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Long- and short-term association of low-grade systemic inflammation with cardiovascular mortality in the LURIC study
Anna-Isabelle Kälsch1, Hubert Scharnagl2, Marcus E Kleber1,3
1Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Insights
Systemic inflammation biomarkers, including serum amyloid A (SAA) and interleukin-6 (IL-6), predict cardiovascular mortality in patients with coronary artery disease (CAD). SAA is a short-term predictor, while IL-6 is a long-term predictor.
Area of Science:
- Cardiovascular Medicine
- Inflammation Research
- Biomarker Discovery
Background:
- Low-grade systemic inflammation is implicated in cardiovascular disease (CAD).
- Identifying reliable biomarkers for inflammation is crucial for predicting cardiovascular mortality.
Purpose of the Study:
- To evaluate biomarkers of systemic inflammation and their association with cardiovascular mortality.
- To assess the prognostic relevance of IL-6, SAA, and CRP in the LURIC cohort.
Main Methods:
- Prospective study of 3134 patients undergoing coronary angiography.
- Measurement of plasma IL-6, SAA, and CRP levels.
- Genotyping of SAA and IL-6 polymorphisms and assessment of genetic risk scores.
Main Results:
- High IL-6, SAA, and CRP levels were associated with unstable CAD and traditional risk factors.
- SAA independently predicted short-term cardiovascular mortality (HR per SD 1.41).
- IL-6 independently predicted long-term cardiovascular mortality (HRs per SD 1.18-1.22). CRP lost significance after adjustment.
Conclusions:
- Inflammatory biomarkers, particularly SAA and IL-6, are important in CAD.
- These biomarkers independently predict cardiovascular mortality, highlighting inflammation's role in CAD prognosis.
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.
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