Plasma cytokines as predictors of coronary heart disease.

BACKGROUND AND OBJECTIVE: Growing body of evidence explicitly suggests the significant role of inflammatory processes in vascular diseases related to atherosclerosis. Monocytes, present in every phase of atherogenesis, are the principal cells accumulating in atherosclerotic plaque. Monocyte Chemotactic Protein 1 (MCP-1) seems to influence firm adherence of rolling monocytes and infiltration into the artery wall. Although the significant meaning of inflammation in atherogenesis has been proved, potential role of antiinflammatory cytokines remains unknown. Interleukin 10 (IL-10) is a major cytokine of pleiotropic antiinflammatory function known to exert inhibitory effects on monocytes. Recent data emerging from clinical and pathological studies suggest important role of thrombosis and fibrinolytic disorders in atherosclerosis complications especially in coronary heart disease (CHD). Individuals with greater Plasminogen Activator Inhibitor 1 (PAI-1) level are believed to be more susceptible to cardiovascular disease. METHODS: In our study we measured the plasma levels of MCP-1, IL-10 and PAI-1 in 10 patients with stable angina and 10 healthy subjects. We also estimated its mutual correlations. The plasma levels of MCP-1, IL-10 and PAI-1 were determined with R&D kits (ELISA). RESULTS: Plasma levels of MCP-1 were significantly higher (261.5+/-40.7 pg/mL vs 73.3+/-3.05 pg/mL; p<0.0002) and also levels of PAI-1 were higher (79.36+/-5.8 ng/mL vs 35.88+/-1.38 ng/mL; p<0.0001) in patients with SA compared with the healthy control subjects. Whereas plasma levels of IL-10 were lower (11.6+/-0.5 pg/mL vs 16.5+/-0.4 pg/mL; p<0.0001) compared with control group and correlated with both MCP-1 plasma level (r=-0.67; p<0.0015) and PAI-1 concentration (r=-0.69; p<0.0008). CONCLUSION: The data obtained confirm the predictive role of cytokines in patients with stable coronary heart disease. The negative correlation of anti-inflammatory IL-10 and PAI-1 was also found.

Effects of fibrates on plasma prothrombotic activity in patients with type IIb dyslipidemia.

OBJECTIVE: Increased levels of fibrinogen and plasminogen activator inhibitor 1 (PAI-1) are associated with an increased risk of ischemic coronary disease and its complications. Since atherogenic dyslipidemias are well-known risk factors for coronary heart disease, this study aimed to determine whether Type IIb dyslipidemia, one of the most atherogenic dyslipidemias, is accompanied by increased PAI-1 and fibrinogen synthesis. The additional aim of this study was to evaluate the effect of micronized fibrates on the levels of PAI-1 and fibrinogen in patients with Type IIb dyslipidemia. SUBJECTS: Thirty patients with Type IIb dyslipidemia and 12 age-matched control subjects were studied. Fourteen patients were treated with fenofibrate and 16 were treated with ciprofibrate for 1 month. METHODS: Plasma PAI-1 levels were measured by the ELISA method with Diagnostica Stago kit. The level of fibrinogen was measured by the Clauss method. RESULTS: PAI-1 levels in dyslipidemic patients before treatment differed significantly in both the fenofibrate and ciprofibrate treatment groups (101.18 +/- 36.47 ng/ml, 87.64 +/- 32.06 ng/ml, respectively) from those in the control group (32.32 +/- 7.39 ng/ml, p < 0.001). Compared with the control subjects (2.91 +/- 0.35 g/l), fibrinogen levels before treatment were higher in patients with dyslipidemia treated with ciprofibrate (3.42 +/- 0.59 g/l, NS) and fenofibrate (3.65 +/- 1.10 g/l, p < 0.05). One-month ciprofibrate treatment resulted in an insignificant decrease in PAI-1 levels (76.28 21.60 ng/ml, NS) and in a significant decrease in fibrinogen levels (2.73 +/- 0.40 g/l, p < 0.01). After one-month fenofibrate treatment PAI-1 levels (81.22 +/- 25.01 ng/ml, p < 0.01) and fibrinogen levels (2.95 0.72 g/l, p < 0.01) decreased significantly. CONCLUSION: Type IIb dyslipidemic patients have increased levels of PAI-1 and fibrinogen. Micronized fibrates decreased not only lipid levels but also the levels of fibrinogen and PAI-1 in these patients.