Skip to main content
SpringerLink
Log in

Higher hemoglobin A1c levels are associated with impaired left ventricular diastolic function and higher incidence of adverse cardiac events in patients with nonischemic dilated cardiomyopathy

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

We aimed to elucidate the relationship between glycated hemoglobin (HbA1c), cardiac systolic/diastolic function, and heart failure (HF) prognosis during guideline-directed medical therapy in patients with nonischemic dilated cardiomyopathy (NIDCM). We evaluated 283 hospitalized NIDCM patients, who were grouped according to baseline (BL) and 1-year (1Y) levels of HbA1c (<6.0, 6.0–6.9, and ≥7.0 %). The primary endpoint was defined as either readmission for HF worsening or cardiac death. Approximately half of the patients had BL- or 1Y-HbA1c ≥6.0 % (31 % at BL, 34 % at 1Y had 6.0–6.9 %; 12 % at BL, 12 % at 1Y had ≥7.0 %). The absolute value of left ventricular ejection fraction (LVEF) and its improvement during 1 year showed no significant difference among the 1Y-HbA1c groups (p = 0.273), whereas a lower absolute value and a more significant reduction in the early diastolic velocity of the mitral annulus (E a) were seen in the group with 1Y-HbA1c ≥7.0 % (both p < 0.001). In multiple regression analysis, higher 1Y-plasma B-type natriuretic peptide and lower 1Y-Ea were independently associated with higher 1Y-HbA1c (both adjusted p < 0.05). The cumulative incidence of the primary endpoint was highest in the group with 1Y-HbA1c ≥7.0 % (log-rank p = 0.001). Multivariate analysis demonstrated that higher 1Y-HbA1c was independently associated with a higher incidence of the primary endpoint (adjusted p = 0.005). In conclusion, hyperglycemia during clinical follow-up is a risk factor for progression of concomitant LV abnormal relaxation, leading to poor HF prognosis in patients with NIDCM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29:1377–1385

    Article  PubMed  Google Scholar 

  2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL (2013) 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128:e240–e327

    Article  PubMed  Google Scholar 

  3. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Køber L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Rønnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, McDonagh T, Sechtem U, Bonet LA, Avraamides P, Ben Lamin HA, Brignole M, Coca A, Cowburn P, Dargie H, Elliott P, Flachskampf FA, Guida GF, Hardman S, Iung B, Merkely B, Mueller C, Nanas JN, Nielsen OW, Orn S, Parissis JT, Ponikowski P (2012) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 14:803–869

    Article  CAS  PubMed  Google Scholar 

  4. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 30:595–602

    Article  CAS  PubMed  Google Scholar 

  5. Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G (2013) Diabetic cardiomyopathy: pathophysiology, diagnostic evaluation and management. World J Diabetes 4:177–189

    PubMed  PubMed Central  Google Scholar 

  6. Jefferies JL, Towbin JA (2010) Dilated cardiomyopathy. Lancet 375:752–762

    Article  PubMed  Google Scholar 

  7. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation 93:841–842

    Article  CAS  PubMed  Google Scholar 

  8. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113:1807–1816

    Article  PubMed  Google Scholar 

  9. Ikeda Y, Inomata T, Iida Y, Iwamoto-Ishida M, Nabeta T, Ishii S, Sato T, Yanagisawa T, Mizutani T, Naruke T, Koitabashi T, Takeuchi I, Nishii M, Ako J (2016) Time course of left ventricular reverse remodeling in response to pharmacotherapy: clinical implication for heart failure prognosis in patients with idiopathic dilated cardiomyopathy. Heart Vessels 31:545–554

    Article  PubMed  Google Scholar 

  10. Ikeda Y, Inomata T, Fujita T, Iida Y, Nabeta T, Ishii S, Maekawa E, Yanagisawa T, Mizutani T, Naruke T, Koitabashi T, Takeuchi I, Ako J (2016) Cardiac fibrosis detected by magnetic resonance imaging on predicting time course diversity of left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy. Heart Vessels. doi:10.1007/s00380-016-0805-2

    Google Scholar 

  11. Rihal CS, Nishimura RA, Hatle LK, Bailey KR, Tajik AJ (1994) Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy. Relation to symptoms and prognosis. Circulation 90:2772–2779

    Article  CAS  PubMed  Google Scholar 

  12. Fukuda M (1994) Classification and treatment of diabetic retinopathy. Diabetes Res Clin Pract 24(Suppl):S171–S176

    Article  PubMed  Google Scholar 

  13. JCS Joint Working Group (2013) Guidelines for treatment of acute heart failure (JCS 2011). Circ J 77:2157–2201

    Article  Google Scholar 

  14. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 32:193–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18:1440–1463

    Article  PubMed  Google Scholar 

  16. Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000) Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 101:2271–2276

    Article  CAS  PubMed  Google Scholar 

  17. Kannel WB, Hjortland M, Castelli WP (1974) Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 34:29–34

    Article  CAS  PubMed  Google Scholar 

  18. The SOLVD Investigattors (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327:685–691

    Article  Google Scholar 

  19. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D (1993) Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 88:107–115

    Article  CAS  PubMed  Google Scholar 

  20. Shiba N, Nochioka K, Miura M, Kohno H, Shimokawa H (2011) Trend of westernization of etiology and clinical characteristics of heart failure patients in Japan—first report from the CHART-2 study. Circ J 75:823–833

    Article  PubMed  Google Scholar 

  21. Tsuchihashi-Makaya M, Hamaguchi S, Kinugawa S, Yokota T, Goto D, Yokoshiki H, Kato N, Takeshita A, Tsutsui H (2009) 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 73:1893–1900

    Article  PubMed  Google Scholar 

  22. Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP (2005) Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 149:209–216

    Article  PubMed  Google Scholar 

  23. Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL (2014) ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD—summary. Diabetes Vasc Dis Res 11:133–173

    Article  Google Scholar 

  24. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW (1997) Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 30:474–480

    Article  CAS  PubMed  Google Scholar 

  25. Sakakibara M, Hirashiki A, Cheng XW, Bando Y, Ohshima K, Okumura T, Funahashi H, Ohshima S, Murohara T (2011) Association of diabetes mellitus with myocardial collagen accumulation and relaxation impairment in patients with dilated cardiomyopathy. Diabetes Res Clin Pract 92:348–355

    Article  CAS  PubMed  Google Scholar 

  26. Boudina S, Abel ED (2007) Diabetic cardiomyopathy revisited. Circulation 115:3213–3223

    Article  PubMed  Google Scholar 

  27. Capomolla S, Febo O, Gnemmi M, Riccardi G, Opasich C, Caporotondi A, Mortara A, Pinna GD, Cobelli F (2000) Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol. Am Heart J 139:596–608

    Article  CAS  PubMed  Google Scholar 

  28. Palazzuoli A, Quatrini I, Vecchiato L, Calabria P, Gennari L, Martini G, Nuti R (2005) Left ventricular diastolic function improvement by carvedilol therapy in advanced heart failure. J Cardiovasc Pharmacol 45:563–568

    Article  CAS  PubMed  Google Scholar 

  29. Pierce GN, Russell JC (1997) Regulation of intracellular Ca2+ in the heart during diabetes. Cardiovasc Res 34:41–47

    Article  CAS  PubMed  Google Scholar 

  30. Iribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S, Selby JV (2001) Glycemic control and heart failure among adult patients with diabetes. Circulation 103:2668–2673

    Article  CAS  PubMed  Google Scholar 

  31. Gerstein HC, Swedberg K, Carlsson J, McMurray JJ, Michelson EL, Olofsson B, Pfeffer MA, Yusuf S (2008) The hemoglobin A1c level as a progressive risk factor for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. Arch Intern Med 168:1699–1704

    Article  CAS  PubMed  Google Scholar 

  32. Tomova GS, Nimbal V, Horwich TB (2012) Relation between hemoglobin a(1c) and outcomes in heart failure patients with and without diabetes mellitus. Am J Cardiol 109:1767–1773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Aguilar D, Bozkurt B, Ramasubbu K, Deswal A (2009) Relationship of hemoglobin A1C and mortality in heart failure patients with diabetes. J Am Coll Cardiol 54:422–428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Eshaghian S, Horwich TB, Fonarow GC (2006) An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure. Am Heart J 151:91

    Article  PubMed  Google Scholar 

  35. Dungan KM, Binkley P, Nagaraja HN, Schuster D, Osei K (2011) The effect of glycaemic control and glycaemic variability on mortality in patients hospitalized with congestive heart failure. Diabetes Metab Res Rev 27:85–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yu PC, Bosnyak Z, Ceriello A (2010) The importance of glycated haemoglobin (HbA(1c)) and postprandial glucose (PPG) control on cardiovascular outcomes in patients with type 2 diabetes. Diabetes Res Clin Pract 89:1–9

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan

    Yuki Ikeda, Teppei Fujita, Yuichiro Iida, Toyoji Kaida, Takeru Nabeta, Shunsuke Ishii, Emi Maekawa, Tomoyoshi Yanagisawa, Takashi Naruke, Toshimi Koitabashi, Ichiro Takeuchi & Junya Ako

  2. Department of Cardiovascular Medicine, Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan

    Takayuki Inomata & Tomohiro Mizutani

Authors
  1. Yuki Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Inomata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teppei Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuichiro Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toyoji Kaida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeru Nabeta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shunsuke Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Emi Maekawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tomoyoshi Yanagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tomohiro Mizutani
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Takashi Naruke
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshimi Koitabashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ichiro Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Junya Ako
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takayuki Inomata.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ikeda, Y., Inomata, T., Fujita, T. et al. Higher hemoglobin A1c levels are associated with impaired left ventricular diastolic function and higher incidence of adverse cardiac events in patients with nonischemic dilated cardiomyopathy. Heart Vessels 32, 446–457 (2017). https://doi.org/10.1007/s00380-016-0895-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-016-0895-x

Keywords

Search

Navigation