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Predictors of mortality in heart failure with reduced ejection fraction: interaction between diabetes mellitus and impaired renal function

  • Nephrology - Original Paper
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Abstract

Background

The harmful effect of diabetes mellitus (DM) on mortality in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. Furthermore, it seems that no consistent conclusion on whether chronic kidney disease (CKD) modifies the relationship of DM and poor prognosis in patients with HFrEF.

Methods

We analyzed the individuals with HFrEF from the Cardiorenal ImprovemeNt (CIN) cohort between January 2007 and December 2018. The primary endpoint was all-cause mortality. The patients were divided into four groups (control vs. DM alone vs. CKD alone vs. DM and CKD). Multivariate Cox proportional hazards analysis was conducted to examine the association among DM, CKD and all-cause mortality.

Results

There were 3,273 patients included in this study (mean age: 62.7 ± 10.9 years, 20.4% were female). During a median follow-up of 5.0 years (interquartile range: 3.0–7.6 years), 740 (22.6%) patients died. Patients with DM have a higher risk of all-cause mortality (HR [95% confidence interval (CI)]:1.28[1.07–1.53]) than those without DM. In patients with CKD, DM had a 61% (HR [95% CI]:1.61[1.26–2.06]) increased adjusted risk of death relative to non-DM, while in patients with non-CKD, there was no significantly difference in risk of all-cause mortality (HR [95% CI]:1.01[0.77–1.32]) between DM and non-DM (p for interaction = 0.013).

Conclusions

Diabetes is a potent risk factor for mortality in patients with HFrEF. Furthermore, DM had a substantially different effect on all-cause mortality depending on CKD. The association between DM and all-cause mortality was only observed in patients with CKD.

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Abbreviations

DM:

Diabetes mellitus

HF:

Heart failure

CKD:

Chronic kidney disease

HFrEF:

Heart failure with reduced ejection fraction

CIN:

Cardiorenal ImprovemeNt

CAG:

Coronary angiography

PCI:

Percutaneous coronary intervention

LVEF:

Left ventricular ejection fraction

eGFR:

Estimated glomerular filtration rate

MDRD:

Modification of diet in renal disease

AMI:

Acute myocardial infarction

CAD:

Coronary artery disease

AF:

Atrial fibrillation

NLR:

Neutrophil-to-lymphocyte ratio

LDL-C:

Low-density lipoprotein cholesterol

HDL-C:

High-density lipoprotein cholesterol

TRIG:

Triglycerides

PGC:

Poor glycemic control

RAAS:

Renin–angiotensin–aldosterone system

References

  1. Bloom MW, Greenberg B, Jaarsma T, Januzzi JL, Lam CSP, Maggioni AP et al (2017) Heart failure with reduced ejection fraction. Nat Rev Dis Primers 3:17058

    Article  PubMed  Google Scholar 

  2. Sharma A, Zhao X, Hammill BG, Hernandez AF, Fonarow GC, Felker GM et al (2018) Trends in noncardiovascular comorbidities among patients hospitalized for heart failure: insights from the get with the guidelines-heart failure registry. Circ Heart Fail 11(6):e004646

    Article  PubMed  Google Scholar 

  3. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL et al (2016) 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 37(29):2315–2381

    Article  PubMed  PubMed Central  Google Scholar 

  4. Paolillo S, Rengo G, Pagano G, Pellegrino T, Savarese G, Femminella GD et al (2013) Impact of diabetes on cardiac sympathetic innervation in patients with heart failure: a 123I meta-iodobenzylguanidine (123I MIBG) scintigraphic study. Diabetes Care 36(8):2395–2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Parissis JT, Rafouli-Stergiou P, Mebazaa A, Ikonomidis I, Bistola V, Nikolaou M et al (2012) Acute heart failure in patients with diabetes mellitus: clinical characteristics and predictors of in-hospital mortality. Int J Cardiol 157(1):108–113

    Article  PubMed  Google Scholar 

  6. MacDonald MR, Jhund PS, Petrie MC, Lewsey JD, Hawkins NM, Bhagra S et al (2008) Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail 1(4):234–241

    Article  PubMed  Google Scholar 

  7. Kamalesh M, Cleophas TJ (2009) Heart failure due to systolic dysfunction and mortality in diabetes: pooled analysis of 39,505 subjects. J Card Fail 15(4):305–309

    Article  PubMed  Google Scholar 

  8. van Deursen VM, Urso R, Laroche C, Damman K, Dahlström U, Tavazzi L et al (2014) Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail 16(1):103–111

    Article  PubMed  Google Scholar 

  9. van Deursen VM, Damman K, van der Meer P, Wijkstra PJ, Luijckx GJ, van Beek A et al (2014) Co-morbidities in heart failure. Heart Fail Rev 19(2):163–172

    Article  CAS  PubMed  Google Scholar 

  10. Damman K, Valente MA, Voors AA, O’Connor CM, van Veldhuisen DJ, Hillege HL (2014) Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J 35(7):455–469

    Article  PubMed  Google Scholar 

  11. Radbill B, Murphy B, LeRoith D (2008) Rationale and strategies for early detection and management of diabetic kidney disease. Mayo Clin Proc 83(12):1373–1381

    Article  PubMed  Google Scholar 

  12. de Miguel-Yanes JM, Méndez-Bailón M, Marco-Martínez J, Zapatero-Gaviria A, Barba-Martín R (2014) Absence of interaction of diabetes mellitus with chronic kidney disease on mortality in acute heart failure. Ren Fail 36(10):1536–1540

    Article  PubMed  Google Scholar 

  13. Aguiar-Souto P, Ferrante G, Del Furia F, Barlis P, Khurana R, Di Mario C (2010) Frequency and predictors of contrast-induced nephropathy after angioplasty for chronic total occlusions. Int J Cardiol 139(1):68–74

    Article  PubMed  Google Scholar 

  14. Sarma S, Mentz RJ, Kwasny MJ, Fought AJ, Huffman M, Subacius H et al (2013) Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial. Eur J Heart Fail 15(2):194–202

    Article  CAS  PubMed  Google Scholar 

  15. Undas A, Wiek I, Stêpien E, Zmudka K, Tracz W (2008) Hyperglycemia is associated with enhanced thrombin formation, platelet activation, and fibrin clot resistance to lysis in patients with acute coronary syndrome. Diabetes Care 31(8):1590–1595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ritchie C, Ekundayo OJ, Muchimba M, Campbell RC, Frank SJ, Liu B et al (2009) Effects of diabetes mellitus in patients with heart failure and chronic kidney disease: a propensity-matched study of multimorbidity in chronic heart failure. Int J Cardiol 134(3):330–335

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tonelli M, Muntner P, Lloyd A, Manns BJ, Klarenbach S, Pannu N et al (2012) Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 380(9844):807–814

    Article  PubMed  Google Scholar 

  18. Miura M, Sakata Y, Miyata S, Nochioka K, Takada T, Tadaki S et al (2015) Prognostic impact of diabetes mellitus in chronic heart failure according to presence of ischemic heart disease—with special reference to nephropathy. Circ J 79(8):1764–1772

    Article  CAS  PubMed  Google Scholar 

  19. Urina-Jassir M, Herrera-Parra LJ, Hernández Vargas JA, Valbuena-García AM, Acuña-Merchán L, Urina-Triana M (2021) The effect of comorbidities on glycemic control among Colombian adults with diabetes mellitus: a longitudinal approach with real-world data. BMC Endocr Disord 21(1):128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Braunwald E (2019) Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis 62(4):298–302

    Article  PubMed  Google Scholar 

  21. Farha S, Lundgrin EL, Erzurum SC (2013) Novel therapeutic approaches to preserve the right ventricle. Curr Heart Fail Rep 10(1):12–17

    Article  PubMed  PubMed Central  Google Scholar 

  22. Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL et al (2019) Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation 139(16):e840–e878

    Article  PubMed  Google Scholar 

  23. Kovesdy CP, Sharma K, Kalantar-Zadeh K (2008) Glycemic control in diabetic CKD patients: where do we stand? Am J Kidney Dis 52(4):766–777

    Article  PubMed  Google Scholar 

  24. Aguilar D (2016) Heart failure, diabetes mellitus, and chronic kidney disease: a clinical conundrum. Circ Heart Fail 9(7)

  25. Rosendorff C, Lackland DT, Allison M, Aronow WS, Black HR, Blumenthal RS et al (2015) Treatment of hypertension in patients with coronary artery disease: a scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Circulation 131(19):e435–e470

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This research was funded and supported by Natural Science Foundation of Fujian Province (2018J01405, 2019J01617), Young and Middle-aged expert Fund for Outstanding Contributions to Hygiene and Health in Fujian Province, Longyan City Science and Technology Plan Project (2015LY33), Startup Fund for Scientific Research by Fujian Medical University (2019QH1205), Beijing Lisheng Cardiovascular Health Foundation (No. LHJJ20141751), Study on the function and mechanism of the potential target for early warning of cardiorenal syndrome after acute myocardial infarction based on transformism (DFJH201919), Natural Science Foundation of Guangdong Province General Project (2020A1515010940), and Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention (2017B030314041). The funders had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript; the work was not funded by any industry sponsors.

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Author notes

  1. Yanfang Yang, Bo Wu and Jin Lu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, China

    Yanfang Yang, Bo Wu, Jin Lu, Jiaming Xiu, Jiabin Tu, Shaowen Chen, Yuxiong Pan, Kunming Bao, Junjie Wang, Weihua Chen, Kaihong Chen & Liling Chen

  2. Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Zhidong Huang, Jin Liu, Yong Liu & Shiqun Chen

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  1. Yanfang Yang
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Contributions

The authors’ responsibilities were as follows—research idea and study design: LLC, YFY, SQC, KHC and YL; data acquisition: LLC, YFY, ZDH, BW, JLU, JMX, JBT, SWC, YXP, WHC, KMB, JJW and JLIU; data analysis/interpretation: KHC, YL; statistical analysis: BW, JLU and ZDH; supervision and mentorship: SQC, LLC; writing guidance: KHC. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions on the accuracy or integrity of any portion of the work are appropriately investigated and resolved. The authors declare that there is no competing interest. All authors read and approved the final version.

Corresponding authors

Correspondence to Shiqun Chen, Kaihong Chen or Liling Chen.

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Conflict of interest

Authors declare that there is no conflict of interest.

Ethical approval

All traceable personal identifiers were removed from the analytic dataset to protect patients’ privacy. The study protocol was approved by Guangdong Provincial People’s Hospital ethics committee and the study was performed according to the declaration of Helsinki.

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Yang, Y., Huang, Z., Wu, B. et al. Predictors of mortality in heart failure with reduced ejection fraction: interaction between diabetes mellitus and impaired renal function. Int Urol Nephrol 55, 2285–2293 (2023). https://doi.org/10.1007/s11255-023-03525-0

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