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
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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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