Abstract
Background
Using standard cutoffs derived from healthy adults, high-sensitivity cardiac troponin
T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are frequently
elevated in patients with reduced glomerular filtration rate (GFR), with unclear implications.
We sought to compare GFR-specific cutoffs of each biomarker with standard cutoffs
for discrimination of cardiovascular risk in asymptomatic patients with chronic kidney
disease.
Methods
We investigated a prospective cohort of 1956 participants with median GFR of 27 mL/min/1.73
m2. Cox proportional hazards models were used to examine the association between each
biomarker and first adjudicated cardiovascular event (unstable angina, myocardial
infarction, heart failure, stroke, cardiovascular death). We used an outcome-based
approach to identify optimal risk-based cutoffs for each biomarker within GFR strata
(< 20, 20-29, 30-44 mL/min/1.73 m2). We evaluated the added prognostic value of each biomarker to a multivariable base
model, comparing GFR-specific with standard cutoffs.
Results
Hs-cTnT and NT-proBNP were elevated in 76% and 82% of participants, respectively.
A total of 401 events were recorded during 6772 person-years at risk. Both biomarkers
were independent predictors of cardiovascular events. Optimal cutoffs for each biomarker
were higher than standard thresholds, being highest at GFR values < 20 mL/min/1.73
m2. Addition of hs-cTnT to the base model using GFR-specific cutoffs significantly improved
reclassification for events (52%) and nonevents (21%). Similar findings were observed
for NT-proBNP. In contrast, use of standard cutoffs failed to reclassify patients
who had no event as lower risk.
Conclusions
Among asymptomatic patients with advanced chronic kidney disease, optimal cutoffs
for hs-cTnT and NT-proBNP differed according to GFR level and outperformed standard
cutoffs for discrimination of cardiovascular risk.
Résumé
Contexte
À l’aune des valeurs seuils standard établies chez les adultes en bonne santé, on
constate que les taux de troponines cardiaques hypersensibles et de propeptide natriurétique
de type B N-Terminal (NT-proBNP) sont fréquemment élevés chez les patients présentant
un débit de filtration glomérulaire (DFG) réduit. Les implications de cette observation
restent à élucider. Nous avons cherché à comparer les valeurs seuils de chaque biomarqueur
selon le DFG aux valeurs seuils standards afin de déterminer le risque cardiovasculaire
chez des patients asymptomatiques atteints d’insuffisance rénale chronique.
Méthodologie
Nous avons mené une étude de cohorte prospective regroupant 1956 sujets présentant
un DFG médian de 27 ml/min/1,73 m2. Des modèles à risques proportionnels de Cox ont servi à examiner l’association entre
chaque biomarqueur et le premier événement cardiovasculaire confirmé (angine instable,
infarctus du myocarde, insuffisance cardiaque, accident vasculaire cérébral, décès
d’origine cardiovasculaire). Nous avons adopté une approche axée sur la survenue des
événements afin de déterminer les valeurs seuils optimales fondées sur le risque au
regard de chaque biomarqueur selon la stratification du DFG (< 20, 20-29, 30-44 ml/min/1,73
m2). Nous avons évalué la valeur pronostique ajoutée de chaque biomarqueur dans un modèle
de base à variables multiples, comparant les valeurs seuils selon le DFG aux valeurs
seuils standards.
Résultats
Les taux de troponines cardiaques hypersensibles et de NT-proBNP étaient élevés chez
76 % et 82 % des participants, respectivement. Au total, 401 événements ont été consignés
au cours de 6772 années-personnes à risque. Les deux biomarqueurs ont constitué des
prédicteurs indépendants des événements cardiovasculaires. Les valeurs seuils optimales
de chaque biomarqueur étaient plus élevées que les valeurs seuils standards, culminant
en présence d’un DFG < 20 ml/min/1,73 m2. L’ajout de la troponine cardiaque hypersensible au modèle de base compte tenu des
valeurs seuils selon le DFG a amélioré sensiblement la reclassification des cas où
il y avait présence d’événements (52 %) ou absence d’événements (21 %). Des résultats
similaires ont été observés pour la NT-proBNP. En revanche, l’utilisation des valeurs
seuils standards n’a pas entraîné la reclassification des patients n’ayant pas eu
d’événement dans une catégorie de risque inférieure.
Conclusions
Chez les patients asymptomatiques atteints d’insuffisance rénale chronique avancée,
les valeurs seuils optimales de troponines cardiaques hypersensibles et de NT-proBNP
différaient selon le DFG et se sont avérées plus concluantes que les valeurs seuils
standards pour déterminer le risque cardiovasculaire.
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Article info
Publication history
Published online: June 20, 2019
Accepted:
June 16,
2019
Received:
March 8,
2019
Footnotes
See editorial by Hundemer and Sood, pages 1082–1084 of this issue.
See page 1112 for disclosure information.
Identification
Copyright
© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Is It Time to Recalibrate Cardiac Prediction Tools to Accommodate Chronic Kidney Disease?Canadian Journal of CardiologyVol. 35Issue 9
- PreviewCardiovascular disease disproportionately affects patients with chronic kidney disease (CKD) compared with the remainder of the population. In fact, CKD has historically been considered a cardiovascular disease “risk equivalent” along with other well known risk factors such as diabetes mellitus and peripheral vascular disease.1 Moreover, there is a clear “dose-response” relationship with more advanced stages of CKD associated with progressively higher rates of cardiovascular disease.2
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