Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Clin Res Cardiol. 2020 Mar;109(3):358-373. doi: 10.1007/s00392-019-01516-9. Epub 2019 Jul 1.
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.
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.
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.
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.
本研究旨在评估代表低水平系统性炎症的生物标志物及其与路德维希港风险和心血管健康（LURIC）研究中心血管死亡率的关系。
本研究纳入了 3134 例连续患者，他们于 1997 年 6 月至 2001 年 5 月期间接受了冠状动脉造影检查，中位随访时间为 9.9 年。检测了 IL-6 和急性期反应物血清淀粉样蛋白 A（SAA）和 C 反应蛋白（CRP）的血浆水平。对 SAA 和 IL-6 多态性进行了基因分型。
在中位观察时间为 9.9 年期间，有 949 例患者（30.3%）死亡，其中 597 例（19.2%）死于心血管原因。高血浆 IL-6、CRP 和 SAA 水平与不稳定型 CAD 以及包括 2 型糖尿病、吸烟、肾小球滤过率低、甘油三酯低和高密度脂蛋白胆固醇低在内的既定危险因素相关。在校正了既定心血管风险标志物和其他两种炎症标志物后，SAA 在短期随访（6 个月-1 年）后被发现是心血管死亡率的独立危险因素，SD 每增加一个单位，HR 为 1.41。IL-6 被确定为长期随访（3、5 和 9.9 年）的独立危险因素，SD 每增加一个单位，HR 分别为 1.21、1.22 和 1.18。CRP 在调整后失去了意义。尽管 27 个 SAA SNP 中有 6 个与 SAA 血浆浓度显著相关，但遗传风险评分与心血管死亡率无关。
本研究从大型前瞻性 LURIC 队列中发现，炎症在 CAD 中的重要性以及独立预测心血管死亡率的炎症生物标志物的预后相关性。
