Tissue factor pathway inhibitor: a new link among arterial stiffness, pulse pressure, and coagulation in postmenopausal women.

OBJECTIVE To investigate in women older than 60 whether aortic stiffness or pulse pressure (PP) is associated with selected procoagulant or anticoagulant factors and to examine whether pulsatile stretch influences these factors in human vascular smooth muscle cells (VSMCs) in vitro. METHODS AND RESULTS Aortic pulse wave velocity (PWV) and carotid PP were studied in 123 apparently healthy postmenopausal women. PWV, PP, von Willebrand factor, and free tissue factor pathway inhibitor (TFPI), but not mean arterial pressure, increased with age. Free TFPI and PWV were positively correlated, even after adjustment for age and PP and other confounding parameters. In vitro, 5% or 10% pulsatile stretch (at 1 Hz) enhanced TFPI synthesis and secretion by VSMCs in a time-independent manner (1 to 48 hours) without changes in protein level of smooth muscle myosin heavy chain. Application of 5% static stretch had no effect. CONCLUSIONS In postmenopausal women, free TFPI increases as vascular wall function deteriorates and PP increases. These findings are supported by the increase in TFPI synthesized by VSMCs in response to cyclic stress in vitro. They suggest that VSMCs require pulsatility to interfere with the coagulation process and highlight the relevance of plasma free TFPI levels to cardiovascular diseases.