Development and validation of cardiovascular risk scores for haemodialysis patients
Introduction
Chronic kidney disease (CKD) represents a major public health problem, affecting 13% of adults in the United States of America [1] and 6–11% in Europe [2]. Poor quality of life, high incidence of morbidity and an increased risk of death [3] all contribute to the substantial disease burden. The premature mortality risk for haemodialysis patients exceeds not only that in the general population but also that of patients with other chronic diseases: a mortality rate of 19.2 per 100 person-years was recently estimated for incident European haemodialysis patients, versus 1.2 per 100 person-years in the general population [4].
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in CKD patients, and in dialysis patients CVD is responsible for approximately 45% of all-cause mortality [5], [6]. Despite this, a simple clinical tool to assess short-term CVD risk in haemodialysis patients does not exist. Use of the Framingham Heart Study score – a tool designed to derive ten-year coronary CVD risk in the general population – to assess CV risk in haemodialysis patients may be inadequate [7], [8] as a number of traditional risk factors for cardiovascular disease in the general population (e.g. elevated serum cholesterol [9] or Body Mass Index (BMI) [10]) are not related to reduced survival in advanced CKD. Furthermore, the CVD risk in CKD patients is also affected by a large number of non-traditional risk factors, such as disturbed mineral-bone homeostasis, uremic toxins, anaemia, oxidative stress and protein energy wasting (PEW). Thus, there is an obvious need to develop a CVD risk score specifically for patients with ESRD. The objective of this study was to derive and validate risk scores for two-year CVD in a European haemodialysis patient population. Specifically we sought to differentiate fatal CV events from any CV events (fatal and non-fatal).
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Study population and baseline recruitment
The Analysing Data, Recognising Excellence and Optimising Outcomes (‘ARO’) research initiative [11] comprises haemodialysis patients at participating European Fresenius Medical Care (EU-FMC) facilities. Anonymized patient-level medical and drug history data are captured quarterly, as are ICD-10 coded hospitalizations and deaths. The current study used the second ARO cohort (‘AROii’), which consists of consecutive incident adult patients with no history of renal transplantation and < 6 months on
Study population
Between 01 January 2007 and 31 December 2009, 11,242 AROii patients were recruited (Fig. 1). Of these, 692 were excluded as non-chronic HD patients, having a history of transplantation or missing data and 923 patients did not complete the 3 months baseline period, leaving 9627 patients in the study. During the two-year follow-up, 723 fatal CV events were reported (an event rate of 5.0 per 100 person-years [95%CI 4.6–5.4]), 951 patients (10.7%) left the study due to a renal transplant and 2035
Discussion
Using a large European cohort of incident haemodialysis patients we have developed dedicated CVD risk scores. Of particular note, our haemodialysis population initiated haemodialysis in 2007 to 2009 and, thus, reflects contemporary medical therapy. Internal validation demonstrated that the predictive scores were applicable for subjects from the whole underlying population and, importantly, the subset of that population experiencing MACE. External validation in DOPPS confirmed the worldwide
Study collaborators
ARO Steering Committee members:
P. Aljama, Reina Sofia University Hospital, Cordoba, Spain.
S.D. Anker, University Medical Center Göttingen (UMG), Göttingen, Germany.
T. Drueke, Paul Brousse Hospital, Paris Sud University, Villejuif, France.
K.-U. Eckardt (co-chair), University of Erlangen-Nuremberg, Germany.
J. Floege (chair), RWTH University of Aachen, Aachen, Germany.
A. de Francisco, Hospital Universitario Valdecilla, Universidad de Cantabria, Santander, Spain.
F. Kronenberg, Medical University of
Disclosures
PA, SDA, BC, TD, KUE, JF, ADF, FK, IM, GS, PS and DW received consultancy fees from Amgen.
BM, and SR are full-time Amgen employees. IAG and MF were full-time Amgen employees when the study was conducted.
IG & JT were contractors to Amgen when the study was conducted.
RLP and BMR are full-time Arbor Research employees. BMR has received a speaker's fee from Kyowa Hakko Kirin. RLP has received speaker's fees from Amgen, Kyowa Hakko Kirin, and Vifor and has served on an advisory panel for Merck and
Conflicts of interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgments
The authors wish to thank the participating Fresenius Medical Care centres for collecting the data. We wish to thank Mrs. Jennie Corrigan for editorial assistance.
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Acknowledgement of grant support: The ARO CKD Research Initiative is a joint observational research commitment from Amgen and Fresenius Medical Care, fully funded by Amgen (Europe) GmbH, Zug, Switzerland.
The DOPPS Program is supported by Amgen, Kyowa Hakko Kirin, Sanofi Renal, Baxter Healthcare, and Vifor Fresenius Medical Care Renal Pharma Ltd. Additional support for specific projects and countries is also provided in Canada by Amgen, BHC Medical, Janssen, Takeda, Kidney Foundation of Canada (for logistics support); in Germany by Hexal, DGfN, Shire, WiNe Institute; and for PDOPPS in Japan by the Japanese Society for Peritoneal Dialysis (JSPD). All support is provided without restrictions on publications.
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This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.