Cholesterol feeding increases C-reactive protein and serum amyloid A levels in lean insulin-sensitive subjects

Background - Inflammatory markers associated with elevated cardiovascular risk are increased by cholesterol feeding in animal models. However, whether dietary cholesterol increases inflammatory marker levels in humans is not known. Methods and Results - C-reactive protein (CRP), serum amyloid A (SAA), and lipoprotein levels were compared in 201 healthy subjects on an American Heart Association-National Cholesterol Education Program step 1 diet at baseline and after addition of 4 eggs per day for 4 weeks. Subjects were classified a priori into 3 groups based on their body mass index (BMI) and insulin sensitivity index (S_I): lean insulin sensitive (LIS), mean±SEM BMI, 23.2±0.3 kg/m², and S_I, 6.7±0. 3×10^-4min^-1/(μU/mL), n=66; lean insulin resistant (LIR), BMI, 24.5±0.2 kg/m² and S_I, 2.9±0.1×1.0^-4min^-1/ (μU/mL), n=76; or obese insulin resistant (OIR), BMI, 31.4±0.5 kg/m² and S _I, 2.1±0.1×10^-4min^-1/(μU/mL), n=59. Insulin resistance and obesity each were associated with increased baseline levels of both CRP (P for trend, <0.001) and SAA (P for trend=0.015). Egg feeding was associated with significant increases in both CRP and SAA in the LIS group (both P<0.01) but not in the LIR or OIR groups. Egg feeding also was associated with a significant increase in non-HDL cholesterol (P<0.001) in LIS subjects; however, there was no correlation between the change in non-HDL cholesterol or changes in either CRP or SAA in this group. Conclusions - A high-cholesterol diet leads to significant increases in both inflammatory markers and non-HDL cholesterol levels in insulin-sensitive individuals but not in lean or obese insulin-resistant subjects.