title: Changes in D-dimer and inflammatory biomarkers before ischemic events in patients with peripheral artery disease: The BRAVO Study.
abstract: Whether circulating biomarker levels increase shortly before an ischemic heart disease (IHD) event is unknown. We studied whether levels of D-dimer, C-reactive protein (CRP), and serum amyloid A (SAA) are higher within 2 months of an IHD event compared to time periods more than 2 months before the IHD event. We assembled 595 participants with peripheral artery disease (PAD) and followed them for up to 3 years. Blood samples were obtained every 2 months. The primary outcome was IHD events: myocardial infarctions, unstable angina, or IHD death. We used a nested case-control design. Fifty participants (cases) had events and were each matched by age, sex, duration in the study, and number of blood draws to two controls without events. Among cases, the mean D-dimer value of 1.105 obtained within 2 months of the event was higher than values obtained 10 months (0.68 mg/L, p<0.001), 12 months (0.71 mg/L, p=0.001), 16 months (0.65 mg/L, p=0.008), 20 months (p=0.032), 22 months (p=0.033), 26 months (p=0.038), and 32 months (p=0.04) before the event. Compared to controls, median D-dimer levels in cases were higher 4 months (p=0.017), 6 months (p=0.005), and 8 months (p=0.028) before the event. Values of CRP and SAA obtained within two months of an IHD event not consistently higher than values obtained during the prior months. In PAD participants with an IHD event, D-dimer was higher within 2 months of the event, compared to most values obtained 10 to 32 months previously. D-dimer was also higher in cases as compared to controls during most visits within 8 months of the IHD event.
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA mdm608@northwestern.edu.
authors.forename: Mary McGrae
authors.initials: MM
authors.lastname: McDermott
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Greenland
authors.affiliation: Department of Health Research and Policy, Stanford University, Stanford, CA, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
authors.forename: Melina
authors.initials: M
authors.lastname: Kibbe
authors.affiliation: Department of Pathology - Colchester Research Facility, University of Vermont College of Medicine, Colchester, VT, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Wilkins
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Huffman
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Joseph J Zilber School of Public Health, University of Wisconsin at Milwaukee, Milwaukee, WI, USA.
authors.forename: Chiang-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Auerbach
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Skelly
authors.affiliation: Department of Surgery, Rush Medical Center, Chicago, IL, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: McCarthy
authors.affiliation: Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Lloyd Jones
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002641:Chicago; D018450:Disease Progression; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; C036309:fibrin fragment D
keywords: C-reactive protein; D-dimer; biomarkers; cardiovascular mortality; ischemic heart disease; peripheral artery disease; risk factors