Accepted Manuscript Association of hypocalcemia with mortality in hospitalized patients with heart failure and chronic kidney disease Shunsuke Miura, Akiomi Yoshihisa, Mai Takiguchi, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Shoji Iwaya, Takashi Owada, Makiko Miyata, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi PII:
S1071-9164(15)00126-8
DOI:
10.1016/j.cardfail.2015.04.015
Reference:
YJCAF 3505
To appear in:
Journal of Cardiac Failure
Received Date: 10 January 2015 Revised Date:
22 April 2015
Accepted Date: 24 April 2015
Please cite this article as: Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Miyata M, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S-i, Takeishi Y, Association of hypocalcemia with mortality in hospitalized patients with heart failure and chronic kidney disease, Journal of Cardiac Failure (2015), doi: 10.1016/ j.cardfail.2015.04.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Association of hypocalcemia with mortality in hospitalized patients
RI PT
with heart failure and chronic kidney disease
Shunsuke Miura1, Akiomi Yoshihisa1,2*, Mai Takiguchi1, Takeshi Shimizu1, Yuichi Nakamura1, Hiroyuki Yamauchi1, Shoji Iwaya1, Takashi Owada1, Makiko Miyata1,
SC
Satoshi Abe1, Takamasa Sato1, Satoshi Suzuki1,2, Masayoshi Oikawa1, Takayoshi
Yamaki1, Koichi Sugimoto1, Hiroyuki Kunii1, Kazuhiko Nakazato1, Hitoshi Suzuki1,
1
M AN U
Shu-ichi Saitoh1, and Yasuchika Takeishi1,2
Department of Cardiology and Hematology, Fukushima Medical University,
Fukushima, Japan; and 2Department of Advanced Cardiac Therapeutics, Fukushima
TE D
Medical University, Fukushima, Japan
A short title: Hypocalcemia predicts adverse prognosis of HF and CKD
EP
*Corresponding author.
Tel: +81 24 547 1190, Fax: +81 24 548 1821, Email: [email protected]
AC C
Akiomi Yoshihisa, MD, PhD.
Department of Cardiology and Hematology, Fukushima Medical University 1 Hikarigaoka, Fukushima 960-1295, Japan Total word count of manuscript:
2726 words
Total number of tables and figures:
5 tables and 2 figure
1
ACCEPTED MANUSCRIPT
Abstract Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are
RI PT
associated with vascular calcification and abnormal electrolytes that lead to cardiovascular disease and mortality. CKD-MBD is identified by imbalances in serum
SC
calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the relation of
M AN U
phosphate and PTH with the prognosis of HF patients has been reported, the association of Ca with prognosis in patients with heart failure (HF) and CKD remains unclear. Methods and Results: We examined 191 patients admitted for HF and CKD (estimated GFR < 60 ml/min/1.73m2), and they were divided into 2 groups based on levels of
TE D
corrected Ca: low Ca (Ca < 8.4 mg/dl, n = 32) and normal-high Ca (8.4 ≤ Ca, n = 159). We compared laboratory and echocardiographic findings, and also followed cardiac and
EP
all-cause mortality. The low Ca group had: 1) higher levels of alkaline phosphatase
AC C
(308.9 vs. 261.0 U/l, P=0.026), 2) lower levels of 1,25-dihydroxy vitamin D (26.1 vs. 45.0 pg/ml, P=0.011) and hydrogencarbonate (22.4 vs. 24.5 mmol/l, P=0.031), and 3) a tendency to have a higher PTH level (87.5 vs. 58.6 pg/ml, P=0.084). In contrast, left and right ventricular systolic function, estimated GFR, urine protein, phosphate, sodium, potassium, magnesium, and zinc did not differ between the two groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality were significantly higher in low
2
ACCEPTED MANUSCRIPT
Ca group than in normal-high Ca group (P90 mmHg. Diabetes was defined as the recent use of insulin or antidiabetic drugs, a fasting blood glucose value of >126 mg/dL, and/or a hemoglobin A1c value of >6.5%. Dyslipidemia
6
ACCEPTED MANUSCRIPT
was defined as the recent use of cholesterol-lowering drugs, a triglyceride value of >150 mg/dL, a low-density lipoprotein cholesterol value of >140 mg/dL, and/or a
RI PT
high-density lipoprotein cholesterol value of
S1071-9164(15)00126-8
DOI:
10.1016/j.cardfail.2015.04.015
Reference:
YJCAF 3505
To appear in:
Journal of Cardiac Failure
Received Date: 10 January 2015 Revised Date:
22 April 2015
Accepted Date: 24 April 2015
Please cite this article as: Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Miyata M, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S-i, Takeishi Y, Association of hypocalcemia with mortality in hospitalized patients with heart failure and chronic kidney disease, Journal of Cardiac Failure (2015), doi: 10.1016/ j.cardfail.2015.04.015. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Association of hypocalcemia with mortality in hospitalized patients
RI PT
with heart failure and chronic kidney disease
Shunsuke Miura1, Akiomi Yoshihisa1,2*, Mai Takiguchi1, Takeshi Shimizu1, Yuichi Nakamura1, Hiroyuki Yamauchi1, Shoji Iwaya1, Takashi Owada1, Makiko Miyata1,
SC
Satoshi Abe1, Takamasa Sato1, Satoshi Suzuki1,2, Masayoshi Oikawa1, Takayoshi
Yamaki1, Koichi Sugimoto1, Hiroyuki Kunii1, Kazuhiko Nakazato1, Hitoshi Suzuki1,
1
M AN U
Shu-ichi Saitoh1, and Yasuchika Takeishi1,2
Department of Cardiology and Hematology, Fukushima Medical University,
Fukushima, Japan; and 2Department of Advanced Cardiac Therapeutics, Fukushima
TE D
Medical University, Fukushima, Japan
A short title: Hypocalcemia predicts adverse prognosis of HF and CKD
EP
*Corresponding author.
Tel: +81 24 547 1190, Fax: +81 24 548 1821, Email: [email protected]
AC C
Akiomi Yoshihisa, MD, PhD.
Department of Cardiology and Hematology, Fukushima Medical University 1 Hikarigaoka, Fukushima 960-1295, Japan Total word count of manuscript:
2726 words
Total number of tables and figures:
5 tables and 2 figure
1
ACCEPTED MANUSCRIPT
Abstract Background: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are
RI PT
associated with vascular calcification and abnormal electrolytes that lead to cardiovascular disease and mortality. CKD-MBD is identified by imbalances in serum
SC
calcium (Ca), phosphate, and parathyroid hormone (PTH). Although the relation of
M AN U
phosphate and PTH with the prognosis of HF patients has been reported, the association of Ca with prognosis in patients with heart failure (HF) and CKD remains unclear. Methods and Results: We examined 191 patients admitted for HF and CKD (estimated GFR < 60 ml/min/1.73m2), and they were divided into 2 groups based on levels of
TE D
corrected Ca: low Ca (Ca < 8.4 mg/dl, n = 32) and normal-high Ca (8.4 ≤ Ca, n = 159). We compared laboratory and echocardiographic findings, and also followed cardiac and
EP
all-cause mortality. The low Ca group had: 1) higher levels of alkaline phosphatase
AC C
(308.9 vs. 261.0 U/l, P=0.026), 2) lower levels of 1,25-dihydroxy vitamin D (26.1 vs. 45.0 pg/ml, P=0.011) and hydrogencarbonate (22.4 vs. 24.5 mmol/l, P=0.031), and 3) a tendency to have a higher PTH level (87.5 vs. 58.6 pg/ml, P=0.084). In contrast, left and right ventricular systolic function, estimated GFR, urine protein, phosphate, sodium, potassium, magnesium, and zinc did not differ between the two groups. In the Kaplan-Meier analysis, cardiac and all-cause mortality were significantly higher in low
2
ACCEPTED MANUSCRIPT
Ca group than in normal-high Ca group (P90 mmHg. Diabetes was defined as the recent use of insulin or antidiabetic drugs, a fasting blood glucose value of >126 mg/dL, and/or a hemoglobin A1c value of >6.5%. Dyslipidemia
6
ACCEPTED MANUSCRIPT
was defined as the recent use of cholesterol-lowering drugs, a triglyceride value of >150 mg/dL, a low-density lipoprotein cholesterol value of >140 mg/dL, and/or a
RI PT
high-density lipoprotein cholesterol value of
