論文 - 海北 幸一
-
Yamanaga K., Tsujita K., Komura N., Kaikita K., Sakamoto K., Miyazaki T., Saito M., Ishii M., Tabata N., Akasaka T., Sato K., Horio E., Arima Y., Kojima S., Tayama S., Nakamura S., Hokimoto S., Ogawa H.
American Journal of Physiology - Heart and Circulatory Physiology 308 ( 5 ) H478 - H484 2015年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Physiology - Heart and Circulatory Physiology
Endothelial and vascular smooth muscle dysfunction of epicardial coronary arteries play a pivotal role in the pathogenesis of vasospastic angina (VSA). However, coronary microvascular (MV) function in patients with VSA is not fully understood. In the present study, subjects without coronary obstruction were divided into two groups according to the acetylcholine provocation test: VSA group (n = 29) and non-VSA group (n = 21). Hyperemic MV resistance (hMR) was measured using a dual-sensor (Doppler velocity and pressure)-equipped guidewire, and guidewire-derived hemodynamic parameters were compared. There were no between-group differences in clinical demographics, including potential factors affecting MV function (e.g., diabetes). Although coronary flow velocity reserve was similar between the two groups [2.4 ± 1.0 (VSA group) vs. 2.4 ± 0.9 (non-VSA group); P ± 0.8], coronary vessel resistance and hMR were significantly elevated in the VSA group compared with the non-VSA group (2.6 ± 3.1 vs. 1.2 ± 0.8, P = 0.04; 1.9 ± 0.6 vs. 1.6 ± 0.5, P = 0.03, respectively). Coronary vasospasm, older age, E/e’, and estimated glomerular filtration rate were significantly associated with MV dysfunction [defined as ≥ median value of hMR (1.6)] in univariate analysis. Coronary vasospasm most strongly predicted higher hMR in multivariate logistic regression analysis (odds ratio, 4.61; 95% confidence interval, 0.98 –21.60; P = 0.053). In conclusion, coronary MV resistance is impaired in patients with VSA compared with non-VSA patients, whereas coronary flow velocity reserve is maintained at normal levels in both groups. In vivo assessment of hMR might be a promising index of coronary MV dysfunction in patients with VSA.
-
Hirata Y., Yamamoto E., Tokitsu T., Kusaka H., Fujisue K., Kurokawa H., Sugamura K., Maeda H., Tsujita K., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
Journal of the American Heart Association 4 ( 2 ) 2015年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of the American Heart Association
BACKGROUND: Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD.
-
Gender differences in impact of CYP2C19 polymorphism on development of coronary artery disease 査読あり
Hokimoto S., Tabata N., Akasaka T., Arima Y., Kaikita K., Morita K., Kumagae N., Oniki K., Nakagawa K., Ogawa H.
Journal of Cardiovascular Pharmacology 65 ( 2 ) 148 - 152 2015年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiovascular Pharmacology
The aim was to clarify whether CYP2C19 polymorphism is associated with the development of coronary artery disease (CAD). This study enrolled 723 patients with CAD (men 71%, 70 years) and healthy subjects undergoing a medical checkup (n = 453) as controls (men 69%, 53 years). We analyzed the incidence of CYP2C19 polymorphism and its association with the development of CAD in the absence of diabetes, dyslipidemia, and chronic kidney disease to minimize the influence of conventional coronary risk factors. In the analysis without risk factors, there was no difference in the incidence of the CYP2C19 genotype between CAD (n = 115) and control (n = 194) groups [extensive metabolizer, intermediate metabolizer, poor metabolizer (PM) in non-risk CAD: 33%, 46%, 21%, respectively; in non-risk control: 31%, 52%, 17%, respectively]. Analysis between CAD and control groups by the χ test showed that there was significant difference in distribution of CYP2C19 genotype in women alone (P = 0.025) but not in total subjects (P = 0.471) or men (P = 0.678), respectively. CYP2C19 PM was an independent predictor of CAD risk in women alone (odds ratio, 10.717; 95% confidence interval, 1.753-65.505; P = 0.010) but not in men. CYP2C19 PM status might be associated with the development of CAD as a disease susceptibility gene, especially in women.
-
Hirata Y., Yamamoto E., Tokitsu T., Kusaka H., Fujisue K., Kurokawa H., Sugamura K., Maeda H., Tsujita K., Yamamuro M., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
International Journal of Cardiology 179 305 - 308 2015年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
-
Sueta D., Hokimoto S., Tayama S., Tsujita K., Sakamoto K., Yamamoto E., Tanaka T., Izumiya Y., Yamamuro M., Yamanaga K., Akasaka T., Tababa N., Arima Y., Kaikita K., Ogawa H.
International Journal of Cardiology 182 ( C ) 85 - 87 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
-
Ishii M., Hokimoto S., Akasaka T., Fujimoto K., Miyao Y., Kaikita K., Oshima S., Nakao K., Shimomura H., Tsunoda R., Hirose T., Kajiwara I., Matsumura T., Nakamura N., Yamamoto N., Koide S., Oka H., Morikami Y., Sakaino N., Matsui K., Ogawa H.
Circulation Journal 79 ( 5 ) 1115 - 1124 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
Background: The aim of this study was to examine the effects of different statins on the clinical outcomes of Japanese patients with coronary stent implants. Methods and Results: This study included 5,801 consecutive patients (males, 4,160; age, 69.7}11.1 years, mean } SD) who underwent stent implantation between April 2008 and March 2011. They were treated with a strong statin (n=3,042, 52%, atorvastatin, pitavastatin, or rosuvastatin), a regular statin (n=1,082, 19%, pravastatin, simvastatin, or fluvastatin) or no statin (n=1,677, 29%). The patients with chronic kidney disease (CKD) were divided into mildto- moderate CKD (30≤eGFR<60, n=1,956) and severe CKD (eGFR <30, n=559). Primary endpoints included cardiovascular death and nonfatal myocardial infarction, including stent thrombosis and ischemic stroke. The clinical outcome for the primary endpoint in mild-to-moderate CKD patients treated with a strong statin (hazard ratio 0.50, 95% confidence interval 0.31–0.81; P=0.005) was significantly lower than in those on no statins, but that in the patients treated with a regular statin was not (P=0.160). The clinical outcome for the primary endpoint in severe CKD patients treated with a strong or regular statin was no different than not being on statin therapy (P=0.446, P=0.194, respectively). Conclusions: In patients with mild-to-moderate CKD, only strong statins were associated with lower risk compared with no statin, but regular statins were not. It is possible that taking a strong statin from the early stage of CKD is useful for suppression of cardiovascular events.
-
Hokimoto S., Mizuno Y., Sueta D., Morita S., Akasaka T., Tabata N., Harada E., Arima Y., Yamamuro M., Tanaka T., Yamamotoa E., Sakamoto K., Tsujita K., Kaikita K., Yasue H., Ogawa H.
International Journal of Cardiology 182 ( C ) 171 - 173 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
-
Tokitsu T., Yamamoto E., Hirata Y., Fujisue K., Sugamura K., Maeda H., Tsujita K., Kaikita K., Hokimoto S., Sugiyama S., Ogawa H.
Journal of Hypertension 33 ( 9 ) 1780 - 1790 2015年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Hypertension
Objective: Recent studies have shown that inter-arm blood pressure differences (IAD) may be a risk factor for cardiovascular events; however, none have addressed them in patients with coronary artery disease (CAD). Methods: We measured blood pressure bilaterally with the ankle brachial index (ABI) in 657 patients with suspected CAD and assessed the presence of CAD by coronary angiography, and the severity of coronary atherosclerosis with the Gensini score. Results: Mean IADs were significantly greater in risk factor matched patients with CAD than in those without it (P=0.01), whereas Gensini scores were significantly greater in those with high IAD (≥10 mmHg) than in those with low-IAD (P=0.01) according to cross-sectional analysis. Patients with high IAD had a significantly greater probability of cardiovascular events than those in whom it was low (log-rank test, P<0.01, mean follow-up range; 827.3±268.1 days). The presence of hypertension, ABI, usage of calcium channel blocker and high IAD were independent predictors of cardiovascular events according to longitudinal analysis (IAD; hazard ratio: 2.90, 95% confidence interval: 1.41-5.94, P<0.01) in these patients. Patients with high IAD and peripheral artery disease had the highest Gensini scores according to cross-sectional analysis (P<0.01) and highest probability of cardiovascular events according to longitudinal analysis (log-rank test, P<0.001). Conclusion: IADs were increased in CAD patients and correlated with its severity. Greater than 10mmHg of IAD was independently associated with future cardiovascular events. Assessing IAD by ABI measurement may facilitate risk stratification in CAD patients.
-
Hokimoto S., Tabata N., Akasaka T., Arima Y., Tsujita K., Yamamoto E., Izumiya Y., Yamamuro M., Sakamoto K., Kaikita K., Sugamura K., Ogawa H.
International Journal of Cardiology 177 ( 2 ) 723 - 725 2014年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
-
Marume K., Arima Y., Igata M., Nishikawa T., Yamamoto E., Yamamuro M., Tsujita K., Tanaka T., Kaikita K., Hokimoto S., Ogawa H.
Journal of Cardiology Cases 10 ( 6 ) 226 - 230 2014年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 58-year-old man was admitted for non-ST-elevation myocardial infarction. A medicated stent was used for severe coronary artery stenosis. However, consciousness level progressively deteriorated after angioplasty. Computed tomography showed no brain lesion but laboratory tests showed hyponatremia (serum sodium: 113. meq./l) and urine analysis showed syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH was first suspected to be drug-induced by enalapril. However, hyponatremia persisted even after withdrawal of enalapril and required oral sodium intake. Hormone assays indicated secondary adrenal insufficiency, which was caused by adrenocorticotropic hormone (ACTH) deficiency. Furthermore, in addition to ACTH deficiency, adult growth hormone deficiency was diagnosed following tests. Treatment with hydrocortisone relieved hyponatremia and re-institution of enalapril did not reduce serum sodium concentration. The final diagnosis was hyponatremia caused by hypopituitarism.<. Learning objective: Secondary adrenal insufficiency with subsequent hypopituitarism should be suspected in cases with sudden-onset and prolonged hyponatremia in acute illness. Furthermore, the management of hypopituitarism should include assessment of growth hormone release to exclude growth hormone deficiency.>.
-
Tabata N., Yamamuro M., Sugiyama S., Mizobe M., Takashio S., Tsujita K., Yamamoto E., Tanaka T., Kojima S., Kaikita K., Tayama S., Hokimoto S., Syudo C., Miyakawa T., Mitsuya H., Ogawa H.
Journal of Cardiology Cases 10 ( 5 ) 167 - 170 2014年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 34-year-old man presented with heart failure (HF). He suffered opportunistic infections and was shown to be human immunodeficiency virus (HIV)-positive (viral load: 156,013copies/mL) and have low CD4 lymphocytes (3/mm ), so he was initially treated for the opportunistic infections. Initial investigations showed high elevation of brain natriuretic peptide (BNP: 969pg/mL). Transthoracic echocardiography showed an enlarged left ventricle (LV: 70mm), a reduced LV ejection fraction (EF: 19%), but no LV hypertrophy or significant valvular diseases. After treatments for the infections, we started standard HF medications. Cardiac catheterization, after recovery from the opportunistic infections with negative inflammatory markers, showed no significant coronary stenosis, and endomyocardial biopsy did not show findings of myocarditis, without HIV structural protein on immunohistochemistry. Despite reduced EF, the cardiac output was elevated at 7.1l/min [cardiac index (CI): 4.3l/min/m ] and the systemic vascular resistance index was decreased at 1358dyness/cm m . Hematologists began anti-retroviral therapy; the viral load was gradually reduced to negative, and the CD4 count was increased to 50/mm at Day 182. EF was accordingly improved up to 54%, but the cardiac output decreased to a normal level at 3.9l/min (CI: 2.4l/min/m ), leading to normalization of plasma BNP (<5pg/mL). This case indicates that high cardiac output might be involved in the pathogenic mechanisms of HIV-related HF.<. Learning objective: The etiology of HIV-related HF remains unclarified. We report on a man with HIV-associated HF. There were no apparent causes of the HF, but the patient did demonstrate high cardiac output despite impaired systolic function. After anti-retroviral therapy, his systolic function was improved with a reduction and normalization of cardiac output. Therefore, this case indicates that high cardiac output might be involved in the pathogenic mechanisms of HIV-related HF>. 3 2 5 2 3 2
-
Yamanaga K., Tsujita K., Shimomura H., Ogura Y., Matsumuro Y., Onoue Y., Chazono N., Morisaki S., Komura N., Sakamoto K., Kaikita K., Tayama S., Hokimoto S., Ogawa H.
Journal of Cardiology Cases 10 ( 5 ) 184 - 187 2014年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
Although spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS) or sudden cardiac death, its standard management, especially primary percutaneous coronary intervention (PCI) in ACS patients with ongoing ischemia, has not been established. We experienced three ACS patients with SCAD who were treated with a different strategy of primary PCI. Each PCI strategy led to different clinical and procedural results. We describe here such PCI strategies and results, and also discuss the literature regarding primary PCI strategies for SCAD-induced ACS patients with ongoing ischemia. < Learning objective: SCAD is a cause of ACS. However, the treatment strategy of primary PCI for SCAD has not been fully investigated. We used different PCI strategies for three SCAD patients with ongoing ischemia. Our case series suggested that plain old balloon angioplasty is an acceptable option to avoid coronary stenting because the majority of patients were young menstruating women. Coronary vasospasm might be associated with SCAD. Treatment with vasodilators could be a potential pharmacological option for avoiding recurrence of SCAD>.
-
Akasaka T., Hokimoto S., Oshima S., Nakao K., Fujimoto K., Miyao Y., Shimomura H., Tsunoda R., Hirose T., Kajiwara I., Matsumura T., Nakamura N., Yamamoto N., Koide S., Oka H., Morikami Y., Sakaino N., Kaikita K., Nakamura S., Matsui K., Ogawa H.
International Journal of Cardiology 176 ( 3 ) 1385 - 1387 2014年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Cardiology
-
Takaoka N., Tsujita K., Kaikita K., Hokimoto S., Yamanaga K., Komura N., Chitose T., Ono T., Mizobe M., Horio E., Sato K., Nakayama N., Saito M., Iwashita S., Kojima S., Tayama S., Sugiyama S., Nakamura S., Ogawa H.
Heart and Vessels 29 ( 5 ) 584 - 595 2014年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Heart and Vessels
Despite current standards of care aimed at achieving targets for low-density lipoprotein cholesterol (LDL-C), many patients remain at high residual risk of cardiovascular events. We sought to assess the LDL-C-dependent differences in culprit intravascular ultrasound (IVUS) morphologies and clinical characteristics in patients with acute coronary syndrome (ACS). Eighty-six consecutive ACS patients whose culprit lesions imaged by preintervention IVUS were divided into two groups based on the fasting LDL-C level on admission: a low-LDL-C group (LDL-C <2.6 mmol/l, n = 45) and a high-LDL-C group (LDL-C ≥2.6 mmol/l, n = 41). Patients with stable angina with LDL-C <2.6 mmol/l (n = 30) were also enrolled as an age- and gender-matched control. The low-LDL-C ACS group was significantly older (72 ± 12 vs 64 ± 14 years, P = 0.007) and more diabetic (47 % vs 15 %, P = 0.001). Importantly, IVUS morphologies were comparable between low- and high-LDL-C ACS groups (all P not significant), whereas culprit plaque was more hypoechoic and less calcified in the low-LDL-C ACS group than in the low-LDL-C stable angina group. Furthermore, compared with the low-LDL-C ACS nondiabetic group, the low-LDL-C ACS diabetic group was more obese, more triglyceride rich (1.3 ± 0.6 vs 0.9 ± 0.4 mmol/l, P = 0.003), and more endothelially injured, but no different for the culprit IVUS morphologies. In multivariate analysis, diabetes was independently associated with a low LDL-C level on admission in patients with ACS. There was no relationship between the LDL-C level at onset and culprit-plaque IVUS morphologies in ACS patients, although culprit plaque in the low-LDL-C ACS group was more vulnerable than in the low-LDL-C stable angina group. In patients with low-LDL-C levels, diabetes with atherogenic dyslipidemia might be the key residual risk.
-
Mizobe M., Hokimoto S., Akasaka T., Arima Y., Kaikita K., Morita K., Miyazaki H., Oniki K., Nakagawa K., Ogawa H.
Thrombosis Research 134 ( 1 ) 72 - 77 2014年7月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Objective The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM). Methods CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n = 249), and non-DM (n = 270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele. Results The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501 +/- 1668 versus 3691 +/- 1714AUmin, P < 0.01; events, 32/178 versus 2/92, P < 0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P = 0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P = 0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P = 0.618). Conclusion The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents. © 2014 Elsevier Ltd.
-
Hokimoto S., Chitose T., Mizobe M., Akasaka T., Arima Y., Kaikita K., Iwashita S., Morita K., Miyazaki H., Oniki K., Matsui K., Nakagawa K., Ogawa H.
European Journal of Clinical Pharmacology 70 ( 6 ) 667 - 673 2014年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Journal of Clinical Pharmacology
Background: High residual platelet reactivity in patients receiving clopidogrel is associated with an increased risk of a cardiovascular event after coronary stenting. The aim of our study was to evaluate the impact of the cytochrome P450 (CYP) 3A5 and CYP2C19 polymorphisms on platelet reactivity during dual antiplatelet therapy. Methods: We determined the CYP2C19 and CYP3A5 genotypes of 101 angina patients (65 male patients, mean age 64 years) receiving dual antiplatelet therapy with aspirin and clopidogrel and evaluated the effect of these polymorphism on platelet reactivity at the early and late phases of treatment using a conventional light transmission aggregometry. Early and late phases were defined as 24 h after the loading dose and after 9 months on a maintenance dose of 75 mg daily, respectively. Results: The distribution of the CYP2C19 genotype was 30 % in extensive metabolizers (EM; CYP2C19*1/ *1), 46 % in intermediate metabolizers (IM;*1/*2,*1/ *3), and 25 % in poor metabolizers (PM;*2/*2,*2/ *3,*3/*3). Platelet reactivity levels in during the early and late phases were 3,793±1,476 and 2,960±1,410, respectively, in EM, 4,706±1,417 and 3,239±1,479, respectively, in IM, and 5,402±776 and 4,736±1,356 aggregation units (AU)•min, respectively in EM. The distribution of the CYP3A5 genotype was 33 % in patients carrying the wild-type or one loss-of-function allele (Expressor phenotype; *1/*1 and *1/*3, respectively) and 67 % in those carrying two loss-of-function alleles (Non-expressor; *3/*3). In total, eight patients were EM+Expressor, 22 were EM+Non-expressor, 18 were IM+Expressor, 28 were IM+Non-expressor, eight were PM+Expressor, and 17 were PM+Non-expressor. In the late phase of PM with the CYP2C19 polymorphism, the levels of platelet reactivity according to CYP3A5 genotype were 3,963±1,436 and 5,100±1,190 AU•min in Expressor and Non-expressor, respectively (P<0.05), however, there was no difference in platelet reactivity between Expressor and Non-expressor in EM and IM. Conclusions: Our results suggest that antiplatelet response to clopidogrel in the late phase depends on the CYP3A5 polymorphism in PM with CYP2C19. © 2014 Springer-Verlag.
-
Mid-systolic flow reversal in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy 査読あり
Ito M., Misumi I., Rokutanda T., Kusuhara K., Akahoshi R., Matsumoto M., Shojima T., Yasuda H., Kaikita K., Hokimoto S., Ogawa H.
Journal of Echocardiography 12 ( 2 ) 78 - 80 2014年6月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Echocardiography
-
Takashio S., Yamamuro M., Uemura T., Utsunomiya D., Morita K., Izumiya Y., Sugiyama S., Kojima S., Yamamoto E., Tsujita K., Tanaka T., Tayama S., Kaikita K., Hokimoto S., Yasuda O., Yamashita Y., Ogawa H.
American Journal of Cardiology 113 ( 10 ) 1697 - 1704 2014年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Cardiology
Persistently high cardiac troponin T (cTnT) levels reflect myocardial damage in heart failure (HF). The presence and extent of myocardial fibrosis assessed by cardiac magnetic resonance (CMR) and high levels of cTnT predict poor prognosis in various cardiomyopathies. However, the association between myocardial fibrosis and transcardiac cTnT release has not been evaluated. This study investigated the correlation between myocardial fibrosis and transcardiac cTnT release from nonischemic failing myocardium. Serum cTnT levels were measured in aortic root (Ao) and coronary sinus (CS) using highly sensitive assay (detection limit >5 ng/L) in 74 nonischemic patients with HF who underwent CMR. Transcardiac cTnT release (ΔcTnT [CS-Ao]) represented the difference between CS and Ao-cTnT levels. Myocardial fibrosis was quantified by late gadolinium enhancement (LGE) volume and %LGE on CMR. cTnT was detectable in 65 patients (88%), and ΔcTnT (CS-Ao) levels were available (ΔcTnT [CS-Ao] >0 ng/L) in 60 patients (81%). LGE was observed in 42 patients (57%), and ΔcTnT (CS-Ao) levels were available in 41 LGE-positive patients (98%). In patients with available cTnT release, ΔcTnT (CS-Ao) levels were significantly higher in LGE-positive patients than those in LGE-negative patients (4.3 [2.2-5.5] vs 1.5 [0.9-2.6] ng/L; p = 0.001). Log (ΔcTnT [CS-Ao]) levels were correlated with LGE volume (r = 0.460, p = 0.003) and %LGE (r = 0.356, p = 0.03). In conclusion, the amount of transcardiac cTnT release was higher in LGE-positive patients than LGE-negative patients and correlated with the extent of LGE in nonischemic patients with HF. These results suggested that ongoing myocardial damage correlates with the presence and extent of myocardial fibrosis. © 2014 Elsevier Inc. All rights reserved.
-
Hokimoto S., Mizobe M., Akasaka T., Arima Y., Kaikita K., Nakagawa K., Ogawa H.
Thrombosis Research 133 ( 4 ) 599 - 605 2014年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Thrombosis Research
Background The response to clopidogrel, and some kind of the drug interaction are multifactorial. Methods and Results We enrolled 174 consecutive patients and determined CYP2C19 genotypes, measured platelet aggregation, and assessed the relationship between CYP2C19 genotype and platelet reactivity 24 hours after clopidogrel administration, and the risk of cardiovascular events over 18 months follow-up. A sub analysis examined the impact of rabeprazole, a proton pump inhibitor (PPI) less affected by CYP2C19. The CYP2C19 genotype was extensive metabolizer (EM) in 36%, intermediate metabolizer (IM) in 45%, and poor metabolizer (PM) in 19%. Platelet reactivity was significantly lower in the EM group than in the IM and PM groups (EM, IM, PM: 3560 ± 1404, 4203 ± 1302, 5084 ± 1007 AU•min, P < 0.05). The cardiovascular event rate was higher in the IM and PM groups than in the EM group (12.7% and 12.5% vs 1.6%; Hazard ratio for IM 10.6, P = 0.029; for PM 11.3, P = 0.040). No differences were seen between patients taking (N = 50) and not taking (N = 124) rabeprazole in residual platelet aggregation (4407 ± 1360 vs 4048 ± 1394, AU•min, P = 0.2782), or in cardiovascular events (10.0% vs 8.1%, HR 0.97, P = 0.97). Conclusions CYP2C19 genotype is associated with an increased risk of cardiovascular events following stent implantation in Japanese patients. © 2013 Elsevier Ltd.
-
Horio E., Kadomatsu T., Miyata K., Arai Y., Hosokawa K., Doi Y., Ninomiya T., Horiguchi H., Endo M., Tabata M., Tazume H., Tian Z., Takahashi O., Terada K., Takeya M., Hao H., Hirose N., Minami T., Suda T., Kiyohara Y., Ogawa H., Kaikita K., Oike Y.
Arteriosclerosis, Thrombosis, and Vascular Biology 34 ( 4 ) 790 - 800 2014年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Arteriosclerosis, Thrombosis, and Vascular Biology
Objective-cardiovascular disease (CVD), the most common morbidity resulting from atherosclerosis, remains a frequent cause of death. Efforts to develop effective therapeutic strategies have focused on vascular inflammation as a critical pathology driving atherosclerosis progression. Nonetheless, molecular mechanisms underlying this activity remain unclear. Here, we ask whether angiopoietin-like protein 2 (Angptl2), a proinflammatory protein, contributes to vascular inflammation that promotes atherosclerosis progression. Approach and results-Histological analysis revealed abundant Angptl2 expression in endothelial cells and macrophages infiltrating atheromatous plaques in patients with cardiovascular disease. Angptl2 knockout in apolipoprotein E-deficient mice (ApoE /Angptl2 ) attenuated atherosclerosis progression by decreasing the number of macrophages infiltrating atheromatous plaques, reducing vascular inflammation. Bone marrow transplantation experiments showed that Angptl2 deficiency in endothelial cells attenuated atherosclerosis development. Conversely, ApoE mice crossed with transgenic mice expressing Angptl2 driven by the Tie2 promoter (ApoE /Tie2-Angptl2 Tg), which drives Angptl2 expression in endothelial cells but not monocytes/macrophages, showed accelerated plaque formation and vascular inflammation because of increased numbers of infiltrated macrophages in atheromatous plaques. Tie2-Angptl2 Tg mice alone did not develop plaques but exhibited endothelium-dependent vasodilatory dysfunction, likely because of decreased production of endothelial cell-derived nitric oxide. Conversely, Angptl2 mice exhibited less severe endothelial dysfunction than did wild-type mice when fed a high-fat diet. In vitro, Angptl2 activated proinflammatory nuclear factor-κB signaling in endothelial cells and increased monocyte/macrophage chemotaxis. Conclusions-Endothelial cell-derived Angptl2 accelerates vascular inflammation by activating proinflammatory signaling in endothelial cells and increasing macrophage infiltration, leading to endothelial dysfunction and atherosclerosis progression. © 2014 American Heart Association, Inc. -/- -/- -/- -/- -/-