TY - JOUR
T1 - Cross-sectional relations of multiple inflammatory biomarkers to peripheral arterial disease
T2 - The Framingham Offspring Study
AU - Murabito, Joanne M.
AU - Keyes, Michelle J.
AU - Guo, Chao Yu
AU - Keaney, John F.
AU - Vasan, Ramachandran S.
AU - D'Agostino, Ralph B.
AU - Benjamin, Emelia J.
N1 - Funding Information:
The Framingham Heart Study is supported by NIH/NHLBI contract N01-HC-25195. Additional funding for this work supported by NIH grants RO1 HL064753, HL076784, AG028321 (E.J.B.); HL 080124, HL 077477, HL71039, K24 HL 4334 (R.S.V.); tumor necrosis factor-alpha concentrations measured via American Diabetes Association Career Development Award and NCRR GCRC M01-RR-01066 James B. Meigs, MD, MPH. Lipoprotein-associated phospholipase-A2 Lp-PLA2 activity measurements were provided by GlaxoSmithKline at no cost to the FHS.
PY - 2009/4
Y1 - 2009/4
N2 - Background: Emerging evidence suggests that different inflammatory biomarkers operate through distinct biologic mechanisms. We hypothesized that the relation to peripheral arterial disease (PAD) varies for individual markers. Methods: In a community-based sample we measured 12 biomarkers including plasma CD40 ligand, fibrinogen, lipoprotein-associated phospholipase-A2 mass and activity, osteoprotegerin, P-selectin, and tumor necrosis factor receptor 2 (TNFR2); and serum C-reactive protein, intracellular adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1, and myeloperoxidase in Framingham Offspring Study participants (n = 2800, 53% women, mean age 61 years). We examined the cross-sectional relation of the biomarker panel to PAD using (1) a global test of significance to determine whether at least one of 12 biomarkers was related to PAD using the TEST statement in the LOGISTIC procedure in SAS and (2) stepwise multivariable logistic regression with forward selection of markers with separate models for (1) ankle-brachial index (ABI) category (<0.9, 0.9-1.0, >1.0) and (2) presence of clinical PAD (intermittent claudication or lower extremity revascularization). Results: The group of inflammatory biomarkers were significantly related to both ABI and clinical PAD (p = 0.01 and p = 0.02, respectively, multi-marker adjusted global significance test). Multivariable forward elimination regression retained interleukin-6 and TNFR2 as significantly associated with PAD. For one standard deviation change in interleukin-6 and TNFR2 concentrations, there was a 1.21 (p = 0.005) and 1.19 (p = 0.009) increased odds of a change in ABI level respectively. Similar results were observed for clinical PAD. Conclusion: Interleukin-6 and TNFR2 were significantly associated with PAD independent of established risk factors and each other, suggesting that each marker represents a distinct biologic pathway.
AB - Background: Emerging evidence suggests that different inflammatory biomarkers operate through distinct biologic mechanisms. We hypothesized that the relation to peripheral arterial disease (PAD) varies for individual markers. Methods: In a community-based sample we measured 12 biomarkers including plasma CD40 ligand, fibrinogen, lipoprotein-associated phospholipase-A2 mass and activity, osteoprotegerin, P-selectin, and tumor necrosis factor receptor 2 (TNFR2); and serum C-reactive protein, intracellular adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1, and myeloperoxidase in Framingham Offspring Study participants (n = 2800, 53% women, mean age 61 years). We examined the cross-sectional relation of the biomarker panel to PAD using (1) a global test of significance to determine whether at least one of 12 biomarkers was related to PAD using the TEST statement in the LOGISTIC procedure in SAS and (2) stepwise multivariable logistic regression with forward selection of markers with separate models for (1) ankle-brachial index (ABI) category (<0.9, 0.9-1.0, >1.0) and (2) presence of clinical PAD (intermittent claudication or lower extremity revascularization). Results: The group of inflammatory biomarkers were significantly related to both ABI and clinical PAD (p = 0.01 and p = 0.02, respectively, multi-marker adjusted global significance test). Multivariable forward elimination regression retained interleukin-6 and TNFR2 as significantly associated with PAD. For one standard deviation change in interleukin-6 and TNFR2 concentrations, there was a 1.21 (p = 0.005) and 1.19 (p = 0.009) increased odds of a change in ABI level respectively. Similar results were observed for clinical PAD. Conclusion: Interleukin-6 and TNFR2 were significantly associated with PAD independent of established risk factors and each other, suggesting that each marker represents a distinct biologic pathway.
KW - Ankle-brachial index
KW - Interleukin-6
KW - Peripheral arterial disease
KW - Tumor necrosis factor receptor 2
UR - http://www.scopus.com/inward/record.url?scp=62949090529&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2008.06.031
DO - 10.1016/j.atherosclerosis.2008.06.031
M3 - Article
C2 - 18701106
AN - SCOPUS:62949090529
SN - 0021-9150
VL - 203
SP - 509
EP - 514
JO - Atherosclerosis
JF - Atherosclerosis
IS - 2
ER -