Background: Cardiovascular disease (CVD) is the primary cause of premature death and disability worldwide. There is extensive evidence that inflammation represents an important pathogenetic mechanism in the development and prognosis of CVD. C-reactive protein (CRP) is a potential marker of vascular inflammation and plays a direct role in CVD by promoting vascular inflammation. The objective of this study (ClinTrials.gov identifier: NCT01045070) was to assess the prognostic impact of CRP protein levels and genetic variants of CRP gene events on cardiovascular (CV) outcome (10-year follow-up) in patients suffering from CVD. Methods: CVD patients were prospectively included in this study (n = 1002) and followed up (10 years) regarding combined CV endpoint (CV death, death from stroke, myocardial infarction (MI), and stroke/transient ischemic attack (TIA)). CRP protein level (particle-enhanced immunological turbidity test) and genetic variants (rs1130864, rs1417938, rs1800947, rs3093077; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) after DNA extraction from EDTA-blood) were evaluated. Results: In survival analyses, increased CRP protein levels of ≥5 mg/L (log-rank test: p < 0.001, Cox regression: p = 0.002, hazard ratio = 1.49) and CT + TT genotype of rs1130864 (log-rank test: p = 0.041; Cox regression: p = 0.103, hazard ratio = 1.21) were associated with a weaker CV prognosis considering combined CV endpoint. Conclusions: Elevated CRP level and genetic variant (rs1130864) were proven to provide prognostic value for adverse outcome in CVD patients within the 10-year follow-up period.

Background: Worldwide, cardiovascular disease (CVD) is the leading cause of premature death. The proinflammatory cytokine interleukin 6 (IL-6) is a essential marker of innate immunity that is considered to play an important proatherogenic role for cardiovascular disease. The aim of this study (substudy of ClinTrials.gov identifier: NCT01045070) was to evaluate IL-6 protein level and genetic variants (rs1800795, rs1800797) with respect to CV outcome (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death, death according to stroke) among patients CVD within 10-years follow-up. Material and methods: Overall 1002 in-patients with CVD were included. IL-6 protein level was determined by electrochemiluminescence immunoassay (fasting, between 7 and 8 a.m.). Genetic analyses were carried out by single specific primer-polymerase chain reaction. Results: In survival analyses, IL-6 protein levels of ≥6.4 pg/mL (log-rank test: p = 0.034; cox regression: p = 0.032, hazard ratio = 1.29) and CC genotype of rs1800795 (log-rank test: p < 0.001, cox regression: p < 0.001, hazard ratio = 1.72) and AA genotype of rs180797 (log-rank test: p = 0.002, cox regression: p < 0.001, hazard ratio = 1.62) were associated with a poorer CV prognosis considering combined CV endpoint. Conclusion: This study was the first to investigate both elevated IL-6 levels and genetic variants for their prognostic value for adverse CV outcomes in CVD patients within the 10-year follow-up period.

Background: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. Patients and methods: At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). Results: In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). Conclusion: In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients.