Iwata Hiroshi, Miyauchi Katsumi, Naito Ryo, Iimuro Satoshi, Ozaki Yukio, Sakuma Ichiro, Nakagawa Yoshihisa, Hibi Kiyoshi, Hiro Takefui, Fukumoto Yoshihiro, Hokimoto Seiji, Saito Yasushi, Ogawa Hisao, Shimokawa Hiroaki, Daida Hiroyuki, Kimura Takeshi, Nagai Ryozo
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Innovation and Research Support Center, International University of Health and Welfare, Tokyo, Japan.
JACC Adv. 2024 Jun 5;3(7):100996. doi: 10.1016/j.jacadv.2024.100996. eCollection 2024 Jul.
The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS.
This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients.
The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP.
Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; = 0.60) hs-CRP.
The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
慢性冠状动脉综合征（CCS）患者持续性低度炎症的预后意义尚未得到充分研究。REAL-CAD（匹伐他汀积极或适度降脂治疗对冠状动脉疾病的随机评估）研究证明了高强度匹伐他汀对日本CCS患者的益处。
这项REAL-CAD研究的预先指定亚分析旨在评估以高敏C反应蛋白（hs-CRP）为代表的持续性低度炎症对CCS患者的预后影响。
本分析纳入了随机分组后6个月内无事件发生且基线和6个月时hs-CRP水平可用的患者（n = 10460）。主要终点是心血管死亡、心肌梗死、中风和不稳定型心绞痛住院的复合终点。标志性分析根据基线和6个月时hs-CRP的中位数水平（均为0.5mg/L）评估了4组持续炎症的预后影响。这4组包括hs-CRP持续低、升高（增加）、降低和持续高的患者。
校正后的Cox比例风险分析表明，与以持续低hs-CRP组为参照相比，持续高hs-CRP组的主要终点风险增加（校正后HR：1.48，95%CI：1.18-1.89；P = 0.001），但hs-CRP升高组（HR：1.07，95%CI：0.77-1.49，P = 0.68）和降低组（HR：0.92；95%CI：0.66-1.27；P = 0.60）的风险相似。
该研究表明，持续性低度炎症与不良预后相关，并强调了应对CCS患者残余炎症风险的必要性。（冠状动脉疾病匹伐他汀积极或适度降脂治疗的随机评估[REAL-CAD]；NCT01042730）
