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Significance of Plasma Free Fatty Acid and Amino Acid Profile in Obesity-related Heart Failure
The 19th Annual Scientific Meeting Trousseau’s sign were positive. Coronary angiography performed on twelfth day of admission showed no fixed stenosis. Laboratory tests showed serum total calcium 5.2 mg/dl (normal 8.2-10.0 mg/dl) and serum phosphate 5.2 mg/dl (normal 2.5-4.5 mg/dl). The serum parathormone (i-PTH) level was 49 pg/ml (normal 10-65 pg/ ml). A low serum calcium level, high serum phosphate level and relative decrease of i-PTH level were all consistent with the diagnosis of hypoparathyroidism. She had treatment of heart failure and calcium supplementation by intravenous calcium, long-term oral calcium and vitamin-D preparation. Her symptoms and signs of heart failure rapidly improved, but LV function did not improve at the time of discharge. Repeat echocardiography done at six month and one year of follow-up showed dramatic improvement in the LV functions (EF563% on one-year followup). In concludion, hypoparathyroidism with severe hypocalcemia is an important cause of left venitcular dysfunction and heart failure.
OP44-1 Effect of Serum Trace Elements and Macro Minerals on Myocardial Infarction MOHAMMAD SAFIQUL ISLAM1,2, MD. ZAHEDUR RAHAMAN1, S.M. NAIM UDDIN1, TANMIN JARANA TAMMI1, SHAHID SARWAR1, KAZUSHIGE YOKOTA2 1 Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali-3814, Bangladesh; 2Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Japan
JHFS
S195
2 Department of Cardiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Background: Some type of heart failure (HF) is an obesity-related diseases and obesity can contribute to developing HF. However, the factors contributing to development of HF in obese are not fully elucidated. We analyzed potential plasma biomarkers related with metabolisms and neuro humoral factors, from the patients of HF with or without obesity. Method: We measured various biomarkers including amino acid profile, free fatty acid (FFA), endocrinological markers from the patients of HF. We divided into 2 groups (obesity group (BMIO23) and non-obesity group (BMI!23)) and analyzed these serum markers. Result: Plasma FFA (0.7 vs 0.4 mEq/l, p50.02), alanine (444.9 vs 375.7, p50.03) and valine (257.1 vs 228.5 umol/l, p50.03) were significantly higher in obesity group than in non-obesity group. Plasma noradrenaline (778.8 vs 408.2 ng/ml, p50.01) and aldosterone (132.7 vs 79.8 pg/ml, p50.05) levels were higher in obese group. There were no difference in brain natriuretic peptide (329.9 vs 464.1 pg/ml, p50.25), high sensitive C-reactive protein (0.2 vs 0.2 mg/dl, p50.8) between in obesity group and in non-obesity group. Conclusion: Obesity-related HF revealed higher serum FFA and branched-chain amino acids accompanied with sympathetic nerve activation and the elevated aldosterone levels. These biomarkers suggested that various metabolic remodelings might be characters of patients with HF.
OP44-4 Myocardial infarction (MI) is one of the leading causes of death associated with cardiovascular disease in recent years. The current study investigated the concentration of trace elements and macro minerals in MI patients of Bangladesh. MI patients (n5 74) were selected and recruited by random sampling from Dhaka Medical College and Hospital, Bangladesh. Serum trace elements (Zn, Fe, Se) and macro minerals (Ca, K, Na) were determined by flame atomic absorption spectroscopy. Independent sample t-test and Pearson’s correlation test were used for the statistical analysis. Serum concentrations of Zn, Fe, Se, Ca, K, and Na in MI patients were 0.266 0.01, 0.766 0.05, 0.016 0.0004, 33.756 1.39, 67.636 5.25, and 3189.36 47.63 mg/L while in control subjects those were 0.826 0.04, 0.156 0.01, 0.066 0.004, 87.396 4.17, 166.906 3.71, and 30006137.20 mg/L respectively. It was observed that serum level of Zn, Se, Ca, and K was significantly (p! 0.001) lower in patients but the concentration of Fe and Na in patient group was significantly (p! 0.001) and insignificantly (pO 0.001) higher respectively. Different inter-element relationships evidenced that there is a disturbance in the element homeostasis between the patient and control groups. Our data indicates that MI patients have considerably lower level of essential trace elements in serum and thus recommend necessary supplementation therapy to prevent disease progression.
OP44-2 Human Epididymis Protein 4 is a Useful Biomarker in Patients with Dilated Cardiomyopathy SHINSUKE HANATANI, YASUHIRO IZUMIYA, YOSHIRO ONOUE, YUICHI KIMURA, SATORU YAMAMURA, SATOSHI ARAKI, HISAO OGAWA Department of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Interstitial fibrosis play a crucial role in the pathophysiology of dilated cardiomyopathy (DCM). Human epididymis protein 4 (HE-4) is a secreted protein that is expected to have the usefulness in the evaluation of ongoing fibrosis. Hypothesis: In patients with DCM, HE-4 could be a useful biomarker to evaluate disease severity and predict future cardiovascular events. Methods and Results: We measured serum HE-4 levels in 28 patients with DCM. Serum HE-4 concentrations were measured by ELISA. The endpoint was a composite of total mortality and cardiovascular hospitalization. Median HE-4 levels in all participants was 6189.6 pg/ml. Serum HE-4 levels (ln[HE-4]) were positively correlated with serum high sensitive cardiac troponin T (hsTnT) levels (ln[hsTnT]) (r50.62; p50.0017) and pulmonary capillary wedge pressure (r50.38; p50.048). Plasma B-type natriuretic peptide levels (BNP) (ln[BNP]) and left ventricular end-diastolic pressure also had tendency to be correlated with serum HE-4 levels, although these correlations did not reach statistical significance (r50.34; p50.076, r50.43, p50.054, respectively). Kaplan Meier curve revealed that the event-free rate was decreased in the high HE-4 group (Omedian) than in the low HE-4 group (log-rank test p50.03). Univariate Cox hazard analysis identified HE-4 (hazard ratio: 10.92; 95% confidence interval: 1.44-82.60, p50.021) as effective predictor of adverse events. Conclusions: HE-4 could be a useful biomarker for evaluating disease severity and providing prognostic information in patients with DCM.
OP44-3 Significance of Plasma Free Fatty Acid and Amino Acid Profile in Obesityrelated Heart Failure TAKAYUKI NAMBA1, TOYOKAZU KIMURA1, SHUNPEI HORII1, YASUNAGA SHIRAISHI1, ATSUSHI SATO1, RISAKO YASUDA1, HIROTAKA YADA1, AKIO KAWAMURA1, DAIHIKO HAKUNO2, TAKESHI ADACHI1 1 Department of Cardiology, National Defense Medical College, Tokorozawa, Japan;
Metabolomic Analysis Reveals New Insights Towards Understanding Skeletal Muscle Mass and Exercise Capacity in Patients with Heart Failure MASAYA TSUDA, SHINTARO KINUGAWA, ARATA FUKUSHIMA, SHINGO TAKADA, TAKASHI YOKOTA, SHOJI MATSUSHIMA, TAKAAKI FURIHATA, JUNICHI MATSUMOTO, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Exercise intolerance is a major clinical manifestation and known to be a substantial prognostic factor in heart failure (HF) patients. A recent publication reported global metabolic disturbances are associated with outcomes in HF patients. However, metabolic profiling changes associated with skeletal muscle mass and exercise capacity has not been elucidated. Methods and Results: We studied consecutive HF patients with reduced ejection fraction (57612 years old, New York Heart Association class II-III) and 5 age-matched healthy subjects as controls (5663 years old). Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO2) was measured by cardiopulmonary exercise test. A total of 233 charged metabolites were detected and quantified absolutely using standard chemicals for each metabolite. Significant increases in arginine methylation, phospholipid metabolites, glutamine, and urea cycle metabolites were observed in HF patients compared to controls. Thigh circumference was negatively associated with glutamine (r5-0.80, P!0.01). Peak VO2 was negatively correlated with asymmetric dimethylarginine (ADMA) (r5-0.77, P!0.01) levels and phospholipid metabolites including choline (r5-0.63, P50.049) and N,N-dimethylglycine (r5-0.75, P50.011) levels in HF patients. Conclusions: Increases in methylated arginine derivatives, phospholipid metabolites and urea cycle components were associated with reduced exercise capacity in HF. In addition, plasma glutamine level was concerned with skeletal muscle wasting in HF.
OP44-5 Serum Cystatin C is Associated with Left Ventricular Hypertrophy and Impaired Left Ventricular Relaxation in Patients with Chronic Kidney Disease SATORU SAKURAGI, KEISHI ICHIKAWA, TAKAHIRO NISHIHARA, MASAHIRO TSUJI Department of Cardiovascular Medicine, Iwakuni Clinical Center Background: In this cross-sectional study, we aimed to determine the associations between serum cystatin C levels and structural and functional cardiac changes in patients with stage 2 or 3 chronic kidney disease (CKD). Methods and Results: We enrolled 429 consecutive patients (aged 24 to 97 years) with CKD stage 2 or 3 and left ventricular (LV) ejection fraction (LVEF) O 40%. Echocardiographic parameters, including LV mass index (LVMI), early diastolic mitral annulus velocity (e velocity), left atrial volume index (LAVI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) were measured. Patients were categorized into quartiles according to serum cystatin C levels. Cystatin C was associated with LAVI (p50.0055), LVEF (p50.0432), LVMI (p50.0409), E (p50.0051), E/e (p50.0027), and log-transformed NT-proBNP (p!0.0001) according to multivariate linear regression analysis, after adjustment for confounding factors including creatinine-based estimated glomerular filtration rate (eGFRcreat) and urinary albumin to creatinine ratio. Incidence of eccentric and concentric hypertrophy increased with increasing cystatin C (Q1, 38%; Q2 49%; Q3, 51%; Q4, 66%, p50.0008), mainly because of increasing concentric hypertrophy (Q1, 30%; Q2, 39%; Q3, 39%; Q4, 51%, p50.0187). Conclusion: A high serum cystatin C is strongly associated with structural cardiac abnormalities such as LVH and left atrial enlargement, impaired LV relaxation, and an increased NT-proBNP, independently of eGFRcreat in patients with stage 2 or 3 CKD.
OP44-1 Effect of Serum Trace Elements and Macro Minerals on Myocardial Infarction MOHAMMAD SAFIQUL ISLAM1,2, MD. ZAHEDUR RAHAMAN1, S.M. NAIM UDDIN1, TANMIN JARANA TAMMI1, SHAHID SARWAR1, KAZUSHIGE YOKOTA2 1 Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali-3814, Bangladesh; 2Department of Life Science and Biotechnology, Faculty of Life and Environmental Science, Shimane University, Japan
JHFS
S195
2 Department of Cardiology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Background: Some type of heart failure (HF) is an obesity-related diseases and obesity can contribute to developing HF. However, the factors contributing to development of HF in obese are not fully elucidated. We analyzed potential plasma biomarkers related with metabolisms and neuro humoral factors, from the patients of HF with or without obesity. Method: We measured various biomarkers including amino acid profile, free fatty acid (FFA), endocrinological markers from the patients of HF. We divided into 2 groups (obesity group (BMIO23) and non-obesity group (BMI!23)) and analyzed these serum markers. Result: Plasma FFA (0.7 vs 0.4 mEq/l, p50.02), alanine (444.9 vs 375.7, p50.03) and valine (257.1 vs 228.5 umol/l, p50.03) were significantly higher in obesity group than in non-obesity group. Plasma noradrenaline (778.8 vs 408.2 ng/ml, p50.01) and aldosterone (132.7 vs 79.8 pg/ml, p50.05) levels were higher in obese group. There were no difference in brain natriuretic peptide (329.9 vs 464.1 pg/ml, p50.25), high sensitive C-reactive protein (0.2 vs 0.2 mg/dl, p50.8) between in obesity group and in non-obesity group. Conclusion: Obesity-related HF revealed higher serum FFA and branched-chain amino acids accompanied with sympathetic nerve activation and the elevated aldosterone levels. These biomarkers suggested that various metabolic remodelings might be characters of patients with HF.
OP44-4 Myocardial infarction (MI) is one of the leading causes of death associated with cardiovascular disease in recent years. The current study investigated the concentration of trace elements and macro minerals in MI patients of Bangladesh. MI patients (n5 74) were selected and recruited by random sampling from Dhaka Medical College and Hospital, Bangladesh. Serum trace elements (Zn, Fe, Se) and macro minerals (Ca, K, Na) were determined by flame atomic absorption spectroscopy. Independent sample t-test and Pearson’s correlation test were used for the statistical analysis. Serum concentrations of Zn, Fe, Se, Ca, K, and Na in MI patients were 0.266 0.01, 0.766 0.05, 0.016 0.0004, 33.756 1.39, 67.636 5.25, and 3189.36 47.63 mg/L while in control subjects those were 0.826 0.04, 0.156 0.01, 0.066 0.004, 87.396 4.17, 166.906 3.71, and 30006137.20 mg/L respectively. It was observed that serum level of Zn, Se, Ca, and K was significantly (p! 0.001) lower in patients but the concentration of Fe and Na in patient group was significantly (p! 0.001) and insignificantly (pO 0.001) higher respectively. Different inter-element relationships evidenced that there is a disturbance in the element homeostasis between the patient and control groups. Our data indicates that MI patients have considerably lower level of essential trace elements in serum and thus recommend necessary supplementation therapy to prevent disease progression.
OP44-2 Human Epididymis Protein 4 is a Useful Biomarker in Patients with Dilated Cardiomyopathy SHINSUKE HANATANI, YASUHIRO IZUMIYA, YOSHIRO ONOUE, YUICHI KIMURA, SATORU YAMAMURA, SATOSHI ARAKI, HISAO OGAWA Department of Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan Introduction: Interstitial fibrosis play a crucial role in the pathophysiology of dilated cardiomyopathy (DCM). Human epididymis protein 4 (HE-4) is a secreted protein that is expected to have the usefulness in the evaluation of ongoing fibrosis. Hypothesis: In patients with DCM, HE-4 could be a useful biomarker to evaluate disease severity and predict future cardiovascular events. Methods and Results: We measured serum HE-4 levels in 28 patients with DCM. Serum HE-4 concentrations were measured by ELISA. The endpoint was a composite of total mortality and cardiovascular hospitalization. Median HE-4 levels in all participants was 6189.6 pg/ml. Serum HE-4 levels (ln[HE-4]) were positively correlated with serum high sensitive cardiac troponin T (hsTnT) levels (ln[hsTnT]) (r50.62; p50.0017) and pulmonary capillary wedge pressure (r50.38; p50.048). Plasma B-type natriuretic peptide levels (BNP) (ln[BNP]) and left ventricular end-diastolic pressure also had tendency to be correlated with serum HE-4 levels, although these correlations did not reach statistical significance (r50.34; p50.076, r50.43, p50.054, respectively). Kaplan Meier curve revealed that the event-free rate was decreased in the high HE-4 group (Omedian) than in the low HE-4 group (log-rank test p50.03). Univariate Cox hazard analysis identified HE-4 (hazard ratio: 10.92; 95% confidence interval: 1.44-82.60, p50.021) as effective predictor of adverse events. Conclusions: HE-4 could be a useful biomarker for evaluating disease severity and providing prognostic information in patients with DCM.
OP44-3 Significance of Plasma Free Fatty Acid and Amino Acid Profile in Obesityrelated Heart Failure TAKAYUKI NAMBA1, TOYOKAZU KIMURA1, SHUNPEI HORII1, YASUNAGA SHIRAISHI1, ATSUSHI SATO1, RISAKO YASUDA1, HIROTAKA YADA1, AKIO KAWAMURA1, DAIHIKO HAKUNO2, TAKESHI ADACHI1 1 Department of Cardiology, National Defense Medical College, Tokorozawa, Japan;
Metabolomic Analysis Reveals New Insights Towards Understanding Skeletal Muscle Mass and Exercise Capacity in Patients with Heart Failure MASAYA TSUDA, SHINTARO KINUGAWA, ARATA FUKUSHIMA, SHINGO TAKADA, TAKASHI YOKOTA, SHOJI MATSUSHIMA, TAKAAKI FURIHATA, JUNICHI MATSUMOTO, HIROYUKI TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Background: Exercise intolerance is a major clinical manifestation and known to be a substantial prognostic factor in heart failure (HF) patients. A recent publication reported global metabolic disturbances are associated with outcomes in HF patients. However, metabolic profiling changes associated with skeletal muscle mass and exercise capacity has not been elucidated. Methods and Results: We studied consecutive HF patients with reduced ejection fraction (57612 years old, New York Heart Association class II-III) and 5 age-matched healthy subjects as controls (5663 years old). Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO2) was measured by cardiopulmonary exercise test. A total of 233 charged metabolites were detected and quantified absolutely using standard chemicals for each metabolite. Significant increases in arginine methylation, phospholipid metabolites, glutamine, and urea cycle metabolites were observed in HF patients compared to controls. Thigh circumference was negatively associated with glutamine (r5-0.80, P!0.01). Peak VO2 was negatively correlated with asymmetric dimethylarginine (ADMA) (r5-0.77, P!0.01) levels and phospholipid metabolites including choline (r5-0.63, P50.049) and N,N-dimethylglycine (r5-0.75, P50.011) levels in HF patients. Conclusions: Increases in methylated arginine derivatives, phospholipid metabolites and urea cycle components were associated with reduced exercise capacity in HF. In addition, plasma glutamine level was concerned with skeletal muscle wasting in HF.
OP44-5 Serum Cystatin C is Associated with Left Ventricular Hypertrophy and Impaired Left Ventricular Relaxation in Patients with Chronic Kidney Disease SATORU SAKURAGI, KEISHI ICHIKAWA, TAKAHIRO NISHIHARA, MASAHIRO TSUJI Department of Cardiovascular Medicine, Iwakuni Clinical Center Background: In this cross-sectional study, we aimed to determine the associations between serum cystatin C levels and structural and functional cardiac changes in patients with stage 2 or 3 chronic kidney disease (CKD). Methods and Results: We enrolled 429 consecutive patients (aged 24 to 97 years) with CKD stage 2 or 3 and left ventricular (LV) ejection fraction (LVEF) O 40%. Echocardiographic parameters, including LV mass index (LVMI), early diastolic mitral annulus velocity (e velocity), left atrial volume index (LAVI), and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) were measured. Patients were categorized into quartiles according to serum cystatin C levels. Cystatin C was associated with LAVI (p50.0055), LVEF (p50.0432), LVMI (p50.0409), E (p50.0051), E/e (p50.0027), and log-transformed NT-proBNP (p!0.0001) according to multivariate linear regression analysis, after adjustment for confounding factors including creatinine-based estimated glomerular filtration rate (eGFRcreat) and urinary albumin to creatinine ratio. Incidence of eccentric and concentric hypertrophy increased with increasing cystatin C (Q1, 38%; Q2 49%; Q3, 51%; Q4, 66%, p50.0008), mainly because of increasing concentric hypertrophy (Q1, 30%; Q2, 39%; Q3, 39%; Q4, 51%, p50.0187). Conclusion: A high serum cystatin C is strongly associated with structural cardiac abnormalities such as LVH and left atrial enlargement, impaired LV relaxation, and an increased NT-proBNP, independently of eGFRcreat in patients with stage 2 or 3 CKD.