Renal Function and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Systematic Review
Emanuele Di Angelantonio1, John Danesh1*, Gudny Eiriksdottir2, Vilmundur Gudnason2,3
1. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom, 2. Icelandic Heart Association, Kopavogur, Iceland, 3. University of Iceland, Reykjavik, Iceland
Background
End-stage chronic kidney disease is associated with striking excesses of cardiovascular mortality, but it is uncertain to what exten t renal function is related to risk of subsequent coronary heart disease (CHD) in apparently healthy adults. This study aims to quantify the association of markers of renal function with CHD risk in essentially general populations.
Methods and Findings
Estimated glomerular filtration rate (eGFR) was calculated using standard prediction equations based on serum creatinine measurements made in 2,007 patients diagnosed with nonfatal myocardial infarction or coronary death during follow-up and in 3,869 people without CHD in the Reykjavik population-based cohort of 18,569 individuals. There were small and nonsignificant odds ratios (ORs) for CHD risk over most of the range in eGFR, except in the lowest category of the lowest fifth (corresponding to values of <60 ml/min/1.73m2), in which the OR was 1.33 (95% confidence interval 1.01–1.75) after adjustment for several established cardiovascular risk factors. Findings from the Reykjavik study were reinforced by a meta-analysis of six previous reports (identified in electronic and other databases) involving a total of 4,720 incident CHD cases (including Reykjavik), which yielded a combined risk ratio of 1.41 (95% confidence interval 1.19–1.68) in individuals with baseline eGFR less than 60 ml/min/1.73m2 compared with those with higher values.
Conclusions
Although there are no strong associations between lower-than-average eGFR and CHD risk in apparently healthy adults over most of the range in renal function, there may be a moderate increase in CHD risk associated with very low eGFR (i.e., renal dysfunction) in the general population. These findings could have implications for the further understanding of CHD and targeting cardioprotective interventions.
Funding: This study was supported by a programme grant from the British Heart Foundation (JD and VG) and by the Raymond and Beverly Sackler Research Award in the Medical Sciences (JD). Aspects of the work were supported by an unrestricted educational grant from GlaxoSmithKline (JD). The funding sources had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Academic Editor: Anushka Patel, The George Institute, Australia
Citation: Di Angelantonio E, Danesh J, Eiriksdottir G, Gudnason V (2007) Renal Function and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Systematic Review. PLoS Med 4(9): e270 doi:10.1371/journal.pmed.0040270
Received: April 18, 2007; Accepted: July 27, 2007; Published: September 4, 2007
Copyright: © 2007 Di Angelantonio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abbreviations: BMI, body mass index; CG, Cockcroft-Gault; CHD, coronary heart disease (defined as nonfatal myocardial infarction or coronary death); CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; MI, myocardial infarction; OR, odds ratio
* To whom correspondence should be addressed. E-mail: john.danesh@phpc.cam.ac.uk
