with slow filling and/or slow emptying; and TIMI grade 3 (complete perfusion) represented normally brisk flow. TIMI 2 or 3 was defined as the presence of coronary reperfusion. TIMI frame count was also evaluated as an objective and quantitative measure of reperfusion in patients with TIMI grade 2 or 3. As described previously, the number of frames from the first frame, in which contrast enters the ostium, to the last frame, when contrast reaches the standardized distal landmark branch, was counted and defined as the TIMI frame count. The distal landmarks included the “moustache” branch for the left anterior descending artery. Because the left anterior descending artery physiologically requires more frames for the contrast to fill, the TIMI frame counts were corrected by dividing this frame count by 1.7 to derive the corrected TIMI frame count (CTFC). Every case was analyzed by 2 cardiologists who were blinded to the patients' identity, ECG, and echocardiographic outcome; a third cardiologist provided the final result if there was disparity in the TIMI flow grades (TFGs) between the 2 cardiologists. The CTFC for every case was calculated by the mean value of the 2 cardiologists' measurements.17, 18, 19
Electrocardiography Analysis
An 18‐lead ECG was recorded just before and at the end of procedure. Analysis was performed by one observer who was unaware of the clinical and angiographic data. The sum of ST‐segment elevation (ΣSTe) was measured manually 20 ms after the end of QRS complex from leads exploring the infarct area. Resolution of ΣSTe after PCI was quantified as a percentage of the value obtained from the basal ECG. A >50% reduction of the initial value was considered significant ΣSTe recovery.
Echocardiography Analysis
A 2‐dimensional echocardiogram was performed in‐hospital for the evaluation of left ventricular (LV) wall motion and LV ejection fraction (LVEF). The analysis was carried out by 2 observers blinded to the clinical and angiographic data.
Clinical Follow‐Up
Clinical follow‐up data were obtained from outpatient examinations or by the investigators who made telephone contact with patients at about 6 months post‐PCI. In‐hospital and 6‐month complications included death, heart failure, reinfarction, and angina requiring revascularization.
Statistical Analysis
Analyses were performed using SPSS software, version 13.0 (SPSS, Inc., Chicago, IL). Continuous data are expressed as mean values ± standard deviation. The Student t test was used to analyze continuous variables. Categorical variables were analyzed by the χ 2 or Fisher exact test. A P value <0.05 was considered statistically significant.
Results
Baseline Clinical Characteristics
Baseline clinical characteristics of the patients grouped by admission urinary albumin concentration are provided in Table 1. The creatine level, plasma glucose level, and peak CK level were higher in the patients with NA (94.3 ± 38.8 µmol/L vs 79.0 ± 22.1 µmol/L, P = 0.001; 10.1 ± 4.5 mmol/L vs 8.3 ± 3.0 mmol/L, P = 0.001; and 285.8 ± 193.4 vs 197.3 ± 148.8, P = 0.049, respectively). Difference in concomitant therapy and device use including thrombus aspirator and stent implantation during PCI between the 2 groups had no statistical significance. None of patients underwent thrombolysis prior to their PCI, which may have affected TIMI flow evaluation.
Table 1.
Baseline Characteristics of Study Population
| NA Group, n = 139 | MA Group, n = 108 | P Value | |
|---|---|---|---|
| Age, y | 61.1 ± 11.2 | 61.8 ± 13.6 | 0.653 |
| Male sex | 105 (75.5) | 75 (69.4) | 0.286 |
| Hypertension | 81 (58.3) | 67 (62.0) | 0.55 |
| Duration of hypertension, y | 8.5 ± 6 | 7.9 ± 5 | 0.827 |
| Hyperlipidemia | 17 (12.2) | 13 (12.0) | 0.963 |
| DM | 32 (23.0) | 31 (28.7) | 0.31 |
| Duration of diabetes, y | 7.8 ± 6 | 8.2 ± 6 | 0.76 |
| Current smoker | 97 (69.8) | 74 (68.5) | 0.97 |
| Previous MI | 32 (23.0) | 16 (14.8) | 0.107 |
| Location of MI | |||
| Anterior | 74 (53.3) | 56 (52.3) | 0.814 |
| Inferior or posterior | 65 (46.7) | 52 (47.7) | 0.922 |
| Time to reperfusion, hr | 6.8 ± 3.9 | 6.9 ± 4.2 | 0.56 |
| Creatinine, µmol/L | 79.0 ± 22.1 | 94.3 ± 38.8 | 0.001a |
| WBC count on admission, mm3 | 11 502 ± 3580 | 11 873 ± 3500 | 0.417 |
| Hs‐CRP on admission, mmol/L | 4.8 ± 3.9 | 5.5 ± 4.2 | 0.192 |
| Glucose on admission, mmol/L | 8.3 ± 3.0 | 10.1 ± 4.5 | 0.001a |
| Peak CK level, IU/L | 197.3 ± 148.8 | 285.8 ± 193.4 | 0.001a |
| LDL‐C, mmol/L | 2.8 ± 0.6 | 2.9 ± 0.7 | 0.469 |
| Concomitant therapy | |||
| GP IIb/IIIa antagonist | 23 (16.5) | 26 (24.1) | 0.134 |
| Aspirin | 139 (100) | 108 (100) | 1.0 |
| Clopidogrel | 139 (100) | 108 (100) | 1.0 |
| β‐Blocker | 129 (92.8) | 101 (93.5) | 0.998 |
| ACEI/ARB | 122 (87.8) | 99 (91.7) | 0.412 |
| Statin | 139 (100) | 108 (100) | 1.0 |
| Devices used in PCI | |||
| Thrombus aspirator | 29 (20.1) | 24 (22.2) | 0.797 |
| Stent implantation | 133 (95.7) | 107 (99.1) | 0.112 |
Abbreviations: ACEI, angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor‐blocker; CK, creatine kinase; DM, diabetes mellitus; GP, glycoprotein; hs‐CRP, high‐sensitivity C‐reactive protein; LDL‐C, low‐density lipoprotein cholesterol; MA, microalbuminuria; MI, myocardial infarction; NA, normoalbuminuria; PCI, percutaneous coronary intervention; WBC, white blood cell. Values are presented as mean ± standard deviation or n (%).
Denotes statistical difference (P < 0.05) compared with NA group.
Angiographic and Electrocardiographic Characteristics
The comparison of angiographic characteristics of the 2 groups showed no statistically significant difference except for the percentage of lower admission TFGs and CTFCs. Not only was the percentage of lower admission TFGs in the MA group higher than in the NA group, but also CTFCs were higher in the MA group than in the NA group. In addition, significant ΣSTe recovery occurred less frequently in the MA group (Table 2).
Table 2.
Coronary Angiographic Outcomes
| NA Group, n = 139 | MA Group, n = 108 | P Value | |
|---|---|---|---|
| No. of narrowed coronary arteries | |||
| 1 | 34 (24.5) | 29 (26.9) | 0.669 |
| 2 | 46 (33.1) | 32 (29.6) | 0.562 |
| 3 | 59 (42.4) | 47 (43.5) | 0.866 |
| TFGs 0–2 | 13 (9.4) | 23 (21.2) | <0.001a |
| TFGs 3 | 126 (90.6) | 85 (78.8) | |
| CTFC | 23.9 ± 18.5 | 29.8 ± 23.5 | 0.032a |
| Significant ΣSTe recovery | 111 (79.8) | 59 (54.6) | <0.001a |
Abbreviations: CTFC, corrected TIMI frame count; MA, microalbuminuria; MI, myocardial infarction; NA, normoalbuminuria; ΣSTe, sum of ST‐segment elevation; TFG, TIMI flow grade; TIMI, thrombolysis in myocardial infarction. Values are presented as mean ± standard deviation or n (%).
Denotes statistical difference (P < 0.05) compared with normal group.
Clinical and Echocardiographic Outcomes
There were no differences between the 2 groups in terms of major adverse cardiac events (MACE; 2.8% vs 6.3%, P < 0.05) and deaths (0.7% vs 0.9%, P > 0.05) at discharge; however, there were statistical differences in mortality at 6‐month follow‐up (1.4% vs 8.3%, P < 0.05). The LVEF was lower in the MA group compared with the NA group before discharge and at 6‐month follow up (Table 3).
Table 3.
Clinical and Echocardiographic Outcomes
| NA Group, n = 139 | MA Group, n = 108 | P Value | |
|---|---|---|---|
| Success rate of PCI | 137 (98.6) | 107 (99.1) | 0.716 |
| In hospital | |||
| MACE | 4 (2.8) | 7 (6.3) | 0.174 |
| Deaths | 1 (0.7) | 1 (0.9) | 0.858 |
| LVEF | 57.3 ± 9.9 | 54.8 ± 8.6 | 0.045a |
| At 6‐month follow‐up | |||
| MACE | 20 (14.4) | 20 (18.5) | 0.383 |
| Deaths | 2 (1.4) | 9 (8.3) | 0.01a |
| LVEF | 62.6 ± 10.7 | 53.5 ± 2.2 | 0.006a |
Abbreviations: LVEF, left ventricular ejection fraction; MA, microalbuminuria; MACE, major adverse cardiovascular events; MI, myocardial infarction; NA, normoalbuminuria; PCI, percutaneous coronary intervention. Value are presented as mean ± standard deviation.
Denotes statistical difference (P < 0.05) compared with normal group.
Admission MA (relative risk [RR]: 3.143, 95% confidence interval [CI]: 0.99–6.78), CTFC > 27 (RR: 1.43, 95% CI: 0.37–5.35), age > 70 years (RR: 1.13, 95% CI: 0.80–1.98), DM (RR: 1.402, 95% CI: 0.57–2.03), Killip class II–IV (RR: 1.78, 95% CI: 1.33–2.55), number of narrowed coronary arteries (RR: 1.31, 95% CI: 1.07–1.66), TFGs 0–2 (RR: 1.21. 95% CI: 1.11–2.14), and significant ΣSTe recovery (RR: 2.54, 95% CI: 1.57–4.36) were independent predictors of a higher rate of 6‐month mortality in STEMI patients undergoing primary PCI (Table 4).
Table 4.
Effects of Several Variables on Mortality at 6‐Month Follow‐Up in Multivariate Regression Analyses
| Variables | Adjusted RR | 95% CI | P Value |
|---|---|---|---|
| Age >70 years | 1.24 | 0.80–1.98 | 0.034 |
| Male gender | 1.04 | 0.87–1.96 | 0.76 |
| Hypertension | 0.88 | 0.33–2.17 | 0.35 |
| DM | 1.40 | 0.57–2.03 | 0.206 |
| Microalbuminuria | 3.14 | 0.99–6.78 | 0.01 |
| Killip class II–IV | 1.78 | 1.33–2.55 | 0.042 |
| No. of narrowed vessels (≥2) | 1.31 | 1.07–1.66 | 0.44 |
| TFGs 0–2 | 1.21 | 1.11–2.14 | 0.49 |
| CTFC >27 | 1.43 | 0.37–5.53 | 0.606 |
| Significant ΣSTe recovery | 2.54 | 1.57–4.36 | 0.011 |
Abbreviations: CI, confidence interval; CTFC, corrected TIMI frame count; DM, diabetes mellitus; LVEF, left ventricular ejection fraction; RR, relative risk; TFGs, TIMI flow grades; TIMI, thrombolysis in myocardial infarction. Relative risk was adjusted by age, gender, hypertension, DM, microalbuminuria, Killip class, LVEF, number of narrowed vessels, TFGs 0–2, significant ΣSTe recovery, and CTFC.
Admission MA (RR: 1.584, 95% CI: 0.74–3.39) and Killip class II–IV (RR: 3.139, 95% CI: 0.89–11.11) were also independent predictors of poor myocardial perfusion detected by CTFC in STEMI patients undergoing primary PCI (Table 5).
Table 5.
Effects of Several Variables on Poor Myocardial Perfusion in Multivariable Regression Analyses
| Variable | Adjusted RR | 95% CI | P Value |
|---|---|---|---|
| Age >70 years | 1.28 | 0.52–3.19 | 0.593 |
| Male gender | 1.00 | 0.38–2.64 | 0.993 |
| Hypertension | 0.95 | 0.37–2.47 | 0.915 |
| DM | 1.22 | 0.52–2.88 | 0.654 |
| Microalbuminuria | 1.58 | 0.74–3.3 | 0.041 |
| Killip class II–IV | 3.14 | 0.89–11.11 | <0.001 |
| No. of narrowed vessels (≥2) | 1.22 | 0.54–2.75 | 0.629 |
Abbreviations: CI, confidence interval; DM, diabetes mellitus; LVEF, left ventricular ejection fraction; RR, relative risk. Relative risk was adjusted by age, gender, hypertension, DM, microalbuminuria, Killip class, LVEF, and number of narrowed vessels.
Discussion
Microalbuminuria has been found to be present in 3%–15% of the general population and has been associated with increased coronary risk. Several investigators have concluded that MA is a significant predictor of long‐term cardiovascular morbidity and mortality, mainly among patients with DM and hypertension.20, 21 In addition, as was shown by Marso et al, proteinuria is an important predictor of death in diabetic patients who have undergone coronary artery bypass surgery, suggesting that this parameter can be used as a risk stratifier even in the future.22 The pathophysiological link between MA and increased coronary risk still needs to be elucidated. Microalbuminuria may imply a vulnerability for atherosclerosis due to its association with inflammatory and prothrombotic changes involved in endothelial dysfunction.
In our study, interactive relationships of admission MA and myocardial blood flow and short‐term mortality in STEMI patients undergoing primary PCI were investigated, and were not systematically observed previously.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 The results demonstrated that in the setting of STEMI, patients with MA had greater impairment of myocardial blood flow and LVEF and more short‐term death after primary PCI. Microalbuminuria predicted poor myocardial flow independently, which predicted 6‐month mortality in STEMI patients undergoing primary PCI despite age, Killip grade at presentation, and number of narrowed coronary arteries. In‐hospital death rate was similar in the NA and MA groups. Mortality is different as compared with virtually all the studies with this setting.20 Six‐month mortality is very low as compared with other similar studies.21 This could indicate a strong baseline patient selection, because the lower‐risk patients received the advanced medication such as aspirin, clopidogrel, LMWH, ACEI, β‐blocker, statin, etc.
In the last few years, both high‐sensitivity C‐reactive protein (hs‐CRP) and MA have been identified as independent risk markers for mortality in patients with AMI.23, 24 Several mechanisms have been proposed to explain the association between CRP and MA. Animal studies have shown that CRP administration in rat models resulted in endothelial dysfunction and impaired vasoreactivity by inhibiting endothelial nitric oxide synthase.25 Decreased nitric oxide production promotes vasoconstriction, leukocyte adherence, platelet activation, impaired coagulation and vascular inflammation.26 C‐reactive protein also promotes proinflammatory cytokine production leading to mesangial cell proliferation, matrix overproduction, and increased vascular permeability resulting in albuminuria.27 There was no difference between the MA and NA groups regarding hs‐CRP in the present study. This could be explained in that all of the enrolled subjects were AMI patients who were associated with the higher hs‐CRP level.
Previous studies have shown that patients with MA have increased cardiovascular risk.28, 29, 30, 31 In addition, they showed the existence of significant differences in baseline patient characteristics between those with and those without MA, and suggested that poor outcomes in patients with MA could be explained by the multitude of comorbid conditions and worse preprocedural cardiac status. In our study, there was significant difference in terms of mortality between the patients with MA and without MA. These results were in agreement with previous studies of patients with MA.20, 21
In our study population, patients with MA had higher serum creatinine levels, higher glucose levels on admission, and worse in‐hospital LVEF than patients without MA. Nevertheless, the effect of MA on short‐term mortality was independent of these risk factors when evaluated in a multivariate model. In our opinion, several factors may have contributed to these results. First, the higher level of serum creatinine also reflects clinical pathophysiological mechanisms such as low cardiac output, resulting in decreased renal blood flow, decreased myocardial flow, chronic volume overload, and diastolic LV dysfunction. Second, MA reflects subclinical vascular damage in the kidneys, but it may also signify systemic endothelial dysfunction that itself predisposes to cardiovascular events.32 Hyperglycemia per se impairs the endothelium vasodilation properties, leading to endothelial dysfunction.33
Several investigators have documented that the no‐reflow phenomenon was observed in >30% of the patients after thrombolysis or catheter‐based PCI for AMI.13, 34 In addition, it has been demonstrated that no‐flow predicts short‐ and long‐term adverse clinical outcomes in AMI.13, 16, 34, 35 The severity of the no‐reflow phenomenon correlates well with the severity of myocardial damage.11 The angiographic no‐reflow phenomenon strongly predicts cardiac complications independent of other well‐known early predictors of long‐term outcome after AMI, such as age, Killip class, and LVEF.35 Recently, Kazuyoshi et al. found that lesion length and blood glucose level on admission could be used to stratify AMI patients into a lower or higher risk for angiographic slow‐ or no‐flow before optimal coronary intervention. Moreover, angiographic slow‐ or no‐flow predicts an adverse outcome in AMI patients.36
However, the divergence in mortality rates among patients with TIMI grade 3 flow is also associated with a degree of microvascular dysfunction and subsequent impairment of tissue perfusion. In our study, there was a significant difference in epicardial coronary flow evaluated by TFGs and CTFC between the MA and NA groups. The likelihood that no‐reflow will occur correlates with the severity of myocardial damage incurred during infarction and the resulting TIMI flow. No‐reflow in the IRA after reperfusion therapy is mainly ascribed to the dysfunction of distal microcirculation. Reperfusion injury and free‐radical release, as well as microvascular endothelial dysfunction and microvascular constriction, may play a significant role in the development of no‐reflow.37, 38 Although the exact pathophysiologic mechanisms by which MA increases the risk of poor myocardial perfusion development after primary PCI are not clearly elucidated, one could propose that anemia, oxidative stress, inflammation, elevation of proinflammatory cytokines, more unfavorable lipid profile, derangements in calcium phosphate homeostasis, and conditions promoting coagulation—all of which are associated with accelerated atherosclerosis and endothelial dysfunction—play an essential role in this pathophysiology.39, 40 Microalbuminuria is considered to correlate with systemic vascular damage, extensive endothelial dysfunction, a glomerular hemodynamic state of hyperperfusion and hyperfiltration, a prothrombotic state, and a low‐grade chronic inflammatory state. From that point of view, one can conclude that microvascular endothelial dysfunction, conditions promoting coagulation, and increased free‐radical release may be responsible for poor myocardial perfusion after primary PCI in patients with MA.
In our study, MA in the STEMI patients who underwent primary PCI, measured by easily acquired admission UAER 20–200 µg/minute, signified poor myocardial flow compared with STEMI patients who had NA, which was observed by TFGs and CTFC. In the multivariable regression analyses, admission MA was an independent predictor of poor myocardial perfusion after primary PCI in patients with STEMI.
Conclusion
In conclusion, although MA is associated with short‐term prognosis in STEMI patients undergoing primary PCI, it is associated with impaired coronary flow in those patients, which may contribute at least in part to worse cardiac function. Therefore, we believe that baseline MA detection by the use of UAER might be helpful in identifying patients with a greater risk of poor coronary blood flow.
References
- 1. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med. 1983;309:331–336. [DOI] [PubMed] [Google Scholar]
- 2. Stevenson R, Ranjadayalan K, Wilkinson P, et al. Short and long term prognosis of acute myocardial infarction since introduction of thrombolysis [published correction appears in BMJ. 1993;307:909]. BMJ. 1993;307:349–353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Nicod P, Gilpin E, Dittrich H, et al. Influence on prognosis and morbidity of left ventricular ejection fraction with and without signs of left ventricular failure after acute myocardial infarction. Am J Cardiol. 1988;61:1165–1171. [DOI] [PubMed] [Google Scholar]
- 4. Moss AJ, Benhorin J. Prognosis and management after a first myocardial infarction. N Engl J Med. 1990;322:743–753. [DOI] [PubMed] [Google Scholar]
- 5. Gosling P, Hughes EA, Reynolds TM, et al. Microalbuminuria is an early response following acute myocardial infarction. Eur Heart J. 1991;12:508–513. [DOI] [PubMed] [Google Scholar]
- 6. Taskiran M, Feldt‐Rasmussen B, Jensen GB, et al. Urinary albumin excretion in hospitalized patients with acute myocardial infarction: prevalence of microalbuminuria and correlation to left ventricle wall thickness. Scand Cardiovasc J. 1998;32:163–166. [DOI] [PubMed] [Google Scholar]
- 7. Berton G, Citro T, Palmieri R, et al. Albumin excretion rate increase during acute myocardial infarction and strongly predicts early mortality. Circulation. 1997;96:3338–3345. [DOI] [PubMed] [Google Scholar]
- 8. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity‐onset diabetes. N Engl J Med. 1984;310:356–360. [DOI] [PubMed] [Google Scholar]
- 9. Kuusisto J, Mykkänen L, Pyörälä, et al. Hyperinsulinemic microalbuminuria: a new risk indicator for coronary heart disease. Circulation. 1995;91:831–837. [DOI] [PubMed] [Google Scholar]
- 10. Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria as predictor of vascular disease in non‐diabetic subjects. Islington Diabetes Survey. Lancet. 1988;2:530–533. [DOI] [PubMed] [Google Scholar]
- 11. King SB III, Smith SC Jr, Hirshfeld JW Jr, et al. 2007. focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol. 2008;51:172–209. [DOI] [PubMed] [Google Scholar]
- 12. Gibson CM, Cannon CP, Murphy SA, et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation. 2000;101:125–130. [DOI] [PubMed] [Google Scholar]
- 13. Ito H, Maruyama A, Iwakura, et al. Clinical implication of the “no‐reflow” phenomenon: a predictor of complication and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation. 1996;93:223–228. [DOI] [PubMed] [Google Scholar]
- 14. Iliceto S, Galiuto L, Marchese A, et al. Functional role of microvascular integrity in patients with infarct‐related artery patency after acute myocardial infarction. Eur Heart J. 1997;18:618–624. [DOI] [PubMed] [Google Scholar]
- 15. Morishima I, Sone T, Mokuno S, et al. Clinical significance of no‐reflow phenomenon observed on angiography after successful treatment of acute myocardial infarction with percutaneous transluminal coronary angiography. Am Heart J. 1995;130:239–243. [DOI] [PubMed] [Google Scholar]
- 16. Morishima I, Sone T, Okumura K, et al. Angiographic no‐reflow phenomenon as a predictor of adverse long‐term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol. 2000;36:1202–1209. [DOI] [PubMed] [Google Scholar]
- 17. Anderson JL, Karagounis LA, Becker LC, et al. TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction: ventriculographic, enzymatic, and electrocardiographic evidence from the TEAM‐3 study. Circulation. 1993;87:1829–1839. [DOI] [PubMed] [Google Scholar]
- 18. Gibson CM, Cannon CP, Daley WL, et al. The TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93:879–888. [DOI] [PubMed] [Google Scholar]
- 19. Gibson CM, Murphy SA, Rizzo MJ, et al. Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis in Myocardial Infarction (TIMI) Study Group. Circulation. 1999;99:1945–1950. [DOI] [PubMed] [Google Scholar]
- 20. Bandyopadhyay SK, Ghosh S, Bandyopadhyay R, et al. Micro‐albuminuria: a predictor of 7‐day mortality in acute myocardial infarction. J Indian Med Assoc. 2010;108:826–828. [PubMed] [Google Scholar]
- 21. Apostolovic S, Stanojevic D, Djordjevic V, et al. Prognostic significance of microalbuminuria in patients with acute myocardial infarction. Clin Lab. 2011;57:229–235. [PubMed] [Google Scholar]
- 22. Marso SP, Ellis SG, et al. Proteinuria is a key determinant of death in patients with diabetes after isolated coronary artery bypass grafting. Am Heart J. 2000;139:939–944. [DOI] [PubMed] [Google Scholar]
- 23. Suleiman M, Khatib R, Agmon Y, et al. Early inflammation and risk of long‐term development of heart failure and mortality in survivors of acute myocardial infarction: predictive role of C‐reactive protein. J Am Coll Cardiol. 2006;47:962–968. [DOI] [PubMed] [Google Scholar]
- 24. Weber M, Hamm C. Redefinition of myocardial infarction: relevance of biomarkers [in German]. Herz. 2008;33:115–121. [DOI] [PubMed] [Google Scholar]
- 25. Guan H, Wang P, Hui R, et al. Adeno‐associated virus‐mediated human C‐reactive protein gene delivery causes endothelial dysfunction and hypertension in rats. Clin Chem. 2009;55:274–284. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Verma S, Wang CH, Li SH, et al. A self‐fulfilling prophecy: C‐reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation. 2002;106:913–919. [DOI] [PubMed] [Google Scholar]
- 27. Horii Y, Iwano M, Hirata E, et al. Role of interleukin‐6 in the progression of mesangial proliferative glomerulonephritis. Kidney Int Suppl. 1993;39:S71–S75. [PubMed] [Google Scholar]
- 28. Dinneen F, Gerstein HC. The association of microalbuminuria and mortality in non‐insulin dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med. 1997;157:1413–1418. [PubMed] [Google Scholar]
- 29. Garq JP, Bakris GL. Microalbuminuria: marker of vascular dysfunction, risk factor for coronary heart disease. Vasc Med. 2002;7:35–43. [DOI] [PubMed] [Google Scholar]
- 30. Jinxia L, Tianchang L. Value of microalbuminuria in predicting the risk of coronary heart disease. Chin J Med Chem. 2006;8:83–87. [Google Scholar]
- 31. Klausen K, Borch‐Johnsen K, Feldt‐Rasmussen B, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation. 2004;110:32–35. [DOI] [PubMed] [Google Scholar]
- 32. Weir MR. Microalbuminuria and cardiovascular disease. Clin J Am Soc Nephrol. 2007;2:581–590. [DOI] [PubMed] [Google Scholar]
- 33. Kocsis E, Pacher P, Pósa I, et al. Hyperglycaemia alters the endothelium‐dependent relaxation of canine coronary arteries. Acta Physiol Scand. 2000;169:183–187. [DOI] [PubMed] [Google Scholar]
- 34. Ito H, Tomooka T, Sakai N, et al. Lack of myocardial perfusion immediately after successful thrombolysis: a predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation. 1992;85:1699–1705. [DOI] [PubMed] [Google Scholar]
- 35. Halkin A, Singh M, Nikolsky E, et al. Prediction of mortality after primary percutaneous coronary intervention for acute myocardial infarction: the CADILLAC risk score. J Am Coll Cardiol. 2005;45:1397–1405. [DOI] [PubMed] [Google Scholar]
- 36. Kazuyoshi S, Nobuo S, Kinya S, et al. Predictors and long‐term prognostic implications of angiographic slow/no‐flow during percutaneous coronary intervention for acute myocardial infarction. Intern Med. 2008;47:899–906. [DOI] [PubMed] [Google Scholar]
- 37. Ma XL, Tsao PS, Viehman GE, et al. Neutrophil‐mediated vasoconstriction and endothelial dysfunction in low‐flow perfusion reperfused cat coronary artery. Circ Res. 1991;69:95–106. [DOI] [PubMed] [Google Scholar]
- 38. Gibson CM, Murphy SA, Kirtane AJ, et al. Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST‐segment elevation myocardial infarction. J Am Coll Cardiol. 2004;44: 980–987. [DOI] [PubMed] [Google Scholar]
- 39. Ping L, Yu L, Jianjun Y. Relationship between microalbuminuria and endothelium‐dependent vasodilation in type 2 diabetes mellitus. Chin J Misdiagnostics. 2004;4:1640–1641. [Google Scholar]
- 40. Yibin Y, Zhongxia C, Kun X. Measurement of the marker for endothelial damages and their links with urinary protein in patients with diabetes mellitus. J Postgrad Med. 2005;28:21–23. [Google Scholar]