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

本翻譯僅作學術交流用,無商業意圖,請勿轉載,如有疑議問請來信

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

Guo L, Lv H, Wang J, Zhang B, Zhu Y, Zhang X, Zhu H, Zhou X, Xia Y. Predictive value of high sensitivity C-reactive protein in three-vessel disease patients with and without type 2 diabetes. Cardiovasc Diabetol. 2023 Apr 20;22(1):91. doi: 10.1186/s12933-023-01830-7. PMID: 37081535; PMCID: PMC10120230.

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

參考資料

Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019 doi: 10.1016/j.diabres.2019.107843. – DOI – PubMed

Guo L, Wang J, Ding H, et al. Long-term outcomes of medical therapy versus successful recanalisation for coronary chronic total occlusions in patients with and without type 2 diabetes mellitus. Cardiovasc Diabetol. 2020;19:100. doi: 10.1186/s12933-020-01087-4. – DOI – PMC – PubMed

Luscher TF, Creager MA, Beckman JA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Circulation. 2003;108:1655–61. doi: 10.1161/01.CIR.0000089189.70578.E2. – DOI – PubMed

Thuijs DJFM, Kappetein AP, Serruys PW, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. The Lancet. 2019;394:1325–34. doi: 10.1016/S0140-6736(19)31997-X. – DOI – PubMed

Zhao J, Lv H, Yin D, et al. Systemic immune-inflammation index predicts long-term outcomes in patients with three-vessel coronary disease after revascularization: results from a large cohort of 3561 patients. J Inflamm Res. 2022;15:5283–92. doi: 10.2147/JIR.S385990. – DOI – PMC – PubMed

Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association between low-grade systemic inflammation and type 2 diabetes mellitus among men and women from the ATTICA Study. Rev Diabet Stud. 2007;4:98–104. doi: 10.1900/RDS.2007.4.98. – DOI – PMC – PubMed

Lucci C, Cosentino N, Genovese S, et al. Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus. Cardiovasc Diabetol. 2020;19:183. doi: 10.1186/s12933-020-01157-7. – DOI – PMC – PubMed

Odegaard AO, Jacobs DR, Jr, Sanchez OA, Goff DC, Jr, Reiner AP, Gross MD. Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes. Cardiovasc Diabetol. 2016;15:51. doi: 10.1186/s12933-016-0369-6. – DOI – PMC – PubMed

Wolf D, Ley K. Immunity and inflammation in atherosclerosis. Circ Res. 2019;124:315–27. doi: 10.1161/CIRCRESAHA.118.313591. – DOI – PMC – PubMed

Shitara J, Ogita M, Wada H, et al. Clinical impact of high-sensitivity C-reactive protein during follow-up on long-term adverse clinical outcomes in patients with coronary artery disease treated with percutaneous coronary intervention. J Cardiol. 2019;73:45–50. doi: 10.1016/j.jjcc.2018.06.002. – DOI – PubMed

Świątkiewicz I, Magielski P, Kubica J. C-Reactive protein as a risk marker for post-infarct heart failure over a multi-year period. Int J Mol Sci. 2021;22:3169. doi: 10.3390/ijms22063169. – DOI – PMC – PubMed

Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J. 2019;40:87–165. doi: 10.1093/eurheartj/ehy394. – DOI – PubMed

Association AD. Standards of medical care in diabetes-2016: summary of revisions. Diabetes Care. 2016;39(Suppl 1):4–5. – PubMed

Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions: a case for standardized definitions. Circulation. 2007;115:2344–51. doi: 10.1161/CIRCULATIONAHA.106.685313. – DOI – PubMed

Zhao X, Jiang L, Xu L, et al. Predictive value of in-hospital white blood cell count in chinese patients with triple-vessel coronary disease. Eur J Prev Cardiol. 2019;26:872–82. doi: 10.1177/2047487319826398. – DOI – PubMed

Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation. 2001;103:1194–7. doi: 10.1161/01.CIR.103.9.1194. – DOI – PubMed

Wada H, Dohi T, Miyauchi K, et al. Preprocedural high-sensitivity C-Reactive protein predicts long-term outcome of percutaneous coronary intervention. Circ J. 2016;81:90–5. doi: 10.1253/circj.CJ-16-0790. – DOI – PubMed

Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation. 2000;102:1000–6. doi: 10.1161/01.CIR.102.9.1000. – DOI – PubMed

Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation. 2003;107:398–404. doi: 10.1161/01.CIR.0000052617.91920.FD. – DOI – PubMed

Kalkman DN, Aquino M, Claessen BE, et al. Residual inflammatory risk and the impact on clinical outcomes in patients after percutaneous coronary interventions. Eur Heart J. 2018;39:4101–08. doi: 10.1093/eurheartj/ehy633. – DOI – PubMed

Oemrawsingh RM, Cheng JM, Akkerhuis KM, et al. High-sensitivity C-reactive protein predicts 10-year cardiovascular outcome after percutaneous coronary intervention. EuroIntervention. 2016;12:345–51. doi: 10.4244/EIJY15M07_04. – DOI – PubMed

Ortolani P, Marzocchi A, Marrozzini C, et al. Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention. Eur Heart J. 2008;29:1241–9. doi: 10.1093/eurheartj/ehm338. – DOI – PubMed

Sharif S, Van der Graaf Y, Cramer MJ, et al. Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes. Cardiovasc Diabetol. 2021;20:220. doi: 10.1186/s12933-021-01409-0. – DOI – PMC – PubMed

Soinio M, Marniemi J, Laakso M, Lehto S, Rönnemaa T. High-sensitivity C-reactive protein and coronary heart disease mortality in patients with type 2 diabetes: a 7-year follow-up study. Diabetes Care. 2006;29:329–33. doi: 10.2337/diacare.29.02.06.dc05-1700. – DOI – PubMed

Yan Y, Li S, Liu Y, et al. Temporal relationship between inflammation and insulin resistance and their joint effect on hyperglycemia: the Bogalusa heart study. Cardiovasc Diabetol. 2019;18:109. doi: 10.1186/s12933-019-0913-2. – DOI – PMC – PubMed

Xia M, Zhang C, Gu J, et al. Impact of C-reactive protein on long-term mortality in acute myocardial infarction patients with diabetes and those without. Clin Chim Acta. 2018;480:220–24. doi: 10.1016/j.cca.2018.02.025. – DOI – PubMed

Cho DH, Joo HJ, Kim MN, Lim DS, Shim WJ, Park SM. Association between epicardial adipose tissue, high-sensitivity C-reactive protein and myocardial dysfunction in middle-aged men with suspected metabolic syndrome. Cardiovasc Diabetol. 2018;17:95. doi: 10.1186/s12933-018-0735-7. – DOI – PMC – PubMed

Pradhan AD, Ridker PM. Do atherosclerosis and type 2 diabetes share a common inflammatory basis? Eur Heart J. 2002;23:831–4. doi: 10.1053/euhj.2001.3052. – DOI – PubMed

Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–9. doi: 10.1056/NEJM199704033361401. – DOI – PubMed

Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82. doi: 10.1016/S0140-6736(09)60447-5. – DOI – PubMed

Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–31. doi: 10.1056/NEJMoa1707914. – DOI – PubMed

Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391:319–28. doi: 10.1016/S0140-6736(17)32814-3. – DOI – PubMed