Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study

Ioanna Tzoulaki, Gordon D. Murray, Amanda J. Lee, Ann Rumley, Gordon D. O. Lowe, F. Gerald R. Fowkes

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Aims: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies.

Methods and results: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for.

Conclusions: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.

Original languageEnglish
Pages (from-to)354-362
Number of pages9
JournalEuropean Heart Journal
Volume28
Issue number3
Early online date9 Jan 2007
DOIs
Publication statusPublished - Feb 2007

Keywords

  • epidemiology
  • peripheral arterial disease
  • risk factors
  • inflammation
  • coagulation
  • fibrinolysis
  • blood viscosity
  • coronary-heart-disease
  • c-reactive protein
  • intercellular-adhesion molecule-1
  • cardiovascular-disease
  • intermittent claudication
  • general-population
  • risk-factors
  • plasma-fibrinogen
  • atherosclerosis
  • lipoprotein(a)

Cite this

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease : Edinburgh Artery Study. / Tzoulaki, Ioanna; Murray, Gordon D.; Lee, Amanda J.; Rumley, Ann; Lowe, Gordon D. O.; Fowkes, F. Gerald R.

In: European Heart Journal, Vol. 28, No. 3, 02.2007, p. 354-362.

Research output: Contribution to journalArticle

Tzoulaki, Ioanna ; Murray, Gordon D. ; Lee, Amanda J. ; Rumley, Ann ; Lowe, Gordon D. O. ; Fowkes, F. Gerald R. / Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease : Edinburgh Artery Study. In: European Heart Journal. 2007 ; Vol. 28, No. 3. pp. 354-362.
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abstract = "Aims: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. Methods and results: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95{\%} CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. Conclusions: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.",
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T1 - Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease

T2 - Edinburgh Artery Study

AU - Tzoulaki, Ioanna

AU - Murray, Gordon D.

AU - Lee, Amanda J.

AU - Rumley, Ann

AU - Lowe, Gordon D. O.

AU - Fowkes, F. Gerald R.

PY - 2007/2

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N2 - Aims: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. Methods and results: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. Conclusions: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.

AB - Aims: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. Methods and results: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. Conclusions: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.

KW - epidemiology

KW - peripheral arterial disease

KW - risk factors

KW - inflammation

KW - coagulation

KW - fibrinolysis

KW - blood viscosity

KW - coronary-heart-disease

KW - c-reactive protein

KW - intercellular-adhesion molecule-1

KW - cardiovascular-disease

KW - intermittent claudication

KW - general-population

KW - risk-factors

KW - plasma-fibrinogen

KW - atherosclerosis

KW - lipoprotein(a)

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DO - 10.1093/eurheartj/ehl441

M3 - Article

VL - 28

SP - 354

EP - 362

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 3

ER -