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 level correlates with unfavorable outcomes in unstable angina. Total TFPI (t-TFPI) represents mainly the lipid-bound form which seems to have a poor anticoagulant activity. Until now, it is not known whether the variations of f-TFPI plasma levels are determined by environmental factors. The aim of our study 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 349 women) attending a metabolic ward for primary prevention of coronary disease. Free and total TFPI plasma levels were poorly correlated. f-TFPI levels increased with age in both sexes, t-TFPI in women only. Age-adjusted correlations of TFPI levels with conventional cardiovascular risk factors and endothelial cell markers showed different patterns for 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 fibrinogen and endothelial cell markers: t-PA, thrombomodulin (TM) and von Willebrand factor (vWF). t-TFPI correlated strongly with LDL-C in both sexes. It also correlated negatively with parameters of the insulin resistance syndrome. t-TFPI also correlated with TM but not with other endothelial cell markers. The results of the multivariate step by step analysis showed that cardiovascular 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 differently. f-TFPI strongly correlates with endothelial cell markers and t-TFPI is more related to conventional cardiovascular risk factors. The strong gender effect on f-TFPI levels remains to be explained.
Morange
P E
PE
Lab. Hématologie CHU Timone Marseille, Genevilliers, France.
Renucci
J F
JF
Charles
M A
MA
Aillaud
M F
MF
Giraud
F
F
Grimaux
M
M
Juhan-Vague
I
I
D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood*; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood / Q000737:chemistry; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012995:Solubility; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D008074:Lipoproteins; D010743:Phospholipids; D018180:Thrombomodulin; C051928:lipoprotein-associated coagulation inhibitor; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator