The Relationship Between Nontraditional Risk Factors and Outcomes in Individuals with Stage 3 to 4 CKD

Background: Chronic kidney disease is associated with increased risk for cardiovascular disease and mortality. Both traditional and nontraditional cardiovascular disease risk factors may contribute.

Study Design: Cohort.

Settings & Participants: Community-based adult population of the Atherosclerosis Risk in Communities and Cardiovascular Health Studies with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2).

Predictors: Nontraditional cardiovascular disease risk factors, including body mass index, diastolic blood pressure, and triglyceride, albumin, uric acid, fibrinogen, C-reactive protein, and hemoglobin levels.

Outcomes: Composite of myocardial infarction, stroke, and all-cause mortality. Secondary outcomes included individual components of the composite.

Results: Of 1,678 individuals with decreased eGFR (mean, 51.1 +/- 8.5 mL/min/1.73 m(2)), 891 (53%) reached the composite end point during a median follow-up of 108 months; 23% had a cardiac event, 45% died, and 14% experienced a stroke. Serum albumin level less than 3.9 g/dL (hazard ratio, 0.68 for every 0.3-g/dL decrease; 95% confidence interval, 0.60 to 0.77), increased serum triglyceride level (hazard ratio, 1.07 for every 50-mg/dL increase; 95% confidence interval, 1.02 to 1.12), C-reactive protein level (hazard ratio, 1.15 per log-unit increase; 95% confidence interval, 1.07 to 1.24), and fibrinogen level (hazard ratio, 1.12 per 50-mg/dL increase; 95% confidence interval, 1.07 to 1.18) independently predicted composite events. Both decreased (<14.5 g/dL) and increased (>14.5 g/dL) hemoglobin levels predicted composite events. Serum albumin level less than 3.9 g/dL and increased serum fibrinogen level independently predicted cardiac events. For serum albumin and hemoglobin levels, the relationship with composite and mortality outcomes was nonlinear (P < 0.001).

Limitations: Single assessment of eGFR. No albuminuria data.

Conclusions: Several nontraditional cardiovascular disease risk factors predict adverse outcomes in individuals with stage 3 to 4 chronic kidney disease. The relationship between risk factors and outcomes is often nonlinear.