The study population consisted of 12,831 men and women drawn from the NHANES 1999 to 2004 after exclusion of 1,543 individuals whose urinary albumin or creatinine data were not measured, 673 individuals whose CRP data were absent, and 285 individuals with macroalbuminuria (). The study population included 52% women, with a mean age of 46 years. Seventy-one percent were non-Hispanic white, whereas 13% and 10% were Hispanic and non-Hispanic African-American, respectively. The 1,378 participants (11%) with microalbuminuria were more likely to be older, non-White, and of lower socioeconomic status (assessed by education and income levels) than participants without microalbuminuria. The prevalences of diabetes, current smoking, hypertension, heart failure, cerebrovascular disease, peripheral vascular disease, and anemia were significantly higher in participants with microalbuminuria compared with those without microalbuminuria. Unadjusted mean total, low-density lipoprotein, and high-density lipoprotein cholesterol levels were similar among participants with and without microalbuminuria (reflected in summary statistics), but these differences were significant after adjustment for demographic factors (reflected in p values).
Pearson correlations coefficient measuring how CRP and the remaining individual variables were linearly associated in our sample were low overall (all values p <0.1) (). Although correlation coefficients slightly differed depending on the computing method adopted, some common patterns were observed. CRP was positively correlated with age, triglyceride levels, and urinary albumin-to-creatinine ratio (the raw variable for microalbuminuria). In contrast, serum creatinine and high-density lipoprotein cholesterol consistently showed negative correlation with CRP concentration.
Correlation coefficients* between C-reactive protein (CRP) and other risk factors
Multivariate logistic regression modeling identified 10 predictors of prevalent microalbuminuria (age, race, education, current smoking status, history of heart failure, systolic blood pressure, diabetes mellitus, peripheral vascular disease, anemia, and CRP) among study participants (). Of the well-known traditional risk factors, diabetes, systolic blood pressure, current smoking status, and history of heart failure demonstrated the strongest associations with microalbuminuria. Of note, none of the lipid variables (i.e., triglycerides and total, low-density lipoprotein, and high-density lipoprotein cholesterol) were significant in multivariate models.
Multivariate logistic regression model for microalbuminuria in National Health and Nutrition Examination Surveys (NHANES) 1999 to 2004
The mean CRP concentration among participants with microalbuminuria was 6.3 mg/L compared with a mean concentration of 4.0 mg/L among controls (p = 0.0002) (). On the basis of logistic regression analyses, CRP concentration was positively associated with microalbuminuria (). In the multivariate model, a 1 mg/L increase in CRP was associated with a 2% increased odds of microalbuminuria (OR 1.02, 95% CI 1.01 to 1.02, p = 0.0003). Nonlinear relationships assessed by squared and cubic terms of CRP were not detected.
Using categorized CRP levels (quartiles and AHA/CDC recommendations), multivariate models showed a positive trend for the association of CRP with microalbuminuria (). Multivariable-level adjustments yielded attenuated associations in all conducted analyses. Participants in the highest quartile of CRP concentration, ≥4.6 mg/L, demonstrated a significant association with microalbuminuria (OR 1.35, 95% CI 1.06 to 1.72, p = 0.017) controlling for a set of traditional risk factors. According to the AHA/CDC cutpoints, compared with persons with CRP concentrations <1 mg/L, persons with CRP concentrations between 1 and 3 mg/L and >3 mg/L were 1.15 times (95% CI 0.94 to 1.42) and 1.33 times (95% CI 1.08 to 1.65) more likely to have microalbuminuria, respectively.
Association between C-reactive protein (CRP) levels and prevalence of microalbuminuria in multivariate logistic regression models in National Health and Nutrition Examination Surveys (NHANES) 1999 to 2004
The association between diabetes and microalbuminuria was the strongest of any variable in the model. We repeated analyses excluding diabetics to determine how sensitive the association between CRP and albuminuria was to the diabetic status. Comparable discrimination was observed (area under the curve [AUC] = 0.71 to 0.72) in all multivariate analyses, but the associations were stronger in the highest levels of the multivariate models in (ORs increased to 1.82 and 1.57 compared with 1.35 and 1.33, respectively). Gender-specific microalbuminuria cutpoints resulted in slightly attenuated association and discrimination (ORs of 1.28 and AUC of 0.72), but increased statistical significance (i.e., smaller p ≤0.0006) for CRP. Extending the endpoint to encompass microalbuminuria and macroalbuminuria together (omitting the corresponding exclusion criterion) yielded respective ORs of 1.36 (p = 0.01) and 1.39 (p = 0.001), but with increased discrimination (AUC = 0.75).