title: Associations of factor VIIIc, D-dimer, and plasmin-antiplasmin with incident cardiovascular disease and all-cause mortality.
abstract: To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Joseph A C
authors.initials: JA
authors.lastname: Delaney
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Lutsey
authors.forename: Neil A
authors.initials: NA
authors.lastname: Zakai
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Polak
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
mesh_terms: D000367:Age Factors; D000368:Aged; D002118:Calcium / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000473:pathology; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D017540:Tunica Media / Q000473:pathology; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; D005169:Factor VIII; D002118:Calcium