Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study.
BACKGROUND
Traditional atherosclerotic risk factors predict long-term cardiovascular disease events but are poor predictors of near-term events.


OBJECTIVE
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.


METHODS
Prospective cohort study with a mean follow-up of 3.4 years.


METHODS
Academic medical center.


METHODS
377 men and women with PAD.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The small number of deaths limited the statistical power of the analyses.


CONCLUSIONS
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
Himabindu
H
Feinberg School of Medicine, Northwestern University, Chicago, Illinois; University of California at San Diego, San Diego, California, USA.
Tian
Lu
L
Liu
Kiang
K
Criqui
Michael H
MH
Ferrucci
Luigi
L
Pearce
William H
WH
Greenland
Philip
P
Green
David
D
Tan
Jin
J
Garside
Daniel B
DB
Guralnik
Jack
J
Ridker
Paul M
PM
Rifai
Nader
N
McDermott
Mary M
MM
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002423:Cause of Death; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000401:mortality*; D011446:Prospective Studies; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D013927:Thrombosis / Q000097:blood*
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D000685:Serum Amyloid A Protein; C036309:fibrin fragment D; D002097:C-Reactive Protein