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Doi:10.1016/j.ijcard.2008.11.139

International Journal of Cardiology xx (2008) xxx – xxx Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to left ventricular systolic dysfunction Raymond Lee a,⁎, Siew-Pang Chan b, Jennifer Wong c, Diana Lau d, Clinical Research Unit, Tan Tock Seng Hospital, c Casemix Department, Tan Tock Seng Hospital, Singapor d Physiotherapy Department, Tan Tock Seng Hospital, e Department of Cardiology, Tan Tock Seng Hospital, Received 10 November 2008; received in revised form 18 November 2008; accepted 22 November 2008 Objective: We assessed the impact of diabetes mellitus on survival CTED in South East Asian patients with congestive heart failure.
Methods: 1668 consecutive patients with chronic heart failure (age 65 ± 13 years, ejection fraction 28 ± 12%, 67% male) were followed up for 36 ± 12months. 837 patients (50.2%) were diabetic and 1076 patients (65%) had ischemic cardiomyopathy. Primary outcome measure was all-cause mortality. Secondary outcome measures were heart failure readmission and the composite end-point.
Results: There were 223 (13.4%) deaths and 112 (7%) heart failure readmissions. Ischemic cardiomyopathy, renal failure, hypertension, cerebrovascular disease, peripheral vascular disease, and hyperlipidemia were more prevalent in diabetics (all p b 0.01). All-cause mortality (17.3% vs 9.4%), heart failure readmission (8.1% vs 5.3%) and the composite end-point (21.9% vs 12.6%) occurred more frequently in diabetics (all p b 0.05). Diabetes was an independent predictor of all-cause mortality (OR = 1.70, p = 0.01), as were ischemic cardiomyopathy (OR = 1.85, p = 0.01), hypertension (OR = 1.78, p = 0.01), GFR (OR = 0.98, p b 0.01), and beta-blocker use (OR = 0.55, p b 0.01).
Conclusions: In spite of advances in heart ORRE failure treatment, the presence of diabetes mellitus significantly worsens survival in South East Asian patients with congestive heart failure.
2008 Published by Elsevier Ireland Ltd.
Keywords: Diabetes mellitus; Congestive heart failure; Death; Readmission; South East Asian population general population (4–6%) . DM also increases the risk of 33developing CHF, the poorer the control, the greater the risk 34 . In patients with established CHF, randomized trials show 35 congestive heart failure (CHF) (15–25%), compared to the that DM increases morbidity and mortality, especially in 36those with ischemic cardiomyopathy .
congestive heart failure; DM, diabetes mellitus; LV, However, these studies were conducted in predominantly 38 Left ventricular; EF, ejection fraction; NHYA, New York Heart Association; Caucasian CHF populations, most were retrospective , 39 ACEI, Angiotensin converting enzyme inhibitor; ARB, Angiotensin and some were conducted in a clinical trial setting and 40 receptor blocker; GFR, glomerular filtration rate.
hence may not represent CHF patients in the general 41 ⁎ Corresponding author. Novena Heart Centre 10, Sinaran Drive, #09-05 population. Some studies were also performed before 42 Novena Medical Centre, SQ2 Singapore 307506, Singapore.
Tel.: +65 63972004; fax: +65 63972051.
widespread use of ACEIs and beta-blockers , and the 43 findings may not be applicable currently.
0167-5273/$ - see front matter 2008 Published by Elsevier Ireland Ltd.
Please cite this article as: Lee R, et al, Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to leftventricular systolic dysfunction, Int J Cardiol (2008), R. Lee et al. / International Journal of Cardiology xx (2008) xxx–xxx Accordingly, we conducted this prospective observational study to evaluate the impact of DM on survival in a large population of South East Asian patients with CHF on Continuous variables in text and tables are expressed as 76 mean ± standard deviation and compared by Kruskal–Wallis 77test. Chi-square test was used to test associations between 78 categorical variables. Multiple logistic regression was applied 79to identify independent predictors of all-cause mortality.
Survival analysis was performed using the Kaplan–Meier 81 method. The log rank test was used to compare differences 82 The study population consisted of 1668 consecutive CHF between strata. Statistical analysis was performed using the 83 patients enrolled into the National Healthcare Group Multi- statistical package Stata 9.0 (Stata Corp, Texas, USA). Statistical 84 disciplinary Heart Failure Disease Management Program in significance was defined as a two tailed p value of b0.05.
Singapore from October 2002 to September 2004. The current study included approximately 20% of the CHF patients mentioned in an earlier report Patients were classified as diabetic if they were on oral hypoglycemic 1668 consecutive patients with CHF were followed up for 87 agents or insulin, or had a history of elevated (N126 mg/dl) a mean duration of 36 months. Follow-up was complete for 88 fasting blood glucose documented on at least two separate all study patients. 837 patients (50.2%) were diabetic and 89 occasions. Patients were classified as having ischemic 1076 patients (65%) had ischemic cardiomyopathy. At the 90 cardiomyopathy if they had previous myocardial infarction, end of follow-up, 223 patients (13.4%) died and 112 patients 91 severe multivessel coronary artery disease on coronary angiography, or previous coronary revascularization (percu- cardiomyopathy (77.5% vs 60.7%), hyperten- 93 taneous coronary intervention or coronary bypass surgery).
sion (81.6% vs 59.9%), cerebrovascular disease (15.5% vs 948.2%), peripheral vascular disease (4.2% vs 1.2%) and 95 hyperlipidemia (66.2% vs 46.6%) were more prevalent 96among diabetics (all p b 0.01).
In this prospective observational study, baseline demo- At 3 years, all-cause mortality (17.3% vs 9.4%), CHF 98 graphics and clinical data including information on readmission (8.1% vs 5.3%) and the composite end-point 99 tions, New York Heart Association (NYHA) functional class (21.9% vs 12.6%) were greater in diabetics compared to non- 100 and quality of life measures were recorded. Information on diabetics (all p b 0.05). Diabetic patients had a worse all- 101 the number of hospitalizations and deaths were collected cause mortality free survival compared to non-diabetics (log 102 prospectively. Patients were followed up at one to six monthly intervals. Cardiac medications were uptitrated The univariate and multivariate predictors of all-cause 104 accordingly until maximal tolerated doses. This study was mortality are shown in In a logistic regression 105 approved by the hospital ethics committee.
analysis, DM was an independent predictor of all-cause 106 Fig. 1. Kaplan–Meier survival curves comparing all-cause mortality free survival between diabetic and non-diabetic CHF patients.
Please cite this article as: Lee R, et al, Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to leftventricular systolic dysfunction, Int J Cardiol (2008), doi: R. Lee et al. / International Journal of Cardiology xx (2008) xxx–xxx Univariate and multivariate predictors of all-cause mortality in the study population ECTED 1.42(1.02–1.97) 1.78(1.13–2.54) Please cite this article as: Lee R, et al, Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to leftventricular systolic dysfunction, Int J Cardiol (2008), R. Lee et al. / International Journal of Cardiology xx (2008) xxx–xxx Income = monthly income NSGD$1000; single = unmarried; education = greater than secondary school level education; CVA = peripheral vascular disease; CRF = chronic renal failure; EF = ejection fraction; GFR = glomerular filtration rate; NYHA = New York Heart Association;CABG = coronary bypass surgery; PCI = percutaneous coronary intervention; AICD = implantable defibrillator; ACEI/ARB = angiotensin converting enzymeinhibitor/angiotensin receptor blocker; OR = odds ratio; 95% CI = 95% confidence intervals.
mortality (OR = 1.70, p = 0.01), as were ischemic cardiomyo- 65%) may have reduced the negative prognostic impact of 146 pathy (OR = 1.85, p = 0.01), hypertension (OR = 1.78, DM in their overall study population.
p = 0.01), GFR (OR = 0.98, p b 0.01), and beta-blocker use The reasons for a negative impact of DM on survival in 148 patients with CHF are multifactorial. In our study, DM was 149associated with an increased prevalence of other comorbidities 150 cardiomyopathy, renal failure, cerebrovascular 151 vascular disease and hypertension. Due to 152 Our study is the first in reported literature to prospectively more extensive coronary disease, diabetics with acute coronary 153 evaluate the prognostic impact of DM in a large population syndromes have higher reinfarction rates, and hence greater 154 of South East Asian patients with CHF on contemporary long-term mortality Recurrent myocardial infarction could 155 medical therapy. In spite of advances in CHF treatment, DM also worsen outcome in CHF patients with DM. Furthermore, a 156 was associated with an increased risk for all-cause mortality, specific diabetic cardiomyopathy may occur in some patients 157 CHF readmission and the composite end-point.
, and certain anti-diabetic drugs especially insulin and 158 Mortality rate in our study (13.4%), was lower glitazone may adversely affect myocardial function .
to previous studies by Domanski et al. (32%) and Kamalesh et al. (32%) . Our patients had less advanced CHF at enrollment, with a lower proportion in NYHA class III/IV (25%) compared to patients in de Groote's (28%) and Varela- In spite of advances in CHF treatment, the presence of 161 Roman et al.'s (67%) studies Greater use of beta- DM worsens survival in South East Asian patients with CHF, 162 blockers and/or ACEI/ARB (64% and 79%) in our patients, which reinforces the need for aggressive preventive 163 compared to those in the SOLVD (25% and 50%) and BEST strategies to improve outcomes in these patients.
trials (50% and 91%), and the benefits of a multidisciplinary CHF disease management program could also have Our diabetic CHF patients had a 84% higher all-cause We would like to thank all the patients who participated in this 166 mortality rate, 53% higher CHF readmission rate and 74% study as well as Geraldine Raj and Yow Ei Mua who were 167 end-point rate compared to non-diabetics, responsible for the care and follow-up of the patients.
confirming the findings of earlier studies Kamalesh et al.'s study demonstrated a 30% higher mortality in diabetic compared to non-diabetic CHF patients. Varela- Roman et al.'s study showed a worse survival at 1, 3 and [1] Kannel WB, Mc Gee DL. Diabetes and cardiovascular disease. The 170 5 years among diabetics (78.9%, 57.2% and 39.0%), Framingham study. JAMA 1997;241:2035–8.
[2] Domanski M, Krause-Steinrauf H, Deedwania P, et al. The effect of 172 compared to non-diabetics (84.7%, 68.3% and 52.7%). In diabetes on outcomes of patients with advanced heart failure in the 173 De Groote et al.'s study DM was not associated with BEST trial. J Am Coll Cardiol 2003;42:914–22.
increased cardiovascular mortality in the overall study cohort.
[3] Dries D, Sweitzer N, Drazner M, Stevenson LW, Gersh BJ. Prognostic 175 Although DM predicted an increased cardiovascular mortal- impact of diabetes mellitus in patients with heart failure according to the 176 ity in the ischemic cardiomyopathy subgroup, DM was aetiology of left ventricular dysfunction. J Am Coll Cardiol 1772001;38:421–8.
surprisingly associated with decreased cardiovascular mor- [4] Lee R, Chan SP, Chan YH, Wong J, Lau D, Ng K. Impact of race on 179 tality in those with non-ischemic cardiomyopathy. This morbidity and mortality in patients with congestive heart failure: a study 180 finding together with the lower prevalence of ischemic of the multiracial population in Singapore. Int J Cardiol 2008 [Electronic 181 cardiomyopathy in their study compared to ours (45% vs Please cite this article as: Lee R, et al, Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to leftventricular systolic dysfunction, Int J Cardiol (2008), doi: R. Lee et al. / International Journal of Cardiology xx (2008) xxx–xxx [5] De Groote P, Lamblin N, Mouquet F, et al. Impact of diabetes mellitus on the survival of patients hospitalized with heart failure: a 12-year study. 191 on long-term survival in patients with congestive heart failure. Eur Heart Eur J Heart Fail Aug 2005;7(5):859–64.
[8] Lingman M, Herlitz J, Bergfeldt L, Karlsson T, Caidahl K, Hartford M. 193 [6] Kamalesh M, Subramaniam U, Sawada S, Eckert G, Temkit M'Hamed, Acute coronary syndromes — the prognostic impact of hypertension, 194 Tierney W. Decreased survival in diabetic patients with heart failure due diabetes and its combination on long-term outcome. Int J Cardiol Aug 195 to systolic dysfunction. Eur J Heart Fail 2006;8(4):404–8.
2008;26 [Electronic publication ahead of print].
[7] Varela-Roman A, Grigorian Shamagian L, Barge Caballero E, Mazon [9] Tang WH. Glycemic control and treatment patterns in patients with heart 197 Ramos P, Rigueiro Veloso P, Gonzalez-Juanatey JR. Influence of diabetes failure. Heart Fail Monit 2006;5(1):10–4.
Please cite this article as: Lee R, et al, Impact of diabetes mellitus on survival in South East Asian patients with congestive heart failure due to leftventricular systolic dysfunction, Int J Cardiol (2008),

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