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新研究揭示：高敏感性C反應蛋白於2型糖尿病患者中預測心腦血管事件風險

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最新研究發現，高敏感性C反應蛋白（hs-CRP）可作為2型糖尿病患者中三管病變（TVD）的長期預後因子。研究涵蓋2734名患者，發現hs-CRP水平升高與2型糖尿病患者心腦血管事件風險增加相關，但在無糖尿病患者中則無此現象。此發現對於心腦血管疾病的預防與治療提供新的洞見。

高敏感性C反應蛋白在有和無2型糖尿病的三血管疾病患者中的預測價值

Predictive value of high sensitivity C-reactive protein in three-vessel disease patients with and without type 2 diabetes

Lei Guo 1, Haichen Lv 1, Junjie Wang 1, Bo Zhang 1, Yifan Zhu 2, Xiaoyan Zhang 3, Hao Zhu 1, Xuchen Zhou 1, Yunlong Xia 4
Affiliations expand
PMID: 37081535 PMCID: PMC10120230 DOI: 10.1186/s12933-023-01830-7
https://pubmed.ncbi.nlm.nih.gov/37081535/

摘要

背景：糖尿病（DM）和動脈粥樣硬化是多因素疾病，並共享一個共同的炎症基礎。三管病變（TVD）對冠狀動脈介入手術來說代表一個重大的挑戰。然而，高敏感性C反應蛋白（hs-CRP）對有或無2型糖尿病的TVD患者的預測價值仍然未知。在此，我們旨在從一個大型隊列中確定hs-CRP對TVD患者（按照2型糖尿病的狀態）的長期預測價值。

方法：共有2734名有（n = 1040，38%）和無（n = 1694，62%）2型糖尿病的TVD患者，基於hs-CRP（< 2 mg/L vs. ≥ 2 mg/L）進行分層。進行了三種多變量分析模型，以評估潛在混淆因素對hs-CRP水平與臨床結果之間關係的影響。計算了一致性指數，網絡再分類改進（NRI）和整合歧視改進（IDI），以評估hs-CRP和基線模型與已確定的風險因素對臨床結果歧視的增加效果。主要終點是主要不良心臟和腦血管事件（MACCE）。

結果：中位追蹤時間為2.4年。多變量Cox迴歸分析顯示，與非糖尿病組相比，糖尿病組的主要不良心臟和腦血管事件（MACCE）的發生率（調整風險比例 [HR] 1.17，95%信賴區間 [CI] 1.01-1.35，p = 0.031）和全因死亡率（HR 1.82，95% CI 1.07-3.11，p = 0.026）顯著較高。在糖尿病組中，高hs-CRP組的MACCE發生率（調整HR 1.51，95% CI 1.09-2.10，p = 0.013）顯著高於低hs-CRP組；全因死亡率無顯著差異（HR 1.63；95% CI 0.58-4.58，p = 0.349）。在非糖尿病組中，兩組間MACCE的盛行率（調整HR 0.93，95% CI 0.71-1.22，p = 0.613）相近。最後，在糖尿病組中，加入hs-CRP後，MACCE的NRI（0.2074，p = 0.001）和IDI（0.0086，p = 0.003）也顯著增加。

結論：hs-CRP的升高是2型糖尿病患者中三管病變（TVD）患者MACCE長期結果的獨立預後因子，但在無2型糖尿病的患者中則非如此。與傳統風險因素相比，hs-CRP提高了2型糖尿病患者中TVD患者不良心血管事件風險預測。

關鍵詞：冠狀動脈疾病；糖尿病；高敏感性C反應蛋白；結果；三管病變。

Abstract

Background: Diabetes mellitus (DM) and atherosclerosis are multifactorial conditions and share a common inflammatory basis. Three-vessel disease (TVD) represents a major challenge for coronary intervention. Nonetheless, the predictive value of high-sensitivity C-reactive protein (hs-CRP) for TVD patients with or without type 2 DM remains unknown. Herein, we aimed to ascertain the long-term predictive value of hs-CRP in TVD patients according to type 2 DM status from a large cohort.

Methods: A total of 2734 TVD patients with (n = 1040, 38%) and without (n = 1694, 62%) type 2 diabetes were stratified based on the hs-CRP (< 2 mg/L vs. ≥ 2 mg/L). Three multivariable analysis models were performed to evaluate the effect of potential confounders on the relationship between hs-CRP level and clinical outcomes. The Concordance index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess the added effect of hs-CRP and the baseline model with established risk factors on the discrimination of clinical outcomes. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE).

Results: The median follow-up duration was 2.4 years. Multivariate Cox regression analyses showed that the incidence of MACCE (adjusted hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.01-1.35, p = 0.031) and all-cause death (HR 1.82, 95% CI 1.07-3.11, p = 0.026) were significantly higher in the diabetic group compared to the non-diabetic group. In the diabetic group, the incidence of MACCE (adjusted HR 1.51, 95% CI 1.09-2.10, p = 0.013) was significantly higher in the high hs-CRP group than in the low hs-CRP group; no significant difference was found for all-cause death (HR 1.63; 95% CI 0.58-4.58, p = 0.349). In the non-diabetic group, the prevalence of MACCE (adjusted HR 0.93, 95% CI 0.71-1.22, p = 0.613) was comparable between the two groups. Finally, the NRI (0.2074, p = 0.001) and IDI (0.0086, p = 0.003) for MACCE were also significantly increased after hs-CRP was added to the baseline model in the diabetic group.

Conclusions: Elevated hs-CRP is an independent prognostic factor for long-term outcomes of MACCE in TVD patients with type 2 diabetes but not in those without type 2 diabetes. Compared to traditional risk factors, hs-CRP improved the risk prediction of adverse cardiovascular events in TVD patients with type 2 diabetes.

Keywords: Coronary artery disease; Diabetes; High-sensitivity C-reactive protein; Outcomes; Three-vessel disease.

利益衝突聲明

作者宣稱沒有利益衝突。

圖1

研究流程圖。hs-CRP：高敏感度C反應蛋白，TVD：三支血管疾病

圖2

ROC曲線分析以評估hs-CRP對MACCE的預測價值。AUC：曲線下面積，hs-CRP：高敏感度C反應蛋白，MACCE：主要不良心臟和腦血管事件，ROC：接收器操作曲線

圖3

根據hs-CRP水平在分層之前（A）及之後（B和C），所有有和無糖尿病患者的臨床結果。*P < 0.05。**P < 0.01。***P < 0.001。hs-CRP：高敏感度C反應蛋白，MACCE：主要不良心臟和腦血管事件，NS：無顯著性

圖4

每個子組患者在隨訪期間MACCE和全因死亡的Kaplan-Meier曲線。A和B：根據糖尿病狀況，所有患者在隨訪期間MACCE（A）和全因死亡（B）的Kaplan-Meier曲線；C和D：根據hs-CRP水平，有糖尿病的患者在隨訪期間MACCE（C）和全因死亡（D）的Kaplan-Meier曲線；圖E和F：根據hs-CRP水平，無糖尿病的患者在隨訪期間MACCE（E）和全因死亡（F）的Kaplan-Meier曲線；hs-CRP：高敏感度C反應蛋白，MACCE：主要不良心臟和腦血管事件

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