Associations of candidate biomarkers of vascular disease with the ankle-brachial index and peripheral arterial disease

Zi Ye, Zeenat Ali, George G. Klee, Thomas H. Mosley, Iftikhar Jan Kullo

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs). Methods Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use. Results After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers-myeloperoxidase, NT-proBNP, and D-dimer-were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs. Conclusiona multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.

Original languageEnglish (US)
Pages (from-to)495-502
Number of pages8
JournalAmerican Journal of Hypertension
Volume26
Issue number4
DOIs
StatePublished - Apr 2013

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Ankle Brachial Index
Peripheral Arterial Disease
Vascular Diseases
Biomarkers
African Americans
Brain Natriuretic Peptide
Lipoprotein(a)
Tumor Necrosis Factor Receptors
Atrial Natriuretic Factor
C-Reactive Protein
Fibrinogen
Interleukin-6
Osteoprotegerin
Arginine Vasopressin
Peroxidase
Atherosclerosis
Multivariate Analysis
Regression Analysis

Keywords

  • ankle-brachial index
  • biomarker
  • blood pressure
  • hypertension
  • peripheral arterial disease

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Associations of candidate biomarkers of vascular disease with the ankle-brachial index and peripheral arterial disease. / Ye, Zi; Ali, Zeenat; Klee, George G.; Mosley, Thomas H.; Kullo, Iftikhar Jan.

In: American Journal of Hypertension, Vol. 26, No. 4, 04.2013, p. 495-502.

Research output: Contribution to journalArticle

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abstract = "Background The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs). Methods Study participants included 1,291 AAs (71.1{\%} women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5{\%} women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use. Results After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers-myeloperoxidase, NT-proBNP, and D-dimer-were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs. Conclusiona multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.",
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AU - Ali, Zeenat

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AU - Mosley, Thomas H.

AU - Kullo, Iftikhar Jan

PY - 2013/4

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N2 - Background The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs). Methods Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use. Results After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers-myeloperoxidase, NT-proBNP, and D-dimer-were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs. Conclusiona multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.

AB - Background The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs). Methods Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use. Results After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers-myeloperoxidase, NT-proBNP, and D-dimer-were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs. Conclusiona multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.

KW - ankle-brachial index

KW - biomarker

KW - blood pressure

KW - hypertension

KW - peripheral arterial disease

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