Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community

Renate B. Schnabel, Xiaoyan Yin, Martin G. Larson, Jennifer F. Yamamoto, Joao Daniel T. Fontes, Sekar Kathiresan, Jian Rong, Daniel Levy, John F. Keaney, Thomas J. Wang, Joanne M. Murabito, Ramachandran S. Vasan, Emelia J. Benjamin

Research output: Contribution to journalArticle

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Abstract

Objective-Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. Approach and Results-We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Conclusions-Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.

Original languageEnglish (US)
Pages (from-to)1728-1733
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

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Cardiovascular Diseases
Biomarkers
Tumor Necrosis Factor Receptors
Mortality
Confidence Intervals
C-Reactive Protein
Interleukin-6
Intercellular Adhesion Molecule-1
Oxidative Stress
1-Alkyl-2-acetylglycerophosphocholine Esterase
Inflammation
CD40 Ligand
P-Selectin
Chemokine CCL2
Fibrinogen
Peroxidase

Keywords

  • Cardiovascular Disease
  • Cohort
  • Epidemiology
  • Inflammation
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community. / Schnabel, Renate B.; Yin, Xiaoyan; Larson, Martin G.; Yamamoto, Jennifer F.; Fontes, Joao Daniel T.; Kathiresan, Sekar; Rong, Jian; Levy, Daniel; Keaney, John F.; Wang, Thomas J.; Murabito, Joanne M.; Vasan, Ramachandran S.; Benjamin, Emelia J.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 33, No. 7, 07.2013, p. 1728-1733.

Research output: Contribution to journalArticle

Schnabel, RB, Yin, X, Larson, MG, Yamamoto, JF, Fontes, JDT, Kathiresan, S, Rong, J, Levy, D, Keaney, JF, Wang, TJ, Murabito, JM, Vasan, RS & Benjamin, EJ 2013, 'Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 7, pp. 1728-1733. https://doi.org/10.1161/ATVBAHA.112.301174
Schnabel, Renate B. ; Yin, Xiaoyan ; Larson, Martin G. ; Yamamoto, Jennifer F. ; Fontes, Joao Daniel T. ; Kathiresan, Sekar ; Rong, Jian ; Levy, Daniel ; Keaney, John F. ; Wang, Thomas J. ; Murabito, Joanne M. ; Vasan, Ramachandran S. ; Benjamin, Emelia J. / Multiple inflammatory biomarkers in relation to cardiovascular events and mortality in the community. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2013 ; Vol. 33, No. 7. pp. 1728-1733.
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abstract = "Objective-Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. Approach and Results-We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53{\%} women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95{\%} confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95{\%} CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95{\%} CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95{\%} CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95{\%} CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Conclusions-Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.",
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AU - Yin, Xiaoyan

AU - Larson, Martin G.

AU - Yamamoto, Jennifer F.

AU - Fontes, Joao Daniel T.

AU - Kathiresan, Sekar

AU - Rong, Jian

AU - Levy, Daniel

AU - Keaney, John F.

AU - Wang, Thomas J.

AU - Murabito, Joanne M.

AU - Vasan, Ramachandran S.

AU - Benjamin, Emelia J.

PY - 2013/7

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N2 - Objective-Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. Approach and Results-We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Conclusions-Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.

AB - Objective-Evidence suggests that chronic low-grade inflammation and oxidative stress are related to cardiovascular disease (CVD) and mortality. Approach and Results-We examined 11 established and novel biomarkers representing inflammation and oxidative stress (C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase-A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, P-selectin, and tumor necrosis factor receptor II [TNFRII]) in relation to incident major CVD and mortality in the community. We studied 3035 participants (mean age, 61±9 years; 53% women). During follow-up (median, 8.9 years), 253 participants experienced a CVD event and 343 died. C-reactive protein (hazard ratio [HR] reported per SD ln-transformed biomarker, 1.18; 95% confidence interval [CI], 1.02-1.35; nominal P=0.02) and TNFRII (HR, 1.15; 95% CI, 1.01-1.32; nominal P=0.04) were retained in multivariable-adjusted models for major CVD, but were not significant after adjustment for multiple testing. The biomarkers related to mortality were TNFRII (HR, 1.33; 95% CI, 1.19-1.49; P<0.0001), ICAM-1 (HR, 1.24; 95% CI, 1.12-1.37; P<0.0001), and interleukin-6 (HR, 1.25; 95% CI, 1.12-1.39; P<0.0001). The addition of these markers to the model, including traditional risk factors, increased discrimination and reclassification for risk of death (P<0.0001), but not for CVD. Conclusions-Of 11 inflammatory biomarkers tumor necrosis factor receptor II was related to cardiovascular disease and mortality in the Framingham Heart Study. The combination of TNFRII with C-reactive protein in relation to CVD and with interleukin-6 to mortality increased the predictive ability in addition to CVD risk factors for total mortality but not for incident CVD.

KW - Cardiovascular Disease

KW - Cohort

KW - Epidemiology

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