© 2000 American Heart Association, Inc.
Thrombosis |
Intravascular Free Tissue Factor Pathway Inhibitor Is Inversely Correlated With HDL Cholesterol and Postheparin Lipoprotein Lipase but Proportional to Apolipoprotein A-II
From the National Cardiovascular Center Research Institute (A.K., A.Y., H.K.) and Hospital (Y.M., T.N., H.N., M.Y., K.M., M.T.) and Chemo-Sera Therapeutics Research Institute (Y.K., K.K.), Osaka, Japan.
Correspondence to Akito Kawaguchi, MD, Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita-shi, Osaka 565-8565, Japan. E-mail akitok{at}ri.ncvc.go.jp
Abstract—To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell–anchor pools in 156 patients with coronary artery disease (average age, 61.2±9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59.6±9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15.9±6.5 versus 19.2±8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0.454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell–anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low–HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high–LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0.5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.
Key Words: TFPI • HDL cholesterol • lipoprotein lipase • apolipoprotein A-II • coronary artery disease
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