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Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c4986 (Published 30 September 2010) Cite this as: BMJ 2010;341:c4986
  1. Emanuele Di Angelantonio, university lecturer1,
  2. Rajiv Chowdhury, research associate1,
  3. Nadeem Sarwar, university lecturer12,
  4. Thor Aspelund, senior statistician34,
  5. John Danesh, professor1,
  6. Vilmundur Gudnason, professor34
  1. 1Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
  2. 2Section of Population Health Sciences, University of Aberdeen, Aberdeen, UK
  3. 3Icelandic Heart Association, Kopavogur, Iceland
  4. 4University of Iceland, Reykjavík, Iceland
  1. Correspondence to: E Di Angelantonio emanuele.diangelantonio{at}phpc.cam.ac.uk
  • Accepted 16 August 2010

Abstract

Objective To quantify associations of chronic kidney disease stages with major cardiovascular disease and non-vascular mortality in the general adult population.

Design Prospective population based cohort study.

Setting Reykjavik, Iceland.

Participants 16 958 people aged 33-81 years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry.

Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality.

Results 1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 4010 coronary heart disease outcomes, 559 deaths from stroke, and 3875 deaths from non-vascular causes were recorded. Compared with the reference group (estimated glomerular filtration rate 75-89 ml/min/1.73 m2 and no proteinuria), people with lower renal function within the normal range of glomerular filtration rate did not have significantly higher risk of coronary heart disease. By contrast, in 1210 (7%) participants with chronic kidney disease at entry, hazard ratios for coronary heart disease, adjusted for several conventional cardiovascular risk factors, were 1.55 (95% confidence interval 1.02 to 2.35) for stage 1, 1.72 (1.30 to 2.24) for stage 2, 1.39 (1.22 to 1.58) for stage 3a, 1.90 (1.22 to 2.96) for stage 3b, and 4.29 (1.78 to 10.32) for stage 4. Information on chronic kidney disease increased discrimination and reclassification indices for coronary heart disease when added to conventional risk factors (P<0.01). The incremental gain provided by chronic kidney disease was lower than that provided by diabetes or smoking (C index increases of 0.0015, 0.0024, and 0.0124 respectively). Hazard ratios with chronic kidney disease were 0.97 (0.82 to 1.15) for cancer mortality and 1.26 (1.07 to 1.50) for other non-vascular mortality.

Conclusions In people without manifest vascular disease, even the earliest stages of chronic kidney disease are associated with excess risk of subsequent coronary heart disease. Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease in this population. Further studies are needed to investigate associations between chronic kidney disease and non-vascular mortality from causes other than cancer.

Footnotes

  • Contributors: EDA and RC contributed equally to this work, as did JD and VG. All authors contributed to the study concept and design. TA and VG were responsible for acquisition of data. All authors were involved in analysis and interpretation of data. EDA and JD drafted the manuscript, and all authors critically revised it for important intellectual content. EDA, RC, and TA did the statistical analysis. JD and VG supervised the study. EDA and JD are the guarantors.

  • Funding: This work is underpinned by a programme grant from the British Heart Foundation. RC is supported by a Gates Cambridge PhD scholarship. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that (1) they have not received any support for the submitted work; (2) they have no relationships with companies that might have an interest in the submitted work in the previous 3 years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) they have no non-financial interests that may be relevant to the submitted work.

  • Ethical approval: The National Bioethics Committee and the Data Protection Authority of Iceland approved the study protocol, and participants gave informed consent.

  • Data sharing: No additional data available.

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