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

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.

• Authors: Renate B Schnabel, Xiaoyan Yin, Martin G Larson, Jennifer F Yamamoto, João D Fontes, Sekar Kathiresan, Jian Rong, Daniel Levy, John F Keaney Jr, Thomas J Wang, Joanne M Murabito, Ramachandran S Vasan, Emelia J Benjamin
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 33 Issue 7 Pg. 1728-33 (Jul 2013) ISSN: 1524-4636 [Electronic] United States
• PMID: 23640499 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• ICAM1 protein, human
• IL6 protein, human
• Inflammation Mediators
• Interleukin-6
• Receptors, Tumor Necrosis Factor, Type II
• TNFRSF1B protein, human
• Intercellular Adhesion Molecule-1
• C-Reactive Protein

Topics

• Aged
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Cardiovascular Diseases (blood, mortality)
• Disease-Free Survival
• Female
• Health Surveys
• Humans
• Incidence
• Inflammation (blood, mortality)
• Inflammation Mediators (blood)
• Intercellular Adhesion Molecule-1 (blood)
• Interleukin-6 (blood)
• Male
• Massachusetts (epidemiology)
• Middle Aged
• Multivariate Analysis
• Principal Component Analysis
• Prognosis
• Proportional Hazards Models
• Receptors, Tumor Necrosis Factor, Type II (blood)
• Risk Assessment
• Risk Factors
• Time Factors