Protein Z levels in acute coronary syndromes

Abstract number: P0507

Sofi F., Fedi S., Tellini I., Cesari F., Brogi D., Marcucci R., Prisco D., Pepe G., Abbate R., Gensini G. F.

University of Florence, Italy

Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by the liver. In vivo and in vitro studies suggest that protein Z plays an important role in inhibiting coagulation as it serves as cofactor for the inactivation of factor Xa on phospholipid surfaces by forming a complex with the plasma protein Z-dependent protease inhibitor (ZPI). Recent data indicate low levels of PZ deficiency among patients with ischemic stroke suggesting a moderate ischemic risk associated with PZ deficiency but the role of PZ in thrombotic disorders is nevertheless controversial. Aim of our study was to investigate the role of PZ in acute coronary syndromes (ACS). Plasma levels of PZ were determined in 140 patients (22F, 118M) with ACS underwent percutaneous coronary angioplasty (PTCA) who were referred to the Coronary Intensive Therapy Unit of University of Florence and in 162 (34F, 128M) healthy subjects. We also investigated the possible relationship among PZ, homocysteine and lipoprotein (a) plasma levels. Patients treated by oral anti-coagulation and patients with liver and renal failure were excluded. The median PZ plasma levels was lower in patients (1.385 mg mL^-1; range: 0.054–3.786) than in controls (1.770 mg mL^-1; range: 0.436–3.266) (P < 0.0001). Among patients and controls, PZ plasma levels were similar in men and women. Protein Z levels below the 5th percentile of normal values distribution in control subjects were found in 27.1% of patients and in 4.9% of controls (P < 0.0001). Hyperhomocysteinemia, defined as a concentration of homocysteine above the 95th percentile of controls was diagnosed in 33.7% of patients and in 5.5% of controls (P < 0.0001). Levels of Lp (a) >300 mg L^-1, cut-off of cardiovascular risk, were found in 28.6% of patients and in 9.9% of controls (P < 0.0001). At univariate analysis PZ levels below 0.683 mg mL^-1 were associated with ACS (OR = 7.2; 95% CI 3.2–15.9; P < 0.0001) similar results were described in relation to homocysteine (OR = 8.6; 95% CI 4.0–18.3; P < 0.0001) and lipoprotein (a) (OR = 3.6; 95% CI 1.9–6.9; P < 0.0001). The multivariate analysis, adjusted for all traditional cardiovascular risk factors, body mass index (BMI), homocysteine and lipoprotein (a) levels showed that PZ deficiency was an independent risk factor for ACS (OR = 3.2; 95% CI 1.2–8.8; P < 0.05). Our preliminary data show that protein Z deficiency could be involved in the pathogenesis of thrombotic complications of atherosclerosis.