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

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 m(2) 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.

Fig 1 Renal function and risk of coronary heart disease and non-vascular mortality. Hazard ratios are adjusted for age, sex, smoking status, history of diabetes, total cholesterol, log triglycerides, systolic blood pressure, and body mass index. All hazard ratios are compared with people without chronic kidney disease with estimated glomerular filtration rate (eGFR) of 75-89 ml/min/1.73 m² and plotted against mean eGFR within each group. Size of data markers is proportional to inverse of variance of hazard ratios. Confidence intervals are calculated using floating variances; eGFR is calculated using MDRD equation

Fig 2 Risk of vascular and non-vascular outcomes in people with chronic kidney disease compared with people without chronic kidney disease. Analysis restricted to participants with complete information on smoking status, history of diabetes, total cholesterol, triglycerides (log transformed), systolic blood pressure, and body mass index. Hazard ratios are adjusted for age, sex, smoking status, history of diabetes, systolic blood pressure, total cholesterol, log triglycerides, and body mass index. Size of data markers is proportional to inverse of variances of hazard ratios