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There has been no previous report evaluating the long impact of atrial fibrillation (AF) on the clinical outcomes stratified by the initial management [conservative or aortic valve replacement (AVR)] strategies of severe aortic stenosis (AS).We analyzed 3815 patients with severe AS enrolled in the CURRENT AS registry. Patients with AF were defined as those having a history of AF when severe AS was found on the index echocardiography. The primary outcome measure was a composite of aortic valve-related death or hospitalization for heart failure.The cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2 % versus 33.2 %, HR 1.54, 95 % CI 1.35-1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95 % CI 1.16-1.56). The magnitude of excess adjusted risk of AF for the primary outcome measure was greater in the initial AVR stratum (N = 1197, HR 1.95, 95 % CI 1.36-2.78) than in the conservative stratum (N = 2618, HR 1.26, 95 % CI 1.08-1.47) with a significant interaction (p = 0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (N = 254) relative to chronic AF (N = 528) for the primary outcome measure (HR 1.34, 95 % CI 1.01-1.78).In patients with severe AS, concomitant AF was independently associated with worse clinical outcomes regardless of the initial management strategies. In those patients with conservative strategy, paroxysmal AF is stronger risk factor than chronic AF.

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Recently, one observational study showed that patients with ST-segment elevation myocardial infarction (STEMI) without standard cardiovascular risk factors were associated with increased mortality compared with patients with risk factors. This unexpected result should be evaluated in other populations including those with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and chronic coronary syndrome (CCS). Among 30,098 consecutive patients undergoing first coronary revascularization in the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) registry cohort-2 and 3, we compared clinical characteristics and outcomes between patients with and without risk factors stratified by their presentation (STEMI n = 8,312, NSTE-ACS n = 3,386, and CCS n = 18,400). Patients with risk factors were defined as having at least one of the following risk factors: hypertension, dyslipidemia, diabetes, and current smoking. The proportion of patients without risk factors was low (STEMI: 369 patients [4.4%], NSTE-ACS: 110 patients [3.2%], and CCS: 462 patients [2.5%]). Patients without risk factors compared with those with risk factors more often had advanced age, low body weight, and malignancy and less often had history of atherosclerotic disease and prescription of optimal medical therapy. In patients with STEMI, patients without risk factors compared with those with risk factors were more often women and more often had atrial fibrillation, long door-to-balloon time, and severe hemodynamic compromise. During a median of 5.6 years follow-up, patients without risk factors compared with those with risk factors had higher crude incidence of all-cause death. After adjusting confounders, the mortality risk was significant in patients with CCS (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01 to 1.49, p = 0.04) but not in patients with STEMI (HR 1.06, 95% CI 0.89 to 1.27, p = 0.52) and NSTE-ACS (HR 1.07, 95% CI, 0.74 to 1.54, p = 0.73). In conclusion, among patients undergoing coronary revascularization, patients without standard cardiovascular risk factors had higher crude incidence of all-cause death compared with those with at least one risk factor. After adjusting confounders, the mortality risk was significant in patients with CCS but not in patients with STEMI and NSTE-ACS.

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, ptrend

The clinical significance of the CHADSsub2/subscore remains unclear in patients with coronary artery disease (CAD) without atrial fibrillation (AF). Therefore, the purpose of this study was to evaluate the association between the CHADSsub2/subscore and the long-term risk of ischemic stroke and its severity in patients with CAD with and without AF. Using the CREDO (Coronary Revascularization Demonstrating Outcome study)-Kyoto Registry Cohort-3, the present study population consisted of 11,516 patients with CAD who underwent percutaneous coronary intervention without oral anticoagulants at discharge. We divided the patients into 2 groups according to the presence (n = 721) or absence (n = 10,795) of AF. As the CHADSsub2/subscore increased from 0 or 1 to 6, the cumulative 5-year incidence of ischemic stroke incrementally increased from 2.1% to 17.1% in patients without AF and from 4.2% to 40.7% in patients with AF. The cumulative 5-year incidence of ischemic stroke in patients without AF and a CHADSsub2/subscore of 2 were numerically comparable to that in patients with AF and a CHADSsub2/subscore of 1 (3.4% and 3.7%). In the 423 patients who developed ischemic stroke, the modified Rankin Scale score was not significantly different between patients with and without AF (p for trend = 0.12). In patients with and without AF, the increase in the CHADSsub2/subscore was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 andlt;0.001, respectively). An increasing CHADSsub2/subscore was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF.

Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese.The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate.The group with TTR ≥70 % based on PT-INR range ≥1.5 and2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked).The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes.

Background It remains controversial whether long‐term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. Methods and Results The current study population from the CREDO‐Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave‐2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long‐term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow‐up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5‐year incidence of all‐cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P P P P P P =0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35–2.22; P P P P Conclusions Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF.

BACKGROUND Optimal intensity is unclear for P2Y12receptor blocker therapy after percutaneous coronary intervention (PCI) in real-world clinical practice.Methods and Results:From the CREDO-Kyoto Registry, the current study population consisted of 25,419 patients (Cohort-2: n=12,161 and Cohort-3: n=13,258) who underwent their first PCI. P2Y12receptor blocker therapies were reduced dose of ticlopidine (200 mg/day), and global dose of clopidogrel (75 mg/day) in 87.7% and 94.8% of patients in Cohort-2 and Cohort-3, respectively. Cumulative 3-year incidence of GUSTO moderate/severe bleeding was significantly higher in Cohort-3 than in Cohort-2 (12.1% and 9.0%, P

Background Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). Methods and Results Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P =0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P P =0.77). Conclusions There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure.

There is a scarcity of data on ischemic and bleeding events in patients who experienced major bleeding after percutaneous coronary intervention (PCI). Moreover, there also is a shortage of data on comparative outcomes between patients with and without interruption of an antithrombotic drug after major bleeding. We evaluated the incidence and prognostic impacts of ischemic (myocardial infarction or ischemic stroke) and bleeding (Bleeding Academic Research Consortium type 3 or 5) events after major bleeding in 12,691 consecutive patients who underwent first PCI in the Coronary Revascularization Demonstrating Outcome Study in Kyoto PCI registry cohort-3. In the entire cohort, incidence of the first ischemic event and bleeding event was 2.3 per 100 person-years and 3.8 per 100 person-years, respectively. Major bleeding (Bleeding Academic Research Consortium type 3) occurred in 2,142 patients during a median follow-up of 5.7 years. In patients with major bleeding, cumulative 30-day, 1-year, and 5-year incidence of an ischemic event was 2.6%, 4.8%, and 13.2% (3.2 per 100 person-years), respectively, whereas that of a bleeding event was 6.3%, 16.1%, and 29.2% (8.5 per 100 person-years), respectively. Ischemic and bleeding events were independently associated with mortality (hazard ratio 2.36, 95% confidence interval 1.87 to 2.96, p

BACKGROUND The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P

Background: Despite recommendations in the guidelines and consensus documents, there has been no randomized controlled trial evaluating oral anticoagulation (OAC) alone without antiplatelet therapy (APT) in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after coronary stenting. Methods: This study was a prospective, multicenter, open-label, noninferiority trial comparing OAC alone to combined OAC and single APT among patients with atrial fibrillation beyond 1 year after stenting in a 1:1 randomization fashion. The primary end point was a composite of all-cause death, myocardial infarction, stroke, or systemic embolism. The major secondary end point was a composite of the primary end point or major bleeding according to the International Society on Thrombosis and Haemostasis classification. Although the trial was designed to enroll 2000 patients during 12 months, enrollment was prematurely terminated after enrolling 696 patients in 38 months. Results: Mean age was 75.0±7.6 years, and 85.2% of patients were men. OAC was warfarin in 75.2% and direct oral anticoagulants in 24.8% of patients. The mean CHADS 2 score was 2.5±1.2. During a median follow-up interval of 2.5 years, the primary end point occurred in 54 patients (15.7%) in the OAC-alone group and in 47 patients (13.6%) in the combined OAC and APT group (hazard ratio, 1.16; 95% CI, 0.79–1.72; P =0.20 for noninferiority, P =0.45 for superiority). The major secondary end point occurred in 67 patients (19.5%) in the OAC-alone group and in 67 patients (19.4%) in the combined OAC and APT group (hazard ratio, 0.99; 95% CI, 0.71–1.39; P =0.016 for noninferiority, P =0.96 for superiority). Myocardial infarction occurred in 8 (2.3%) and 4 (1.2%) patients, whereas stroke or systemic embolism occurred in 13 (3.8%) and 19 (5.5%) patients, respectively. Major bleeding occurred in 27 (7.8%) and 36 (10.4%) patients, respectively. Conclusions: This randomized trial did not establish noninferiority of OAC alone to combined OAC and APT in patients with atrial fibrillation and stable coronary artery disease beyond 1 year after stenting. Because patient enrollment was prematurely terminated, the study was underpowered and inconclusive. Future larger studies are required to establish the optimal antithrombotic regimen in this population. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01962545.

BACKGROUND Data evaluating the effects of acute coronary syndrome (ACS) relative to stable coronary artery disease (CAD) on bleeding risk after percutaneous coronary intervention (PCI) are scarce.Methods and Results:From the CREDO-Kyoto Registry Cohort-3, 13,258 patients undergoing first PCI (5,521 ACS; 7,737 stable CAD) were identified. Patients were further stratified according to ACS presentation and Academic Research Consortium High Bleeding Risk (HBR): ACS/HBR: n=2,502; ACS/no-HBR: n=3,019; stable CAD/HBR: n=3,905; and stable CAD/no-HBR: n=3,832. The primary bleeding endpoint was Bleeding Academic Research Consortium 3/5 bleeding, whereas the primary ischemic endpoint was myocardial infarction (MI)/ischemic stroke. Compared with stable CAD, ACS was associated with a significantly higher adjusted risk for bleeding (hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.68-2.03; P

BACKGROUND The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P

Chronic kidney disease (CKD) might be an important determinant in choosing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). However, there is a scarcity of studies evaluating the effect of CKD on long-term outcomes after PCI relative to CABG in the population including severe CKD. Among 30257 consecutive patients patients who underwent first coronary revascularization with PCI or isolated CABG in the CREDO-Kyoto PCI/CABG registry Cohort-2 (n = 15330) and Cohort-3 (n = 14,927), we identified the current study population of 12,878 patients with multivessel or left main disease, and compared long-term clinical outcomes between PCI and CABG stratified by the subgroups based on the stages of CKD (no CKD: eGFR >=60 ml/min/1.73m2, moderate CKD: 60> eGFR >=30 ml/min/1.73m2, and severe CKD: eGFR

Long-term safety of percutaneous coronary intervention (PCI) as compared with coronary artery bypass grafting (CABG) is still controversial in patients with unprotected left main coronary artery disease (ULMCAD), and there is a scarcity of real-world data on the comparative long-term clinical outcomes between PCI and CABG for ULMCAD in new-generation drug-eluting stents era. The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013, and we identified 855 patients with ULMCAD (PCI: N = 383 [45%], and CABG: N = 472 [55%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.5 (interquartile range: 3.9 to 6.6) years. The cumulative 5-year incidence of all-cause death was not significantly different between the PCI and CABG groups (21.9% vs 17.6%, Log-rank p = 0.13). After adjusting confounders, the excess risk of PCI relative to CABG remained insignificant for all-cause death (HR, 1.00; 95% CI, 0.68 to 1.47; p = 0.99). There were significant excess risks of PCI relative to CABG for myocardial infarction and any coronary revascularization (HR, 2.07; 95% CI, 1.30 to 3.37; p = 0.002, and HR, 2.96; 95% CI, 1.96 to 4.46; p0.001), whereas there was no significant excess risk of PCI relative to CABG for stroke (HR, 0.85; 95% CI, 0.50 to 1.41; p = 0.52). In conclusion, there was no excess long-term mortality risk of PCI relative to CABG, while the excess risks of PCI relative to CABG were significant for myocardial infarction and any coronary revascularization in the present study population reflecting real-world clinical practice in Japan.

We herein report the case of a sixty-four-year-old woman with stage IV lung adenocarcinoma with thymoma. The adenocarcinoma showed 95% tumor proportion scores of PD-L1 (Programmed death-ligand 1) expression without driver mutations. She was treated with pembrolizumab as 1st-line chemotherapy. Creatine kinase elevation was observed on the 15th day, and fatal myocarditis developed on the 20th day despite steroid therapy. The autopsy showed lymphocyte-infiltrated cardiac muscle, and pembrolizumab-induced myocarditis was diagnosed. Our case indicates that lung cancer combined with thymoma should alert clinicians to monitor the early onset of myocarditis in patients on immune checkpoint inhibitor therapy.

We herein report a case of congenital long QT syndrome (LQTS) in which the QT interval was prolonged by Takotsubo syndrome (TTS), inducing ventricular fibrillation (VF). The patient was a 55-year-old woman who had been diagnosed with LQTS. Cardiopulmonary arrest occurred while coughing during sleep. VF was observed, and her heartbeat returned after two defibrillations. An electrocardiogram showed marked QT prolongation and large negative T waves. Echocardiography demonstrated hyperkinesis at the base of the left ventricle and akinesis at the apex. As there was no significant stenosis in the coronary artery, she was diagnosed with TTS.

One-month duration of dual antiplatelet therapy (DAPT) has widely been adopted after bare-metal stent (BMS) implantation in the real clinical practice. However, it has not been adequately addressed yet whether DAPT for only 1-month could provide sufficient protection from ischemic events beyond 1-month after BMS implantation. We assessed the effects of short DAPT relative to prolonged DAPT on clinical outcomes with the landmark analysis at 2 month after BMS implantation. Among 13,058 consecutive patients enrolled in the CREDO-Kyoto registry cohort-2, this study population consisted of 4905 patients treated with BMS only in whom the information on the status of antiplatelet therapy was available at 2 month after stent implantation [single-antiplatelet therapy (SAPT) group: N = 2575 (acute myocardial infarction (AMI): N = 1257, and non-AMI: N = 1318), and DAPT group: N = 2330 (AMI: N = 1304, and non-AMI: N = 1026)]. Cumulative 3-year incidence of the primary outcome measure (a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, and GUSTO moderate/severe bleeding) was not significantly different between the SAPT and DAPT groups (9.8 versus 10.6 %, P = 0.34). After adjusting confounders, the risk of SAPT relative to DAPT for the primary outcome measure remained insignificant in the entire cohort (HR 0.97, 95 % CI 0.79–1.19, P = 0.77), and in both AMI and non-AMI strata without any significant interaction between clinical presentation (AMI versus non-AMI) and the effect of SAPT relative to DAPT (P interaction = 0.56). In conclusion, short DAPT

Objective Few studies have reported on aortic valve replacement (AVR) in patients aged >80 years who have small aortic annuli. Various surgical techniques have been proposed for treating such patients. We investigated AVR using small-diameter mechanical valves, in patients aged >80 years, to determine its effectiveness. Methods Eighteen consecutive patients (15 women; 3 men) aged >80 (mean: 83.3 ± 2.7) years underwent surgical AVR with a 17-mm prosthesis. The clinical status and results of pre- and post-operative echocardiography were evaluated. Midterm examination was conducted at 12.0 ± 1.0 months after AVR. Results The average preoperative body surface area of the patients was 1.39 ± 0.15 m 2 ; the average New York Heart Association functional class was 3.28 ± 0.75. Echocardiography showed a peak pressure gradient of 99.1 ± 38.4 mm Hg. Operative mortality was absent. A significant decrease in the peak pressure gradient was found on early (22.6 ± 7.2 mm Hg) and midterm (22.2 ± 8.0 mm Hg) postoperative echocardiography, compared with that in the preoperative period. During this follow-up, 16 patients improved to class I, a significant change in each perioperative period compared with the preoperative period. No mortality was observed at 1 year postoperatively. Conclusions In patients aged >80 years who have small aortic annuli, AVR using a 17-mm prosthesis showed satisfactory clinical and hemodynamic results and provided a satisfactory remote prognosis.

We herein describe an adult case of double-chambered right ventricle (DCRV) with symptomatic drug-intolerant paroxysmal atrial fibrillation (PAf). The woman was referred to undergo radiofrequency ablation (RFA), and mapping of the pulmonary veins (PVs) demonstrated that a spontaneous spike potential originating from the left inferior PV (LIPV) induced sustained Af in the second procedure. Accordingly, the LIPV was regarded as the arrhythmogenic PV. Since complete isolation of the PVs, the sinus rhythm has been maintained for at least two years. This is the first report to describe that RFA for drug-intolerant PAf was useful in a patient with DCRV.

The aim of this study was to evaluate the prognostic impact of left ventricular ejection fraction (LVEF) in patients with severe aortic stenosis (AS).The prognostic impact of LVEF in severe AS remains controversial.Among 3,815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study population consisted of 3,794 patients after excluding 21 patients without LVEF data. Patients were divided into 4 groups according to LVEF at index echocardiography (50%, 50% to 59%, 60% to 69%, and ≥70%; conservative strategy: n = 388, n = 390, n = 1,025, and n = 800; initial aortic valve replacement strategy: n = 206, n = 170, n = 375, and n = 440). Echocardiographic data were site reported, and there was no echocardiography core laboratory.In the conservative group, the cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significantly higher in patients with LVEFs 50% and 50% to 59% than in those with LVEFs 60% to 69% and ≥70% (72.3%, 58.4%, 38.7%, and 35.0%, respectively, p 0.001), whereas in the initial aortic valve replacement group, the negative effect of low LVEF was markedly attenuated (20.2%, 20.3%, 17.7%, and 12.4%, respectively, p = 0.03). After adjusting for confounders, LVEF 50% (hazard ratio: 1.82; 95% confidence interval: 1.44 to 2.28; p 0.001) and 50% to 59% (hazard ratio: 1.77; 95% confidence interval: 1.42 to 2.20; p 0.001) but not 60% to 69% (hazard ratio: 1.14; 95% confidence interval: 0.94 to 1.39; p = 0.17) were independently associated with poorer outcomes compared with LVEF ≥70% (reference) in the conservative group. In the initial aortic valve replacement group, the adjusted risk for the primary outcome measure was not significantly different across the 4 LVEF groups.This study demonstrates that survival in patients with severe AS is impaired when LVEF is 60%, and these findings have implications for decision making with regard to the timing of surgical intervention.

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in “real-world” patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p

Summary Background The Japan Atherosclerosis Society's 2007 Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases (JAS2007GL) advocate reducing LDL cholesterol (LDL-C) to target levels in patients with dyslipidemia, but achievement rates are frequently unsatisfactory even in the presence of lipid-lowering therapy. This multicenter, open-label, randomized, parallel-group study compared the efficacy of rosuvastatin and atorvastatin on JAS2007GL LDL-C goals in Japanese patients not achieving their target goal with atorvastatin treatment. Methods The study involved 20 clinical institutes in Japan (Kishiwada Atherosclerosis Prevention Study [KAPS] Group). Patients with category II or III risk of coronary artery disease (CAD), or those with a history of CAD (secondary prevention), who had not achieved their JAS2007GL LDL-C goals during treatment with atorvastatin for at least 4 weeks were switched either to rosuvastatin 5 mg/day (from atorvastatin 10 mg/day) or rosuvastatin 10 mg/day (from atorvastatin 20 mg/day) (n = 75) or continued to receive atorvastatin (n = 77). The primary endpoint was achievement of LDL-C goals at 3 months. The main secondary endpoint was achievement of LDL-C goal + high-sensitivity C-reactive protein level

Background:In hypertensive patients, left ventricular hypertrophy (LVH) may persist despite satisfactory blood pressure (BP) control. The efficacy of thiazide diuretics in Western countries has been reported, but whether this applies to hypertensive Japanese patients is uncertain.Methods and Results:We randomly assigned 94 patients whose BP was poorly controlled with usual doses of angiotensin-II receptor blockers (ARB), to losartan/hydrochlorothiazide (HCTZ) fixed-dose combination vs. maximum doses of ARB. After 6 months follow-up, decrease in BP, regression of electrocardiographic LVH, and changes in laboratory measurements were examined. Although a similar decrease in BP was observed in both groups, the decrease in LV Sokolow-Lyon voltage, from 34.4±9.2 to 29.4±8.8 mm in the losartan/HCTZ vs. from 29.9±10.2 to 29.1±8.4 mm in the ARB group (P=0.0003), and the decrease in serum B-type natriuretic peptide (BNP) level, from 30.1±28.5 to 26.8±28.0 pg/ml vs. from 23.7±14.8 to 29.8±29.3 pg/ml (P=0.045) were greater in the losartan/HCTZ group. By single variable logistic regression analysis, ∆BNP (P=0.012) and treatment with losartan/HCTZ (P

In brief: Monocyte phagocytic function was studied in nine competitive athletes before and after a two-week weight-reduction program of calorie restriction. The phagocytic activity of monocytes before the program was higher in the athletes than in the sedentary controls, but decreased significantly after the weight-reduction program. Furthermore, plasma fibronectin concentrations and the response of lymphocytes to phytohemagglutinin decreased after the calorie restriction. These findings suggest that weight reduction by calorie restriction may adversely affect the integrity of defense mechanisms, even in healthy athletes. Thus, calorie restriction in athletes must be conducted with caution to protect them from adverse effects on their physiologic defense mechanisms.

Long-term safety and efficacy of drug-eluting stents remains controversial. The CREDO-Kyoto registry cohort-2 is a physician-initiated non-company sponsored multi-center registry enrolling consecutive patients undergoing first coronary revascularization in 26 centers in Japan. We compared 3-year outcome between patients treated with sirolimus-eluting stent (SES) only (5092 patients) and bare-metal stent (BMS) only (5405 patients). SES-use as compared with BMS-use was associated with significantly lower adjusted risk for all-cause death [hazard ratio (HR) [95% confidence interval (CI)] 0.72 (0.59–0.87), P = 0.0007], which was mainly driven by the reduction in non-cardiac death [HR (95% CI) 0.64 (0.48–0.85), P = 0.002]. The risk of cardiac death [HR (95% CI) 0.82 (0.63–1.07), P = 0.15], myocardial infarction [HR (95% CI) 0.73 (0.51–1.03), P = 0.07] and definite stent thrombosis [HR (95% CI) 0.62 (0.35–1.09), P = 0.1] was not different between the two groups. Despite longer duration of thienopyridine administration, SES-use was associated with significantly lower risk for bleeding [HR (95% CI) 0.75 (0.6–0.95), P = 0.02] and similar risk for stroke [HR (95% CI) 1.0 (0.75–1.34), P = 1.0]. The risk for target-lesion revascularization (TLR) was markedly lower in the SES group [HR (95% CI) 0.42 (0.36–0.48), P < 0.0001]. The direction and magnitude of the effect of SES relative to BMS in patients presenting acute myocardial infarction (AMI) were similar to those in patients presenting otherwise. In conclusion, SES-use as compared with BMS-use was associated with marked reduction of TLR without any increases in death, myocardial infarction, stent thrombosis, stroke and bleeding in real world clinical practice regardless of clinical presentation including AMI.

Previous studies have shown inconsistent results regarding the effects of concomitant use of clopidogrel and proton pump inhibitors (PPI) on cardiovascular outcomes. We sought to evaluate the clinical impact of PPI-use in patients treated with thienopyridines after percutaneous coronary intervention (PCI) in a large Japanese observational database. Among 12446 patients discharged alive on thienopyridines (ticlopidine 90.4% and clopidogrel 9.6%), 3223 patients were treated with PPIs and 9223 patients without PPI at the time of hospital discharge. The PPI group included more patients with co-morbidities than the non-PPI group. The adjusted hazard ratio (HR) of PPI-use for a composite of cardiovascular death, myocardial infarction, and stroke was 1.26 (95% confidence interval (CI) 1.09-1.47, p = 0.002). The adjusted HR of PPI-use for bleeding was 1.26 (95% CI 1.05-1.52, p = 0.013). Cardiovascular and bleeding outcomes were not different among the three groups receiving three different types of PPI. The negative effect of PPI on cardiovascular outcome was consistently seen in both drug-eluting stent (DES) [HR 1.31 (95% CI 1.07-1.6, p = 0.0097)] and non-DES strata [HR 1.25 (95% CI: 0.99-1.57, p = 0.057)] (Interaction p = 0.79) despite the fact that the duration of thienopyridine administration was significantly longer in patients receiving DES. In conclusion, cardiovascular outcomes after PCI were significantly worse in patients with PPI than in patients without PPI in the Japanese real clinical practice. However, the observed poorer cardiovascular outcome in patients receiving PPI was most likely to be related to residual confounding and seemed not causally related to attenuation of antiplatelet effect of thienopyridine through interaction with PPI.

Low friction and low wear of SiC sliding against itself in water at room temperature have been well reported in the past 20 years, and some practical applications have been developed. However, the properties of friction and wear in pure, deionized or distilled water have been mainly observed and not in water from sources in nature. In this article, the fundamental properties of friction and wear between SiC ball and disk are observed in water from ground, river, and sea, and the results are compared with those in deionized water in the viewpoints of modes of lubrication and wear and the resultant values of friction coefficient and wear rate. The smallest friction coefficient (μl = 0.005) in steady state is observed in deionized water and the largest (μl = 0.013) in sea water. The smallest wear rate (w s = 2.2 × 10−7 mm3/Nm) is observed in sea water and the largest (w s = 3.1 × 10−7 mm3/Nm) in deionized water. The intermediate values of μl and w s between the smallest and the largest ones are observed in ground and river water. The modes of lubrication and wear, which generated observed values of μl and w s, are considered as mixed lubrication and tribochemical wear. The chemical elements of Na, Cl, Mg, and K in sea water observed on wear particles and pits are thought effective to generate the largest value of μl and the smallest value of w s.

Hyperinsulinemia and insulin resistance have been proposed as having a causal role in pathogenesis of atherosclerosis; however, the relationship between post-load insulin levels and long-term survival is not clear. We investigated whether post-load insulin response is a predictor of outcome in patients without previously recognized diabetes.Data from 933 Japanese patients who underwent both a 75 g oral glucose tolerance test and coronary angiography with suspected coronary artery disease were analyzed. The determinant factors in association with all-cause death or cardiovascular events, including reinfarction, heart failure or angina requiring re-hospitalization, and coronary revascularization were examined by multivariate Cox regression analysis.The numbers of patients with normal glucose tolerance, impaired glucose regulation and diabetes were 326, 408 and 199, respectively. During the follow-up period (median 1113 days), death occurred in 37 patients including 13 cardiac causes. There were no significant differences in mortality or cardiovascular event incidence between glucose tolerance status. Kaplan-Meier curves indicated that the lower-response group of 2-hour insulin levels (75.3 mU/L; median) was associated with higher mortality rates (Log-rank P=0.006). Multivariate Cox regression analysis revealed that 2-hour insulin level was an independent predictor of all-cause death (P=0.026) after adjustment for age, gender, number of stenosed vessels, ejection fraction, metabolic factors, and treatments.Post-load low insulin response is seen as a predictor of mortality rates for patients with no previous diagnosis of diabetes mellitus.

SummaryA 49-year-old woman was admitted to the hospital because of cardiac tamponade. The hemorrhagic pericardial effusion was cytologically negative for malignant cells. Cardiac magnetic resonance imaging showed two masses in the anterior and lateral right atrium; however, positron emission tomography (PET) image using 18F-fluorodeoxyglucose revealed strong uptake in the anterior right atrium, without other tumors or metastasis. Intraoperatively, the lateral mass was confirmed as a thrombus, whereas the anterior mass was removed surgically and was diagnosed as an angiosarcoma with histopathological examination. However, she was re-admitted to the hospital 1 month after the operation because of cerebral hemorrhage, suspicious of distant metastasis. PET is useful for the detection of cardiac angiosarcoma.

Summary Background and objective Plasma B-type natriuretic peptide (BNP) levels are determined by several factors. The presence of atrial fibrillation (AF) is one of these factors. Meanwhile, plasma BNP levels are well correlated with left ventricular (LV) filling pressure in patients with sinus rhythm. Furthermore, LV filling pressure can be estimated by the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity ( E / e ′ ratio) in patients with sinus rhythm or with AF. However, it is still unclear if elevated plasma BNP levels reflect increases in LV filling pressure in patients with AF, especially with preserved LV systolic function. This study was designed to examine which factors determine plasma BNP levels in patients with persistent nonvalvular AF and preserved LV systolic function. Methods and results We examined 195 clinically stable outpatients with persistent nonvalvular AF and preserved LV systolic function. They underwent comprehensive 2-dimensional and Doppler echocardiography, plasma BNP and creatinine levels, clinical history, and heart rate were determined. Then we statistically analyzed the correlation between plasma BNP levels and several variables including E / e ′ ratio. On univariate analyses, plasma BNP levels were significantly correlated with age, LV diastolic diameter (LVDd), E / e ′ ratio, and mitral E wave deceleration time. In addition, plasma BNP levels were significantly higher in males and in patients with a history of congestive heart failure and those who had been administered a β-blocker. On multiple linear regression analyses, E / e ′ ratio, age, LVDd, and administration of β-blocker were independent determinant factors of plasma BNP levels. Conclusions Plasma BNP levels in patients with persistent AF and preserved LV systolic function are affected by E / e ′ ratio, age, LVDd, and administration of β-blockers.

application/pdf, An increase in arterial stiffness with advancing age is associated with several pathological states, including hypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffness and has a protective effect against these diseases. However, not all individuals respond to exercise to the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure, blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms in ANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectional study of 291 healthy middle-aged and older Japanese subjects (63±1 years), examining the relationship between daily physical activity–induced improvements in arterial stiffness, estimated by brachial-ankle arterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A) in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor (NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen in blood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higher plasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MM genotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotype subjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphism in older Japanese subjects may affect the cardiovascular response to regular exercise.

application/pdf, High physical activity or aerobic exercise training increases central arterial distensibility in older humans. However, the effect of a single bout of exercise on central arterial distensibility in older humans is unknown. Furthermore, the effect of exercise training on central arterial distensibility during exercise is unclear. We investigated whether systemic arterial compliance (SAC) changes after acute exercise in older humans, and, if so, whether this change in SAC is enhanced by aerobic exercise training. Seven untrained older women (61−69 years old) participated in a 6-month exercise intervention study. We measured SAC after acute exercise (cycling exercise at 80% of their individual ventilatory threshold for 30 min) before and after 6 months of aerobic exercise training. After exercise training, the individual ventilatory threshold was significantly increased. In addition, both the SAC at rest and that 30 min after acute exercise were significantly increased after the exercise training program. Before exercise training, there was no significant increase in SAC after acute exercise, whereas, after exercise training, the SAC was significantly increased 30 min after acute exercise. The present study suggests that, after aerobic exercise training, SAC increases after acute exercise in older humans, and that the SAC at rest and after acute exercise is enhanced by aerobic exercise training, thereby causing an effective adaptation in increase in cardiac output during exercise.

Background The cardio-ankle vascular index (CAVI) has been recently reported as a new index of aortic stiffness, which is less influenced by blood pressure than pulse wave velocity (PWV). The present study investigated the relationship between the levels of CAVI and carotid and coronary arteriosclerosis. Methods and Results The 443 consecutive patients who underwent CAVI, carotid sonography, and coronary angiography in hospital were examined. Intima - media thickness (IMT) and carotid plaque were evaluated by ultrasonography. The severity of coronary artery disease (CAD) was evaluated by coronary angiography and the subjects were divided into 4 groups (0, no significant organic stenosis: 1, 1-vessel disease: 2, 2-vessel disease: 3, 3-vessel disease). Univariate analyses showed that both CAVI and brachial-ankle PWV (baPWV) were associated with IMT and the presence of carotid plaque. Multiple stepwise regression analyses revealed that CAVI (p=0.0427), but not baPWV, was associated with the IMT. Both CAVI (p

Increased arterial stiffness is an independent risk factor for cardiovascular disease. The estrogen system (estrogen and estrogen receptor-alpha [ER-alpha]) has potent vasodilator and antiatherosclerotic activity in vascular tissue and therefore was implicated in the regulation of arterial stiffness. We hypothesized that the relationship between arterial stiffness and gene polymorphisms in ER-alpha has a sex-specific component in older humans.Two hundred healthy older subjects, comprised of 85 men and 115 postmenopausal women (men, 66 +/- 5 years old; women, 64 +/- 7 years old; mean +/- SD) participated in a cross-sectional study. We determined the genotypes of single-nucleotide polymorphisms (SNPs) at -401T/C of intron 1 and at 30T/C of exon 1 of ER-alpha, using a TaqMan-polymerase chain reaction method. Arterial stiffness was estimated by brachial-ankle pulse-wave velocity (baPWV).Polymorphisms of both -401T/C and 30T/C in ER-alpha affected baPWV values in postmenopausal women but did not affect men. The baPWV in women was significantly lower in the CC genotype at both -401T/C and 30T/C than in the TT genotype (both P.05), and the CC genotype of two SNPs in women was significantly lower than in men.The present study suggests that the relationship between arterial stiffness and -401T/C or 30T/C polymorphisms in ER-alpha is different between sexes in older humans. These polymorphisms may be important in the health and clinical care of cardiovascular function and disease in older women.

制御/リビングラジカル重合(C/LRP)の一つである MADIX 法(Macromolecular Design via Interchange of Xanthate)について概説する．種々のザンテート Z′O-(C=S)S-R について置換基の影響を調べた．脱離基 R は置換基の脱離のしやすさに相関し，連鎖移動定数(Ctr)に大きな影響を及ぼした．活性基 Z′は中間ラジカルの安定性に強い影響があり，多分散度(PDI)を劇的に変えた．界面活性を有するザンテートを用いる MADIX 法は，通常の ab initio 乳化重合にそのまま適用できるほとんど唯一の C/LRP 法である．シード重合でブロックポリマーを合成しコアシェル型のナノ複合粒子を作製した．ザンテート末端を不活性化するためのチオール化やアルカン化を確立した．さらにブロックポリマー・櫛形ポリマー・マイクロゲル・星型ポリマーなどの高分子設計とその応用についても紹介する．

Background Hypoadiponectinemia has been reported to indicate an increased risk of cardiovascular disease, so the present study investigated the significance of serum adiponectin (APN) levels for predicting clinical outcomes after percutaneous coronary intervention (PCI). Methods and Results The APN levels were evaluated in 184 consecutive patients who underwent PCI. The patients were divided into Group A [the lowest quartile of APN levels (APN ≤4.5 μg/ml), n=46] and Group B [the upper 3 quartiles of APN levels (APN >4.5 μg/ml), n=138]. During a mean follow-up period of 27.3 months, the rate of major adverse cardiac and cerebrovascular events (MACCE: death from any cause, re-infarction, repeat coronary revascularization, hospitalization because of congestive heart failure, and cerebral infarction) was higher in Group A (58.7%) than in Group B (37.0%, p=0.0101). Moreover, when the APN levels were calculated by adjusting for sex, age, body mass index, and triglyceride levels, patients in the lowest quartile of residual APN levels had a higher risk of MACCE (p=0.0405). Multiple logistic analyses showed that hypoadiponectinemia (APN ≤4.5 μg/ml) was independently correlated with MACCE. Kaplan-Meier analysis demonstrated a higher MACCE rate in Group A than in Group B (Log-rank χ2=7.89, p=0.0050). Conclusion The APN level may be helpful for predicting clinical outcomes after PCI. (Circ J 2007; 71: 675 - 680)

Background Adjunctive thrombus aspiration ( TA ) during primary percutaneous coronary intervention ( PCI ) was reported to promote better coronary and myocardial reperfusion. However, long‐term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long‐term clinical outcomes in patients with ST ‐segment elevation myocardial infarction (STEMI) undergoing primary PCI . Methods and Results The CREDO ‐Kyoto AMI Registry is a large‐scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005–2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI . Clinical outcomes were compared between the 2 patient groups with or without TA . During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA ( TA group). The cumulative 5‐year incidence of all‐cause death was significantly lower in the TA group than in the non‐ TA group (18.5% versus 23.9%, log‐rank P TA group was not significantly lower than that in the non‐ TA group (hazard ratio: 0.90, 95% CI : 0.76 to 1.06, P =0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target‐lesion revascularization were also not significantly different between the 2 groups. Conclusions Adjunctive TA during primary PCI was not associated with better 5‐year mortality in STEMI patients.

Aerobic exercise training is associated with lower central arterial stiffness, but little information exists on the effects of physical activity intensity or duration on central arterial stiffness. Using a cross-sectional and interventional approach, we tested the hypothesis that both moderate and vigorous physical activity reduce central arterial stiffness in postmenopausal women.Carotid arterial stiffness (via ultrasound and applanation tonometry) and duration of physical activity at low, moderate, and vigorous intensities (via electronic accelerometer) were measured in 103 apparently healthy sedentary or recreationally active women 47 to 82 years of age. Moderate intensity physical activity was defined as 4.0 to 6.0 metabolic equivalents (MET) in subjects aged65 years and as 3.0 to 5.0 MET in subjectsor=65 years. A subgroup of 17 sedentary subjects was randomly assigned to moderate (n = 8) or vigorous (n = 9) intensity cycling exercise training (900 kcal/week, three to five sessions per week, for 12 weeks). Carotid arterial stiffness was measured before and after training.Carotid beta-stiffness index was significantly correlated with the duration of moderate and vigorous intensity physical activity (r = -0.25 and r = -0.22) even after adjustment for age, height, and mean BP. Carotid beta-stiffness index significantly decreased after moderate and vigorous intensity cycling training. There were no significant group differences in the magnitude of beta-stiffness index change even after adjustment for expected confounders (eg, baseline beta-stiffness index, height, body mass index, heart rate, and post-training body mass, body mass index, and mean BP).These results suggest that both moderate and vigorous physical activities have favorable effects on central arterial stiffness in postmenopausal women.

Increase in arterial stiffness is associated with aging, which is improved by regular exercise. Endothelin (ET) system has crucial roles in regulating vascular tone and in the progression of atherosclerosis. We hypothesized that molecular variations (ie, gene polymorphisms) in ET-related gene might affect exercise-induced improvement in arterial stiffness with age in human subjects. The present study provides a cross-sectional investigation of 191 healthy middle-aged and older (65±1 years) human subjects to clarify the relationship between the regular exercise-induced improvement of arterial stiffness and the gene polymorphisms of ET converting enzyme (ECE)-1, ECE-2, ET-A receptor (ET-A), and ET-B receptor (ET-B). The study subjects were divided into active and inactive groups based on the median value (186 kcal/d) of energy expenditure. Brachial-ankle arterial pulse wave velocity (baPWV) was used to evaluate arterial stiffness. All individuals were genotyped for 4 different polymorphisms of the ET system: 2013(+289)A/G in intron 17 of ECE-1, 669(+17)T/C in intron 5 of ECE-2, 958A/G in exon 6 of ET-A, and 831A/G in exon 4 of ET-B. The baseline baPWV was significantly lower in the active group without any change in blood pressure. Polymorphisms in ECE-1 influenced basal blood pressure. Polymorphisms in ECE-1 and ECE-2 had no effect on baPWV between active and inactive groups. However, polymorphisms in both ET-A and ET-B affected baPWV in the 2 groups. The present results suggest that differences in ET-A and ET-B polymorphisms may influence the response of the vascular wall to exercise whereas ECE-1 polymorphisms may affect basal blood pressure.