Development and validation of cardiovascular risk scores for haemodialysis patients

https://doi.org/10.1016/j.ijcard.2016.04.151Get rights and content

Abstract

Background

A simple clinical tool to predict cardiovascular disease risk does not exist for haemodialysis patients. The long-term coronary risk Framingham Heart Study Risk score (FRS), although used in this population, may be inadequate. Therefore, we developed separate risk-scores for cardiovascular mortality (CVM) and cardiovascular morbidity & mortality (CVMM) in a Fresenius Medical Care-based haemodialysis patient cohort (AROii).

Methods

Applying a modified FRS approach, we derived and internally validated two-year risk-scores in incident European adult patients randomly assigned to a development (N = 4831) or a validation (N = 4796) dataset. External validation was conducted in the third Dialysis Outcomes and Practice Patterns Study (DOPPS III) cohort. Additional discrimination comparing to the FRS was performed.

Results

The overall two-year CVM and CVMM event rates were 5.0 and 22.6 per 100 person-years respectively. Common risk predictors included increasing age, cardiovascular disease history, primary diabetic nephropathy, low blood pressure, and inflammation. The CVM score was more predictive in AROii (c-statistic 0.72) and in DOPPS III (c-statistic 0.73–0.74) than the CVMM score (c-statistic 0.66–0.67 & 0.63 respectively). The FRS was not predictive of either CVM (c-statistic 0.54) or CVMM (c-statistic 0.56) in AROii.

Conclusions

We describe novel, easy-to-apply and interpret CV risk-scores for haemodialysis patients. Our improved cardiovascular prediction performance over traditional (FRS) scores reflected its tailored development and validation in haemodialysis populations, and the integration of non-classical cardiovascular risk factors. The lower expected versus observed CVM and CVMM risk suggests the existence of novel cardiovascular risk factors in this patient population not measured in this study.

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).

Section snippets

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.

References (42)

  • J. Perk et al.

    European Guidelines on cardiovascular disease prevention in clinical practice (2012): The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice

    Atherosclerosis

    (2012)
  • K.U. Eckardt et al.

    High cardiovascular event rates occur within the first weeks of starting hemodialysis

    Kidney Int.

    (2015)
  • J.G. van Manen et al.

    How to adjust for comorbidity in survival studies in ESRD patients: a comparison of different indices

    Am. J. Kidney Dis.

    (2002)
  • J. Coresh et al.

    Prevalence of chronic kidney disease in the United States

    J. Am. Med. Assoc.

    (2007)
  • A. Meguid El Nahas et al.

    Chronic kidney disease: the global challenge

    Lancet

    (2005)
  • D.J. de Jager et al.

    Cardiovascular and noncardiovascular mortality among patients starting dialysis

    J. Am. Med. Assoc.

    (2009)
  • A.S. Go et al.

    Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization

    N. Engl. J. Med.

    (2004)
  • R.N. Foley et al.

    Epidemiology of cardiovascular disease in chronic renal disease

    J. Am. Soc. Nephrol.

    (1998)
  • J.C. Huang et al.

    Performance of the Framingham risk score in patients receiving hemodialysis

    Nephrology

    (2013)
  • Y. Liu et al.

    Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition

    J. Am. Med. Assoc.

    (2004)
  • P. Stenvinkel et al.

    Inflammation modifies the paradoxical association between body mass index and mortality in hemodialysis patients

    J. Am. Soc. Nephrol.

    (2015)
  • Cited by (0)

    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.

    1

    This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

    View full text