Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by the liver. Studies in vivo and in vitro suggest that PZ plays an important role in inhibiting coagulation as it serves as cofactor for the inactivation of factor Xa by forming a complex with the plasma PZ-dependent protease inhibitor. Recently, conflicting findings on plasma PZ levels in patients with ischemic stroke have been published. Aim of our study was to investigate the role of PZ in acute coronary syndromes (ACS). PZ plasma levels were determined in 223 (189 M; 34 F) patients with ACS referring to the Coronary Intensive Therapy Unit of University of Florence and in 265 (219 M; 46 F) healthy subjects. Patients under oral anticoagulation treatment as well as subjects with positivity for antiphospholipid antibodies were excluded. None had liver or kidney dysfunction. The mean PZ plasma level was lower in patients (1508 +/- 730 ng/mL) than in controls (1728 +/- 594 ng/mL) (p < 0.0001). PZ levels below the 5th percentile (565 ng/mL) of normal values distribution in control subjects were found in 15.7% of patients and in 4.9% of controls (p <0.0001). At multivariate analysis, PZ levels below 565 ng/mL were associated with ACS (OR=3.3; 99%CI 1.1-9.7; p = 0.004). The contemporary presence of low PZ levels and smoking habit leads to an increased risk of ACS (OR=9.5; 99%CI 2.4-37.2; p < 0.0001). In conclusion, our results suggest a possible role of PZ in the occurrence of arterial thrombosis.

Background: Low dietary intake and low serum concentrations of vitamin B 6 and/or folate are associated with increased risk of vascular events, possibly because of their association with inflammation, which plays a crucial role in the pathogenesis of cardiovascular diseases. Methods: Using data from 1320 participants in the population-based InCHIANTI study (586 men and 734 women; median age, 69 years; range, 21-102 years) for whom complete data on folate, vitamin B 6 , inflammatory markers, 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T sequence variant, and important covariates were available, we evaluated the association of inflammatory markers with circulating concentrations of vitamin B 6 and folate, independently of dietary vitamin intake, circulating vitamin concentrations, and MTHFR C677T sequence variant. Results: According to multiple linear regression analysis, C-reactive protein and interleukin-6 receptor were strongly and negatively associated with circulating vitamin B 6 but not with folate concentrations, independent of age, sex, serum creatinine, serum albumin, total energy intake, smoking history, dietary nutrient intake,

High circulating concentrations of IL-1ra and IL-6 are independent correlates of hyperhomocysteinemia and may explain, at least in part, the association between homocysteine and atherosclerosis.