The alteration of cytokine concentration and the resulting progress of coronary artery calcification: a two-year Follow-Up study

Objectives: In a two-year Follow-Up we wanted to prove the reduction of antiinflammatory biomarkers and the preponderance of proinflammatory cytokines being responsible for the development of coronary artery calcification.

Methods: 455 patients obtained a cardiac computertomography (DSCT) to quantify the coronary calcification (study group, n=235, Agatston-score 144, 79.6% male, 61.8±8.6 years; control group: n=220, Agatston-score 0, 57.3% male, 56.1±10.6 years). After two years, 88 patients were able to be recruited for a further cardiac computertomography and a second blood withdrawal. The concentration of 21 cytokines was quantified with the fluorescence-based Luminex-technology.

Results: After an average of two (2.11+/-0.54) years, we found increased concentrations of IL-8, TNF-α, MCP-1 und IP-10. In contrast, the levels of IL-1α, IL-1β, IL-2, IL-4, IL-10, IL-13, IFN-γ and Eotaxin decreased in the Follow-Up period. Statistically significant (specified as mean difference (md) in pg/ml) was the increase of MCP-1 (md=91.1) and IP-10 (md=59.6) and the decrease of IL-1β (md=-16.6) and IFN-γ (md=-17.4). Showing the highest increase, the concentration of MCP-1 was correlated with the progress of coronary calcification in the Follow-Up group. Thereby, patients with a high concentration of MCP-1 (>50 pg/ml) showed a more dynamic progress of coronary calcium.

Conclusions: In summary, we found an increase of proinflammatory and a reduction of protective antiinflammatory biomarkers in the two-year Follow-Up. These findings thus support a role for a cytokine-mediated inflammation in atherogenesis responsible for plaque rupture and myocardial infarction.