Elevated Admission Serum Creatinine Predicts Poor Myocardial Blood Flow (Full title below)
- Volume 21 - Issue 10 - October, 2009
- Posted on: 10/7/09
- 0 Comments
- 10914 reads
Clinical and echocardiographic outcomes. In-hospital and 1-year deaths were significantly higher in patients with elevated serum creatinine (4.7% vs. 1.2%, p < 0.05; 7.0% vs. 2.4%, p < 0.05). There were no differences between the two groups in terms of major adverse cardiac events (MACE) at discharge (5.6% vs. 7.0%, p > 0.05), however there were statistical differences in MACE at 1-year follow up (14.0% vs. 7.3%, p < 0.05). LVEF was lower in the elevated group compared to the normal group before discharge and at 1-year follow up (Table 3).
Admission serum creatinine ≥ 1.3 mg/dl (relative risk [RR] = 1.41, 95% confidence interval [CI]: 1.24–2.69), TMPGs 0–2 (RR = 1.54, 95% CI: 1.27–2.09), age ≥ 70 years (RR = 1.09, 95% CI: 1.04–1.19), previous MI (RR = 1.24, 95% CI: 1.05–1.84), in-hospital worsened creatinine (RR = 1.40, 95% CI: 0.96–1.74), Killip Class II–IV (RR = 1.96, 95% CI: 1.56–2.38), number of narrowed coronary arteries (RR = 1.32, 95% CI: 1.05–1.79), TFGs 0–2 (RR = 1.17, 95% CI: 1.01–1.54), and significant ΣSTe recovery (RR = 2.35, 95% CI: 1.24–4.23) were independent predictors of a higher rate of 1-year mortality in STEMI patients undergoing primary PCI (Table 4).
Admission serum creatinine ≥ 1.3 mg/dl (RR = 3.93, 95% CI: 1.13–6.84), discharge serum creatinine ≥ 1.3 mg/dl (RR = 2.01, 95% CI: 1.59–4.32), in-hospital worsened creatinine (RR = 2.84, 95% CI: 1.65–5.32), and number of narrowed coronary arteries (RR = 1.41, 95% CI: 1.07–1.68) were also independent predictors of poor myocardial perfusion detected by TMPG in STEMI patients undergoing primary PCI (Table 5).
In our study, interactive relationships of admission serum creatinine and myocardial blood flow and long-term mortality in STEMI patients undergoing primary PCI were investigated, and were not systematically observed previously.1–11 The results demonstrated that in the setting of STEMI, patients with elevated admission creatinine levels had less complete ST-segment resolution, greater impairment of myocardial blood flow and more short- and long-term MACE and death after primary PCI. Elevated admission serum creatinine predicted poor myocardial flow independently, which predicted 1-year mortality in STEMI patients undergoing primary PCI despite age, admission creatinine level, Killip’s grades at presentation and number of narrowed coronary arteries.
Previous studies have shown that patients with baseline renal dysfunction have increased cardiovascular risk.22–26 In addition, they showed the existence of significant differences in baseline patient characteristics between those with and those without renal insufficiency, and suggested that poor outcomes in the renal insufficiency patients could be explained by the multitude of comorbid conditions and worse preprocedural cardiac status.
Our result expands on previous analyses demonstrating that impaired renal function is associated with an increased risk of death in patients with STEMI. These results were in agreement with previous studies of patients undergoing PCI.22–26 In our study population, patients with elevated serum creatinine levels were older, more likely to present with symptoms of heart failure (Killip Class ≥ II), systemic hypertension, multivessel disease, were more prone to have in-hospital worsened creatinine levels, and have a history of MI than patients without renal decline. Nevertheless, the effect of an elevation of serum creatinine concentration on long-term mortality was independent of these risk factors when evaluated in a multivariate model. In our opinion, three 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, the elevated serum creatinine group had a greater prevalence of multivessel coronary disease and a history of MI. Although the precise mechanisms of the interaction between impaired renal function and coronary artery disease are not clear, the serum creatinine concentration may be a marker for concomitant cardiovascular risk factors such as diabetes mellitus, systemic hypertension and advanced age. Third, patients with elevated serum creatinine are easier to show worsening serum creatinine levels during hospitalization, which has been proven to correlate with higher short- and long-term mortality.27–29 In our study, in-hospital worsened creatinine level, defined as a 25% elevation in serum creatinine during hospitalization or an absolute increase of 0.5 mg/dl compared to the admission level, was an independent predictor of 1-year mortality, which is consistent with previous studies.27–29
Several investigators have documented that the no-reflow phenomenon was observed in > 30% of the patients after thrombolysis or catheter-based PCI for AMI.14,30 In addition, it has been demonstrated that no-reflow predicts short- and long-term adverse clinical outcomes in the clinical setting of AMI.14,16,17,30 The severity of the no-reflow phenomenon correlates well with the severity of myocardial damage.12 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.31 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.32
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. More specifically, the restoration of blood flow in the IRA may not be a reliable predictor of restoration of tissue reperfusion supplied by the IRA, hence the creation of TMPG.13 In our study, there was no difference in epicardial coronary flow evaluated by TFGs between the elevated and normal creatinine groups, but a significant difference was found when evaluated by CTFC and TMPG, which are much more sensitive and useful than TFGs and are associated with impaired microvascular flow. At the same time, TMPG was an independent risk predictor of 1-year mortality in our study. We therefore concluded that abnormal myocardial flow may contribute to poorer outcomes.
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,33 as well as microvascular endothelial dysfunction and microvascular constriction,34 may play a significant role in the development of no-reflow. Although the exact pathophysiologic mechanisms by which baseline renal dysfunction increase 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 calciumphosphate homeostasis and conditions promoting coagulation — all of which are associated with accelerated atherosclerosis and endothelial dysfunction — play an essential role in this pathophysiology.35 Serum creatinine concentration is considered to correlate with oxidative stress, endothelial dysfunction, inflammation and more progressive atherosclerosis.36–41 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 renal impairment.
In our study, renal impairment in the STEMI patients who underwent primary PCI, measured by an easily-acquired admission creatinine ≥ 1.3 mg/dl, signified poor myocardial flow compared with STEMI patients who had normal serum creatinine, which was observed by TMPGs and significant ΣSTe recovery. In the multivariable regression analyses, admission creatinine level was an independent predictor of poor myocardial perfusion after primary PCI in patients with STEMI.
Study limitations. First, the number of study participants was limited. The statistical power thus might not be adequate for any negative data. Secondly, because the level of serum creatinine is of limited value in the early detection of renal insufficiency and is influenced by factors such as age, gender, race and lean muscle mass, there may be a claim that the serum creatinine level is an unreliable estimate of renal insufficiency, which limits our study, but these findings warrant further investigation regarding the role of renal insufficiency measured by direct GFR in STEMI patients. Thirdly, pathophysiological mechanisms of admission serum creatinine, increasing the risk of poor myocardial flow and adverse events in this study are not well studied, which could be explained by confounding variables that were not accounted for in the multivariable analysis, except for poor myocardial blood flow.
In conclusion, the elevated admission serum creatinine levels, acquired easily and directly, are associated with impaired coronary flow in STEMI patients undergoing primary PCI, which may contribute at least in part to worse cardiac function and poor short- and long-term prognosis. Therefore, we believe that baseline renal impairment detection by the use of simple serum creatinine test might be helpful in identifying patients with a greater risk of poor coronary blood flow and worse short- and long-term prognosis.
From the Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 27, 2009, provisional acceptance given May 7, 2009, final version accepted May 28, 2009.
Address for correspondence: Lin Zhao, MD, Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, No.95 Yong’an Road, Xuanwu District, Beijing, 100050, China. E-mail: [email protected]