Multiple Inflammatory Biomarkers in Relation to Cardiovascular Events and Mortality in the Community
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 biomarkers, TNFRII was associated nominally with incident major CVD, and significantly with all-cause mortality, which renders it an interesting target for future research. 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.
- Received January 14, 2013.
- Accepted April 18, 2013.
- © 2013 American Heart Association, Inc.