Himabindu Vidula, MD; Lu Tian, ScD; Kiang Liu, PhD; Michael H. Criqui, MD, MPH; Luigi Ferrucci, MD, PhD; William H. Pearce, MD; Philip Greenland, MD; David Green, MD, PhD; Jin Tan, MS; Daniel B. Garside, BS; Jack Guralnik, MD, PhD; Paul M Ridker, MD; Nader Rifai, PhD; Mary M. McDermott, MD
Grant Support: By grants R01-HL58099, R01-HL64739, and R01-HL076298 from the National Heart, Lung, and Blood Institute and grant RR-00048 from the National Center for Research Resources, National Institutes of Health.
Potential Financial Conflicts of Interest:Grants received: P.M. Ridker (National Heart, Lung, and Blood Institute, National Cancer Institute, Reynolds Foundation, Doris Duke Foundation, Leducq Foundation); M.M. McDermott (National Heart, Lung, and Blood Institute). Patents received: P.M. Ridker (Brigham and Women's Hospital). Royalties: P.M. Ridker (Brigham and Women's Hospital).
Requests for Single Reprints: Mary M. McDermott, MD, 750 North Lake Shore Drive, 10th Floor, Chicago, IL 60611.
Current Author Addresses: Dr. Vidula: 320 Avena Circle, Naperville, IL 60565.
Drs. Tian, Liu, and Greenland; Mr. Tan; and Mr. Garside: 680 North Lake Shore Drive, Suite 1102, Chicago, IL 60611.
Dr. Criqui: University of California San Diego, Family & Preventive Medicine, 9500 Gilman Drive, La Jolla, CA 92093.
Dr. Ferrucci: National Institute on Aging, Clinical Research Branch, Harbor Hospital, 5th Floor, 3001 South Hanover Street, Baltimore, MD 21225.
Dr. Pearce: 201 East Huron, Suite 10-105, Chicago, IL 60611.
Dr. Green: 676 North St. Clair, Suite 850, Chicago, IL 60611.
Dr. Guralnik: Gateway Building, Room 3-C309, 7201 Wisconsin Avenue, Bethesda, MD 20892.
Dr. Ridker: Brigham and Women's Hospital, Center for Cardiovascular Disease Prevention, 900 Commonwealth Avenue, Boston, MA 02215.
Dr. Rifai: Children's Hospital Boston, Department of Laboratory Medicine, Farley 7, 300 Longwood Avenue, Boston, MA 02115.
Dr. McDermott: 750 North Lake Shore Drive, 10th Floor, Chicago, IL 60611.
Author Contributions: Conception and design: H. Vidula, K. Liu, M.H. Criqui, P. Greenland, D. Green, J. Guralnik, M.M. McDermott.
Analysis and interpretation of the data: H. Vidula, L. Tian, K. Liu, M.H. Criqui, L. Ferrucci, N. Rifai, P. Greenland, D. Green, J. Tan, J. Guralnik, P.M. Ridker.
Drafting of the article: H. Vidula, D. Green, M.M. McDermott.
Critical revision of the article for important intellectual content: H. Vidula, L. Tian, M.H. Criqui, L. Ferrucci, N. Rifai, P. Greenland, D. Green, J. Guralnik, P.M. Ridker, M.M. McDermott.
Final approval of the article: L. Tian, K. Liu, M.H. Criqui, L. Ferrucci, W.H. Pearce, N. Rifai, P. Greenland, D. Green, J. Guralnik, P.M. Ridker, M.M. McDermott.
Provision of study materials or patients: W.H. Pearce, P.M. Ridker.
Statistical expertise: L. Tian, K. Liu, J. Guralnik.
Obtaining of funding: M.H. Criqui, M.M. McDermott.
Administrative, technical, or logistic support: M.H. Criqui, D. Green, D.B. Garside.
Collection and assembly of data: D. Green, D.B. Garside, P.M. Ridker, M.M. McDermott.
Traditional atherosclerotic risk factors predict long-term cardiovascular disease events but are poor predictors of near-term events.
To determine whether elevated levels of d-dimer and biomarkers of inflammation were more closely associated with near-term than long-term mortality in patients with lower-extremity peripheral arterial disease (PAD) and whether greater increases in biomarker levels were associated with higher mortality rates during the first year after the increase than during later years.
Prospective cohort study with a mean follow-up of 3.4 years.
Academic medical center.
377 men and women with PAD.
Mortality within 1 year after biomarker measurement, 1 to 2 years after biomarker measurement, and 2 to 3 years after biomarker measurement. Cox regression analyses were used to evaluate associations of biomarkers levels and changes in biomarkers with cardiovascular and all-cause mortality. Hazard ratios were calculated for each 1-unit increase in log1.5(biomarker level). Analyses were adjusted for age, sex, race, comorbid conditions, ankle–brachial index, and other confounders.
Seventy-six patients (20%) died during follow-up. Higher levels of d-dimer, C-reactive protein, and serum amyloid A were associated with higher all-cause mortality among patients who died within 1 year after biomarker measurement (hazard ratio, 1.20 [95% CI, 1.08 to 1.33], 1.13 [CI, 1.05 to 1.21], and 1.12 [CI, 1.04 to 1.20], respectively; P < 0.001, P < 0.001, and P = 0.003) and among patients who died 1 to 2 years after biomarker measurement (hazard ratio, 1.14 [CI, 1.02 to 1.27], 1.15 [CI, 1.06 to 1.24], and 1.13 [CI, 1.04 to 1.24]; P = 0.022, P = 0.001, and P = 0.005]). However, higher levels of each biomarker were not associated with all-cause mortality for deaths occurring 2 to 3 years after biomarker measurement. Similar results were observed for cardiovascular mortality. Greater increases in each biomarker were associated with higher all-cause and cardiovascular mortality during the following year.
The small number of deaths limited the statistical power of the analyses.
Among persons with PAD, circulating levels of d-dimer and inflammatory markers are higher in the 1 to 2 years before death than in periods more remote from death. Increasing levels of d-dimer and inflammatory biomarkers are independently associated with higher mortality in persons with PAD.
Vidula H, Tian L, Liu K, et al. Biomarkers of Inflammation and Thrombosis as Predictors of Near-Term Mortality in Patients with Peripheral Arterial Disease: A Cohort Study. Ann Intern Med. 2008;148:85–93. doi: https://doi.org/10.7326/0003-4819-148-2-200801150-00003
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Published: Ann Intern Med. 2008;148(2):85-93.
Cardiology, Coronary Risk Factors.
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