Received on July 16, 2008
Accepted on November 6, 2008

Lipids, Lipoproteins, and Cardiovascular Risk Factors (LLP)

Determinants of the Acute-Phase Protein C-Reactive Protein in Myocardial Infarction Survivors: The Role of Comorbidities and Environmental Factors

¹ Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Munich, Germany
² Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Munich, Germany, and Helmholtz Zentrum München, German Research Center for Environmental Health, Focus-Network Nanoparticles and Health (NanoHealth), Munich, Germany
³ Department of Internal Medicine II, Cardiology, University of Ulm Medical Center, Ulm, Germany
⁴ Local Health Authority RM E, Department of Epidemiology ASL RME, Rome, Italy
⁵ Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Munich, Germany, and Central Hospital of Augsburg, MONICA/KORA Myocardial Infarction Registry, Augsburg, Germany
⁶ Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece
⁷ Center for Research in Environmental Epidemiology (CREAL), Municipal Institute of Medical Research (IMIM-Hospital del Mar), CIBER Epidemiologìa y Salud Pública (CIBERESP), and Universitat Pompeu Fabra (UPF), Barcelona, Spain
⁸ Environmental Epidemiology Unit, National Public Health Institute (KTL), Kuopio, Finland
⁹ Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden, and AstraZeneca R&D, Mölndal, Sweden

^* To whom correspondence should be addressed. E-mail: wolfgang.koenig{at}uniklinik-ulm.de.

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 (hs-CRP) in serum has not been carried out previously.

METHODS: We used data from 1003 myocardial infarction (MI) survivors who had hs-CRP 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 hs-CRP concentrations.

RESULTS: Patients with 6.5% glycosylated hemoglobin (HbA1c) had 26.2% higher hs-CRP concentrations (95% CI, 7.2%–48.6%) and 20.7% greater variation in hs-CRP values (P = 0.0034) than patients with typical baseline HbA1c values (<6.5%). Similar but less pronounced differences were seen in patients with a self-reported diagnosis of type 2 diabetes. hs-CRP 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 environmental exposure to tobacco smoke, alcohol consumption, and extreme stress, did not have a major impact.

CONCLUSIONS: One or 2 hs-CRP measurements may not be sufficient to adequately characterize different patient groups after MI with similar precisions. We found hs-CRP concentrations to be especially variable in males, smokers, and patients with increased HbA1c values.