Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy

Karen Johnson, Aaron K. Aragaki, Rebecca Jackson, Alex Reiner, Per Morten Sandset, Jan Rosing, Anders E.A. Dahm, Frits Rosendaal, Joann E. Manson, Lisa W. Martin, Simin Liu, Lewis H. Kuller, Mary Cushman, Jacques E. Rossouw

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective-To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and Results-Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions-Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy.

Original languageEnglish (US)
Pages (from-to)418-424
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume36
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Activated Protein C Resistance
Progestins
Coronary Disease
Estrogens
Thromboplastin
Therapeutics
Women's Health
Hemostatics
lipoprotein-associated coagulation inhibitor
Case-Control Studies
Placebos
Hormones

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy. / Johnson, Karen; Aragaki, Aaron K.; Jackson, Rebecca; Reiner, Alex; Sandset, Per Morten; Rosing, Jan; Dahm, Anders E.A.; Rosendaal, Frits; Manson, Joann E.; Martin, Lisa W.; Liu, Simin; Kuller, Lewis H.; Cushman, Mary; Rossouw, Jacques E.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 36, No. 2, 01.02.2016, p. 418-424.

Research output: Contribution to journalArticle

Johnson, K, Aragaki, AK, Jackson, R, Reiner, A, Sandset, PM, Rosing, J, Dahm, AEA, Rosendaal, F, Manson, JE, Martin, LW, Liu, S, Kuller, LH, Cushman, M & Rossouw, JE 2016, 'Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy', Arteriosclerosis, thrombosis, and vascular biology, vol. 36, no. 2, pp. 418-424. https://doi.org/10.1161/ATVBAHA.115.306905
Johnson, Karen ; Aragaki, Aaron K. ; Jackson, Rebecca ; Reiner, Alex ; Sandset, Per Morten ; Rosing, Jan ; Dahm, Anders E.A. ; Rosendaal, Frits ; Manson, Joann E. ; Martin, Lisa W. ; Liu, Simin ; Kuller, Lewis H. ; Cushman, Mary ; Rossouw, Jacques E. / Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy. In: Arteriosclerosis, thrombosis, and vascular biology. 2016 ; Vol. 36, No. 2. pp. 418-424.
@article{1a27b67fc78f4ea3a582df5fc3e3b97e,
title = "Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy",
abstract = "Objective-To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and Results-Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions-Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy.",
author = "Karen Johnson and Aragaki, {Aaron K.} and Rebecca Jackson and Alex Reiner and Sandset, {Per Morten} and Jan Rosing and Dahm, {Anders E.A.} and Frits Rosendaal and Manson, {Joann E.} and Martin, {Lisa W.} and Simin Liu and Kuller, {Lewis H.} and Mary Cushman and Rossouw, {Jacques E.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1161/ATVBAHA.115.306905",
language = "English (US)",
volume = "36",
pages = "418--424",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Coronary Heart Disease Due to Combined Estrogen Plus Progestin Therapy

AU - Johnson, Karen

AU - Aragaki, Aaron K.

AU - Jackson, Rebecca

AU - Reiner, Alex

AU - Sandset, Per Morten

AU - Rosing, Jan

AU - Dahm, Anders E.A.

AU - Rosendaal, Frits

AU - Manson, Joann E.

AU - Martin, Lisa W.

AU - Liu, Simin

AU - Kuller, Lewis H.

AU - Cushman, Mary

AU - Rossouw, Jacques E.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Objective-To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and Results-Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions-Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy.

AB - Objective-To examine whether tissue factor pathway inhibitor or acquired activated protein C (APC) resistance influences the increased risk of coronary heart disease (CHD) due to estrogen plus progestin therapy. Approach and Results-Prospective nested case-control study of 205 cases of CHD and 481 matched controls in the Women's Health Initiative randomized trial of estrogen plus progestin therapy. After multivariable covariate adjustment, both baseline tissue factor pathway activity (P=0.01) and APC resistance (P=0.004) were associated positively with CHD risk. Baseline tissue factor pathway activity and APC resistance singly or jointly did not significantly modify the effect of estrogen plus progestin on CHD risk. Compared with placebo, estrogen plus progestin decreased tissue factor pathway inhibitor activity and increased APC resistance but these changes did not seem to modify or mediate the effect of estrogen plus progestin on CHD risk. Conclusions-Tissue factor pathway inhibitor activity and APC resistance are related to CHD risk in women, but may not explain the increased CHD risk due to estrogen plus progestin therapy. The data from this study do not support the clinical use of measuring these hemostatic factors to help stratify risk before hormone therapy.

UR - http://www.scopus.com/inward/record.url?scp=84955725930&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955725930&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.115.306905

DO - 10.1161/ATVBAHA.115.306905

M3 - Article

VL - 36

SP - 418

EP - 424

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 2

ER -