論文 - 海北 幸一
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Usuku H., Yamamoto E., Kurogi K., Izumiya Y., Tsujita K., Yamamuro M., Kojima S., Soejima H., Kaikita K., Yamamoto N., Hokimoto S., Noda K., Yamabe H., Oshima S., Ogawa H.
IJC Metabolic and Endocrine 12 52 - 54 2016年9月
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Tsujita K., Yamanaga K., Komura N., Sakamoto K., Sugiyama S., Sumida H., Shimomura H., Yamashita T., Oka H., Nakao K., Nakamura S., Ishihara M., Matsui K., Sakaino N., Nakamura N., Yamamoto N., Koide S., Matsumura T., Fujimoto K., Tsunoda R., Morikami Y., Matsuyama K., Oshima S., Kaikita K., Hokimoto S., Ogawa H.
European Journal of Preventive Cardiology 23 ( 14 ) 1524 - 1528 2016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：European Journal of Preventive Cardiology
Background The IMPROVE-IT trial showed that the clinical benefit of statin/ezetimibe combination appeared to be pronounced in patients with prior statin therapy. We hypothesized that the antiatherosclerotic effect of atorvastatin/ezetimibe combination was pronounced in patients with statin pretreatment. Methods In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound-guided percutaneous coronary intervention were randomized to atorvastatin/ezetimibe combination or atorvastatin alone. The dosage of atorvastatin was uptitrated with a treatment goal of lowering low-density lipoprotein cholesterol to below 70 mg/dl in both groups. Serial volumetric intravascular ultrasound was performed at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients. We compared the intravascular ultrasound endpoints in all subjects, stratified by the presence or absence of statin pretreatment. Results The baseline low-density lipoprotein cholesterol level (100.7 ± 23.1 mg/dl vs. 116.4 ± 25.9 mg/dl, p < 0.001) and lathosterol (55 (38 to 87)) μg/100 mg total cholesterol vs. 97 (57 to 149) μg/100 mg total cholesterol, p < 0.001) was significantly lower, and campesterol/lathosterol ratio (3.9 (2.4 to 7.4) vs. 2.6 (1.5 to 4.1), p < 0.001) was significantly increased in patients with statin pretreatment. Contrary to the patients without statin pretreatment (-'1.3 (-'3.1 to -'0.1)% vs. -'0.9 (-'2.3 to 0.9)%, p = 0.12), the atorvastatin/ezetimibe combination showed a significantly stronger reduction in delta percent atheroma volume, compared with atorvastatin alone, in patients with statin pretreatment (-'1.8 (-'3.6 to -'0.3)% vs. -'0.1 (-'1.6 to 0.8)%, p = 0.002). Conclusion Compensatory increase in cholesterol absorption observed in statin-treated patients might attenuate the inhibitory effects of statins on coronary plaque progression. A low-dose statin/ezetimibe combination might be a promising option in statin-hyporesponder.
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Tsujita K., Yamanaga K., Komura N., Sakamoto K., Sugiyama S., Sumida H., Shimomura H., Yamashita T., Oka H., Nakao K., Nakamura S., Ishihara M., Matsui K., Sakaino N., Nakamura N., Yamamoto N., Koide S., Matsumura T., Fujimoto K., Tsunoda R., Morikami Y., Matsuyama K., Oshima S., Kaikita K., Hokimoto S., Ogawa H.
Atherosclerosis 251 367 - 372 2016年8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：Atherosclerosis
Background and aims Although dual low-density lipoprotein cholesterol (LDL-C)-lowering therapy (DLLT) with statin-ezetimibe combination showed clinical benefit in patients with acute coronary syndrome (ACS) confirming “the lower, the better,” the underlying mechanisms of DLLT are still unknown. Methods PRECISE-IVUS trial evaluated the effects of DLLT on IVUS-derived coronary atherosclerosis and lipid profile, compared with atorvastatin monotherapy, quantifying the coronary plaque response in 100 ACS patients. We explored the potential predictors of plaque regression. Results Lower total cholesterol, LDL-C, triglyceride, remnant-like particles cholesterol, and stronger reduction of small dense LDL-C and cholesterol absorption markers were observed in patients with plaque regression compared to those with progression. Multivariate analysis revealed that achieved LDL-C was the strongest predictor for coronary plaque regression (95% CI: 0.944–1.000, p = 0.05), followed by age (95% CI: 0.994–1.096, p = 0.09). Conclusions Incremental LDL-C lowering by DLLT was associated with stronger coronary plaque regression, reconfirming that lowering LDL-C to levels below previous targets provided additional clinical benefit.
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Nagatsuka K., Miyata S., Kada A., Kawamura A., Nakagawara J., Furui E., Takiuchi S., Taomoto K., Kario K., Uchiyama S., Saito K., Nagao T., Kitagawa K., Hosomi N., Tanaka K., Kaikita K., Katayama Y., Abumiya T., Nakane H., Wada H., Hattori A., Kimura K., Isshiki T., Nishikawa M., Yamawaki T., Yonemoto N., Okada H., Ogawa H., Minematsu K., Miyata T.
Thrombosis and Haemostasis 116 ( 2 ) 356 - 368 2016年8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 and Haemostasis
Several studies have indicated that approximately 25% of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B or urinary 11-dehydro TXB . Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8%>). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients. 2 2
DOI： 10.1160/TH15-11-0864
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A simple sarcopenia screening test predicts future adverse events in patients with heart failure 査読あり
Onoue Y., Izumiya Y., Hanatani S., Tanaka T., Yamamura S., Kimura Y., Araki S., Sakamoto K., Tsujita K., Yamamoto E., Yamamuro M., Kojima S., Kaikita K., Hokimoto S.
International Journal of Cardiology 215 301 - 306 2016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：International Journal of Cardiology
Background Progressive loss of skeletal muscle termed "sarcopenia" is an independent risk factor for mortality in patients with cardiovascular diseases. A simple screening test that can identify sarcopenia using three variables (age, grip strength and calf circumference) was recently developed. We evaluated the clinical utility of this screening test in patients with heart failure (HF). Methods and results HF patients were divided into the sarcopenia (n = 82) and non-sarcopenia (n = 37) groups based on the sarcopenia score. Circulating BNP and high-sensitive cardiac troponin T levels were significantly higher, and left ventricular ejection fraction was lower in the sarcopenia group than non-sarcopenia group. Kaplan-Meier curve showed that HF event-free survival rate was significantly lower in the sarcopenia group. Multivariate Cox proportional hazards analysis identified BNP (ln[BNP]) (hazard ratio [HR]: 1.58; 95% CI: 1.09-2.29, p = 0.02), hs-CRP (ln[CRP]) (HR: 1.82; 95% CI: 1.23-2.68; p < 0.01) and sarcopenia score (HR: 1.03; 95% CI: 1.01-1.05, p < 0.01) as independent predictors of HF events. In receiver operating characteristic analysis, adding the sarcopenia score to BNP levels increased an area under the curve for future HF events (sarcopenia score alone, 0.77; BNP alone, 0.82; combination, 0.89). Conclusions The sarcopenia screening test can be used to predict future adverse events in patients with HF.
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Tabata N., Hokimoto S., Akasaka T., Arima Y., Sakamoto K., Yamamoto E., Tsujita K., Izumiya Y., Yamamuro M., Kojima S., Kaikita K., Ogawa H.
Heart and Vessels 31 ( 7 ) 1038 - 1044 2016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：Heart and Vessels
Chronic kidney disease (CKD) status might modify the predictive effect of peripheral endothelial dysfunction on cardiovascular events after percutaneous coronary intervention (PCI). The aim of this study was to examine the differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients. We conducted a cohort study of 435 patients following PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m . Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low- and high-natural logarithmic RHI (Ln-RHI) group. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, hospitalization due to unstable angina pectoris, and coronary revascularization. A total of 56 patients had a cardiovascular event. Patients who suffered a cardiovascular event had significantly lower Ln-RHI than other patients in the non-CKD group (0.46 ± 0.18 versus 0.60 ± 0.25; P = 0.002). Kaplan–Meier analysis demonstrated a significantly higher probability of cardiovascular events in low Ln-RHI patients in the non-CKD group (log-rank test: P = 0.003). Multivariate Cox proportional hazards analysis identified Ln-RHI as an independent and significant predictor of future cardiovascular events in the non-CKD group (HR: 0.096; 95 % CI 0.02–0.47; P = 0.004) but not in the CKD group. There was a differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients, and peripheral endothelial dysfunction significantly correlates with subsequent cardiovascular events after PCI in non-CKD patients. 2
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Sueta D., Kaikita K., Okamoto N., Yamabe S., Ishii M., Arima Y., Ito M., Oimatsu Y., Iwashita S., Takahashi A., Sakamoto K., Tsujita K., Nakamura E., Hokimoto S., Mizuta H., Ogawa H.
Clinical Trials and Regulatory Science in Cardiology 19 1 - 4 2016年7月
担当区分：責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Clinical Trials and Regulatory Science in Cardiology
Background Deep vein thrombosis (DVT) after total knee arthroplasty (TKA) often results in a fatal pulmonary thromboembolism (PTE). Edoxaban is an activated factor X inhibitor, which has been shown to prevent thromboembolic events in venous thromboembolism (VTE). Recently, the Total-Thrombus-formation Analysis System (T-TAS™), a microchip-based flow chamber system capable of evaluating thrombogenicity, was developed. In this study, utilizing the T-TAS™, we will examine the incidence of VTE after TKA and evaluate how thromboses form. Methods/design This study will be a prospective, single-center, open-label, randomized, controlled clinical trial aimed at exploring the efficacy of edoxaban in reducing the incidence of VTE after TKA. A total of 80 patients who will undergo TKA will be randomly and evenly divided into groups receiving edoxaban plus physiotherapy or physiotherapy alone. The primary outcome measures will include the incidence rate of VTE as detected by ultrasonography 7 days after TKA and the changes in T-TAS™ parameters. The secondary outcome measures will include the changes in prothrombin time and activated partial thromboplastin time, incidence of major/minor bleeding events and adverse effects of edoxaban. Discussion This study will provide clinical evidence on the combined efficacy and safety of edoxaban and physiotherapy compared with that of physiotherapy alone. This is will be the first prospective trial designed to explore how thrombus formation after TKA can be predicted by the T-TAS™.
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Hokimoto S., Tabata N., Sueta D., Akasaka T., Tsujita K., Sakamoto K., Kaikita K., Kojima S., Ogawa H.
Journal of Cardiology 68 ( 1 ) 20 - 28 2016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：Journal of Cardiology
Background: It is unknown to what extent coronary spasm affects cardiovascular events after percutaneous coronary intervention (PCI) in clinical practice. The aim was to examine the prevalence of cardiovascular events related to coronary spasm following PCI according to stent type. Methods: We enrolled 933 consecutive patients treated with coronary stent implantation, including bare metal stents (BMS; n = 238), first-generation drug-eluting stents (1st DES; n = 185), and second-generation DES (2nd DES; n = 510). We compared stent-oriented endpoints (SOEs; stent thrombosis, target vessel myocardial infarction or unstable angina, target lesion revascularization, and cardiac death) and the differences in SOE related to coronary spasm across stent types. Among the SOEs, spasm-related cardiac event was defined based on JCS guideline. Results: The prevalence of SOE for each stent type was 16.8% (BMS), 16.8% (1st DES), and 7.8% (2nd DES) (p < 0.001) and the rates of cardiovascular events related to coronary spasm were 2.9%, 3.2%, and 0.4%, respectively (p = 0.005). Multivariate analysis identified the non-use of statin (HR, 0.275, 95% CI, 0.087-0.871, p = 0.028) and non-use of 2nd DES (hazard ratio, 0.196, 95% confidence interval, 0.043-0.887, p = 0.034) as independent predictors of cardiac events related to coronary spasm. Conclusion: The prevalence of cardiovascular events related to coronary spasm was the lowest in patients with 2nd DES. The 2nd DES may be more efficacious and safer from the point of view of the reduction of cardiac events due to coronary spasm during statin therapy.
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Tabata N., Hokimoto S., Akasaka T., Sueta D., Arima Y., Sakamoto K., Yamamoto E., Izumiya Y., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Morita K., Oniki K., Saruwatari J., Nakagawa K., Ogawa H.
International Journal of Cardiology 212 54 - 56 2016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：International Journal of Cardiology
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Komura N., Tsujita K., Yamanaga K., Sakamoto K., Kaikita K., Hokimoto S., Iwashita S., Miyazaki T., Akasaka T., Arima Y., Yamamoto E., Izumiya Y., Yamamuro M., Kojima S., Tayama S., Sugiyama S., Matsui K., Nakamura S., Hibi K., Kimura K., Umemura S., Ogawa H.
Journal of the American Heart Association 5 ( 6 ) 2016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 the American Heart Association
Background--Drug-eluting stents are replacing bare-metal stents, but in-stent restenosis (ISR) remains a problem. Reactive hyperemia index (RHI) assessed by peripheral arterial tonometry evaluates endothelial function noninvasively. We prospectively assessed the prognostic value of RHI in predicting ISR after percutaneous coronary intervention. Methods and Results--RHI was measured before percutaneous coronary intervention and at follow-up (F/U) angiography (F/U RHI; 6 and 9 months post bare-metal stents- and drug-eluting stents- percutaneous coronary intervention, respectively) in 249 consecutive patients. At F/U, ISR (stenosis > 50% of diameter) was seen in 68 patients (27.3%). F/U natural logarithm (RHI) was significantly lower in patients with ISR than in those without (0.52±0.23 versus 0.65±0.27, P < 0.01); no between-group difference in initial natural logarithm (RHI) (0.60±0.26 versus 0.62±0.25, P=0.56) was seen. By multivariate logistic regression analysis, even after adjusting for other significant parameters in univariate analysis, F/U natural logarithm (RHI) independently predicted ISR (odds ratio: 0.13; 95% CI: 0.04-0.48; P=0.002). In receiver operating-characteristic analysis, F/U RHI was the strongest predictor of ISR (area under the curve: 0.67; 95% CI: 0.60-0.75; P < 0.01; RHI < 1.73 had 67.6% sensitivity, 64.1% specificity); area under the curve significantly improved from 0.62 to 0.70 when RHI was added to traditional ISR risk factors (P=0.02). Net reclassification index was significant after addition of RHI (26.5%, P=0.002). Conclusions--Impaired RHI at F/U angiography independently correlated with ISR, adding incremental prognostic value to the ISRrisk stratification following percutaneous coronary intervention.
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More haste, less speed: Cardiac perforation by a thoracentesis catheter 査読あり
Sueta D., Hokimoto S., Okamoto K., Yasuda H., Usuku H., Tazume H., Yamamoto E., Sakamoto K., Izumiya Y., Tsujita K., Kaikita K., Sakaguchi H., Fukui T., Ogawa H.
IJC Heart and Vasculature 11 17 - 18 2016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：IJC Heart and Vasculature
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Akasaka T., Hokimoto S., Sueta D., Tabata N., Sakamoto K., Yamamoto E., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Kajiwara A., Morita K., Oniki K., Saruwatari J., Nakagawa K., Ogata Y., Ogawa H.
American Journal of Physiology - Heart and Circulatory Physiology 310 ( 11 ) H1494 - H1500 2016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：American Journal of Physiology - Heart and Circulatory Physiology
Categorization as a cytochrome P-450 (CYP) 2C19 poor metabolizer (PM) is reported to be an independent risk factor for cardiovascular disease. It is correlated with an increase in the circulating levels of high-sense C-reactive protein (hs-CRP) in women only, although its role in coronary microcirculation is unclear. We examined sex differences in the impact of the CYP2C19 genotype and low-grade inflammation on coronary microvascular disorder (CMVD). We examined CYP2C19 genotypes in patients with CMVD (n = 81) and in healthy subjects as control (n = 81). CMVD was defined as the absence of coronary artery stenosis and epicardial spasms, the presence of inverted lactic acid levels between the intracoronary and coronary sinuses, or an adenosine triphosphate-induced coronary flow reserve ratio < 2.5. CYP2C19 PMs have two loss-of-function (LOF) alleles (*2, *3). Extensive metabolizers have no LOF alleles, and intermediate metabolizers have one LOF allele. The ratio of CYP2C19 PM and hs-CRP levels in CMVD was significantly higher than that of controls, especially in women (40.9 vs. 13.8%, P = 0.013; 0.11 ± 0.06 vs. 0.07 ± 0.04 mg/dl, P = 0.001). Moreover, in each CYP2C19 genotype, hs-CRP levels in CMVD in CYP2C19 PMs were significantly higher than those of the controls, especially in women (0.15 ± 0.06 vs. 0.07 ± 0.03, P = 0.004). Multivariate analysis for CMVD indicated that the female sex, current smoking, and hypertension were predictive factors, and that high levels of hs-CRP and CYP2C19 PM were predictive factors in women only (odds ratio 3.5, 95% confidence interval 1.26–9.93, P = 0.033; odds ratio 4.1, 95% confidence interval 1.15–14.1, P = 0.038). CYP2C19 PM genotype may be a new candidate risk factor for CMVD via inflammation exclusively in the female population.
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Yamamura S., Fujisue K., Tsujita K., Sakamoto K., Miyazaki Y., Kaikita K., Hokimoto S., Ogawa H.
BMC Cardiovascular Disorders 16 ( 1 ) 116 2016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：BMC Cardiovascular Disorders
Background: Stent malapposition, stent fracture, and deformity, and inadequate anti-thrombotic therapy are known as the risk of stent thrombosis. We report a case of stent deformation with subsequent thrombus adhesion at the site of a partial stent fracture detected by intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Case presentation: A 61-year-old male patient was diagnosed as effort angina pectoris. Coronary angiography revealed obstructions in the proximal segment of the left anterior descending (LAD) and left circumflex artery (LCx). Elective percutaneous coronary intervention (PCI) was scheduled for these lesions in the prior hospital. First, an everolimus-eluting stent (EES) was implanted in the just proximal LAD slightly protruding into left main trunk. One week later, the treatment to residual obstruction at proximal LCx was attempted. During delivery of the stent to LCx, the proximal edge of the previously-implanted LAD stent got stuck with the newly-deploying stent and deformed into the intravascular lumen when retracting the stent into the guide-catheter. He was immediately transferred to our hospital to repair these procedural problems. Two days later after the index procedure to LCx, intracoronary imaging with an IVUS and OCT were performed, and the IVUS/OCT imaging revealed thrombus adhesion around the deformed struts. The three-dimensional OCT guide also helped the detection of the deformed stent and the repair of deformed struts by additional stenting and kissing balloon technique. Conclusion: The current case suggested that thrombus adhesion can occur at the site of deformed and/or fractured stent at very early phase after stent implantation.
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Tabata N., Hokimoto S., Akasaka T., Sueta D., Arima Y., Sakamoto K., Yamamoto E., Izumiya Y., Yamamuro M., Tsujita K., Kojima S., Kaikita K., Morita K., Oniki K., Saruwatari J., Nakagawa K., Yamabe H., Matsui K., Ogawa H.
Clinical Trials and Regulatory Science in Cardiology 17 9 - 14 2016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：Clinical Trials and Regulatory Science in Cardiology
Background Host genetic factors of interleukin (IL)-1 polymorphisms influence Helicobacter pylori infection pathogenic activity. We examined whether H. pylori-infected patients with IL-1 polymorphisms are associated with myocardial infarction (MI). Materials and methods We recruited 594 consecutive coronary artery disease patients and excluded those who met exclusion criteria. After matching age and sex, 82 cases with MI and 82 controls were enrolled. Immunoglobulin G antibodies against H. pylori and IL-1 polymorphisms (IL-1 beta-511 base pairs and IL-1 receptor antagonist) were analyzed. We assessed high sensitivity C-reactive protein (hs-CRP) level and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index (RHI) using the EndoPAT2000 system. Results The simultaneous prevalence of H. pylori-seropositivity and IL-1 polymorphisms was 45.1% and 19.5% in the cases and controls, respectively (P = 0.001). H. pylori-positive patients with IL-1 polymorphisms showed significantly higher serum levels of natural logarithm of hs-CRP in the cases and controls (- 2.8 ± 1.0 vs. - 3.4 ± 0.6, respectively; P = 0.003 and - 2.8 ± 0.9 vs. - 3.2 ± 0.6, respectively; P = 0.02) and significantly lower levels of natural logarithm of RHI in the cases and controls (0.51 ± 0.13 vs. 0.61 ± 0.23, respectively; P = 0.039 and 0.47 ± 0.13 vs. 0.69 ± 0.23, respectively; P = 0.005). H. pylori-seropositivity with IL-1 polymorphisms was significantly associated with MI by logistic regression analysis (odds ratio, 4.83; 95% confidence interval, 1.99-11.7; P < 0.001). Conclusions H. pylori-positive patients with IL-1 polymorphisms showed higher levels of hs-CRP and lower levels of RHI, and were significantly correlated with the MI.
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Impact of Statin Therapy on Clinical Outcome in Patients With Coronary Spasm 査読あり
Ishii M., Kaikita K., Sato K., Yamanaga K., Miyazaki T., Akasaka T., Tabata N., Arima Y., Sueta D., Sakamoto K., Yamamoto E., Tsujita K., Yamamuro M., Kojima S., Soejima H., Hokimoto S., Matsui K., Ogawa H.
Journal of the American Heart Association 5 ( 5 ) 2016年5月
担当区分：責任著者 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: Statin therapy reduces the risk of cardiovascular events in patients with obstructive coronary artery disease. The aim of the present study was to determine the effects of statins on the prognosis of patients with coronary vasospastic angina (VSA) free of significant atherosclerotic stenosis. Methods and Results: After exclusion of 475 from 1877 consecutive patients who underwent an acetylcholine-provocation test between January 1991 and December 2010, data of 640 VSA patients without significant organic stenosis of the remaining 1402 were analyzed retrospectively. Propensity score matching was performed to reduce the effect of treatment-selection bias and possible confounders. The primary endpoint was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and unstable angina. Among the study population, dyslipidemia on admission was identified in 160 of 168 (95.2%) patients of the statin group compared with only 125 of 472 (26.5%) of the no-statin group. Of the 640 patients, 24 (3.8%) developed MACE. Multivariate Cox hazard regression analysis identified statin therapy as a significant negative predictor of MACE (hazard ratio, 0.11; 95% CI, 0.02-0.84; P=0.033). In the propensity-score matched cohorts (n=128 each), Kaplan-Meier survival curve showed a better 5-year MACE-free survival rate for patients of the statin group compared to the no-statin group (100% vs 91.7%, respectively; P=0.002). Conclusions: Statin therapy correlated with a lower rate of cardiovascular events in VSA patients free of significant organic stenosis. Statins seems to improve the prognosis of VSA patients free of significant organic stenosis.
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Arima Y., Kaikita K., Ishii M., Ito M., Sueta D., Oimatsu Y., Sakamoto K., Tsujita K., Kojima S., Nakagawa K., Hokimoto S., Ogawa H.
Journal of Thrombosis and Haemostasis 14 ( 4 ) 850 - 859 2016年4月
担当区分：責任著者 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 Thrombosis and Haemostasis
Background: Accurate evaluation of thrombogenicity helps to prevent thrombosis and excessive bleeding. The total thrombus-formation analysis system (T-TAS) was developed for quantitative analysis of platelet thrombus formation by the use of microchips with thrombogenic surfaces (collagen, platelet chip [PL-chip]; collagen plus tissue factor, atherome chip [AR-chip]). We examined the utility of the T-TAS in the assessment of the efficacy of antiplatelet therapy in patients with coronary artery disease (CAD). Methods and Results: In this cross-sectional study, 372 consecutive patients admitted to the cardiovascular department were divided into three groups: patients not receiving any antiplatelet therapy (control, n = 56), patients receiving aspirin only (n = 69), and patients receiving aspirin and clopidogrel (n = 149). Blood samples were used for the T-TAS to measure the platelet thrombus-formation area under the curve (AUC) at various shear rates (1500 s [PL -AUC ] and 2000 s [PL -AUC ] for the PL-chip; 300 s [AR -AUC ] for the AR-chip). The on-clopidogrel platelet aggregation was measured by the use of P2Y12 reaction units (PRUs) with the VerifyNow system. The mean PL -AUC levels were 358 ± 111 (± standard deviation) (95% confidence interval [CI] 328.9-387.1) in the control group, 256 ± 108 (95% CI 230.5-281.5) in the aspirin group, and 113 ± 91 (95% CI 98.4-127.6) in the aspirin/clopidogrel group. In the aspirin/clopidogrel group, the PL -AUC was higher in poor metabolizers (PMs) with cytochrome P450 2C19(CYP2C19) polymorphisms (152 ± 112, 95% CI 103.4-200.6) than in the non-PM group (87 ± 74, 95% CI 73.8-100.2). Conclusions: Our findings suggest that the PL -AUC level measured by the T-TAS is a potentially suitable index for the assessment of antiplatelet therapy in CAD patients. -1 -1 -1 18 10 24 10 10 30 24 10 24 10 24 10
DOI： 10.1111/jth.13256
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Fragmented QRS complex is a diagnostic tool in patients with left ventricular diastolic dysfunction 査読あり
Onoue Y., Izumiya Y., Hanatani S., Kimura Y., Araki S., Sakamoto K., Yamamoto E., Tsujita K., Tanaka T., Yamamuro M., Kojima S., Kaikita K., Hokimoto S., Ogawa H.
Heart and Vessels 31 ( 4 ) 563 - 567 2016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：Heart and Vessels
Fragmented QRS complex (fQRS) on 12-lead ECG is associated with myocardial fibrosis and ischemic scar. Interstitial fibrosis is one of the histological characteristics of left ventricular diastolic dysfunction (LVDD). However, the clinical importance of fQRS in patients with LVDD remains unclear. Here, we assessed the hypothesis that the presence of fQRS is associated with disease severity in patients with LVDD, and could be used as an additional parameter to differentiate patients with heart failure with preserved ejection fraction (HFpEF) from LVDD. We analyzed 12-lead ECG of 239 patients with LVDD. The patients were divided into two groups according to the presence or absence of fQRS; 88 patients had fQRS (fQRS group) and 151 patients did not have fQRS (non-fQRS group). The percentage of patients with heart failure in the fQRS group was significantly higher than that in the non-fQRS group. The levels of B-type natriuretic peptide (BNP) and high-sensitive troponin T were significantly higher in the fQRS group than those in the non-fQRS group. In univariate logistic regression analysis, fQRS was associated with the presence of heart failure in patients with LVDD. Multivariate logistic regression analysis identified fQRS and BNP as independent indicators for HFpEF. In conclusion, the presence of fQRS on the ECG could be used as an additional tool to differentiate HFpEF from LVDD.
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Ogura Y., Tsujita K., Shimomura H., Yamanaga K., Komura N., Miyazaki T., Ishii M., Tabata N., Akasaka T., Arima Y., Sakamoto K., Kojima S., Nakamura S., Kaikita K., Hokimoto S., Ogawa H.
Heart and Vessels 31 ( 3 ) 341 - 350 2016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：Heart and Vessels
Acute coronary syndrome (ACS) is one of the main causes of cardiovascular death. According to rapid aging of society, the peak age of ACS onset has grown older globally. Despite growing recognition of the necessity to build the ACS prevention strategy in the elderly, patients background and culprit lesion morphology of these elderly ACS patients have not been well studied. We sought to assess the clinical characteristics and intravascular ultrasound (IVUS) findings of the culprit lesions in elderly ACS patients. One-hundred and fifty-eight consecutive ACS patients whose culprit lesions imaged by pre-intervention IVUS were divided into two groups based on the age of onset: elderly [E] group (≥75 years, n = 65) and non-elderly [NE] group (<75 years, n = 93). As compared with NE group, hemoglobin (12.7 ± 2.0 g/dL vs. 13.7 ± 1.6 g/dL, p = 0.001), estimated glomerular filtration rate (62.5 ± 22.5 mL/min/1.73 m vs. 75.5 ± 20.5 mL/min/1.73 m , p = 0.0001), and body mass index (22.9 ± 3.4 kg/m vs. 24.5 ± 3.4 kg/m , p = 0.003) were significantly lower, and comorbid malignancy was more common (20.0 vs 6.5 %, p = 0.01) in E group. Although whole culprit segment was not positively remodeled (mean vessel area was 15.2 ± 5.6 mm /mm vs. 16.2 ± 5.1 mm /mm, p = 0.16) in E group, at maximum external elastic membrane site of the culprit lesion, lumen area was smaller (5.5 ± 3.2 mm vs. 6.7 ± 3.5 mm , p = 0.04), and plaque burden tended to be more abundant (70 ± 13 vs. 66 ± 13 %, p = 0.08). Interestingly, echo attenuation arc of culprit attenuated plaque was significantly greater in E group than in NE group (157 ± 83° vs. 118 ± 60°, p = 0.01). In conclusion, extracardiac comorbidity was more common in elderly ACS patients, and their culprit coronary lesions were still rupture prone, and “vulnerable.” 2 2 2 2 3 3 2 2
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New aspects of onco-cardiology 査読あり
Sueta D., Hokimoto S., Utsunomiya D., Tabata N., Akasaka T., Sakamoto K., Tsujita K., Kaikita K., Yamashita Y., Ogawa H.
International Journal of Cardiology 206 68 - 70 2016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：International Journal of Cardiology
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Yamamoto E., Hirata Y., Tokitsu T., Kusaka H., Tabata N., Tsujita K., Yamamuro M., Kaikita K., Watanabe H., Hokimoto S., Maruyama T., Ogawa H.
ESC Heart Failure 3 ( 1 ) 53 - 59 2016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：ESC Heart Failure
Aims: Although inflammation plays an important role in the pathogenesis of heart failure (HF), the precise pathophysiological role of inflammation in HF with preserved left ventricular ejection fraction (HFpEF) still remains unclear. Hence, we examined the clinical significance of plasma neopterin, an inflammatory biomarker, in HFpEF patients. Methods and results: In the present study, we recruited consecutive HFpEF patients hospitalized in Kumamoto University Hospital, and further measured plasma neopterin by high-performance liquid chromatography and serum derivatives of reactive oxidative metabolites (DROM), a new biomarker of reactive oxygen species. Compared with risk factors (number of patients, age, sex, and equal incidence of diabetes mellitus, hypertension, and dyslipidemia) -matched non-HF patients (n = 68), plasma neopterin levels, but not serum high-sensitivity C-reactive protein levels, were significantly increased in patients with HFpEF (n = 68) (P < 0.001 and P = 0.15, respectively), accompanied by an elevation in serum DROM levels (P < 0.001). Plasma neopterin levels in New York Heart Association (NYHA) class III/IV HFpEF patients were significantly higher than in NYHA class II patients (P < 0.004). Furthermore, plasma ln-neopterin levels had significant and positive correlation with ln-DROM values (r = 0.57) and parameters of cardiac diastolic dysfunction [the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (r = 0.34), left atrial volume index (r = 0.17), and B-type natriuretic peptide (r = 0.38)]. Kaplan–Meier analysis showed that the high-neopterin group (>51.5 nM: median value of neopterin in HFpEF patients) had a higher probability of cardiovascular events than the low-neopterin group (log-rank test, P = 0.003). Conclusions: Plasma neopterin levels significantly increased in HFpEF and correlated with the severity of HF. Furthermore, high neopterin were significantly correlated with future cardiovascular events, indicating that measurement of plasma neopterin might provide clinical benefits for risk stratification of HFpEF patients. © 2015 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
DOI： 10.1002/ehf2.12070