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MIURA M et al.

ORIGINAL ARTICLE

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp

Heart Failure

Prognostic Impact of Diabetes Mellitus in Chronic Heart Failure According to Presence of Ischemic Heart Disease – With Special Reference to Nephropathy – Masanobu Miura, MD, PhD; Yasuhiko Sakata, MD, PhD; Satoshi Miyata, PhD; Kotaro Nochioka, MD, PhD; Tsuyoshi Takada, MD, PhD; Soichiro Tadaki, MD; Ryoichi Ushigome, MD; Takeshi Yamauchi, MD; Kenjiro Sato, MD; Takeo Onose, MD; Kanako Tsuji, MD; Ruri Abe, MD; Jun Takahashi, MD, PhD; Hiroaki Shimokawa, MD, PhD on behalf of the CHART-2 Investigators

Background:  It is unclear whether the prognostic impact of diabetes mellitus (DM) in chronic heart failure (CHF) is influenced by ischemic heart disease (IHD) and/or nephropathy. Methods and Results:  We enrolled 4,065 consecutive patients with stage C/D CHF (mean age, 69.0 years; 68.7% male) in the CHART-2 Study (n=10,219). We defined DM as current history of DM treatment or HbA1c ≥6.5% (National Glycohemoglobin Standardization Program [NGSP]), and nephropathy as urine albumin:creatinine ratio ≥30 mg/g or urine dipstick test ≥(±) at enrollment. Impacts of DM and nephropathy on the composite of death, myocardial infarction, stroke, and HF admission were examined. Among the 4,065 patients, 1,448 (35.6%) had DM, while IHD and nephropathy were also noted in 1,644 (40.4%) and in 1,549 (38.1%), respectively. During the median followup of 2.88 years, 1,025 (25.2%) reached the composite endpoint. On multivariate Cox regression, DM was significantly associated with the composite endpoint in all patients (HR, 1.17; P=0.02), and in those with IHD (HR, 1.38; P=0.004), but not in those without IHD (HR, 1.12; P=0.22; P for interaction=0.12). Furthermore, when the patients were stratified by nephropathy, DM was associated with worse prognosis only in the IHD patients with nephropathy. Conclusions:  The prognostic impact of DM was more evident in patients with IHD than in those without IHD, particularly when complicated with nephropathy.   (Circ J 2015; 79: 1764 – 1772) Key Words: Chronic heart failure; Diabetes; Ischemic heart disease; Nephropathy; Prognosis

D

iabetes mellitus (DM) causes long-term complications, including microvascular (diabetic nephropathy, neuropathy and retinopathy)1,2 and macrovascular complications,3 with resultant cardiovascular disease, stroke and peripheral arterial disease. The Framingham Heart Study showed that DM increases the risk of cardiovascular diseases such as acute myocardial infarction (AMI) and chronic heart failure (CHF).4,5 Indeed, DM is a major health problem worldwide, including in patients with CHF.6,7

Editorial p 1689 In the general population, DM patients without ischemic heart disease (IHD) carry a lifetime risk of cardiovascular death as high as IHD patients without DM.8 In CHF patients, however,

the prognostic impact of DM is still controversial.9–11 Several studies reported that DM was independently associated with increased mortality in CHF patients with IHD but not in those without it.9,10 In contrast, it was also reported that IHD was not the major prognostic factor in diabetic CHF patients.11 Also, diabetic nephropathy, usually defined as the presence of microalbuminuria (30–300 mg/g urinary albumin:creatinine ratio [UACR]), has been reported as an important complication of DM.12 The prognostic impact of DM, however, remains unclear in CHF patients complicated by IHD and/or nephropathy. In the present study, we thus examined the prognostic impact of DM with a special reference to IHD and nephropathy in CHF patients registered in the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study.7,13–15

Received January 25, 2015; revised manuscript received March 28, 2015; accepted April 16, 2015; released online May 22, 2015   Time for primary review: 24 days Department of Cardiovascular Medicine (M.M., Y.S., K.N., T.T., S.T., R.U., T.Y., K.S., T.O., K.T., R.A., J.T., H.S.), Department of Evidencebased Cardiovascular Medicine (S.M.), Tohoku University Graduate School of Medicine, Sendai, Japan The Guest Editor for this article was Yoshihiko Saito, MD. Mailing address:  Yasuhiko Sakata, MD, PhD, Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.   E-mail: [email protected] ISSN-1346-9843  doi: 10.1253/circj.CJ-15-0096 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected] Circulation Journal  Vol.79, August 2015

Prognostic Impact of DM in CHF

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Table 1.  Baseline Patient Characteristics

Age (years)

DM

All patients (n=4,065)

(+) (n=1,448)

(−) (n=2,617)

P-value

69.0±12.8

68.3±11.3

69.0±12.8

0.10

Male (%)

68.7

72.0

66.8

0.001

History of admission for HF (%)

51.6

52.9

50.9

0.43

Ischemic heart disease (%)

40.4

51.0

34.6