Age- and Sex-Dependent Interpretation of C-Reactive Protein Cutoffs: A Sixteen-Year Large-Scale Clinical Laboratory...

Background/Objectives: The clinical meaning of a given C-reactive protein (CRP) threshold may differ by age and sex; however, a comprehensive framework to elucidate demographic differences is lacking. We examined age- and sex-related differences in the central tendency and upper tail of the CRP distribution and their implications for fixed-threshold interpretation. Methods: We retrospectively analyzed 1,845,151 serum CRP results from 336,360 individuals at a single tertiary-care hospital. Quantile regression estimated the median (q = 0.50) and 95th percentile (q = 0.95), and logistic regression assessed frequencies and odds ratios (ORs) for CRP thresholds ≥1, ≥3, and ≥10 mg/dL. Patient-year-first sensitivity and generalized estimating equation (GEE) analyses were performed. Results: CRP showed marked right-skewness, with a progressively heavier upper tail with age. The median increased from 0.19/0.26 mg/dL in females/males aged < 1 year to 2.55/3.44 mg/dL in those aged ≥ 85 years. The 95th percentile increased from 3.28/4.31 to 17.50/18.80 mg/dL. Among records aged ≥ 85 years, CRPs ≥ 1, ≥3, and ≥10 mg/dL occurred in 67.6%/72.3%, 46.6%/53.4%, and 15.3%/19.1% of females/males, respectively. For CRP ≥ 10 mg/dL, ORs increased stepwise to 12.7, 15.4, and 18.1 in those aged 65-74, 75-84, and ≥85 years, respectively. These patterns were preserved in sensitivity and GEE analyses. Conclusions: CRP distributions differed substantially by age and sex, indicating that a single threshold may not have uniform interpretive meaning across demographic groups. These findings support more context-aware interpretation of CRP thresholds in hospital-based practice, while suggesting that observed differences reflect not only demographic variation but also differences in underlying case-mix and clinical complexity.