A novel inflammatory marker for incident coronary heart disease

Symen Ligthart, Sanaz Sedaghat, M. Arfan Ikram, Albert Hofman, Oscar H. Franco, Abbas Dehghan

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Objective-Inflammation plays a key role in atherosclerosis. We hypothesized that novel inflammatory markers may predict the risk of coronary heart disease (CHD).

Approach and Results-We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD-free individuals in a prospective population-based cohort study. A Bonferroni corrected P value of 3.1×10-3 was used as a threshold of statistical significance. The mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all inflammatory biomarkers, neutrophilderived human s100a12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) showed the strongest association with the risk of CHD (P value 2.0×10-3). After multivariable adjustment for established cardiovascular risk factors, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 30% higher risk of incident CHD (hazard ratio, 1.30; 95% confidence interval, 1.06-1.59). Further adjustment for previously studied inflammatory markers did not attenuate the association. Excluding individuals with prevalent type 2 diabetes mellitus, impaired kidney function, or individuals using antihypertensive medication did not change the effect estimates. Cause-specific hazard ratios suggested a stronger association between EN-RAGE and CHD mortality compared with stable CHD.

Conclusions-Our results highlight EN-RAGE as an inflammatory marker for future CHD in a general population, beyond traditional CHD risk factors and inflammatory markers.

Original languageEnglish (US)
Pages (from-to)2695-2699
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number12
StatePublished - Dec 11 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 American Heart Association, Inc.


  • Biomarker
  • Coronary artery disease
  • Cytokines
  • Inflammation


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