研究者詳細 - 小山　雅之

論文 - 小山　雅之

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Postpartum Heart Failure Complicated With Thyroiditis: A Concealed Aggravator of Peripartum Cardiomyopathy?

Hidemichi Kouzu, Toshiyuki Yano, Nobutaka Nagano, Masayuki Koyama, Toshifumi Ogawa, Yugo Fujita, Atsuko Muranaka, Tetsuji Miura

The Canadian journal of cardiology 35 ( 6 ) 796.e1-796.e3 2019年06月 [査読有り] [国際誌]

The etiology of peripartum cardiomyopathy (PPCM) remains unestablished, but the involvement of abnormal autoimmunity has been suggested. We report a case of PPCM that was triggered by postpartum thyroiditis. Despite the presence of myocardial damage indicated by cardiac magnetic resonance imaging, the patient's cardiac function completely recovered with the addition of bromocriptine to standard therapies. We discuss the role of thyroid hormones in the development of PPCM through aggravation of a prolactin-dependent antiangiogenic effect, and we argue that more attention should be paid to postpartum thyroiditis as a novel risk factor for PPCM.

DOI PubMed

Differential Phenotypes in Perivascular Adipose Tissue Surrounding the Internal Thoracic Artery and Diseased Coronary Artery.

Ryosuke Numaguchi, Masato Furuhashi, Megumi Matsumoto, Hiroshi Sato, Yosuke Yanase, Yosuke Kuroda, Ryo Harada, Toshiro Ito, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Norihito Moniwa, Masanori Nakamura, Hirosato Doi, Tetsuji Miura, Nobuyoshi Kawaharada

Journal of the American Heart Association 8 ( 2 ) e011147 2019年01月 [査読有り] [国際誌]

Background Perivascular adipose tissue ( PVAT ) is causally associated with vascular function and the pathogenesis of vascular disease in association with metabolically driven chronic inflammation called metaflammation. However, the difference in PVAT surrounding the coronary artery ( CA - PVAT ) and that surrounding the internal thoracic artery (ITA-PVAT), a vessel resistant to atherosclerosis, remains unclear. Herein, we investigated whether CA - PVAT , ITA - PVAT , and subcutaneous adipose tissue ( SCAT ) have distinct phenotypes. Methods and Results Fat pads were sampled from 44 patients (men/women, 36:8; age, 67±13 years) with CA disease who underwent elective CA bypass grafting. Adipocyte size in ITA - PVAT and that in CA - PVAT were significantly smaller than that in SCAT . A greater extent of fibrosis and increased gene expression levels of fibrosis-related molecules were observed in CA - PVAT than those in SCAT and those in ITA - PVAT . CA - PVAT exhibited more pronounced metaflammation, as indicated by a significantly larger extent of CD 68-positive and CD 11c-positive M1 macrophages, a lower ratio of CD 206-positive M2 to CD 11c-positive M1 macrophages, a lower gene expression level of adiponectin, and higher gene expression levels of inflammatory cytokines and inflammasome- and endoplasmic reticulum stress-related molecules, than did ITA - PVAT and SCAT . Expression patterns of adipocyte developmental and pattern-forming genes were totally different among SCAT , ITA - PVAT, and CA - PVAT . Conclusions The phenotype of ITA - PVAT is closer to that of SCAT than that of CA - PVAT , which may result from inherent differences in adipocytes. ITA - PVAT appears to be protected from metaflammation and consecutive adipose tissue remodeling, which may contribute to the decreased atherosclerotic plaque burden in the ITA.

DOI PubMed

Low energy intake predicts readmission of elderly heart failure patients independently of nutritional status

Masayuki Koyama

European Heart Journal 2019年

Impact of body composition analysis on prediction of short-term readmission events in heart failure: muscle wasting vs. obesity

Masayuki Koyama

European Heart Journal 2019年

Activation of necroptotic pathway by downregulated caspase-8 expression is associated with progression of left ventricular remodeling in nonischemic dilated cardiomyopathy

Masayuki Koyama

European Heart Journal 2019年

Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid.

Masato Furuhashi, Kazuma Mori, Marenao Tanaka, Takuto Maeda, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Masayuki Koyama, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Endocrine journal 65 ( 11 ) 1083 - 1092 2018年11月 [査読有り] [国内誌]

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.

DOI PubMed

Screening of primary aldosteronism by clinical features and daily laboratory tests: combination of urine pH, sex, and serum K.

Tomohisa Yamashita, Sayaka Shimizu, Masayuki Koyama, Kouhei Ohno, Tomohiro Mita, Toshiyuki Tobisawa, Akifumi Takada, Nobuhiko Togashi, Yoshito Ohnuma, Tohru Hasegawa, Akihito Tsuchida, Toshiaki Endo, Toshiaki Ando, Hideaki Yoshida, Shingo Fukuma, Shunichi Fukuhara, Norihito Moniwa, Tetsuji Miura

Journal of hypertension ( LIPPINCOTT WILLIAMS & WILKINS ) 36 ( 2 ) 326 - 334 2018年02月 [査読有り] [国際誌]

OBJECTIVE: To develop and validate a scoring system for selection of patients who should proceed to endocrinologic examinations of primary aldosteronism in newly diagnosed hypertensive patients. METHODS: A multivariate logistic regression analysis for primary aldosteronism was undertaken by use of seven possible primary aldosteronism markers, age less than 40 years, female sex, moderate-to-severe hypertension, hypokalemia, serum Na minus Cl at least 40 mmol/l, serum uric acid 237.92 μmol/l or less (4.0 mg/dl), and urine pH (U-pH) at least 7.0, in consecutive outpatients newly diagnosed with hypertension. The diagnostic criteria of primary aldosteronism were plasma aldosterone concentration-to-plasma renin activity ratio [ARR, (ng/dl)/(ng/ml per h)] at least 20 and at least one positive result in four types of challenge tests. RESULTS: Of 130 patients, 24 were diagnosed with primary aldosteronism. The area under the receiver operating characteristic curve (AUC) for a logistic model incorporating all possible primary aldosteronism markers was 0.73 [95% confidence interval (CI): 0.61-0.85]. Removing high U-pH, female sex, and hypokalemia from the full model decreased the AUC by 0.059, 0.035, and 0.011, respectively. We devised pH of urine, female sex, low serum K (PFK) score, in which one point each was assigned to high U-pH, female sex, and hypokalemia. The prevalences of primary aldosteronism in patients with 0, 1, 2, and 3 points were 11, 14, 42, and 60%, respectively. In external validation datasets (n = 106), AUC of PFK score was significantly higher than that of hypokalemia alone (0.73, 95% CI: 0.63-0.83 vs. 0.53, 95% CI: 0.44-0.63, P < 0.01). CONCLUSION: PFK score may be a better parameter than hypokalemia alone for identifying patients with a high probability of having primary aldosteronism.

DOI PubMed

Cardiac iodine-123 metaiodobenzylguanidine imaging predicts frequent hypotension during hemodialysis in patients with end-stage renal disease

Masayuki Koyama

European Heart Journal 2018年

Screening of Primary Aldosteronism by Clinical Features and Daily Laboratory Tests: Combination of Urine pH, Sex, and Serum K

Tomohisa Yamashita, Norihito Moniwa, Masayuki Koyama, Kohei Ohno, Hideaki Yoshida, Tetsuji Miura

HYPERTENSION ( LIPPINCOTT WILLIAMS & WILKINS ) 70 2017年09月

Everolimus in pregnancy: Case report and literature review.

Mie Yamamura, Takashi Kojima, Masayuki Koyama, Ataru Sazawa, Takahiro Yamada, Hisanori Minakami

The journal of obstetrics and gynaecology research ( WILEY ) 43 ( 8 ) 1350 - 1352 2017年08月 [査読有り] [国際誌]

There have been few reports on the effects of everolimus on the fetus, but none of six infants with documented everolimus exposure in utero had congenital malformations. A 32-year-old nulliparous woman on everolimus (5.0 mg/day) for renal angiomyolipoma (AML) due to tuberous sclerosis complex (TSC) was found to be pregnant at gestational week (GW) 7-5/7, at which time everolimus was withheld. To control AML in this patient, transarterial embolization was performed in the right and left kidneys at GW 21 and 24, respectively, and everolimus was reinitiated at GW 25. The patient gave birth at GW 37 to a normally formed infant weighing 3057 g, but who had cardiac tumors thought to be rhabdomyomas due to inherited TSC. Thus, although data are still limited, everolimus may be promising with respect to teratogenicity. Everolimus concentration in the maternal and umbilical cord blood at birth was 1.1 ng/mL and 1.0 ng/mL, respectively.

DOI PubMed

Lethal heart failure with anti-mitochondrial antibody: an arrhythmogenic right ventricular cardiomyopathy mimetic.

Masayuki Koyama, Toshiyuki Yano, Keisuke Kikuchi, Daigo Nagahara, Hatsue Ishibashi-Ueda, Tetsuji Miura

European heart journal ( OXFORD UNIV PRESS ) 38 ( 2 ) 123 - 123 2017年01月 [査読有り] [国際誌]

DOI PubMed

Impact of the Number of Anti-Thrombosis Agents in Hemodialysis Patients: BOREAS-HD2 Study.

Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Tomohisa Yamashita, Masayuki Koyama, Yufu Gocho, Keitaro Nishizawa, Yukishige Kimura, Hirohito Sugawara, Sayaka Murakami, Yusuke Okazaki, Masato Furuhashi, Hideaki Yoshida, Tetsuji Miura

Kidney & blood pressure research ( KARGER ) 42 ( 3 ) 553 - 564 2017年 [査読有り] [国際誌]

BACKGROUND/AIMS: Relationships between the number of anti-thrombosis agents, clinical benefits and adverse events in hemodialysis (HD) patients are unclear. METHODS: All patients on HD in 22 institutes (n = 1,071) were enrolled and followed up for 3 years. After exclusion of patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204), mortality rate and ischemic and hemorrhagic events were compared between different regimens of anti-thrombosis agents. RESULTS: The use of dual or triple antiplatelet (AP) agents (HR:2.03, 95% CI:1.01-4.13, p = 0.04) and the combination of an AP agent and warfarin (WF) (HR:4.84, 95%CI 1.96-11.96, p < 0.001) were associated with an increase in hemorrhagic events compared with no use of anti-thrombosis agents. No anti-thrombosis regimen was associated with a significant change in risk of ischemic stroke. The use of dual or triple AP agents, but not WF, was associated with an increase in cardiovascular mortality (HR:2.48, 95% CI:1.24-4.76, p = 0.01). CONCLUSION: A significant increase in hemorrhagic events by the use of dual or more AP agents and by co-administration of an AP agent and WF in patients on HD should be considered in planning their anti-thrombosis regimen.

DOI PubMed

Favorable response to an endothelin receptor antagonist in mitomycin-induced pulmonary veno-occlusive disease with pulmonary capillary hemangiomatosis.

Masayuki Koyama, Toshiyuki Yano, Keisuke Kikuchi, Masashi Mizuno, Nobutaka Nagano, Akiyoshi Hashimoto, Tetsuji Miura

International journal of cardiology ( ELSEVIER IRELAND LTD ) 212 245 - 7 2016年06月 [査読有り] [国際誌]

DOI PubMed

Impact of use of angiotensin II receptor blocker on all-cause mortality in hemodialysis patients: prospective cohort study using a propensity-score analysis.

Marenao Tanaka, Tomohisa Yamashita, Masayuki Koyama, Norihito Moniwa, Kohei Ohno, Kaneto Mitsumata, Takahito Itoh, Masato Furuhashi, Hirofumi Ohnishi, Hideaki Yoshida, Kazufumi Tsuchihashi, Tetsuji Miura

Clinical and experimental nephrology ( SPRINGER ) 20 ( 3 ) 469 - 78 2016年06月 [査読有り] [国内誌]

BACKGROUND: It is controversial whether treatment with an angiotensin II receptor blocker (ARB) or a calcium channel blocker (CCB) improves prognosis of hemodialysis (HD) patients. METHODS: This study was designed as a multicenter prospective cohort study. HD patients (n = 1071) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204) were excluded, and 867 patients contributed to analysis of mortality. Propensity score (PS) for use of ARB and that for CCB was calculated using a multiple logistic regression model. RESULTS: ARB and CCB were prescribed in 45.6 and 54.7 % of patients at enrollment. During the 3-year follow-up period, all-cause mortality and cardiovascular mortality rates were 18.8 and 5.1 %, respectively. Kaplan-Meier curves showed that all-cause and cardiovascular mortality rates were lower in the ARB group than in the non-ARB group, though the mortality rates were similar in the CCB group and non-CCB group. In PS-stratified Cox regression analysis, ARB treatment was associated with 34 and 45 % reduction of all-cause death and cardiovascular death, respectively. In PS matching analysis, ARB treatment was associated with a significant reduction (46 % reduction) in the risk of all-cause death. A significant impact of CCB treatment on all-cause or cardiovascular mortality was not detected in PS analysis. CONCLUSIONS: The use of an ARB, but not a CCB, is associated with reduced all-cause and cardiovascular mortalities in patients on HD.

DOI PubMed

Cardiac tamponade leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.

Toshiyuki Yano, Shutaro Ishimura, Tetsuaki Furukawa, Masayuki Koyama, Marenao Tanaka, Shinya Shimoshige, Akiyoshi Hashimoto, Tetsuji Miura

Heart and vessels ( SPRINGER ) 30 ( 6 ) 841 - 4 2015年11月 [査読有り] [国内誌]

Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called Churg-Strauss syndrome, is a necrotizing systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Cardiovascular complications, including eosinophilic myocarditis, are a major cause of mortality in this disorder. Acute pericarditis with slight pericardial effusion is a typical manifestation in EGPA, though hemodynamically significant pericardial effusion has been reported in a few cases. We report a case that initially presented with isolated cardiac tamponade, which was followed by systemic manifestations of EGPA over 3 weeks. Including the present case, previous EGPA cases with cardiac tamponade are reviewed to delineate its clinical characteristics.

DOI PubMed

Everolimus-responsive dilated cardiomyopathy in tuberous sclerosis.

Masayuki Koyama, Toshiyuki Yano, Keisuke Kikuchi, Tetsuji Miura

European heart journal ( OXFORD UNIV PRESS ) 36 ( 34 ) 2338 - 2338 2015年09月 [査読有り] [国際誌]

DOI PubMed

Reduction of endoplasmic reticulum stress by 4-phenylbutyric acid prevents the development of hypoxia-induced pulmonary arterial hypertension

Masayuki Koyama, Masato Furuhashi, Shutaro Ishimura, Tomohiro Mita, Takahiro Fuseya, Yusuke Okazaki, Hideaki Yoshida, Kazufumi Tsuchihashi, Tetsuji Miura

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY ( AMER PHYSIOLOGICAL SOC ) 306 ( 9 ) H1314 - H1323 2014年05月 [査読有り] [国際誌]

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling of the pulmonary artery (PA). Recently, endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) have been disclosed in various types of diseases. Here we examined whether ER stress is involved in the pathogenesis of PAH. Four weeks of chronic normobaric hypoxia increased right ventricular (RV) systolic pressure by 63% compared with that in normoxic controls and induced RV hypertrophy and medial thickening of the PA in C57BL/6J mice. Treatment with 4-phenylbutyric acid (4-PBA), a chemical chaperone, significantly reduced RV systolic pressure by 30%, attenuated RV hypertrophy and PA muscularization, and increased total running distance in a treadmill test by 70% in hypoxic mice. The beneficial effects of 4-PBA were associated with suppressed expression of inflammatory cytokines and ER stress markers, including Grp78 and Grp94 in the activating transcription factor-6 branch, sXbp1 and Pdi in the inositol-requiring enzyme-1 branch and Atf4 in the PKR-like ER kinase branch, and reduced phosphorylation of c-Jun NH2-terminal kinase and eukaryotic translation initiation factor-2 alpha in the lung. The pattern of changes in ER stress and inflammatory markers by 4-PBA in the lung of the PAH model was reproduced in PA smooth muscle cells by chronic stimulation of platelet-derived growth factor-BB or hypoxia. Furthermore, knockdown of each UPR branch sensor activated other branches and promoted proliferation of PA smooth muscle cells. The findings indicate that activation of all branches of the UPR and accompanying inflammation play a major role in the pathogenesis of PAH, and that chemical chaperones are potentially therapeutic agents for PAH.

DOI PubMed

Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Shutaro Ishimura, Masato Furuhashi, Yuki Watanabe, Kyoko Hoshina, Takahiro Fuseya, Tomohiro Mita, Yusuke Okazaki, Masayuki Koyama, Marenao Tanaka, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 11 ) e81318 2013年11月 [査読有り] [国際誌]

Objective: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. Methods: From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1 similar to 5 in their serum samples were assayed. Results: Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMAR after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. Conclusions: Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting preclinical stage of metabolic syndrome, especially insulin resistance, in the general population.

DOI PubMed

Prognostic evaluation of patients with pulmonary hypertension by combined non-invasive assessment of pulmonary vascular resistance and right ventricular function

Masayuki Koyama

European Heart Journal 2013年

DOI

Endoplasmic Reticulum Stress in Pulmonary Artery Smooth Muscle Cells Contributes to the Development of Pulmonary Hypertension Induced by Chronic Hypoxia

Masayuki Koyama

Circulation 2013年

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