Prognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study

doi:10.1016/S0272-6386(03)00746-7

American Journal of Kidney Diseases

Volume 42, Issue 3, September 2003, Pages 513-523

https://doi.org/10.1016/S0272-6386(03)00746-7 Get rights and content

Abstract

Background: Cardiac disease is the main cause of mortality in long-term hemodialysis patients. Cardiac troponins (cTn) have been proposed to be markers of cardiac damage, but their value is still debated in hemodialysis patients. The aim of this prospective study is to assess the prognostic value of biochemical cardiac markers in long-term hemodialysis patients. Methods: We measured serum levels of cTn I (cTnI), cTn T (cTnT), and creatine kinase-MB (CK-MB) in 258 asymptomatic patients (mean age, 60 ± 15 years; 150 men) before the dialysis treatment. All causes of death and major adverse cardiac events (MACEs: cardiac death, myocardial infarction, or unstable angina) were recorded at 1 and 2 years of follow-up. A Cox proportional hazard regression model was used to identify factors predictive of mortality. Results: On inclusion, 48 patients (18.6%) had cTnT levels greater than 0.1 ng/mL, 46 patients (17.8%) had cTnI levels greater than 0.15 ng/mL, and 18 patients (7.0%) had CK-MB levels greater than 3 ng/mL. Of 246 patients followed up at 2 years, 64 patients (26%) had died, including 29 patients (11.8%) of cardiac disease, and 49 patients (19.9%) experienced at least 1 MACE. MACEs were significantly greater for patients with elevated predialysis serum cTnT and CK-MB levels (>0.1 ng/mL and 3 ng/mL, respectively) than for patients with normal levels of these cardiac markers (31.9% versus 17.1%; P = 0.01; 38.9% versus 18.4%; P = 0.02, respectively). No differences were found for cTnI levels. In multivariate analysis, age (relative risk [RR], 1.04; P = 0.002), previous ischemic heart disease (RR, 2.5; P = 0.0001), and serum cTnT levels greater than 0.1 ng/mL (RR, 1.9; P = 0.04) were independent significant factors for MACEs. Conclusion: Increased predialysis serum levels of cTnT and CK-MB, but not cTnI, were predictive of a high risk for overall mortality and MACEs at 2 years in asymptomatic hemodialysis patients.

Section snippets

Study protocol

We included for a 2-year follow-up all consecutive patients older than 18 years who attended 1 of 3 Parisian hemodialysis centers between April 12 and 26, 1999. All patients had been treated with bicarbonate hemodialysis for more than 3 months (3 sessions/wk). Exclusion criteria were rhabdomyolysis, hemoglobin concentration less than 8 g/dL (80 g/L) before the dialysis session, surgery or severe infectious episode during the 8 days before the study, myocardial infarction, angina pectoris,

Population

Clinical data were obtained for 302 patients. Forty-four patients were excluded because of severe anemia (2 patients), refusal to participate (7 patients), recent start of dialysis therapy (3 patients), or absence for holidays (32 patients). Thus, blood samples were collected from 258 patients (150 men, 108 women; mean age, 60.2 ± 15.2 years; range, 18 to 88 years). Seventy two percent are white, 15.5% are black, 10.5% are Arabic, and 2% are Asian. Clinical baseline parameters of this

Discussion

This is one of the largest prospective studies of hemodialysis patients enrolled for this purpose to date. Our population study reflects the general dialysis population in France.17

We assessed the predictive value of cTnT and CK-MB levels for fatal and nonfatal cardiac events. Our data suggest that slightly elevated predialysis cTnT and CK-MB levels truly reflect subclinical myocardial damage with a poor cardiac prognosis, regardless of whether heart disease was diagnosed at baseline. Other

Acknowledgements

The authors thank Roche Diagnostics, France, and Dade-Berhing Diagnostics, France, for providing the immunoassays; Sorin, Theradial, and Biodome for technical assistance; and the Biochemical Laboratory of AURA and the medical staff and nurses of the dialysis centers that participated in this study for their substantial contribution.

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Hemodialysis patients have an enhanced risk for cardiovascular events. Cardiac biomarkers provide useful information for stratifying their risk. However the prognosis value of creatine kinase MB isoenzyme (CKMB) has not yet been validated in this population. The aim of the present study is to determine the predictable value of CK-MB in hemodialysis.
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The median value of CKMB was 1 (1–2) ng/mL with no patient exceeding normal laboratory values. Previous heart disease, diabetes mellitus, peripheral vascular disease and systolic and diastolic dysfunction were associated with higher levels of CKMB. Ninety-four patients (44.5%) cardiovascular events were recorded. CKMB levels ≥2 ng/mL was independently associated to cardiovascular events during the follow up after adjusting. Adding CKMB to a model including several variables for predicting cardiovascular events, resulted in 17% improvement in risk discrimination (IDI) with a relative IDI of 9.9% (p = 0.04).
CKMB is a good marker for stratifying cardiovascular risk in hemodialysis patients and adds prognosis information to other well known independent predictors for cardiovascular events.
Los pacientes en hemodiálisis presentan un riesgo cardiovascular elevado. Los biomarcadores cardiacos otorgan información útil para estratificar dicho riesgo cardiovascular. Sin embargo, el valor pronóstico de la isoenzima MB de la creatincinasa (CKMB) no ha sido aún validado en esta población. El objetivo del presente trabajo es evaluar el valor predictivo de CKMB en una población en hemodiálisis.
Una cohorte de 211 pacientes en hemodiálisis (58,3% varones, con una edad media de 73 [60–80] años) fueron seguidos durante 39 (19–56) meses. Se recogieron basalmente los valores de diferentes biomarcadores cardiacos incluyendo CKMB. Se evaluaron los factores asociados a niveles más elevados de CKMB, así como su valor predictivo independiente.
La mediana de CKMB fue de 1 (1–2) ng/mL. Todos los pacientes presentaron valores dentro de los establecidos de referencia en la población normal. Los antecedentes de cardiopatía, diabetes mellitus, enfermedad periférica y la disfunción diastólica y sistólica se asociaron a niveles más elevados de CKMB. Un total de 94 pacientes (44,5%) presentaron un evento cardiovascular. Los niveles de CKMB ≥ 2 ng/mL se asociaron de manera independiente a presentar eventos cardiovasculares durante el seguimiento tras el ajuste para diferentes factores. La adición de CKMB a un modelo predictor con diferentes factores generó una mejoría del 17% en la estimación de la probabilidad de forma lineal (IDI) con un IDI relativo del 9,9% (p = 0,04).
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Original investigation: dialysis therapiesPrognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study

Abstract

Section snippets

Study protocol

Population

Discussion

Acknowledgements

Am J Kidney Dis

Am Heart J

Am J Kidney Dis

Clin Biochem

J Am Coll Cardiol

J Am Coll Cardiol

Kidney Int Suppl

J Am Coll Cardiol

Am J Kidney Dis

J Am Coll Cardiol

Clin Biochem

Am Heart J

J Am Coll Cardiol

Cardiovascular risk in end-stage renal diseaseVascular aspects

Nephrol Dial Transplant

Poor long-term survival after acute myocardial infarction among patients on long-term dialysis

N Engl J Med

Myocardial infarction definedA consensus document of the Joint European Society of Cardiology /American College of Cardiology Committee for the redefinition of myocardial infarction

J Am Coll Cardiol

Specificity of cardiac troponins I and T in renal disease

Clin Chem Lab Med

Troponin T, a predictor of death in chronic haemodialysis patients

Eur Heart J

Original investigation: dialysis therapies
Prognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study