Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study

Abstract

Background: The present study aimed to evaluate biomarkers representing low-grade systemic inflammation and their association with cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.

Methods: The included 3134 consecutive patients underwent coronary angiography between June 1997 and May 2001 with a median follow-up of 9.9 years. Plasma levels of IL-6, and acute-phase reactants serum amyloid A (SAA) and C-reactive protein (CRP) were measured. SAA and IL-6 polymorphisms were genotyped.

Results: During a median observation time of 9.9 years, 949 deaths (30.3%) occurred, of these 597 (19.2%) died from cardiovascular causes. High plasma levels of IL-6, CRP and SAA were associated with unstable CAD, as well as established risk factors including type 2 diabetes mellitus, smoking, low glomerular filtration rate, low TGs and low HDL-C. After adjusting for established cardiovascular risk markers and the other two inflammatory markers, SAA was found to be an independent risk factor for cardiovascular mortality after a short-term follow-up (6 months-1 year) with a HR per SD of 1.41. IL-6 was identified as an independent risk factor for long-term follow-up (3, 5, and 9.9 years) with HRs per SD of 1.21, 1.22 and 1.18. CRP lost significance after adjustment. Although 6 out of 27 SAA SNPs were significantly associated with SAA plasma concentrations, the genetic risk score was not associated with cardiovascular mortality.

Conclusions: The present findings from the large, prospective LURIC cohort underline the importance of inflammation in CAD and the prognostic relevance of inflammatory biomarkers that independently predict cardiovascular mortality.

Keywords: CRP; Cardiovascular mortality; IL-6; Inflammation; SAA.