NDT Advance Access published online on July 21, 2007
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm266
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
History of acute coronary events during the predialysis phase of chronic kidney disease is a strong risk factor for major adverse cardiac events in patients initiating haemodialysis
Division of Nephrology, Toho University Ohashi Medical Center, Tokyo, Japan
Correspondence and offprint requests to: Hiroki Hase, MD, PhD, Division of Nephrology, Toho University Ohashi Medical Center, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan. Email: hiroki{at}oha.toho-u.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and methodsResultsDiscussionReferences |
|---|
An initial acute coronary event is an important predictor of future cardiovascular events and all-cause mortality in patients with chronic kidney disease. The aim of this study was to identify an association between acute coronary events during the predialysis phase of chronic kidney disease and major adverse cardiac events in patients initiating maintenance haemodialysis. One hundred sixty-nine patients initiating maintenance haemodialysis were enrolled in this study. In the subsequent follow-up period (median: 60 months), subjects experiencing an initial major adverse cardiac event were compared with those who did not have such an event on the basis of several clinical parameter measurements at the end of the predialysis phase. A history of an acute coronary event was present in 21 patients (12%), and these patients had a higher cumulative major adverse cardiac event rate during follow-up than subjects without a history of acute coronary event (75 vs 19%, P < 0.001). Multivariate Cox regression analysis showed that the following four parameters independently predicted major adverse cardiac events: a history of acute coronary events (hazard ratio, 4.19; 95% confidence interval, 1.61 to 8.13; P < 0.001), presence of diabetes (hazard ratio, 7.70; 95% confidence interval, 3.29 to 23.83; P < 0.001), each 1 g/dl increment in haemoglobin (hazard ratio, 1.57; 95% confidence interval, 1.23 to 2.34; P = 0.002) and each 1 kg/m2 decrement in body mass index (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.98; P = 0.005). In conclusion, these results suggest that a history of acute coronary events, presence of diabetes, increased haemoglobin concentration or decreased body mass index at the end of the predialysis phase were significantly associated with the occurrence of a major adverse cardiac event in patients initiating maintenance haemodialysis.
Keywords: acute coronary event; anaemia; diabetes; haemodialysis initiation; major adverse cardiac event
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionReferences |
|---|
Cardiovascular events caused by atherosclerotic coronary artery disease (CAD) represent a major cause of mortality and morbidity in patients with chronic kidney disease (CKD) treated with maintenance haemodialysis. These patients have more than 10 times the risk of an initial cardiac event than the general population [1]. A history of CAD is an important risk factor for a new CAD event among other factors such as diabetes, dyslipidemia, inflammation, hyperhomocystinemia, hypertension, anaemia and malnutrition in patients on maintenance haemodialysis [2–4]. Lindner et al. [4] noted this pattern in their early work, and proposed that CAD is accelerated in populations undergoing long-term maintenance haemodialysis. However, it was recently reported that angiographic advanced CAD is at a high prevalence at the initiation of haemodialysis [5,6], suggesting that coronary atherosclerosis is already accelerated prior to initiation of dialysis therapy.
Furthermore, cardiac events and overall mortality after starting haemodialysis are significantly higher in patients with CAD than in those without the disease prior to initiation of haemodialysis [7]. Indeed, coronary events and cardiac mortality occur with increased frequency in long-term maintenance haemodialysis patients compared with the general population [1,8], leading to the interpretation that maintenance haemodialysis itself accelerates coronary atherosclerosis and increases CAD mortality. However, in other studies, a longer duration of haemodialysis therapy was not associated with an increase in the risk of death from cardiovascular disease [9]. Moreover, acute myocardial infarction is more likely to occur within a short time after the initiation of dialysis than after a prolonged course of dialysis therapy [10]. These findings suggest that coronary atherosclerosis is already advanced and that the risk of death from CAD is already high before starting maintenance haemodialysis. Therefore, with the goal of reducing cardiovascular and all cause mortality in new haemodialysis patients, we determined risk factors during the predialysis phase for initial major adverse cardiac events (MACE), which are strongly associated with acute coronary events after initiation of haemodialysis.
This issue could be better understood by determining the timing of initial acute coronary events during the predialysis phase of CKD, which can be addressed by determining the event rate of an initial MACE and the rate of all cause mortality in new haemodialysis patients. Since screening for CAD is not routinely carried out at the initiation of haemodialysis, we compared baseline clinical factors including a history of acute coronary events between patients with and without an initial MACE occurring after the onset of maintenance haemodialysis.
|
Subjects and methods |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionReferences |
|---|
Study design and cohort eligibility
Eligibility criteria for our study were as follows: end-stage renal disease resulting from any form of CKD; haemodialysis therapy being initiated at our hospital and having follow-up to the primary endpoint of a MACE or follow-up for 5 years from the start of haemodialysis therapy. In our hospital, 169 patients with CKD began maintenance haemodialysis between January 1994 and December 2000; all patients gave written informed consent to be enrolled in this study.
Baseline haematological and biochemical examinations were performed just prior to the initial haemodialysis session. C-reactive protein concentrations were measured using a turbidimetric method. The glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease (MDRD) equation [11], GFR (ml/min/1.73 m2) = 170 x serum creatinine–0.999 x age–0.176 x blood urea nitrogen–0.170 x albumin0.318 x 0.762 (if female) and the body mass index (BMI) was calculated using height and dry weight. Echocardiograms were performed just after haemodialysis when patient weight had attained the dry weight.
Approval was obtained from the Ethics Committee of Toho University Ohashi Medical Center.
Definitions of a history of acute coronary events
A previous acute coronary event was defined as a previous acute myocardial infarction, unstable angina or acute heart failure attributable to CAD. A previous myocardial infarction was diagnosed when abnormal Q waves were present in the resting electrocardiogram (ECG), focal abnormal left ventricular wall motion was present echocardiographically on admission, or when the patient had a history of hospitalization for a myocardial infarction. Previous unstable angina was defined as Braunwald class III unstable angina with symptoms consistent with acute ischaemia occurring as one or more episodes at rest within the preceding 48 h. Coronary angiography (CAG) was obtained in all patients with a history of acute coronary events.
Outcomes
The primary endpoint of interest was occurrence of an initial MACE after starting maintenance haemodialysis. MACE were defined as (1) ST-elevation acute myocardial infarction (requiring new ST-segment elevation exceeding 1 mm in any lead plus symptoms suggesting acute ischaemia plus a serum creatine kinase concentration of at least three times the upper limit of normal and two times the patient's baseline concentration); (2) no-ST-elevation acute myocardial infarction (requiring symptoms suggesting acute ischaemia plus a serum creatine kinase concentration of at least three times the upper limit of normal and two times the patient's baseline concentration); (3) unstable angina (Braunwald class III unstable angina with one or more episodes of acute ischaemic symptoms at rest within the preceding 48 h, requiring emergency admission and revascularization); (4) acute heart failure without typical chest pain, but attributable to CAD with coronary stenosis exceeding 90% or intracoronary thrombus formation demonstrated by CAG or (5) sudden cardiac arrest. CAG was performed in all patients with MACE, except those with sudden cardiac arrest, at the time of the event. Myocardial revascularization was performed when significant coronary stenosis and morphological indications were confirmed by CAG. Acute myocardial infarction and unstable angina were identified retrospectively. A secondary endpoint of interest was all cause death. Patients were followed up for 5 years or until death from all causes. Patients were personally interviewed during the follow-up period. All surgical or percutaneous myocardial revascularization procedures as well as all hospitalizations were recorded prospectively during follow-up.
Statistical analysis
Quantitative variables with normal distribution are presented as means ± SD. A chi-squared test for categorical variables and an unpaired t-test for continuous variables were used to evaluate differences between groups. Correlations between two variables were examined by linear regression analysis. Independent association between variables was evaluated by stepwise multiple regression analysis. Survival analysis was performed by the Kaplan–Meier method and log-rank test. P < 0.05 was considered statistically significant. Statistical analysis was performed with commercially available software for the Windows operating system (StatView, SAS Institute, Car, NC).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionReferences |
|---|
Patient characteristics
The study was conducted in 169 CKD patients (123 males and 46 females) with a mean age of 60 ± 14 years. Demographic, clinical and laboratory characteristics at the end of the predialysis phase of CKD are summarized in Table 1. Twenty-one patients (12%) had a history of acute coronary events (myocardial infarction in 13, unstable angina in 8). Five patients had an initial acute coronary event in stage 3 of CKD, seven in stage 4 and six in stage 5 (Figure 1). Eighteen patients with a history of acute coronary events had successfully undergone coronary revascularization (percutaneous coronary intervention in 15, coronary artery bypass grafting in 3). GFR was significantly higher in patients with than without a history of acute coronary events. BMI, serum phosphate concentration and left ventricular ejection fraction (LVEF) were significantly lower in patients with than without a history of acute coronary events. There were no significant differences between the groups with respect to other predialysis characteristics (P > 0.05).
|
|
30 ml/min/1.73 m2.Outcomes
All of the study patients were followed up for 5 years after initiation of haemodialysis or to the secondary endpoint. Follow-up duration [median (range)] was 60 months (2 to 60 months). Clinical outcomes at 5 years are summarized in Table 2. Fourteen patients (67%) with a history of acute coronary event and 26 patients (18%) without a history of acute coronary event had a MACE during follow-up. Furthermore, 9 patients (43%) with a history of acute coronary events and 19 patients (13%) without a history of acute coronary events had MACE within 1 year after initiation of haemodialysis. Twenty-seven MACE patients successfully underwent coronary revascularization (percutaneous coronary intervention in 24, coronary artery bypass grafting in 3). Nine patients (43%) with a history of acute coronary events and 13 patients (9%) without a history of acute coronary events died during 5-year follow-up.
|
Cumulative MACE events and all-cause mortality curves are shown in Figure 2. Rates of MACE occurrence at 5 years were 75 and 19% for patients with and without a history of acute coronary events, respectively (P < 0.001, log-rank test). Univariate Cox proportional-hazards regression analysis for the variables studied is summarized in Table 3. The presence of a history of acute coronary events, presence of diabetes, older age, decreased BMI, increased haemoglobin concentration and decreased LVEF were positively associated with MACE during 5 years of follow-up. Multivariate Cox proportional-hazards regression analysis was used to determine independent effects of a history of acute coronary events, diabetes, age, BMI, haemoglobin concentration, LVEF and GFR for an initial MACE after initiating haemodialysis. The presence of a history of acute coronary events was a strong independent predictor of initial MACE (hazard ratio, 4.19; 95% confidence interval, 1.61 to 8.13, P < 0.001). Other significant independent predictors of an initial MACE included presence of diabetes, high haemoglobin concentration and low BMI (Table 4). Mortality rates at 5 years were 81 and 33% for patients with and without a history of acute coronary events, respectively (P < 0.001, log-rank test). Univariate Cox proportional-hazards regression analysis for the variables studied is summarized in Table 5. The presence of a history of acute coronary events, older age, decreased mean blood pressure and decreased BMI were positively associated with all cause mortality during 5 years of follow-up. Multivariate Cox proportional-hazards regression analysis was used to determine the independent effects of a history of acute coronary events, age, mean blood pressure, BMI, haemoglobin concentration and GFR for all cause mortality after initiating haemodialysis. The presence of a history of acute coronary events (hazard ratio, 6.39; 95% confidence interval, 2.10 to 11.89, P < 0.001) was the only independent predictor of all cause mortality.
|
|
|
|
Factors associated with haemoglobin concentration
Factors influencing haemoglobin concentration at initiation of haemodialysis were examined using regression analysis in study patients. Haemoglobin concentration showed significant association with GFR (regression coefficient, 0.177; standard error, 0.045; P = 0.0001) and LVEF (regression coefficient, –0.199; standard error, 0.473; P = 0.0121) at initiation of haemodialysis (Figure 3).
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionReferences |
|---|
The results of the present study indicate that (1) acute coronary events during the predialysis phase of CKD occurred primarily in CKD stages 3 to 5; (2) MACE occurred during the 5-year follow-up in 14 patients (67%) with a history of acute coronary events vs 26 patients (18%) without a history of acute coronary events; (3) initial MACE events in patients without a history of acute coronary events occurred within 1 year after initiation of haemodialysis; (4) the all cause mortality rate was significantly higher in patients with a history of acute coronary events (81%) than in patients without a history of acute coronary events (31%); (5) the presence of a history of acute coronary events, presence of diabetes, increased haemoglobin concentration and decreased BMI at the end of the predialysis phase of CKD were independent predictors of initial MACE after initiation of haemodialysis and (6) the presence of a history of acute coronary events was the only independent predictor of 5-year mortality.
Cardiovascular disease, especially CAD, is highly prevalent in patients receiving maintenance haemodialysis therapy, and it affects long-term mortality. Therefore, it is important to both evaluate the extent of CAD in patients with CKD at the time of initiation of haemodialysis and to screen for both traditional and non-traditional cardiovascular risk factors. The Kidney Disease Outcome Quality Initiation (K/DOQI) guidelines [12] emphasize that pharmacological stress echocardiography or nuclear scintigraphy are favourable non-invasive techniques to diagnose CAD in these patients. However, those diagnostic techniques cannot be performed in all of the hospitals or clinics that initiate haemodialysis therapy. Therefore, we designed this study to evaluate the importance of acute coronary event history in predicting future acute coronary events in patients initiating haemodialysis therapy.
During more than 5 years of prospective follow-up, the rate of an initial MACE after the initiation of haemodialysis was 18% in the 148 patients without a history of acute coronary events. This was significantly lower than the rate of 67% observed in the 21 patients having a history of acute coronary events. Interestingly, 70% of all MACE occurred within the first year after initiating haemodialysis. In previous studies, an increased risk of early myocardial infarction was related to the initiation of dialysis, since 29% of infarctions occurred within 1 year and 52% within 2 years after initiation of dialysis [10]. Furthermore, age-standardized rates of death, cardiovascular events and hospitalization increase substantially with progressively lower estimated GFR [13]. Our present findings confirmed the results from these previous studies. Although these results suggest that progression of coronary atherosclerosis is more affected by metabolic abnormalities associated with uraemia than by haemodialysis itself, initiation of haemodialysis may play an important role in coronary plaque destabilization and/or coronary thrombus formation.
Predictors of an initial MACE after starting haemodialysis were identified in our study. Mortality rates from cardiac causes after acute myocardial infarction among haemodialysis patients have been reported to be as high as 70.2% at 5 years [10]. Moreover, recent morphological studies designed to examine risk factors for cardiovascular events have identified a history of CAD and/or congestive heart failure as risk factors [2,4,8]. The identification of a history of CAD as a powerful predictor of future cardiovascular events in haemodialysis patients underscores the importance of determining risk factors for initial MACE after starting haemodialysis. In the present study, we therefore examined such risk factors in haemodialysis patients. The prevalence of a history of acute coronary events was 12% among all of the study patients, which was somewhat lower than that found in previous studies [14–16]. This difference may be explained by the inclusion of all haemodialysis patients, including long-term haemodialysis patients, in data from the United States Renal Data System (USRDS) [15], by the fact that prevalence of CAD in Japanese CKD patients is lower than in American or European CKD patients [16], or by both factors.
Increased haemoglobin concentration was an independent predictor for a MACE in this study. Recently, excessive correction of renal anaemia was associated with an increased risk of mortality or cardiovascular events in CKD patients with haemodialysis [17,18] or without haemodialysis [19,20]. Although it is unclear why higher haemoglobin concentrations in the predialysis phase of CKD are linked with an increased onset of MACE in the haemodialysis phase of CKD, a number of hypotheses are possible. A relatively higher haemoglobin concentration may be related to an earlier requirement for haemodialysis treatment because of complications including pulmonary oedema. Indeed, haemoglobin concentration was significantly associated with GFR in this study. Kumagai et al. [21] demonstrated in chronic haemodialysis patients with chronic heart failure that levels of atrial and brain natriuretic peptide, which suggested cardiac overload or cardiac dysfunction, were strongly correlated with erythropoietin level [21]. In the same article, the authors also suggested that cardiac dysfunction may promote a stimulus for erythropoietin production in haemodialysis patients, despite the fact that end-stage renal disease usually interferes with erythropoietin production. This mechanism may explain how a lower LVEF in our population, caused by symptomatic or asymptomatic CAD, may have lead to erythropoietin production and a relatively higher haemoglobin concentration. Therefore, a higher haemoglobin concentration may directly reflect the presence of severe left ventricular dysfunction in our population. Unfortunately, we did not obtain serum erythropoietin concentration data in our population. If true, this hypothesis would predict the observed higher haemoglobin concentration as an independent predictor of future MACE. As an additional hypothesis, a relatively higher haemoglobin concentration may play an important role in coronary thrombus formation in new haemodialysis patients with destabilized coronary plaques. Indeed, about 42% of new haemodialysis patients without a history of acute coronary events had asymptomatic CAD, and about 50% of these same patients had acute coronary events within 1 year after initiation of haemodialysis [22]. However, it has been demonstrated that anaemia is a strong and independent predictor of acute myocardial infarction or MACE in patients without CKD [23,24]. A large-scale multicentre risk-matched trial will be necessary to clarify the mechanism explaining the association between haemoglobin concentration and acute coronary events in new haemodialysis patients.
Factors such as history of acute coronary events, presence of diabetes, haemoglobin concentration and BMI at the end of the predialysis phase of CKD are easily determined in patients initiating haemodialysis therapy without performing special examinations. These simple parameters supply important information about future severe cardiac events. Diabetic CKD patients with a history of acute coronary events in the predialysis phase may have to undergo evaluation for CAD at the initiation of haemodialysis, and patients with severe CAD diagnosed by CAG may have to undergo aggressive treatment such as coronary artery bypass grafting. In contrast, those patients without evidence of CAD based on invasive and/or non-invasive examinations at the initiation of haemodialysis may simply require careful monitoring of symptoms, of electrocardiographic changes, and changes in left ventricular wall motion by echocardiography.
An important limitation of the present study was that patients with asymptomatic CAD may have been included in the group of patients without a history of acute coronary events. However, we recently demonstrated that about 50% of new haemodialysis patients with asymptomatic CAD had a de novo MACE during 2 years after initiating haemodialysis [22]. Therefore, despite this limitation, we believe that our main finding, that a history of acute coronary events during the predialysis phase predicts initial MACE during the haemodialysis phase in CKD patients, is an important observation.
In conclusion, the present study clearly confirmed that a history of acute coronary events at the initiation of haemodialysis, decreased BMI and increased haemoglobin concentration at the same time point, as well as the presence of diabetes are important predictors of new MACE in patients initiating maintenance haemodialysis. Our results indicate that active prevention of initial acute coronary events before starting haemodialysis may be very important for reducing the rate of cardiovascular and all cause mortality in new haemodialysis patients. If it is impossible to prevent the occurrence of initial acute coronary events before initiating haemodialysis, active screening for CAD by single photon emission computed tomography and/or coronary angiography should be performed at least in patients with a history of acute coronary events at the time of initiation of haemodialysis.
Conflict of interest statement. None declared.
|
References |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionReferences |
|---|
- Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis (1998) 32(Suppl 3):S112–119.[Web of Science][Medline]
- Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Hypoalbuminemia, cardiac morbidity, and mortality in end-stage renal disease. J Am Soc Nephrol (1996) 7:728–736.[Abstract]
- Moustapha A, Naso A, Nahlawi M, et al. Prospective study of hyperhomocysteinemia as an adverse cardiovascular risk factor in end-stage renal disease. Circulation (1998) 97:138–141.
[Abstract/Free Full Text] - Lindner A, Charra B, Sherrard DR, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med (1974) 290:697–701.[Web of Science][Medline]
- Joki N, Hase H, Nakamura R, Yamaguchi T. Onset of coronary artery disease prior to initiation of haemodialysis in patients with end-stage renal disease. Nephrol Dial Transplant (1997) 12:718–723.
[Abstract/Free Full Text] - Ohtake T, Kobayashi S, Moriya H, et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination. J Am Soc Nephrol (2005) 16:1141–1148.
[Abstract/Free Full Text] - Hase H, Joki N, Ishikawa H, et al. Prognostic value of stress myocardial perfusion imaging using adenosine triphosphate at the beginning of haemodialysis treatment in patients with end-stage renal disease. Nephrol Dial Transplant (2004) 19:1161–1167.
[Abstract/Free Full Text] - Ganesh SK, Hulbert-Shearon T, Port FK, Eagle K, Stack AG. Mortality differences by dialysis modality among incident ESRD patients with and without coronary artery disease. J Am Soc Nephrol (2003) 14:415–424.
[Abstract/Free Full Text] - Malatino LS, Mallamaci F, Benedetto FA, et al. Hepatocyte growth factor predicts survival and relates to inflammation and intima media thickness in end-stage renal disease. Am J Kidney Dis (2000) 36:945–952.[Web of Science][Medline]
- Herzog CA, Ma JZ, Collins AJ. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med (1998) 339:799–805.
[Abstract/Free Full Text] - Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med (1999) 130:461–470.
[Abstract/Free Full Text] - Bolton K, Beddhu S, Campese VM, et al. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis (2005) 45(Suppl 3):S1–153.[Medline]
- Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med (2004) 351:1296–1305.
[Abstract/Free Full Text] - Cheung AK, Sarnak MJ, Yan G, et al. HEMO Study Group. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int (2004) 65:2380–2389.[CrossRef][Web of Science][Medline]
- U.S. Renal Data System. USRDS 2001 Annual Data Report. Bethesda, MD: The National Institutes of Health, National Institute of Diabetes and Digestive Diseases.
- Andreucci VE, Fissell RB, Bragg-Gresham JL, et al. Dialysis Outcomes and Practice Patterns Study (DOPPS) data on medications in hemodialysis patients. Am J Kidney Dis (2004) 44(Suppl 3):61–67.[CrossRef][Medline]
- Besarab AB, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. New Engl J Med (1998) 339:584–590.
[Abstract/Free Full Text] - Regidor DL, Kopple JD, Kovesdy CP, et al. Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol (2006) 17:1181–1191.
[Abstract/Free Full Text] - Singh AK, Szczech L, Tang KL, et al. CHOIR Investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med (2006) 355:2085–2098.
[Abstract/Free Full Text] - Drueke TB, Locatelli F, Clyne N, et al. CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med (2006) 355:2071–2084.
[Abstract/Free Full Text] - Kumagai J, Yorioka N, Kawanishi H, et al. Relationship between erythropoietin and chronic heart failure in patients on chronic hemodialysis. J Am Soc Nephrol (1999) 10:2407–2411.
[Abstract/Free Full Text] - Hase H, Tsunoda T, Tanaka Y, et al. Risk factors for de novo acute cardiac events in patients initiating hemodialysis with no previous cardiac symptom. Kidney Int (2006) 70:1142–1148.[CrossRef][Web of Science][Medline]
- Cavusoglu E, Chopra V, Gupta A, et al. Usefulness of the white blood cell count as a predictor of angiographic findings in an unselected population referred for coronary angiography. Am J Cardiol (2006) 98:1189–1193.[CrossRef][Web of Science][Medline]
- Muzzarelli S, Pfisterer M. TIME Investigators. Anemia as independent predictor of major events in elderly patients with chronic angina. Am Heart J (2006) 152:991–996.[CrossRef][Web of Science][Medline]
Revision received 6. 4.07.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Trivedi, Q. Xiang, and J. P. Klein Risk factors for non-fatal myocardial infarction and cardiac death in incident dialysis patients Nephrol. Dial. Transplant., January 1, 2009; 24(1): 258 - 266. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||