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A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Effect of urate-lowering on renal outcomes in patients at high-risk for cardiovascular disease with hyperuricemia without gout is not known. We conducted a post hoc analysis of a randomized trial (Febuxostat for Cerebral and　CaRdiorenovascular Events PrEvEntion StuDy [FREED]). The FREED trial enrolled 1070 asymptomatic, hyperuricemic elderly patients with at least one risk factor for cardiovascular disease, divided into febuxostat (n = 537) and non-febuxostat (n = 533) groups. We compared the effect of these treatments on renal outcomes including 40% decline in estimated glomerular filtration rate, new onset of microalbuminuria and development or worsening macroalbuminuria. The relative risk of developing or worsening macroalbuminuria was 56% lower in the febuxostat group (hazard ratio, 0.44; 95% CI, 0.24-0.82; P = 0.0098). However, the risks for other outcomes were comparable. In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of development or worsening of macroalbuminuria., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events., Methods and results: A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole., Conclusions: Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records (1,800,255 patients) at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9% (32,686 records) had cerebrovascular disease as a comorbidity and 2.1% (11,362 records) included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06-1.14], 2.02 [1.91-2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7% (63,647 records) had cardiovascular disease listed as comorbidity and 3.3% (11,834 records) as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality (adjusted OR [95% confidence interval]: 1.29 [1.22-1.37]). In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial., Competing Interests: Dr. Iihara reports personal fees and other funding from Megwell, personal fees from Daiichi Sankyo. Co. Ltd., personal fees from Otsuka Pharmaceutical, and grants from Idorsia Pharmaceuticals Japan outside of the submitted work. Dr. Komuro reports grants and personal fees from Daiichi Sankyo Company, Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from Takeda Pharmaceutical Company Ltd., grants from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma Ltd., grants from Idorsia Pharmaceuticals Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Toa Eiyo Ltd., and personal fees from AstraZeneca, and personal fees from Pfizer Japan Inc. outside of the submitted work. Dr. Matoba reports grants and personal fees from Bayer Yakuhin, Ltd., grants from Amgen, personal fees from Merck & Co., Inc., and personal fees from Abbott Vascular outside of the submitted work. Dr. Nishimura reports personal fees from Philips Japan, Ltd., personal fees from Tokyo Electric Power Company, personal fees from Terumo Company, and personal fees from H.U. group holdings outside of the submitted work. Dr. Nakayama reports personal fees from Pfizer Japan Inc, AstraZeneca K.K., Astellas Pharma Inc., Toppan Forms Co., InterSystems Corporation, Fujitsu Research Institute, Nikkei Business Publications, Inc., NIHON KOHDEN Co., FUKUDA DENSHI, Deloitte Tohmatsu Consulting LLC, and PwC Consulting LLC, outside of the submitted work. Dr. Toyoda reports personal fees from Daiichi-Sankyo, personal fees from Bayer Yakuhin, personal fees from Bristol-Myers-Squibb, personal fees from Outsuka Pharmaceutical Company Ltd., personal fees from Novartis Pharma Japan., and personal fees from Abbott Medical Japan Co., Ltd.,outside of the submitted work. Dr. Tsujita reports personal fees from Amgen K.K., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Pfizer Japan Inc., grants from AMI Co., Ltd., grants from Bristol-Myers K.K., grants from EA Pharma Co. Ltd., grants from Mochida Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim, grants from Chugai Pharmaceutical Co., Ltd., grants from Edwards Lifesciences Corporation., grants from Johnson & Johnson K.K., grants from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., other funding from Abbott Japan Co., Ltd., other funding from Boston Scientific Japan K.K., other funding from Fides-one, Inc., other funding from ITI Co., Ltd., other funding from Kaneka Medix Co., Ltd., other funding from Nipro Corporation, other funding from Terumo Co., Ltd., other funding from Abbott Medical Co., Ltd., other funding from Cardinal Health Japan, other funding from Fides-one, Inc., other funding from Fukuda Denshi Co., Ltd., other funding from Japan Lifeline Co., Ltd., other funding from Medical Appliance Co., Ltd., and other funding from Medtronic Japan Co., Ltd. outside of the submitted work. Dr. Yasuda reports personal fees from Bristol-Meyers, grants and personal fees from Bayer, personal fees from Daiichi-Sankyo, grants and other funding from Takeda Pharmaceutical Company Ltd., grants from NEC, grants from Daiichi-Sankyo, grants and other funding from Abbott, other funding from Terumo Co., Ltd., other funding from Nihon Kohden, other funding from Medtronic, other funding from Japan Lifeline, other funding from Otsuka, other funding from Ono, other funding from Nippon Boehringer Ingelheim, other funding from Kowa, other funding from Zeon, other funding from Shionogi, other funding from Nippon-Shinyaku, other funding from Mochida, and other funding from Tesco outside of the submitted work. Dr. Miyamoto reports personal fees from Tokyo Marine, personal fees from Nichido Fire Insurance Co., Ltd., personal fees from Fujitsu Co., Ltd., personal fees from Softbank Co., Ltd., personal fees from Meiji Yasuda Life Insurance Company., and personal fees from Saraya Co., Ltd. outside of the submitted work. Dr. Ogawa reports personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., and personal fees from Novartis Pharma Co., Ltd., personal fees from Takeda Pharmaceutical Co., LTD, personal fees from Daiichisankyo Co., Ltd., personal fees from Eisai Co., Ltd., personal fees from Teijin Co., Ltd. personal fees from Behringer Ingelheim Co., Ltd., Abbott Medical Japan Co., Ltd. outside of the submitted work. No other potential conflict of interest relevant to this article was reported. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: We previously reported on the FREED study, which found that febuxostat reduced the risk of adverse clinical outcome in patients with asymptomatic hyperuricemia without gout. We have now investigated outcomes in subgroups of FREED patients with and without a history of cardiovascular disease (CVD)., Methods: We performed a post hoc subgroup analysis of 1070 patients randomized to the febuxostat or non-febuxostat group and followed for 36 months., Results: At baseline, 234 patients (21.9%) had a history of CVD, including 86 patients with stroke (36.8%), 90 with coronary artery disease (38.5%), 74 with heart failure (31.6%), and 25 with vascular disease (10.7%). The risk for the primary composite endpoint, i.e., cerebral, cardiovascular, and renal events and all deaths, was higher in patients with CVD than in those without CVD (34.2% vs 23.7%; p < 0.001). Treatment with febuxostat lowered rates of the primary composite endpoint in patients with CVD (hazard ratio [HR] 0.601, 95% CI 0.384 to 0.940, p = 0.026), and these effects were consistently observed in subgroups with and without CVD (p = 0.227 for treatment by subgroup interaction). Furthermore, in the subgroup with CVD, all-cause mortality was significantly lower in the febuxostat group than in the non-febuxostat group (HR 0.160, 95% CI 0.047 to 0.547, p = 0.004), with a significant subgroup interaction (p = 0.007 for treatment by subgroup interaction)., Conclusions: In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of the composite of cerebral, cardiovascular, and renal events and death in the secondary prevention setting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: Although the relationship between cardiovascular diseases and malignant diseases has recently attracted attention, the associations of cardiovascular risk factors and clinical outcomes in cancer patients remain to be elucidated. We performed a retrospective, observational study that explored the clinical outcomes of patients with cancer or with a history of cancer.We enrolled 30,706 consecutive adult cancer patients from Kumamoto University Hospital. We investigated mortality and morbidity, including cardiovascular conditions (dyslipidemia [DL]/diabetes mellitus [DM]/hypertension [HT]). The primary endpoint was all-cause mortality.Of the enrolled patients, 9032 patients (29.4%) died within the follow-up period. The Kaplan-Meier analysis demonstrated that in the groups classified according to the number of DL/DM/HT (LDH) factors, the LDH1 and LDH2 groups had a significantly higher probability of the primary endpoint than the LDH0 group (P < .001 and P < .001, respectively), whereas there were no significant differences between the LDH0 group and LDH3 group (P = .963). Univariate Cox proportional hazards regression analyses of mortality complemented by the multiple imputation method including various factors demonstrated that the presence of DL in cancer patients was a significant negative predictor of mortality (hazard ratio = 0.79, P < .01).The all-cause mortality rate did not always increase as the number of LDH factors increased. The present study revealed that the presence of DL is a negative risk factor for all-cause mortality in cancer patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Randomized clinical trials demonstrated the benefits of percutaneous coronary interventions (PCI) in diverse clinical settings. Patients with cancer were not routinely included in these studies., Methods/results: Literature search of PubMed, Cochrane, Medline, SCOPUS, EMBASE, and ClinicalTrials was conducted to identify studies that assessed one-year all-cause, cardiovascular and non-cardiovascular mortality in patients with historical or active cancer. Using the random effects model, we computed risk ratios (RRs) and standardized mean differences and their 95% confidence intervals for the dichotomous and continuous measures and outcomes, respectively. Of 171 articles evaluated in total, 5 eligible studies were included in this meta-analysis. In total, 33,175 patients receiving PCI were analyzed, of whom 3323 patients had cancer and 29,852 no cancer history. Patients in the cancer group had greater all-cause mortality [RR 2.22 (1.51-3.26; p<0.001)], including cardiovascular mortality [RR 1.34 (1.1-1.65; p=0.005)] and non-cardiovascular mortality [RR 3.42 (1.74-6.74; p≤0.001], at one-year compared to non-cancer patients. Patients in the cancer group had greater one-month all-cause mortality [RR 2.01 (1.24-3.27; p=0.005)] and greater non-cardiovascular mortality [RR 6.87 (3.10-15.21; p≤0.001)], but no difference in one-month cardiovascular mortality compared to non-cancer patients. Meta-regression analyses showed that the difference in one-year all-cause and cardiovascular mortality between both groups was not attributable to differences in baseline characteristics, index PCI characteristics, or medications prescribed at discharge., Conclusions: Patients with cancer undergoing PCI have worse mid-term outcomes compared to non-cancer patients. Cancer patients should be managed by a multi-specialist team, in an effort to close the mortality gap., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: The prediction of future heart failure (HF) in stable outpatients is often difficult for general practitioners and cardiologists. Recently, the H 2 FPEF score (0-9 points) has been proposed for the discrimination of HF with preserved ejection fraction from non-cardiac causes of dyspnoea. The six clinical and echocardiographic variables that constitute the H 2 FPEF score include the following: (i) obesity (H); (ii) the use of ≥2 antihypertensive drugs (H); (iii) atrial fibrillation (F); (iv) pulmonary hypertension (P); (v) an age > 60 years (E); and (vi) E/e' > 9 (F). We performed an external validation study that investigated whether the H 2 FPEF score could predict future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan., Methods and Results: In this prospective cohort study, after exclusion of 195 from 551 consecutive, stable Japanese outpatients with at least one cardiovascular risk factor who were enrolled between September 2010 and July 2013, the remaining 356 outpatients (171 men, 185 women, mean age 73.2 years) were eligible for the analysis. We calculated the H 2 FPEF score (0-9 points), and followed up the patients for an average of 517 days. In all of the 356 patients, the mean H 2 FPEF score was 3.1 ± 1.8, and 15 developed HF-related events during the follow-up period, including cardiovascular death (n = 2) and hospitalization for HF decompensation (n = 13). Multivariate Cox proportional hazards analysis showed that the H 2 FPEF score was an independent predictor of future HF-related events (P < 0.001 for all three models). Kaplan-Meier survival curves showed a significantly higher probability of HF-related events in the outpatients with a high H 2 FPEF score (P < 0.001). In receiver operating characteristic (ROC) curve analysis, the H 2 FPEF score was significantly associated with the occurrence of future HF-related events (P < 0.001). In ROC curve analysis, the sensitivity, specificity, and positive likelihood ratio of a H 2 FPEF score of 7 points to predict HF-related events were 47%, 96%, and 11.4%, respectively., Conclusions: The H 2 FPEF score could provide useful information for future HF-related events in stable outpatients with cardiovascular risk factor(s) in Japan., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Although attention has been paid to the relationship between malignant diseases and cardiovascular diseases, few data have been reported. Moreover, there have also been few reports in which the preventive factors were examined in patients with or without malignant disease histories requiring percutaneous coronary intervention (PCI).This was a retrospective, single-center, observational study. A total of 1003 post-PCI patients were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, revascularization, and admission due to heart failure within 5 years of PCI. Kaplan-Meier analysis showed a significantly higher probability of the primary endpoint in the malignant group (P = .002). Multivariable Cox hazard analyses showed that in patients without a history of malignant, body mass index (BMI) and the presence of dyslipidemia were independent and significant negative predictors of the primary endpoint (BMI: hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.53-0.99, P = .041; prevalence of dyslipidemia: HR 0.72, 95% CI 0.52-0.99, P = .048), and the presence of multi-vessel disease (MVD) and the prevalence of peripheral artery disease (PAD) were independent and significant positive predictors of the primary endpoint (prevalence of MVD: HR 1.68, 95% CI 1.18-2.40, P = .004; prevalence of PAD: HR 1.51, 95% CI 1.03-2.21, P = .034). In patients with histories of malignancy, no significant independent predictive factors were identified.Patients undergoing PCI with malignancy had significantly higher rates of adverse cardiovascular events but might not have the conventional prognostic factors.

Various antithrombotic agents are clinically used to inhibit the cascade of arterial or venous thrombosis in cardiovascular diseases. Dual antiplatelet therapy with aspirin and P2Y 12 inhibitors is prescribed in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Direct oral anticoagulants (DOACs) are widely used for the prevention or treatment of thromboembolism in patients with atrial fibrillation (AF) and venous thromboembolism. However, there has been no definitive tool to simultaneously monitor the antithrombotic effects of these drugs. The Total Thrombus-Formation Analysis System (T-TAS), a microchip-based flow chamber system that mimics in vivo conditions for evaluating whole blood thrombogenicity, was developed for the quantitative analysis of thrombus formation in whole blood specimens. The utility of T-TAS has been evaluated in CAD patients treated with antiplatelet therapies. The T-TAS PL chip area under the flow pressure curve (AUC) accurately assesses primary hemostasis and is sensitive to the therapeutic effects of various antiplatelet therapies. In addition, low AUC results are a significant predictor of periprocedural bleeding events in CAD patients undergoing PCI. The T-TAS AR chip AUC result is useful for assessing the efficacy of DOACs and warfarin in AF patients undergoing catheter ablation, and it is also a potential independent predictor of periprocedural bleeding events and avoidance of thrombosis in patients having undergone total knee arthroplasty. In conclusion, T-TAS is a useful index for evaluating the total antithrombotic effects of combination antithrombotic agents in patients with various cardiovascular diseases., Competing Interests: K.K. has received grants from Bayer Yakuhin, Ltd., Daiichi-Sankyo Co., Ltd., Novartis Pharma AG., and SBI Pharma K.K.; and honoraria from Bayer Yakuhin, Ltd. and Daiichi-Sankyo Co., Ltd. K.T. has received honoraria from Amgen, Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Daiichi-Sankyo Co., Ltd., MSD K.K., and Sanofi K.K.; and has received grants from AstraZeneca K.K., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Boston Scientific Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Eisai Co., Ltd., Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma, MSD K.K., Pfizer Japan Inc., Sanofi K.K., Shionogi & Co., Ltd., and Takeda Pharmaceutical Co., Ltd. J.R.D. has received consulting fees from Fujimori Kogyo, Co, Ltd. K.H. is an employee of Fujimori Kogyo, Co., Ltd., (Georg Thieme Verlag KG Stuttgart · New York.)

Aims: With the advancement in successfully treating different types of cancers, there is an immediate and increased need to focus on the risk and complexity of treating cardiovascular events in cancer survivors. This has led to the emergence of onco-cardiology/cardio-oncology field. We examined the varying incidence of cardiovascular events after percutaneous coronary intervention (PCI) in patients with or without cancer., Methods and Results: Participants were divided into a non-malignant group and a malignant group, consisting of patients who were receiving or had ever received cancer treatment. The primary endpoint was target lesion revascularization (TLR) within 1 year of PCI. In the patient groups studied, we showed that the malignant group had a significantly higher probability of TLR than the non-malignant group (P = 0.002). Moreover, proportional hazards analyses identified malignancy as an independent predictor of TLR [hazard ratio (HR) 2.28, 95% confidential interval (CI) 1.3-4.0; P = 0.004]. Combining malignancy status with high-sensitivity C-reactive protein levels further increased the HR for TLR (HR 3.01, 95% CI 1.57-5.76; P = 0.001), and the net reclassification improvement was significant (15.2%, 95% CI 4.3-26%; P = 0.02). Time since completion of cancer treatment had an impact on the rate of TLR, with those patients with a current or recent cancer history having more TLR events within 1 year., Conclusion: We demonstrated a significant association between the recent history of cancer and the risk of recurrent coronary atherosclerosis in patients undergoing PCI and showed that malignancy status can predict the likelihood of cardiovascular events following this procedure.

Background: Sarcopenia is frequently observed and associated with poor outcomes in patients with chronic kidney disease (CKD). A simple screening test for sarcopenia using age, grip strength, and calf circumference was recently developed. However, the clinical utility of this sarcopenia score in patients with CKD remains unclear., Methods and Results: We calculated the sarcopenia score of 265 patients with CKD and followed the patients for cardiovascular events. The endpoint of this study was the composite of cardiovascular hospitalization and total mortality. We divided all participants into high (n = 166) and low (n = 99) sarcopenia score groups using a simple scoring system. Patients in the high sarcopenia score group showed significantly higher plasma B-type natriuretic peptide (BNP) levels than those in the low sarcopenia score group (median: 103.1, interquartile range: 46.3-310.0 vs. 46.7, 18.0-91.8 pg/mL; p < 0.0001). The Kaplan-Meier curve revealed that the risk of cardiovascular events was significantly greater in the high sarcopenia score group (log-rank test: p < 0.0001), even after potential confounding factors were corrected using propensity score matching. Multivariate Cox hazard analysis identified a high sarcopenia score (hazard ratio: 3.04, 95% confidence interval: 1.45-6.38, p = 0.003) as an independent predictor of the primary endpoints. Furthermore, the combination of a high sarcopenia score and high BNP level identified patients with a significantly higher probability of future events (p < 0.0001)., Conclusions: This study demonstrates that this simple screening score for sarcopenia could be a useful tool for estimating the future adverse event risk in patients with CKD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to examine the cardiovascular protective effects of candesartan in patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs)., Background: Candesartan has been reported to reduce cardiovascular events when therapy was started 6 months after PCI with bare-metal stents in patients who survived restenosis. Candesartan started immediately after PCI with DESs was also effective in preventing cardiovascular events., Methods: The 4C trial was a multicenter, prospective, randomized, open-label study. A total of 1145 patients at 39 centers in Japan were randomly assigned to receive candesartan plus standard medical treatment or standard medical treatment alone. The primary endpoints were all-cause death, and a composite of non-fatal myocardial infarction (MI), unstable angina pectoris (uAP), congestive heart failure (CHF), and non-fatal cerebrovascular events. The follow-up period was up to 3 years after the index PCI (ClinicalTrials.gov NCT00139386)., Results: The incidence of total death, one of the primary endpoints, was comparable between the two treatment groups (3.8% each, p=0.9702). Another primary endpoint, non-fatal major cardiovascular events, tended to occur more often in the control group than in the candesartan group (9.2% vs. 12.5%, p=0.0985). In contrast, candesartan significantly reduced one of the pre-specified secondary endpoints: cardiovascular events that included non-fatal MI, uAP, and CHF (4.4% vs. 6.7%, p=0.0136). Furthermore, candesartan significantly reduced another secondary endpoint that included cardiovascular events and cardiovascular death (5.0% vs. 7.7%, p=0.0493)., Conclusions: The 4C trial showed that candesartan administered immediately after PCI with DESs did not improve the prognosis after the index procedure, but did reduce some cardiac-related events for 3 years., (Copyright © 2015. Published by Elsevier Ltd.)

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 10  mmHg of IAD was independently associated with future cardiovascular events. Assessing IAD by ABI measurement may facilitate risk stratification in CAD patients.

Aims To provide multi-national, multi-ethnic data on the clinical characteristics and prognosis of patients with microvascular angina (MVA). Methods and results The Coronary Vasomotor Disorders International Study Group proposed the diagnostic criteria for MVA. We prospectively evaluated the clinical characteristics of patients according to these criteria and their prognosis. The primary endpoint was the composite of major cardiovascular events (MACE), verified by institutional investigators, which included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization due to heart failure or unstable angina. During the period from 1 July 2015 to 31 December 2018, 686 patients with MVA were registered from 14 institutes in 7 countries from 4 continents. Among them, 64% were female and the main ethnic groups were Caucasians (61%) and Asians (29%). During follow-up of a median of 398 days (IQR 365–744), 78 MACE occurred (6.4% in men vs. 8.6% in women, P = 0.19). Multivariable Cox proportional hazard analysis disclosed that hypertension and previous history of coronary artery disease (CAD), including acute coronary syndrome and stable angina pectoris, were independent predictors of MACE. There was no sex or ethnic difference in prognosis, although women had lower Seattle Angina Questionnaire scores than men (P < 0.05). Conclusions This first international study provides novel evidence that MVA is an important health problem regardless of sex or ethnicity that a diagnosis of MVA portends a substantial risk for MACE associated with hypertension and previous history of CAD, and that women have a lower quality of life than men despite the comparable prognosis. [ABSTRACT FROM AUTHOR]

BACKGROUND While there is a concern about the increase in the occurrence of acute aortic dissection (AAD) caused by the worsening of hypertension, mental stress, etc., there is a lack of data regarding the influence of disasters on this event. The aim of this study was to address this issue in the acute–subacute phase after the Kumamoto Earthquake occurred on 14 April 2016. METHODS We retrospectively investigated the impacts of the Kumamoto Earthquake on various cardiovascular diseases, including AAD, utilizing the medical records of patients in 16 hospitals in Kumamoto Prefecture during the period from 14 April to 30 June (78 days) in 2014, 2015, 2016, and 2017. RESULTS The occurrence of heart failure and venous thromboembolism increased significantly in the acute–subacute phase after the earthquake. When comparing the earthquake year (2016) to the non-earthquake years (2014, 2015, and 2017), the difference in the occurrences and mortalities of AADs were not significant. When other characteristics of the patients were compared between the earthquake year and the non-earthquake years, there were no differences. CONCLUSIONS It might be possible that the Kumamoto Earthquake did not affect the incidence of AAD or deaths from AAD, possibly because the climate was mild and the preventive efforts based on previous experience were successful. REGISTRATION University Hospital Medical Information Network (UMIN)-CTR (http://www.umin.ac.jp/ctr/). IDENTIFIER UMIN000023864. PUBLIC ACCESS INFORMATION Opt-out materials were available at the following website: http://www.kumadai-junnai.com/home/wp-content/uploads/shinsai.pdf. [ABSTRACT FROM AUTHOR]

Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50 months. The primary and secondary endpoints were composite cardiovascular/cerebrovascular events (cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation, and nonfatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50 months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events among those with a higher H2FPEF score (log-rank test, P = 0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P < 0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (hazard ratio [HR], 1.179; 95% confidence interval [CI], 1.066–1.305; P = 0.001 and HR, 1.288; 95% CI, 1.134–1.463; P = 0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (area under the curve [AUC], 0.626; 95% CI, 0.557–0.693; P < 0.001) and HF-related events (AUC, 0.680; 95% CI, 0.600–0.759; P < 0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score might be a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients. Clinical Trails Registration Trail Number UMIN000029600. [ABSTRACT FROM AUTHOR]

Background Despite standard statin therapy, a majority of patients retain a high “residual risk” of cardiovascular events. Objectives The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention (PCI). Methods This trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol (LDL-C) <70 mg/dl. Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients. Results The combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy (63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl; p < 0.001). For the absolute change in percent atheroma volume (PAV), the mean difference between the 2 groups (–1.538%; 95% confidence interval [CI]: –3.079% to 0.003%) did not exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual lipid-lowering strategy (–1.4%; 95% CI: –3.4% to –0.1% vs. –0.3%; 95% CI: –1.9% to 0.9% with atorvastatin alone; p = 0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary plaque regression (78% vs. 58%; p = 0.004). Both strategies had acceptable side effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. Conclusions Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition–induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380 ) [ABSTRACT FROM AUTHOR]

Summary: Background: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the pathogenesis of acute coronary syndrome. We have recently demonstrated that the administration of edaravone before reperfusion attenuated reperfusion injury in patients with acute myocardial infarction (AMI). Methods: Plasma MCP-1 levels were measured in 45 consecutive patients with AMI (edaravone group, n =25; control group, n =20). In the edaravone group, 30mg edaravone was intravenously infused just before reperfusion. Plasma samples were obtained before and at 24h, 3, 5, 7, and 14 days after reperfusion. Cardiovascular events were defined as cardiac death, subacute thrombosis, or fatal arrhythmia. Heart failure requiring rehospitalization was evaluated at 12 months after reperfusion. Results: Plasma MCP-1 levels were not different between the two groups before reperfusion. Compared with the placebo group, the edaravone group had statistically lower maximum creatine kinase-MB levels (218±31IU/l versus 145±21IU/l, p <0.05) and plasma MCP-1 levels on day 3 after reperfusion (873±118pg/ml versus 516±66pg/ml, p <0.05). Heart failure requiring rehospitalization occurred in four patients in the control group, but did not occur in the edaravone group (p <0.05). At 12 months after reperfusion, left ventricular ejection fraction was statistically higher in the edaravone group than in the control group (62±2% versus 54±3%, p <0.05). Conclusion: Edaravone suppressed plasma MCP-1, improved left ventricular ejection fraction, and reduced rehospitalization due to heart failure. Suppression of plasma MCP-1 level by edaravone might induce better prognosis for AMI patients. [Copyright &y& Elsevier]

The original concept of "onco-cardiology" was developed as cardiotoxicity associated with anticancer treatment; however, recently, the number of cases in which atherosclerotic cardiovascular diseases coexist with malignant diseases has increased, and increasing attention is being paid to the relationship between malignant diseases and cardiovascular diseases, based on the long-term surveillance of cancer survivors. Several studies have described a high risk of cardiovascular disease events in cancer survivors. Similarly, a history of cardiovascular disease also confers higher risk incident cancer. Thus, this relationship has been drawing attention as a new aspect of onco-cardiology. The most troublesome issue in cancer patients is antithrombotic therapy. The clinical benefits of using dual anti-platelet therapy (DAPT) with aspirin and P2Y12 inhibitors in patients with ischemic heart diseases (acute coronary syndrome (ACS) or after percutaneous coronary intervention [PCI]) has been well established; premature discontinuation of DAPT increases the risk of adverse coronary events in those patients. In this joint symposium by JSMO and the Japanese Circulation Society(JCS), we present therapeutic strategies for ischemic heart disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]