Plasma levels of free and total TFPI, relationship with cardiovascular risk factors and endothelial cell markers

Free-TFPI (f-TFPI) presents high anticoagulant activity and its plasma leve l correlates with unfavorable outcomes in unstable angina. Total TFPI (t-TF PI) represents mainly the lipid-hound form which seems to have a poor antic oagulant activity. Until now, it is not known whether the variations of f-T FPI plasma levels are determined by environmental factors. The aim of our s tudy was to evaluate the influence of cardiovascular risk factors on plasma levels of f-TFPI and relations with other endothelial derived molecules in a population of 626 patients (277 men and 339 women) attending a metabolic ward for primary prevention of coronary disease. Free and total TFPI plasma levels were poorly correlated. f-TFPI levels inc reased with age in both sexes, t-TFPI in women only. Age-adjusted correlati ons of TFPI levels with conventional cardiovascular risk factors and endoth elial cell markers showed different patterns fur f-TFPI and t-TFPI. f-TFPI correlated with parameters associated with insulin resistance. particularly in females. f-TFPI was also positively associated in both genders with fib rinogen and endothelial cell markers: t-PA, thrombomodulin (TM) and von Wil lebrand factor (VWF). t-TFPI correlated strongly with LDL-C in both sexes. It also correlated negatively with parameters of the insulin resistance syn drome. t-TFPI also correlated with TM but not with other endothelial cell m arkers. The results of the multivariate step by step analysis showed that c ardiovascular risk factors poorly explained the f-TFPI variability (7% and 4% in men and women, respectively), whereas they explained 16 and 20% of t- TFPI variability in men and women respectively (mostly related to LDL-C). In conclusion. this study showed that free- and total-TFPI are regulated di fferently. f-TFPI strongly correlates with endothelial cell markers and t-T FPI is more related to conventional cardiovascular risk factors. The strong gender effect on f-TFPI levels remains to be explained.