Objectives: Heart failure (HF) patients with diabetes mellitus experience poor prognosis. We assessed the independent predictive effect of prevalent diabetes mellitus on all-cause mortality in HF outpatients. Furthermore, we investigated if optimized HF medication differed in diabetic versus nondiabetic patients. Methods: From 6,289 patients included in the Norwegian HF registry during 2000-2012, 724 diabetic HF outpatients were propensity-score-matched with nondiabetic HF outpatients (1:1), based on 21 measured baseline variables. Baseline characteristics, measured comorbidities and medication were balanced in the matched sample. Results: Diabetes was not an independent predictor of all-cause mortality in the propensity-matched analyses (hazard ratio 1.041; 95% confidence interval 0.875-1.240). No interactions were found between the prognostic impact of diabetes and the strata renal function, systolic function or etiology of chronic HF. Diabetic HF outpatients were independently prescribed higher doses of β-blockers and loop diuretics (both p < 0.001) and were more prone to receive statins (p = 0.003) than nondiabetics. Conclusions: Prevalent diabetes mellitus was not an independent predictor of all-cause mortality in HF outpatients. Explanations other than tight glycemic control should be assessed to improve the prognosis of diabetic HF outpatients. The more intensive, optimized HF medication for diabetic HF outpatients may, to a certain degree, explain our results.

1.
Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM: Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251-259.
2.
Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, Witteman JC, Stricker BH: Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure. The Rotterdam Study. Eur Heart J 2004;25:1614-1619.
3.
Mosterd A, Hoes AW: Clinical epidemiology of heart failure. Heart 2007;93:1137-1146.
4.
King H, Aubert RE, Herman WH: Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414-1431.
5.
Kannel WB, McGee DL: Diabetes and cardiovascular disease. The Framingham Study. JAMA 1979;241:2035-2038.
6.
Gottdiener JS, Arnold AM, Aurigemma GP, Polak JF, Tracy RP, Kitzman DW, Gardin JM, Rutledge JE, Boineau RC: Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000;35:1628-1637.
7.
Dunlay SM, Weston SA, Jacobsen SJ, Roger VL: Risk factors for heart failure: a population-based case-control study. Am J Med 2009;122:1023-1028.
8.
Nichols GA, Hillier TA, Erbey JR, Brown JB: Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001;24:1614-1619.
9.
Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB: The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care 2004;27:1879-1884.
10.
Cohen-Solal A, Beauvais F, Logeart D: Heart failure and diabetes mellitus: epidemiology and management of an alarming association. J Cardiac Fail 2008;14:615-625.
11.
Shindler DM, Kostis JB, Yusuf S, Quinones MA, Pitt B, Stewart D, Pinkett T, Ghali JK, Wilson AC: Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) trials and registry. Am J Cardiol 1996;77:1017-1020.
12.
Mandavia CH, Aroor AR, Demarco VG, Sowers JR: Molecular and metabolic mechanisms of cardiac dysfunction in diabetes. Life Sci 2013;92:601-608.
13.
Kannel WB: Incidence and epidemiology of heart failure. Heart Fail Rev 2000;5:167-173.
14.
Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, Murabito JM, Vasan RS: Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002;347:1397-1402.
15.
Wier L, Pfuntner A, Maeda J, Stranges E, Ryan K, Jagadish P, Collins Sharp B, Elixhauser A: HCUP facts and figures: statistics on hospital-based care in the United States, 2009. Agency for Healthcare Research and Quality, Rockville, 2011. http://www.hcup-us.ahrq.gov/reports.jsp.
16.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, et al; American Heart Association Statistics Committee; Stroke Statistics Subcommittee: Heart disease and stroke statistics - 2013 update: a report from the American Heart Association. Circulation 2013;127:e6-e245.
17.
Rousan TA, Pappy RM, Chen AY, Roe MT, Saucedo JF: Impact of diabetes mellitus on clinical characteristics, management, and in-hospital outcomes in patients with acute myocardial infarction (from the NCDR). Am J Cardiol 2014;114:1136-1144.
18.
Romon I, Rey G, Mandereau-Bruno L, Weill A, Jougla E, Eschwege E, Simon D, Druet C, Fagot-Campagna A: The excess mortality related to cardiovascular diseases and cancer among adults pharmacologically treated for diabetes - the 2001-2006 ENTRED cohort. Diabetic Med 2014;31:946-953.
19.
Dries DL, Sweitzer NK, Drazner MH, Stevenson LW, Gersh BJ: Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol 2001;38:421-428.
20.
MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ; CHARM Investigators: 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 2008;29:1377-1385.
21.
Domanski M, Krause-Steinrauf H, Deedwania P, Follmann D, Ghali JK, Gilbert E, Haffner S, Katz R, Lindenfeld J, Lowes BD, Martin W, McGrew F, Bristow MR; BEST Investigators: The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol 2003;42:914-922.
22.
Niederseer D, Thaler CW, Niederseer M, Niebauer J: Mismatch between heart failure patients in clinical trials and the real world. Int J Cardiol 2013;168:1859-1865.
23.
Austin PC: An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 2011;46:399-424.
24.
van Deursen VM, Urso R, Laroche C, Damman K, Dahlstrom U, Tavazzi L, Maggioni AP, Voors AA: Co-morbidities in patients with heart failure: an analysis of the European Heart Failure pilot survey. Eur J Heart Fail 2014;16:103-111.
25.
Kamalesh M, Subramanian U, Sawada S, Eckert G, Temkit M, Tierney W: Decreased survival in diabetic patients with heart failure due to systolic dysfunction. Eur J Heart Fail 2006;8:404-408.
26.
De Groote P, Lamblin N, Mouquet F, Plichon D, McFadden E, Van Belle E, Bauters C: Impact of diabetes mellitus on long-term survival in patients with congestive heart failure. Eur Heart J 2004;25:656-662.
27.
Bradbury BD, Gilbertson DT, Brookhart MA, Kilpatrick RD: Confounding and control of confounding in nonexperimental studies of medications in patients with CKD. Adv Chronic Kidney Dis 2012;19:19-26.
28.
Remme WJ, Swedberg K; Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology: Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527-1560.
29.
McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, et al; ESC Committee for Practice Guidelines: 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 ESC. Developed in collaboration with the Heart Failure Association of the ESC. Eur J Heart Fail 2012;14:803-869.
30.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.
31.
National Kidney F: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-S266.
32.
Thoemmes F: Propensity Score Matching in SPSS. Ithaca, Cornell University Library, 2012.
33.
Aguilar D, Deswal A, Ramasubbu K, Mann DL, Bozkurt B: Comparison of patients with heart failure and preserved left ventricular ejection fraction among those with versus without diabetes mellitus. Am J Cardiol 2010;105:373-377.
34.
Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, Ordin DL, Krumholz HM: Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Am Heart J 2003;146:250-257.
35.
Lenzen MJ, Boersma E, Reimer WJ, Balk AH, Komajda M, Swedberg K, Follath F, Jimenez-Navarro M, Simoons ML, Cleland JG: Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the European Heart Survey on Heart Failure. Eur Heart J 2005;26:2706-2713.
36.
From AM, Leibson CL, Bursi F, Redfield MM, Weston SA, Jacobsen SJ, Rodeheffer RJ, Roger VL: Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med 2006;119:591-599.
37.
Authors/Task Force Members; Ryden L, Grant PJ, Anker SD, Berne C, et al: ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European society of cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013;34:3035-3087.
38.
Baliga V, Sapsford R: Review article: diabetes mellitus and heart failure - an overview of epidemiology and management. Diabetes Vasc Dis Res 2009;6:164-171.
39.
Shekelle PG, Rich MW, Morton SC, Atkinson CS, Tu W, Maglione M, Rhodes S, Barrett M, Fonarow GC, Greenberg B, Heidenreich PA, Knabel T, Konstam MA, Steimle A, Warner Stevenson L: Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. J Am Coll Cardiol 2003;41:1529-1538.
40.
Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, Granger CB, Hradec J, Kuch J, McKelvie RS, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Held P, Solomon SD, Yusuf S, Swedberg K; Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Investigators and Committees: Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation 2004;110:2618-2626.
41.
Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-1675.
42.
Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, Group E-HS: Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11-21.
43.
Fernandez HM, Leipzig RM: Spironolactone in patients with heart failure. N Engl J Med 2000;342:132; author reply 133-134.
44.
Dei Cas A, Khan SS, Butler J, Mentz RJ, Bonow RO, Avogaro A, Tschoepe D, Doehner W, Greene SJ, Senni M, Gheorghiade M, Fonarow GC: Impact of diabetes on epidemiology, treatment, and outcomes of patients with heart failure. J Am Coll Cardiol Heart Fail 2015;3:136-145.
45.
Gheorghiade M, Bohm M, Greene SJ, Fonarow GC, Lewis EF, Zannad F, Solomon SD, Baschiera F, Botha J, Hua TA, Gimpelewicz CR, Jaumont X, Lesogor A, Maggioni AP; ASTRONAUT Investigators and Coordinators: Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA 2013;309:1125-1135.
46.
Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ASTRONAUT Investigators: Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367:2204-2213.
47.
Deedwania PC, Giles TD, Klibaner M, Ghali JK, Herlitz J, Hildebrandt P, Kjekshus J, Spinar J, Vitovec J, Stanbrook H, Wikstrand J; MERIT-HF Study Group: Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF. Am Heart J 2005;149:159-167.
48.
Testani JM, Cappola TP, Brensinger CM, Shannon RP, Kimmel SE: Interaction between loop diuretic-associated mortality and blood urea nitrogen concentration in chronic heart failure. J Am Coll Cardiol 2011;58:375-382.
49.
Kjekshus J, Apetrei E, Barrios V, Bohm M, Cleland JG, Cornel JH, Dunselman P, Fonseca C, Goudev A, Grande P, Gullestad L, Hjalmarson A, Hradec J, Janosi A, Kamensky G, Komajda M, Korewicki J, Kuusi T, Mach F, Mareev V, McMurray JJ, Ranjith N, Schaufelberger M, Vanhaecke J, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Group: Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357:2248-2261.
50.
Gissi HFI, Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G: Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1231-1239.
51.
Montori VM, Fernandez-Balsells M: Glycemic control in type 2 diabetes: time for an evidence-based about-face? Ann Intern Med 2009;150:803-808.
52.
Tomova GS, Nimbal V, Horwich TB: Relation between hemoglobin A(1c) and outcomes in heart failure patients with and without diabetes mellitus. Am J Cardiol 2012;109:1767-1773.
53.
Eshaghian S, Horwich TB, Fonarow GC: An unexpected inverse relationship between HbA1c levels and mortality in patients with diabetes and advanced systolic heart failure. Am Heart J 2006;151:91.
54.
Aguilar D, Bozkurt B, Ramasubbu K, Deswal A: Relationship of hemoglobin A1c and mortality in heart failure patients with diabetes. J Am Coll Cardiol 2009;54:422-428.
55.
Gerstein HC, Swedberg K, Carlsson J, McMurray JJ, Michelson EL, Olofsson B, Pfeffer MA, Yusuf S; CHARM Program Investigators: 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 2008;168:1699-1704.
56.
Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK: The progression from hypertension to congestive heart failure. JAMA 1996;275:1557-1562.
57.
Waldum B, Westheim AS, Sandvik L, Flonaes B, Grundtvig M, Gullestad L, Hole T, Os I: Baseline anemia is not a predictor of all-cause mortality in outpatients with advanced heart failure or severe renal dysfunction. Results from the Norwegian Heart Failure Registry. J Am Coll Cardiol 2012;59:371-378.
58.
Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, O'Connor CM, Pieper K, Sun JL, Yancy CW, Young JB: Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: findings from OPTIMIZE-HF. Arch Intern Med 2008;168:847-854.
59.
Gheorghiade M, Abraham WT, Albert NM, Gattis Stough W, Greenberg BH, O'Connor CM, She L, Yancy CW, Young J, Fonarow GC: Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J 2007;28:980-988.
60.
Kearney MT, Fox KA, Lee AJ, Prescott RJ, Shah AM, Batin PD, Baig W, Lindsay S, Callahan TS, Shell WE, Eckberg DL, Zaman AG, Williams S, Neilson JM, Nolan J: Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure. J Am Coll Cardiol 2002;40:1801-1808.
61.
Anand I, McMurray JJ, Whitmore J, Warren M, Pham A, McCamish MA, Burton PB: Anemia and its relationship to clinical outcome in heart failure. Circulation 2004;110:149-154.
62.
O'Meara E, Clayton T, McEntegart MB, McMurray JJ, Lang CC, Roger SD, Young JB, Solomon SD, Granger CB, Ostergren J, Olofsson B, Michelson EL, Pocock S, Yusuf S, Swedberg K, Pfeffer MA: Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) program. Circulation 2006;113:986-994.
63.
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD; VADT Investigators: Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139.
64.
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J; ADVANCE Collaborative Group: Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 2009;20:1813-1821.
65.
Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310:356-360.
66.
Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ; Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Investigators: Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 2006;113:671-678.
67.
Waldum B, Westheim AS, Sandvik L, Flonaes B, Grundtvig M, Gullestad L, Hole T, Os I: Renal function in outpatients with chronic heart failure. J Cardiac Fail 2010;16:374-380.
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