Date Published: September 4, 2007
Publisher: Public Library of Science
Author(s): Emanuele Di Angelantonio, John Danesh, Gudny Eiriksdottir, Vilmundur Gudnason, Anushka Patel
Abstract: BackgroundEnd-stage chronic kidney disease is associated with striking excesses of cardiovascular mortality, but it is uncertain to what extent 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 FindingsEstimated 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.ConclusionsAlthough 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.
Partial Text: There is a striking excess (i.e., relative risks of ≈5) of cardiovascular disease mortality in patients with end-stage chronic kidney disease (CKD) compared with the general population [1,2]. Strong associations have also been reported between the occurrence of non-dialysis-dependent CKD and subsequent incidence of cardiovascular outcomes in high-risk groups, including patients with pre-existing ischaemic cardiovascular diseases, heart failure, and high blood pressure [3–7]. Major scientific societies have recommended that all patients with manifest cardiovascular disease should be screened for evidence of kidney disease . There is, by contrast, comparatively sparse and uncertain evidence on renal dysfunction (evaluated using estimated glomerular filtration rate [eGFR]) and risk of cardiovascular diseases in people without known cardiovascular or renal diseases, even though demonstration of even modest risks in the general population could have considerable public health and clinical relevance. A recent systematic review identified only a few prospective studies of non-dialysis-dependent CKD in general populations, three of which were listed as reporting on cardiovascular outcomes, comprising a total of only about 900 cardiovascular deaths . Reports from these [9–11] (and other more recently published [12–18]) studies have yielded apparently conflicting findings, and their interpretation has been further complicated by mixing of vascular outcomes related to different arterial beds (such as diseases of the coronary, cerebrovascular, and peripheral circulations).
The mean age at CHD event among cases in the Reykjavik Study was about 66 y (standard deviation 8 y). As expected, there were highly statistically significant differences between cases and controls with respect to established cardiovascular risk factors (Table 1). Baseline creatinine concentrations and eGFRMDRD showed no significant differences between cases and controls, whereas eGFRCG was significantly higher in cases than in controls (a surprising finding consistent with the possibility of a nonlinear effect, as described below).
In the largest single population-based study of eGFR and CHD to our knowledge thus far, we have shown that 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. A moderate association may, however, exist among individuals with very low eGFR, i.e., those with eGFR near or less than 60 ml/min/1.73 m2 of body surface area. This cut point coincides with the definition of CKD suggested by the American National Kidney Foundation . Such an association implies a nonlinear effect of low eGFR on CHD risk, a possibility that requires evaluation in larger numbers. Moderate associations among individuals with eGFR near or less than 60 ml/min/1.73 m2 of body surface area were consistently observed with CHD risk in many clinically relevant subgroups, such as in women and men and at different levels of established risk factors and other characteristics (e.g., blood glucose levels and haematocrit). Our updated meta-analysis reinforces the validity and generalisability of the new data from the Reykjavik study; examination of several study characteristics in our review did not identify important sources of heterogeneity. Finally, our data demonstrate that the decade-to-decade consistency in renal function in apparently healthy adults is similar to that for blood pressure or total blood cholesterol, although larger assessments will be required to assess whether this variability differs importantly at different levels of renal function.