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Multiple Inflammatory Biomarkers in Relation to Cardiovascular Events and Mortality in the Community.

Publication TypeJournal Article
AuthorsSchnabel, RB, Yin X., Larson MG, Yamamoto JF, Fontes JD, Kathiresan S., Rong J., Levy D., Keaney JF Jr, Wang TJ, Murabito JM, Vasan RS, and Benjamin EJ
AbstractOBJECTIVE: 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.
Year of Publication2013
JournalArteriosclerosis, thrombosis, and vascular biology
Date Published (YYYY/MM/DD)2013/05/02
ISSN Number1079-5642
DOI10.1161/ATVBAHA.112.301174
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23640499?dopt=Abstract