Renal function and risk of coronary heart disease in general populations: new prospective study and systematic review

Abstract

Background: End-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 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/1.73 m2), 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/1.73 m2 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.

Figure 1. Summary of Meta-Analysis Flow

Figure 2. Association between Estimated Baseline GFR and CHD Adjusted for Age, Sex, Period, Smoking Status, and Other Established Risk Factors

eGFR was calculated using Modification of Diet in Renal Disease equation. The size of the data markers is proportional to the inverse of the variance of the ORs. 95% CIs are calculated using floating-variance. Established risk factors included total cholesterol, triglycerides (log transformed), systolic blood pressure, and BMI. eGFR_MDRD, overall χ ² with 6 df = 14.6, p = 0.02.

Figure 3. Meta-analysis of Reported Data from Prospective Studies in Essentially General Western Populations of CHD Risk in Individuals with eGFR_MDRD of <60 versus ≥ 60 ml/min/1.73 m², with Adjustments Reported for Several Established Cardiovascular Risk Factors

The size of the data markers is proportional to the inverse of the variance of the risk ratios. Overall estimate calculated using fixed effect meta-analysis. Random effects overall relative risk 1.32, 95% CI 1.19–1.47. Test for heterogeneity: χ ² = 12.9 with 6 df, p = 0.045; I ² = 56% (95% CI 0%–80%). For adjustments see Table 3. KORA, The MONICA/KORA Augsberg Study; NHANES, National Health and Nutrition Examination Survey.