Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis

I. Tzoulaki, G. D. Murray, J. F. Price, F. B. Smith, Amanda Jane Lee, A. Rumley, G. D. O. Lowe, F. G. R. Fowkes

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p <= 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.

Original languageEnglish
Pages (from-to)334-341
Number of pages7
JournalAmerican Journal of Epidemiology
Volume163
Issue number4
DOIs
Publication statusPublished - Mar 2006

Keywords

  • arteriosclerosis
  • cohort studies
  • hemostasis
  • inflammation
  • peripheral vascular diseases
  • CORONARY-HEART-DISEASE
  • FIBRIN D-DIMER
  • C-REACTIVE PROTEIN
  • TISSUE-PLASMINOGEN ACTIVATOR
  • INTIMA-MEDIA THICKNESS
  • CARDIOVASCULAR-DISEASE
  • GENERAL-POPULATION
  • RISK-FACTORS
  • CIRCULATING MARKERS
  • PLASMA-FIBRINOGEN

Cite this

Tzoulaki, I., Murray, G. D., Price, J. F., Smith, F. B., Lee, A. J., Rumley, A., ... Fowkes, F. G. R. (2006). Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis. American Journal of Epidemiology, 163(4), 334-341. https://doi.org/10.1093/aje/kwj051

Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis. / Tzoulaki, I.; Murray, G. D.; Price, J. F.; Smith, F. B.; Lee, Amanda Jane; Rumley, A.; Lowe, G. D. O.; Fowkes, F. G. R.

In: American Journal of Epidemiology, Vol. 163, No. 4, 03.2006, p. 334-341.

Research output: Contribution to journalArticle

Tzoulaki, I, Murray, GD, Price, JF, Smith, FB, Lee, AJ, Rumley, A, Lowe, GDO & Fowkes, FGR 2006, 'Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis', American Journal of Epidemiology, vol. 163, no. 4, pp. 334-341. https://doi.org/10.1093/aje/kwj051
Tzoulaki, I. ; Murray, G. D. ; Price, J. F. ; Smith, F. B. ; Lee, Amanda Jane ; Rumley, A. ; Lowe, G. D. O. ; Fowkes, F. G. R. / Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis. In: American Journal of Epidemiology. 2006 ; Vol. 163, No. 4. pp. 334-341.
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AU - Murray, G. D.

AU - Price, J. F.

AU - Smith, F. B.

AU - Lee, Amanda Jane

AU - Rumley, A.

AU - Lowe, G. D. O.

AU - Fowkes, F. G. R.

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AB - The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p <= 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.

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KW - peripheral vascular diseases

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KW - CARDIOVASCULAR-DISEASE

KW - GENERAL-POPULATION

KW - RISK-FACTORS

KW - CIRCULATING MARKERS

KW - PLASMA-FIBRINOGEN

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SN - 0002-9262

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