The relationship between nontraditional risk factors and outcomes in individuals with stage 3 to 4 CKD

Abstract

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.

Figure 1

The relationship between serum albumin and study outcomes in fully adjusted models. All models are adjusted for age, sex, race, study, prior cardiovascular disease, diabetes, smoking, systolic blood pressure, LVH and eGFR. Plots are generated using restricted cubic splines with 4 knots generated in S-Plus. Hatch marks represent the relative proportion of individuals at a given albumin level. Overall effect indicates whether albumin is a statistically significant risk factor for the outcome, while the linearity test indicates if the relationship between albumin and the outcome is linear; for composite and mortality outcomes (p<0.001), the relationship is non-linear, while there is a trend toward non-linearity for the cardiac outcome.

Figure 2

The relationship between hemoglobin and study outcomes in fully adjusted models. All models are adjusted for age, sex, race, study, prior cardiovascular disease, diabetes, smoking, systolic blood pressure, LVH and eGFR. Plots are generated using restricted cubic splines with 4 knots generated in S-Plus. Hgb, hemoglobin in g/dL. Hatch marks represent the relative proportion of individuals at a given hemoglobin level. Overall effect indicates whether hemoglobin is a statistically significant risk factor for the outcome, while the linearity test indicates if the relationship between hemoglobin and the outcome is linear; for composite and mortality outcomes (p<0.001), the relationship is non-linear.