Abstract
Introduction Systemic inflammation alters lipid metabolism by suppressing hepatic lipoprotein synthesis, increasing catabolism, and impairing reverse cholesterol transport. These changes result in reduced levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC), despite elevated cardiovascular risk, which is a phenomenon termed the "inflammatory lipid paradox." While well-characterized in chronic inflammatory diseases, such as rheumatoid arthritis, its prevalence and clinical impact in hospitalized adults with systemic inflammation remain underexplored. We investigated whether elevated C-reactive protein (CRP) levels across a range of acute illnesses are associated with progressive reductions in LDL, HDL, and TC, aiming to evaluate the inflammatory lipid paradox as a widespread phenomenon in hospitalized adults. Methods We conducted a retrospective analysis of 5,060 hospitalized adults at a tertiary academic center between January 2020 and May 2024. Inclusion criteria were age ≥18 years, CRP >5 mg/L, and availability of a complete lipid panel. Patients were stratified into four CRP categories: 5-20 mg/L, 20-50 mg/L, 50-100 mg/L, and >100 mg/L. Mean LDL, HDL, TC, and triglyceride levels were compared using one-way analysis of variance (ANOVA) with Tukey's honestly significant difference post-hoc testing. Linear regression, including 95% confidence intervals (CIs) for all regression estimates, was used to assess associations between CRP category and lipid values. Results One-way ANOVA revealed that increasing CRP was significantly associated with stepwise reductions in LDL (105.53-87.94 mg/dL), HDL (48.89-38.68 mg/dL), and TC (187.04-157.28 mg/dL) (p < 0.0001 for all comparisons). Triglycerides showed a non-linear trend. Regression analyses demonstrated strong inverse associations between CRP and LDL (slope = -6.09 mg/dL, 95% CI: -10.79 to -1.38, p = 0.0308, R² = 0.94), HDL (slope = -3.51 mg/dL, 95% CI: -4.55 to -2.47, p = 0.0047, R² = 0.99), and TC (slope = -10.30 mg/dL, 95% CI: -17.76 to -2.83, p = 0.0272, R² = 0.95), consistent with inflammation-driven lipid suppression. The slope for triglycerides was positive (4.29 mg/dL), but the association was not statistically significant (95% CI: -15.04 to 23.62, p = 0.4402, R² = 0.31). Conclusion Elevated CRP is significantly associated with lower LDL, HDL, and TC levels in hospitalized adults, supporting the presence of the inflammatory lipid paradox beyond chronic disease. These findings highlight the need to interpret lipid panels in the context of systemic inflammation, as suppressed lipid values may both obscure and reflect increased cardiovascular risk driven by cytokine-mediated dysregulation of lipid metabolism. Repeat lipid testing following recovery from acute illness is essential to guide accurate cardiovascular risk stratification and appropriate preventive care.