Determinants of the acute-phase protein C-reactive protein in myocardial infarction survivors: the role of comorbidities and environmental factors.

BACKGROUND: C-reactive protein (CRP), a sensitive marker of the acute-phase response, has been associated with future cardiovascular endpoints independently of other risk factors. A joint analysis of the role of risk factors in predicting mean concentrations and variation of high-sensitivity CRP (hsCRP) in serum has not been carried out previously. METHODS: We used data from 1003 myocardial infarction (MI) survivors who had hsCRP measured monthly up to 8 times and multivariate mixed effects statistical models to study the role of time-variant and -invariant factors on the geometric mean of and the intraindividual variation in hsCRP concentrations. RESULTS: Patients with > or =6.5% glycosylated hemoglobin (HbA1c) had 26.2% higher hsCRP concentrations (95% CI, 7.2%-48.6%) and 20.7% greater variation in hsCRP values (P = 0.0034) than patients with lower baseline Hb A(1c) values (<6.5%). Similar but less pronounced differences were seen in patients with a self-reported diagnosis of type 2 diabetes. hsCRP concentrations showed less variation in patients who reported angina pectoris, congestive heart failure, or emphysema (-11.0%, -24.9%, and -41.6%, respectively, vs patients without these conditions) but greater variation in males and smokers (+24.8% and +27.3%, respectively, vs females and nonsmokers). Exposures in the 24 h before blood sampling, including exposure to environmental tobacco smoke, alcohol consumption, and extreme stress, did not have a major impact. CONCLUSIONS: One or 2 hsCRP measurements may not be sufficient to adequately characterize different patient groups after MI with similar precisions. We found hsCRP concentrations to be especially variable in males, smokers, and patients with increased Hb A(1c) values.

DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study.

AIMS: C-reactive protein represents the classical acute-phase protein produced in the liver in response to inflammatory stimuli. This study evaluated the association of gene polymorphisms with differences in C-reactive protein concentrations and assessed its intra-individual variability as a marker of individual response. METHODS AND RESULTS: One thousand and three myocardial infarction (MI) survivors were recruited in six European cities, and C-reactive protein concentrations were measured repeatedly during a 6-month period. We investigated 114 polymorphisms in 13 genes, all involved in the innate inflammatory pathway. We found two polymorphisms within the C-reactive protein (CRP) gene rs1800947 and rs1205, of which the minor alleles were strongly associated with lower levels of C-reactive protein (P < 10(-6)). A haplotype, identified by those two polymorphisms, was associated with the lowest C-reactive protein concentrations (P < 10(-6)). Additionally, the minor alleles of several variants were significantly associated with greater individual variability of C-reactive protein concentrations (P < 10(-3)). CONCLUSION: The present study investigated the association of polymorphisms with inter- and intra-individual variability of C-reactive protein levels. Two minor alleles of C-reactive protein variants were associated with lower C-reactive protein concentrations. Regarding intra-individual variability, we observed associations with the minor alleles of several variants in selected candidate genes, including the CRP gene itself.