Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany.
Department of Medicine, University of Mississippi Medical Center, Jackson, Missouri.
Am J Cardiol. 2022 Oct 15;181:1-8. doi: 10.1016/j.amjcard.2022.06.061. Epub 2022 Aug 13.
The relation between serial high-sensitivity C-reactive protein (hsCRP) and long-term major cardiovascular events (MACEs; cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) has not been explored in optimally-treated patients with atherosclerotic cardiovascular disease. We tested the hypothesis that longitudinal follow-up hsCRP (repeated measures over time) would associate with 30-month MACE rates. We performed a post hoc analysis of ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibitor with Evacetrapib in Patients with High-Risk for Vascular Outcomes), involving optimally-treated patients with high-risk vascular disease, with available baseline and at least 1 follow-up hsCRP level. Using multivariable Cox proportional hazard models, we determined the association of longitudinal follow-up hsCRP with MACE at 30 months among 8,563 patients (aged 64.6 ± 9 years, 22% women). Patients with incident MACE (n = 961) had higher baseline hsCRP levels (1.77 vs 1.46 mg/L, p <0.0001 for patients with and without MACE, respectively) and showed an upward trajectory during follow-up, whereas median hsCRP levels remained <2 mg/L at all time points (1.83 vs 1.53 mg/L, 1.91 vs 1.53 mg/L, 1.76 vs 1.37 mg/L, at 3, 12, and 24 months, respectively). In a multivariable analysis, higher longitudinal hsCRP levels were independently associated with MACE (hazard ratio [95% confidence interval] per SD 1.19 [1.10 to 1.29], p <0.001), the majority of its individual components and all-cause death. Multivariable models containing longitudinal hsCRP provided improved predictive ability of MACE over baseline hsCRP. In the setting of established medical therapies, longitudinal follow-up hsCRP was independently associated with long-term MACE. In conclusion, these findings suggest that longitudinal hsCRP represents a novel approach of residual cardiovascular risk even when on-treatment hsCRP levels remain <2 mg/L.
在经过最佳治疗的动脉粥样硬化性心血管疾病患者中，尚未探讨连续高敏 C 反应蛋白（hsCRP）与长期主要心血管事件（MACE；心血管死亡、心肌梗死、中风、冠状动脉血运重建、不稳定型心绞痛住院）之间的关系。我们检验了这样一个假设，即纵向 hsCRP 随访（随时间重复测量）与 30 个月时的 MACE 发生率相关。我们对 ACCELERATE（评估胆固醇酯转移蛋白抑制剂 Evacetrapib 在高危血管结局患者中的临床效果）进行了事后分析，该研究纳入了接受最佳治疗的高危血管疾病患者，这些患者基线时和至少有 1 次 hsCRP 随访水平可用。我们使用多变量 Cox 比例风险模型，确定了 8563 例患者（年龄 64.6±9 岁，22%为女性）中 30 个月时纵向 hsCRP 与 MACE 的相关性。发生 MACE 的患者（n=961）基线 hsCRP 水平较高（1.77 与 1.46mg/L，p 分别＜0.0001），且随访期间呈上升趋势，而中位数 hsCRP 水平在所有时间点均＜2mg/L（1.83 与 1.53mg/L，1.91 与 1.53mg/L，1.76 与 1.37mg/L，分别在 3、12 和 24 个月时）。在多变量分析中，hsCRP 水平较高与 MACE 独立相关（每标准差增加 1.19[1.10 至 1.29]，p＜0.001），且与 MACE 的各个组成部分及全因死亡均相关。包含纵向 hsCRP 的多变量模型提供了对 MACE 的预测能力的改善，优于基线 hsCRP。在既定的医疗治疗中，纵向 hsCRP 与长期 MACE 独立相关。总之，这些发现表明，即使治疗中的 hsCRP 水平仍＜2mg/L，纵向 hsCRP 也是残余心血管风险的一种新方法。
