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

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

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.	中华医学会心血管病学分会心力衰竭学组, 中国医师协会心力衰竭专业委员会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018. 中华心血管病杂志, 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.	中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版). 中国实用内科杂志, 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.	王念鸿, 聂庆东, 李英姿, 等. 肿瘤坏死因子α与糖尿病肾病病理分期、心血管事件的关系. 实用医学杂志, 2019, 35(2): 261-265, 270.
15.	汪菲, 高向阳, 张蓉. 糖尿病肾病患者血清炎性因子, vWf, VEGF及黏附分子水平变化及意义. 海南医学院学报, 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.	王进红. 糖化血红蛋白对内皮细胞分泌eNOS, NO, t-PA, PAI-1, E-selectin, sICAM-1的作用. 苏州: 苏州大学, 2006.
18.	周福亮, 贾大林. 射血分数保留性心力衰竭与内皮功能障碍. 中国老年学杂志, 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.	刘艳秋, 林宁, 李红林, 等. 血清sP-selectin, sE-selectin水平与糖尿病肾病的相关性研究. 国际检验医学杂志, 2019, 40(8): 994-998.
23.	陈伟, 张静, 陈丹. 血清可溶性P-选择素, E-选择素水平与糖尿病患者胰岛素抵抗的关系. 疑难病杂志, 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.	迟小伟, 刘杰. hs-CRP, IL-6, TNF-α在心血管疾病中的意义. 医学检验与临床, 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. 中华医学会心血管病学分会心力衰竭学组, 中国医师协会心力衰竭专业委员会, 中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018. 中华心血管病杂志, 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. 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版). 中国实用内科杂志, 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. 王念鸿, 聂庆东, 李英姿, 等. 肿瘤坏死因子α与糖尿病肾病病理分期、心血管事件的关系. 实用医学杂志, 2019, 35(2): 261-265, 270.
15. 汪菲, 高向阳, 张蓉. 糖尿病肾病患者血清炎性因子, vWf, VEGF及黏附分子水平变化及意义. 海南医学院学报, 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. 王进红. 糖化血红蛋白对内皮细胞分泌eNOS, NO, t-PA, PAI-1, E-selectin, sICAM-1的作用. 苏州: 苏州大学, 2006.
18. 周福亮, 贾大林. 射血分数保留性心力衰竭与内皮功能障碍. 中国老年学杂志, 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. 刘艳秋, 林宁, 李红林, 等. 血清sP-selectin, sE-selectin水平与糖尿病肾病的相关性研究. 国际检验医学杂志, 2019, 40(8): 994-998.
23. 陈伟, 张静, 陈丹. 血清可溶性P-选择素, E-选择素水平与糖尿病患者胰岛素抵抗的关系. 疑难病杂志, 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. 迟小伟, 刘杰. hs-CRP, IL-6, TNF-α在心血管疾病中的意义. 医学检验与临床, 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

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content