Inflammatory/Hemostatic Biomarkers and Coronary Artery Calcium Progression in Women at Midlife (from the Study of Women's Health Across the Nation, Heart Study).
It is unknown whether inflammatory/hemostatic biomarkers are associated with coronary artery calcium (CAC) progression. Our purpose was to evaluate the associations of baseline levels of C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen, and circulating factor VII with CAC progression in healthy midlife women. Inflammatory/hemostatic biomarkers were measured at baseline. CAC was quantified by computed tomography scans at baseline and after 2.3 ± 0.5 years of follow-up. Significant CAC progression was defined as present if (1) follow-up CAC Agatston score was >0 if baseline CAC score = 0; (2) annualized change in CAC score was ≥10 if baseline CAC score >0 to <100; and (3) annualized percent change in CAC score was ≥10% if baseline CAC score ≥100. Extent of CAC progression was defined as [log(CAC(follow-up)+25) - log(CAC(baseline)+25)]/year. Logistic and linear regression models were used as appropriate, and the final models were adjusted for baseline CAC score, age, study site, race/ethnicity, menopausal status, sociodemographics, traditional cardiovascular disease (CVD) risk factors, family history of CVD, and CVD medication use. The study included 252 women (baseline age 51.2 ± 2.6 years; 67.5% white; 56.4% premenopausal or early perimenopausal). In final models, only log(PAI-1) was associated with presence of CAC progression (odds ratio 1.91, 95% CI 1.24 to 2.93; per 1 log unit increase in PAI-1; p = 0.003). In addition, higher log(PAI-1) was marginally associated with greater extent of CAC progression (p = 0.06). In conclusion, PAI-1 is associated with the presence of CAC progression in middle-aged women. Targeting PAI-1 may decrease atherogenesis beyond conventional CVD risk factors.
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Norman C
NC
Wang
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Karen A
KA
Matthews
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Emma J M
EJ
Barinas-Mitchell
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.
Chung-Chou H
CC
Chang
Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. Electronic address: elkhoudarys@edc.pitt.edu.
Samar R
SR
El Khoudary
D000328:Adult; D000941:Antigens / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D018450:Disease Progression; D005167:Factor VII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000276:immunology; D014057:Tomography, X-Ray Computed
D000941:Antigens; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D005167:Factor VII; D005340:Fibrinogen; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator