Tissue factor pathway inhibitor, vascular risk factors and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis.
BACKGROUND
Tissue factor pathway inhibitor (TFPI) is an endothelial membrane-associated anticoagulant protein. Higher circulating levels might reflect endothelial damage.


OBJECTIVE
We hypothesized an association of higher total TFPI with subclinical atherosclerosis.


METHODS
Total TFPI was measured in 1000 participants of the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 men and women without clinical vascular disease, aged 45-84, from four ethnic groups. Subclinical atherosclerosis measures were coronary artery calcium (CAC), carotid intima-media thickness (IMT) and ankle-brachial index (ABI).


RESULTS
TFPI was higher with age, male gender, higher LDL-cholesterol, smoking and diabetes, but not ethnicity. Adjusting for risk factors, TFPI in the 4th quartile versus 1st quartile was associated with a 1.2-fold increased risk of detectable CAC (95% CI 1.0-1.4), a 2.1-fold increased risk of CAC >400 Agatston units (95% CI 1.1-4.0) and a 1.6-fold (95% CI 1.1-2.5) increased risk of internal carotid IMT above the 80th percentile, but not with external carotid IMT or low ABI. Findings were consistent across ethnic groups.


CONCLUSIONS
In this diverse population, higher total TFPI was associated with prevalent CAC (limited to levels >400 units), and elevated internal carotid IMT, independent of other factors. Higher TFPI may indicate endothelial dysfunction. Further study is needed of TFPI and progression of atherosclerosis.
Mitchell
C T
CT
Department of Medicine, University of Vermont, Burlington, VT 05446, USA.
Kamineni
A
A
Palmas
W
W
Cushman
M
M
D000368:Aged; D000369:Aged, 80 and over; D000842:Ankle / Q000098:blood supply; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001916:Brachial Artery / Q000503:physiopathology; D002118:Calcium / Q000032:analysis; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000208:ethnology / Q000209:etiology / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000208:ethnology / Q000209:etiology / Q000503:physiopathology; D003331:Coronary Vessels / Q000737:chemistry; D003430:Cross-Sectional Studies; D005006:Ethnicity; D005260:Female; D006801:Humans; D016014:Linear Models; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012720:Severity of Illness Index; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
D015415:Biomarkers; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D002118:Calcium