Endothelial function and prognosis of patients with type 2 diabetes mellitus combined with mid-range ejection fraction heart failure_Chinese Journal of Evidence-Based Medicine

Authors：

HAI Rulinisa YA Sen ¹ , YU Zixiang ¹ , LIU Fen ² , YANG Yining ¹ , LI Xiaomei ¹ ,  MA Yitong ³

1. First Department of Coronary Heart Disease, Heart Center of the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P.R.China;
2. The Key Laboratory of Cardiovascular Disease, Urumqi 830054, P.R.China;
3. Heart Center of the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P.R.China;

Corresponding?author：

MA Yitong, Email: myt-xj@163.com

Keywords：

Heart failure with mid-range ejection fraction; Type 2 diabetes mellitus; Endothelial dysfunction; Oxidative stress

DOI：

10.7507/1672-2531.202011060

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Objective To explore the effect of type 2 diabetes mellitus (T2DM) on the vascular endothelial function of patients with heart failure with mid-range ejection fraction (HFmrEF), and the impact of endothelial function damage on the long-term prognosis of HFmrEF. Metohds 87 patients with T2DM and heart failure with mid-range ejection fraction (T2DM-HFmrEF), 98 patients with HFmrEF alone, and 70 healthy control who had been hospitalized at the department of cardiology of the First Affiliated Hospital of Xinjiang Medical University from December 2018 to January 2020 were included. The levels of serum TNF-α, IL-6, vWF, eNOs and E-selectin were determined by enzyme-linked immunosorbent assay. The oxidative stress and vascular endothelial function related indicators of the 3 groups were analyzed. The primary endpoint (all-cause death, exacerbation of heart failure and rehospitalization, or exacerbation of heart failure) and secondary endpoint events (non-fatal myocardial infarction, stable and unstable angina pectoris, or stroke) were followed up for 1 year after discharge.Results The levels of TNF-α, IL-6, vWF, and E-selectin in the HFmrEF combined with diabetes group were higher than those in the HFmrEF without diabetes group (P<0.05). Multivariate Cox regression analysis showed that BNP (HR=1.001, P=0.036), eNOs (HR=1.04, P<0.001), and IL-6 (HR=1.002, P<0.001) were related to the primary end point of all patients with HFmrEF. Glycated hemoglobin (HR=1.37, P=0.046), E-selectin (HR=1.01, P=0.003), vWF (HR=1.02, P=0.017), and IL-6 (HR=1.006, P=0.005) were related to the secondary end point of all patients with HFmrEF. The results of subgroup analyze showed that E-selectin (HR=1.014, P=0.012) and IL-6 (HR=1.008, P=0.007) were related to the secondary endpoint events in the HFmrEF combined with diabetes group, but were not related to the secondary end point events of the non-diabetic group (P>0.05).Conclusions Oxidative stress and vascular endothelial function damage may be involved in the pathogenesis of T2DM-HFmrEF. Serum IL-6 and E-selectin levels are related to the endpoint events in T2DM-HFmrEF patients.

Citation： HAI Rulinisa YA Sen, YU Zixiang, LIU Fen, YANG Yining, LI Xiaomei, MA Yitong. Endothelial function and prognosis of patients with type 2 diabetes mellitus combined with mid-range ejection fraction heart failure. Chinese Journal of Evidence-Based Medicine, 2021, 21(5): 539-545. doi: 10.7507/1672-2531.202011060 Copy

1.	Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J, 2016, 37(27): 2129-2200.
2.	中華醫學會心血管病學分會心力衰竭學組, 中國醫師協會心力衰竭專業委員會, 中華心血管病雜志編輯委員會. 中國心力衰竭診斷和治療指南2018. 中華心血管病雜志, 2018, 46(10): 760-789.
3.	Bhambhani V, Kizer JR, Lima JAC, et al. Predictors and outcomes of heart failure with mid-range ejection fraction. Eur J Heart Fail, 2018, 20(4): 651-659.
4.	Lam CSP, Gamble GD, Ling LH, et al. Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study. Eur Heart J, 2018, 39(20): 1770-1780.
5.	Lund LH, Claggett B, Liu J, et al. Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail, 2018, 20(8): 1230-1239.
6.	Chioncel O, Lainscak M, Seferovic PM, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail, 2017, 19(12): 1574-1585.
7.	Kleber ME, Koller L, Goliasch G, et al. Von Willebrand factor improves risk prediction in addition to N-terminal pro-B-type natriuretic peptide in patients referred to coronary angiography and signs and symptoms of heart failure and preserved ejection fraction. Circ Heart Fail, 2015, 8(1): 25-32.
8.	Garg A, Virmani D, Agrawal S, et al. Clinical application of biomarkers in heart failure with a preserved ejection fraction: a review. Cardiology, 2017, 136(3): 192-203.
9.	Tromp J, Westenbrink BD, Ouwerkerk W, et al. Identifying pathophysiological mechanisms in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol, 2018, 72(10): 1081-1090.
10.	Kapoor JR, Kapoor R, Ju C, et al. Precipitating clinical factors, heart failure characterization, and outcomes in patients hospitalized with heart failure with reduced, borderline, and preserved ejection fraction. JACC Heart Fail, 2016, 4(6): 464-472.
11.	Koh AS, Tay WT, Teng THK, et al. A comprehensive population-based characterization of heart failure with mid-range ejection fraction. Eur J Heart Fail, 2017, 19(12): 1624-1634.
12.	中華醫學會糖尿病學分會. 中國2型糖尿病防治指南(2017年版). 中國實用內科雜志, 2018, 38(4): 292-344.
13.	Tsuchihashi-Makaya M, Hamaguchi S, Kinugawa S, et al. Characteristics and outcomes of hospitalized patients with heart failure and reduced vs preserved ejection fraction. Report from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). Circ J, 2009, 73(10): 1893-1900.
14.	王念鴻, 聶慶東, 李英姿, 等. 腫瘤壞死因子α與糖尿病腎病病理分期、心血管事件的關系. 實用醫學雜志, 2019, 35(2): 261-265, 270.
15.	汪菲, 高向陽, 張蓉. 糖尿病腎病患者血清炎性因子, vWf, VEGF及黏附分子水平變化及意義. 海南醫學院學報, 2017, 23(16): 2207-2210.
16.	Prudente S, Trischitta V. The TRIB3 Q84R polymorphism, insulin resistance and related metabolic alterations. Biochem Soc Trans, 2015, 43(5): 1108-1111.
17.	王進紅. 糖化血紅蛋白對內皮細胞分泌eNOS, NO, t-PA, PAI-1, E-selectin, sICAM-1的作用. 蘇州: 蘇州大學, 2006.
18.	周福亮, 賈大林. 射血分數保留性心力衰竭與內皮功能障礙. 中國老年學雜志, 2018, 38(19): 4852-4855.
19.	Nakagawa T, Tanabe K, Croker BP, et al. Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nat Rev Nephrol, 2011, 7(1): 36-44.
20.	Hanai K, Babazono T, Nyumura I, et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant, 2009, 24(6): 1884-1888.
21.	Aljwaid H, White DL, Collard KJ, et al. Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes. J Diabetes Complications, 2015, 29(7): 943-949.
22.	劉艷秋, 林寧, 李紅林, 等. 血清sP-selectin, sE-selectin水平與糖尿病腎病的相關性研究. 國際檢驗醫學雜志, 2019, 40(8): 994-998.
23.	陳偉, 張靜, 陳丹. 血清可溶性P-選擇素, E-選擇素水平與糖尿病患者胰島素抵抗的關系. 疑難病雜志, 2016, 15(4): 374-377.
24.	Jax T, Peters A, Plehn G, et al. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2. Cardiovascul Diabetol, 2009, 8: 24.
25.	Nauta JF, Hummel YM, van Melle JP, et al. What have we learned about heart failure with mid-range ejection fraction one year after its introduction? Eur J Heart Fail, 2017, 19(12): 1569-1573.
26.	遲小偉, 劉杰. hs-CRP, IL-6, TNF-α在心血管疾病中的意義. 醫學檢驗與臨床, 2008, 19(3): 50-51.
27.	de Boer RA, Nayor M, deFilippi CR, et al. Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction. JAMA Cardiol, 2018, 3(3): 215-224.
28.	Kistorp C, Chong AY, Gustafsson F, et al. Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes. Eur J Heart Fail, 2008, 10(4): 380-387.
29.	Patel TV, Mittal BV, Keithi-Reddy SR, et al. Endothelial activation markers in anemic non-dialysis chronic kidney disease patients. Nephron Clin Pract, 2008, 110(4): c244-250.

1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J, 2016, 37(27): 2129-2200.
2. 中華醫學會心血管病學分會心力衰竭學組, 中國醫師協會心力衰竭專業委員會, 中華心血管病雜志編輯委員會. 中國心力衰竭診斷和治療指南2018. 中華心血管病雜志, 2018, 46(10): 760-789.
3. Bhambhani V, Kizer JR, Lima JAC, et al. Predictors and outcomes of heart failure with mid-range ejection fraction. Eur J Heart Fail, 2018, 20(4): 651-659.
4. Lam CSP, Gamble GD, Ling LH, et al. Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study. Eur Heart J, 2018, 39(20): 1770-1780.
5. Lund LH, Claggett B, Liu J, et al. Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail, 2018, 20(8): 1230-1239.
6. Chioncel O, Lainscak M, Seferovic PM, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail, 2017, 19(12): 1574-1585.
7. Kleber ME, Koller L, Goliasch G, et al. Von Willebrand factor improves risk prediction in addition to N-terminal pro-B-type natriuretic peptide in patients referred to coronary angiography and signs and symptoms of heart failure and preserved ejection fraction. Circ Heart Fail, 2015, 8(1): 25-32.
8. Garg A, Virmani D, Agrawal S, et al. Clinical application of biomarkers in heart failure with a preserved ejection fraction: a review. Cardiology, 2017, 136(3): 192-203.
9. Tromp J, Westenbrink BD, Ouwerkerk W, et al. Identifying pathophysiological mechanisms in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol, 2018, 72(10): 1081-1090.
10. Kapoor JR, Kapoor R, Ju C, et al. Precipitating clinical factors, heart failure characterization, and outcomes in patients hospitalized with heart failure with reduced, borderline, and preserved ejection fraction. JACC Heart Fail, 2016, 4(6): 464-472.
11. Koh AS, Tay WT, Teng THK, et al. A comprehensive population-based characterization of heart failure with mid-range ejection fraction. Eur J Heart Fail, 2017, 19(12): 1624-1634.
12. 中華醫學會糖尿病學分會. 中國2型糖尿病防治指南(2017年版). 中國實用內科雜志, 2018, 38(4): 292-344.
13. Tsuchihashi-Makaya M, Hamaguchi S, Kinugawa S, et al. Characteristics and outcomes of hospitalized patients with heart failure and reduced vs preserved ejection fraction. Report from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). Circ J, 2009, 73(10): 1893-1900.
14. 王念鴻, 聶慶東, 李英姿, 等. 腫瘤壞死因子α與糖尿病腎病病理分期、心血管事件的關系. 實用醫學雜志, 2019, 35(2): 261-265, 270.
15. 汪菲, 高向陽, 張蓉. 糖尿病腎病患者血清炎性因子, vWf, VEGF及黏附分子水平變化及意義. 海南醫學院學報, 2017, 23(16): 2207-2210.
16. Prudente S, Trischitta V. The TRIB3 Q84R polymorphism, insulin resistance and related metabolic alterations. Biochem Soc Trans, 2015, 43(5): 1108-1111.
17. 王進紅. 糖化血紅蛋白對內皮細胞分泌eNOS, NO, t-PA, PAI-1, E-selectin, sICAM-1的作用. 蘇州: 蘇州大學, 2006.
18. 周福亮, 賈大林. 射血分數保留性心力衰竭與內皮功能障礙. 中國老年學雜志, 2018, 38(19): 4852-4855.
19. Nakagawa T, Tanabe K, Croker BP, et al. Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nat Rev Nephrol, 2011, 7(1): 36-44.
20. Hanai K, Babazono T, Nyumura I, et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant, 2009, 24(6): 1884-1888.
21. Aljwaid H, White DL, Collard KJ, et al. Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes. J Diabetes Complications, 2015, 29(7): 943-949.
22. 劉艷秋, 林寧, 李紅林, 等. 血清sP-selectin, sE-selectin水平與糖尿病腎病的相關性研究. 國際檢驗醫學雜志, 2019, 40(8): 994-998.
23. 陳偉, 張靜, 陳丹. 血清可溶性P-選擇素, E-選擇素水平與糖尿病患者胰島素抵抗的關系. 疑難病雜志, 2016, 15(4): 374-377.
24. Jax T, Peters A, Plehn G, et al. Relevance of hemostatic risk factors on coronary morphology in patients with diabetes mellitus type 2. Cardiovascul Diabetol, 2009, 8: 24.
25. Nauta JF, Hummel YM, van Melle JP, et al. What have we learned about heart failure with mid-range ejection fraction one year after its introduction? Eur J Heart Fail, 2017, 19(12): 1569-1573.
26. 遲小偉, 劉杰. hs-CRP, IL-6, TNF-α在心血管疾病中的意義. 醫學檢驗與臨床, 2008, 19(3): 50-51.
27. de Boer RA, Nayor M, deFilippi CR, et al. Association of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction. JAMA Cardiol, 2018, 3(3): 215-224.
28. Kistorp C, Chong AY, Gustafsson F, et al. Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes. Eur J Heart Fail, 2008, 10(4): 380-387.
29. Patel TV, Mittal BV, Keithi-Reddy SR, et al. Endothelial activation markers in anemic non-dialysis chronic kidney disease patients. Nephron Clin Pract, 2008, 110(4): c244-250.

Chinese Journal of Evidence-Based Medicine

Endothelial function and prognosis of patients with type 2 diabetes mellitus combined with mid-range ejection fraction heart failure

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