Intravascular Kinetics of C-Reactive Protein and Their Relationships with Features of the Metabolic Syndrome

Abstract

The objective of the study was to describe, for the first time, the intravascular kinetics of C-reactive protein (CRP), using stable isotopes, and its relationship with features of the metabolic syndrome. Sixteen men and 16 women [aged 49 +/- 9 years, body mass index (BMI) 28.7 +/- 4.5 kg/m(2)] underwent a 12-h primed-constant infusion of 5,5,5-(2)H(3)-l-leucine. CRP was purified from the plasma fraction rho greater than 1.25 g/ml by affinity chromatography, and isotopic enrichment over time was determined by gas chromatography/mass spectrometry. The CRP fractional catabolic rate was 60% higher in men than women (0.49 +/- 1.83 vs. 0.30 +/- 1.80 pool/d, P = 0.03), but this difference was no longer significant in a multivariate model that included several features associated with the metabolic syndrome. The CRP production rate (PR) and pool size were not statistically different between sexes. Plasma CRP concentrations were more strongly correlated with the PR (r = 0.80, P < 0.0001) than with the fractional catabolic rate of CRP (r = 0.39, P < 0.05). The PR of CRP was positively correlated with waist girth (r = 0.53, P < 0.01), plasma low-density lipoprotein apolipoprotein B-100 (r = 0.42, P = 0.07), triglyceride (r = 0.41, P = 0.06), and IL-6 concentrations (r = 0.61, P = 0.0008) and inversely correlated with high-density lipoprotein-cholesterol (r = -0.47, P = 0.03) and adiponectin (r = -0.63, P < 0.0005) after adjustment for sex. Blood pressure and low-density lipoprotein-cholesterol showed no association with CRP kinetics. The PR of CRP appeared as the main determinant of CRP concentrations and showed significant associations with features of the metabolic syndrome as well as with adipose tissue-derived cytokines such as IL-6 and adiponectin.