Association of Cholesterol Levels with Mortality and Cardiovascular Events among Patients with CKD and Different Amounts of Proteinuria

BACKGROUND AND OBJECTIVES: Malnutrition and/or inflammation may modify the risk relationship of total cholesterol with cardiovascular disease in CKD patients. However, it is unclear whether the relationship of total cholesterol with cardiovascular events and mortality varies by proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study enrolled 3303 patients with CKD stages 3-5 from a medical center and a regional hospital between November of 2002 and May of 2009 and followed the patients until July of 2010. RESULTS: During a median 2.8-year follow-up, there were 471 (14.3%) deaths and 545 (16.5%) cardiovascular events. In an adjusted Cox model, the two highest quartiles of total cholesterol (hazard ratio, 1.90; 95% confidence interval, 1.16 to 3.13 and hazard ratio, 2.00; 95% confidence interval, 1.18 to 3.39 versus quartile 1, respectively) were associated with a significant higher risk of all-cause mortality in patients with urine protein-to-creatinine ratio<1 g/g (n=1535), but this higher risk was not seen in those patients with urine protein-to-creatinine ratio ≥ 1 g/g (n=1768; hazard ratio, 0.75; 95% confidence interval, 0.53 to 1.07 and hazard ratio, 0.70; 95% confidence interval, 0.49 to 1.02 versus quartile 1, respectively). The interaction between total cholesterol and proteinuria with all-cause mortality was significant (interaction, P=0.05). However, the relationship between total cholesterol and cardiovascular events did not significantly differ by proteinuria (interaction, P=0.91). CONCLUSIONS: The association between cholesterol and mortality is different among patients with different levels of proteinuria. Large-scale clinical trials to evaluate the mortality benefit should specifically target lowering hypercholesterolemia in CKD patients with different levels of proteinuria.