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Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis: the Edinburgh Artery Study

Ioanna Tzoulaki1, Gordon D Murray, Jacqueline F Price

  • 1Wolfson Unit for Prevention of Peripheral Vascular Diseases, School of Medicine and Veterinary Medicine, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland, UK. I.Tzoulaki@sms.ed.ac.uk

American Journal of Epidemiology
|December 17, 2005
PubMed

Insights

Inflammation, not hypercoagulation, appears more linked to atherosclerosis progression. Key markers like fibrinogen and D-dimer showed associations, but inflammation markers like C-reactive protein and interleukin-6 explained these links.

Area of Science:

  • Cardiovascular Science
  • Hematology
  • Immunology

Background:

  • Atherosclerosis development involves complex interactions between hemostatic and inflammatory pathways.
  • Understanding these interactions is crucial for identifying therapeutic targets and predicting disease progression.

Purpose of the Study:

  • To investigate the independent and combined associations of hemostatic and inflammatory markers with peripheral atherosclerotic progression.
  • To determine whether inflammation or hypercoagulation is more strongly associated with atherosclerosis.

Main Methods:

  • The Edinburgh Artery Study cohort (1,592 participants, aged 55-74) measured baseline levels of fibrinogen, D-dimer, von Willebrand factor, and inflammatory markers (CRP, IL-6).
  • Ankle-brachial index (ABI) was assessed at baseline and after 12 years to track peripheral atherosclerotic progression.
  • Statistical analyses examined associations between hemostatic/inflammatory markers and ABI change, adjusting for cardiovascular risk factors.

Main Results:

  • Fibrinogen and D-dimer showed significant associations with ABI decline, independent of baseline ABI and cardiovascular risk factors.
  • These associations became non-significant after adjusting for C-reactive protein (CRP) or interleukin-6 (IL-6).
  • Elevated levels of both D-dimer and IL-6 were linked to the most substantial ABI decline, suggesting a combined inflammatory and hemostatic effect.

Conclusions:

  • Fibrinogen and D-dimer are associated with peripheral atherosclerosis progression, but this relationship is mediated by inflammatory processes.
  • Inflammation, indicated by CRP and IL-6, appears to be more fundamentally linked to atherosclerosis than hypercoagulation.
  • These findings support the hypothesis that inflammation plays a more dominant role in atherosclerosis than increased blood clotting tendency.

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