Effect of Statin Therapy on the Carboxypeptidase U (CPU, TAFIa, CPB2) System in Patients With Hyperlipidemia: A Proof-of-concept Observational Study

Abstract

Statins are commonly used in patients with hypercholesterolemia to lower their cholesterol levels and to reduce their cardiovascular risk. There is also considerable evidence that statins possess a range of cholesterol-independent effects, including profibrinolytic properties. This pilot study aimed to explore the influence of statins on procarboxypeptidase U (proCPU) biology and to search for possible effects and associations that can be followed up in a larger study. Blood was collected from 16 patients with hyperlipidemia, before and after 3 months of statin therapy (simvastatin 20 mg or atorvastatin 20 mg). Fifteen age-matched normolipemic persons served as control subjects. Lipid parameters and markers of inflammation and fibrinolysis (proCPU levels and clot lysis times) were determined in all samples. Mean (SD) proCPU levels were significantly higher in patients with hypercholesterolemia compared to control subjects (1186 [189] U/L vs 1061 [60] U/L). Treatment of these patients with a statin led to a significant average decrease of 11.6% in proCPU levels and brought the proCPU concentrations to the same level as in the control subjects. On a functional level, enhancement in plasma fibrinolytic potential was observed in the statin group, with the largest improvement in fibrinolysis seen in patients with the highest baseline proCPU levels and largest proCPU decrease upon statin treatment. Increased proCPU levels are present in patients with hyperlipidemia. Statin treatment significantly decreased proCPU levels and improved plasma fibrinolysis in these patients. Moreover, our study indicates that patients with high baseline proCPU levels are most likely to benefit from statin therapy. The latter should be examined further in a large cohort.