Heightened Tissue Factor Associated With Tissue Factor Pathway Inhibitor and Prognosis in Patients With Unstable Angina

Soejima, Hirofumi; Ogawa, Hisao; Yasue, Hirofumi; Kaikita, Koichi; Nishiyama, Koichi; Misumi, Kenji; Takazoe, Keiji; Miyao, Yuji; Yoshimura, Michihiro; Kugiyama, Kiyotaka; Nakamura, Shin; Tsuji, Ichiro; Kumeda, Kousuke

doi:10.1161/01.cir.99.22.2908

Cited by 195 publications

(127 citation statements)

References 27 publications

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“…High levels of sP-sel, TF, and IL-6 have been associated with adverse cardiovascular outcomes and the development of coronary events in subjects without clinically established CVD. 15,16,17 This may explain the risk continuum observed in healthy subjects to patients with diabetes free of overt CVD to patients with established CVD and supports early intensive multifactorial intervention.…”

Section: Lim Et Al Scd40l and Cardiovascular Risk Intervention 2527mentioning

confidence: 64%

“…[15][16][17][18] However, the in vivo relationship(s) between these indices in patients with diabetes, with and without overt CVD, are not clear. Treatment with HMG-CoA reductase inhibitors (statins) and peroxisome proliferator-activated receptor-␥ agonist (glitazones) has been reported to reduce plasma sCD40L levels, 10,11,19 but the effects on plasma IL-6 have been inconsistent.…”

mentioning

confidence: 99%

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Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus

2004

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Background-High levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. CD40L-CD40 interaction has been linked to the pathogenesis of atherothrombotic complications in cardiovascular disease (CVD). We sought to determine whether a "package of care" of intensified multifactorial cardiovascular risk intervention could reduce indices of platelet activation, inflammation, and coagulation in diabetes and whether patients with overt CVD would derive similar benefit compared with those without. Methods and Results-We measured plasma sCD40L, soluble P-selectin (sP-sel, an index of platelet activation), interleukin-6 (IL-6, a proinflammatory cytokine), and tissue factor (TF, an initiator of coagulation) in 97 patients with diabetes mellitus (41 with and 56 without overt CVD) and 39 comparable healthy control subjects. Thirty-six patients with and 32 without overt CVD then participated in a package of care of cardiovascular risk intervention over a period of 1 year. Plasma levels of sCD40L (PϽ0.001), sP-sel (PϽ0.001), IL-6 (Pϭ0.001), and TF (PϽ0.001) were higher in patients with diabetes than in control subjects, with TF levels highest in patients with overt CVD. Multifactorial intervention was associated with significant reductions in sCD40L in both patient groups (both PϽ0.001), but reductions in sP-sel and TF were seen only in patients without overt CVD. There was no significant change in IL-6 levels in both patient groups. Conclusions-Intensive multifactorial risk management can reduce high levels of sCD40L but can only partially correct abnormal platelet activation, inflammation, and coagulation in diabetes, particularly in patients with overt CVD.

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Section: Lim Et Al Scd40l and Cardiovascular Risk Intervention 2527mentioning

confidence: 64%

mentioning

confidence: 99%

Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus

2004

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“…Plasma f-TFPI is elevated in patients with unstable angina and increases the risk of an unfavorable outcome. 16 To the best of our knowledge, this is the first prospective study on the association of CHD and f-TFPI. Individuals with f-TFPI levels below the 10th percentile have a 2.13-fold increased risk of hard CHD.…”

Section: Discussionmentioning

confidence: 90%

“…[11][12][13][14][15] Only a few data are available for TFPI in humans: f-TFPI levels are elevated in patients with unstable angina and increase the risk of a poor outcome. 16 Very recently, a case-control study indicated that low levels of f-TFPI were a risk factor for deep vein thrombosis. 17 Interestingly, mean TFPI levels were not lower in patients with deep vein thrombosis, but f-TFPI levels below the 10th percentile proved to be a risk factor.…”

mentioning

confidence: 99%

Endothelial Cell Markers and the Risk of Coronary Heart Disease

et al. 2004

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on behalf of the PRIME Study Group Background-Tissue factor pathway inhibitor (TFPI), von Willebrand factor (vWF), and thrombomodulin (TM) are 3 major hemostatic regulatory molecules synthesized by endothelium. Data from epidemiological studies aiming to evaluate the relation between plasma levels of these molecules and the development of coronary heart disease (CHD) are sparse or contradictory. Methods and Results-We examined the association between these endothelial-cell markers and the incidence of fatal or nonfatal myocardial infarction (hard CHD) and stable or unstable angina (angina pectoris) in a prospective cohort (the PRIME Study) of nearly 10 000 healthy men recruited in France and Northern Ireland. We measured baseline plasma concentration of the free form of TFPI (f-TFPI), vWF, and the soluble form of TM (sTM) among 296 participants who subsequently developed CHD over the 5-year follow-up (158 with hard CHD and 142 with angina pectoris) and in 563 control subjects by use of a nested case-control design. Individuals with plasma vWF levels in the highest quartile showed a 3.04-fold increase in the risk of hard CHD compared with those in the lowest quartile (95% CI, 1.59 to 5.80). Individuals with f-TFPI levels below the 10th percentile had a 2.13-fold increased risk of hard CHD compared with those with levels above it (95% CI, 1.08 to 4.18). The risk for both molecules persisted after control for inflammatory parameters. Individuals with vWF levels in the highest quartile and f-TFPI levels below the 10th percentile presented a 6.9-fold increased risk of hard CHD compared with those with vWF levels in the lowest quartile and f-TFPI levels above the 10th percentile (95% CI, 1.3 to 37.8). Conclusions-vWF and f-TFPI plasma levels were independent risk factors for hard CHD events.

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“…The thrombogenicity of disrupted human atherosclerotic plaque can be predicted by its TF content and activity. Circulating levels of TF are also associated with increased blood thrombogenicity in patients with unstable angina and chronic coronary artery disease 33) and are predictive of outcomes in patients with unstable angina 34) . Specific inhibition of TF by tissue factor pathway inhibitor (TFPI), a circulating, lipoprotein-associated, Kunitz-type protease inhibitor, has been shown to significantly reduce plaque thrombogenicity 35) .…”

Section: Atherothrombosismentioning

confidence: 99%