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Background: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).
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BACKGROUND: Bleeding events are one of the major concerns in patients using oral anticoagulants (OACs). We aimed to evaluate the association between major bleeding and long-term clinical outcomes in atrial fibrillation (AF) patients taking OACs. METHODS: We analyzed a database comprising two large-scale prospective registries of patients with documented AF: the RAFFINE and SAKURA registries. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, ischemic stroke, and myocardial infarction. Major bleeding was defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis. Cox multivariate analysis was used to determine the impact of major bleeding on the incidence of MACCE. RESULTS: The median follow-up period was 39.7 (interquartile range, 33.1-48.1) months. Among 6,633 patients with AF who were taking OAC, 298 (4.5%) had major bleeding and 737 (11.1%) had MACCE. The incidence of MACCE was higher in patients with bleeding than in those without (18.33 and 3.22, respectively, per 100 patient-years; log-rank p < 0.0001). Multivariate logistic regression analysis revealed older age, vitamin K antagonist use, and antiplatelet drug use as independent predictors of major bleeding. Median duration of MACCE occurrence after major bleeding was 41 (interquartile range, 3-300) days. Multivariate Cox hazard regression analysis showed that the risk of MACCE was significantly higher in patients with major bleeding compared to those without (hazard risk, 4.64; 95% confidence interval, 3.62-5.94; p < 0.0001). CONCLUSIONS: Major bleeding was associated with long-term adverse cardiovascular events among AF patients taking OAC. Therefore, reducing the risk of bleeding is important for improving clinical outcomes in patients with AF.
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To the best of our knowledge, little is known about the association between dietary variety status and sarcopenia in university-affiliated geriatric hospital in elderly. The present study aimed to investigate, in a multidisciplinary setting, the prevalence of sarcopenia and association between dietary variety status and sarcopenia in older outpatients at Juntendo Tokyo Koto Geriatric Medical Center (Tokyo, Japan). Between October 2020 and December 2021, a cross-sectional study of outpatients aged ≥65 years [458 male (44%) and 584 female (56%); mean age, 78.2±6.1 years] was conducted to assess prevalence of sarcopenia, according to Asian Working Group for Sarcopenia 2019 criteria, and the relationship between dietary variety status and sarcopenia. Patient profile, comorbidities, drug use, neuropsychological data, abdominal symptoms, pulmonary function and dietary variety status were collected. Of 1,042 subjects, there were 223 (21.4%) with [142 male (63.7%) and 81 female (36.3%); mean age, 80.6±6.3 years] and 819 (78.6%) without sarcopenia [316 male (38.6%) and 503 female (61.4%); mean age, 77.6±5.8]. In multivariate analysis, older age, male sex, low body mass index, high Brinkman Index and phase angle, low quality of life, history of daycare use, diabetes mellitus, osteoporosis and low Mini-Mental State Examination and Dietary Variety Score were related to sarcopenia. The prevalence of sarcopenia was higher in than in community-dwelling individuals. Dietary variety status was associated with sarcopenia.
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BACKGROUND: Low plasma levels of eicosapentaenoic acid (EPA) are associated with cardiovascular events. This trial aimed to assess the clinical benefits of icosapent ethyl in patients with coronary artery disease, a low EPA/arachidonic acid (AA) ratio, and statin treatment. METHODS: In this prospective, multicenter, randomized, open-label, blinded end-point study, patients with stable coronary artery disease and a low EPA/AA ratio (<0.4) were randomized to EPA (1800 of icosapent ethyl administered daily) or control group. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, unstable angina pectoris, and coronary revascularization. The secondary composite end points of coronary events included sudden cardiac death, fatal and nonfatal myocardial infarction, unstable angina requiring emergency hospitalization and coronary revascularization, or coronary revascularization. RESULTS: Overall, 3884 patients were enrolled at 95 sites in Japan. Among them, 2506 patients had a low EPA/AA ratio, and 1249 and 1257 patients were randomized to the EPA and control group, respectively. The median EPA/AA ratio was 0.243 (interquartile range, 0.180-0.314) and 0.235 (interquartile range, 0.163-0.310) in the EPA and control group, respectively. Over a median period of 5 years, the primary end point occurred in 112 of 1225 patients (9.1%) and 155 of 1235 patients (12.6%) in the EPA and control group, respectively (hazard ratio, 0.79 [95% CI, 0.62-1.00]; P=0.055). Meanwhile, the secondary composite end point of coronary events in the EPA group was significantly lower (81/1225 [6.6%] versus 120/1235 [9.7%] patients; hazard ratio, 0.73 [95% CI, 0.55-0.97]). Adverse events did not differ between the groups, but the rate of new-onset atrial fibrillation was significantly higher in the EPA group (3.1% versus 1.6%; P=0.017). CONCLUSIONS: Icosapent ethyl treatment resulted in a numerically lower risk of cardiovascular events that did not reach statistical significance in patients with chronic coronary artery disease, a low EPA/AA ratio, and statin treatment. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012069.
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Doença da Artéria Coronariana , Ácido Eicosapentaenoico , Inibidores de Hidroximetilglutaril-CoA Redutases , Prevenção Secundária , Humanos , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/uso terapêutico , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/sangue , Masculino , Feminino , Idoso , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Quimioterapia Combinada , Resultado do Tratamento , Japão/epidemiologiaRESUMO
BACKGROUND: The Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial demonstrated non-inferior efficacy endpoints for rivaroxaban monotherapy versus combination therapy (rivaroxaban plus a single antiplatelet) and superior safety endpoints in patients with atrial fibrillation and stable coronary artery disease. AIMS: This post hoc analysis investigated whether the AFIRE trial results reflected the presence or absence of prior revascularisation. METHODS: Among 2,215 patients, 1,697 (76.6%) had previously undergone revascularisation, and the remaining 518 (23.4%) had not undergone prior revascularisation. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation, or death from any cause, while the primary safety endpoint was major bleeding. RESULTS: In 1,697 patients with prior revascularisation, the efficacy and safety endpoints were superior for monotherapy versus combination therapy (efficacy: hazard ratio [HR] 0.62, 95% confidence interval [CI]: 0.45-0.85; p=0.003; safety: HR 0.62, 95% CI: 0.39-0.98; p=0.042). Among 518 without prior revascularisation, there were no significant differences in endpoints (efficacy: HR 1.19, 95% CI: 0.67-2.12; p=0.554; safety: HR 0.47, 95% CI: 0.18-1.26; p=0.134). There was borderline interaction of the efficacy endpoints (p=0.055) between two treatments. The safety benefit of monotherapy on any bleeding was significant in patients without prior revascularisation (HR 0.59, 95% CI: 0.38-0.93; p=0.022). CONCLUSIONS: In high-risk thrombosis patients with a history of prior revascularisation, rivaroxaban monotherapy versus combination therapy demonstrated favourable safety and efficacy outcomes.
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Fibrilação Atrial , Doença da Artéria Coronariana , Acidente Vascular Cerebral , Humanos , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Inibidores da Agregação Plaquetária , Rivaroxabana , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).
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Quimiocina CXCL12 , Doença da Artéria Coronariana , Diabetes Mellitus , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/etiologia , Diabetes Mellitus/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Isoformas de Proteínas , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Células Estromais , Resultado do TratamentoRESUMO
BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-segment-elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS) may reduce the risk of subsequent cardiovascular events but remains challenging. The study aim was to evaluate the clinical characteristics and long-term outcomes of patients undergoing primary PCI for STEMI with CS. METHODS: We conducted an observational cohort study of patients with STEMI who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital. The primary outcome was cardiovascular death (CVD) during the median 3-year follow-up. We performed a landmark analysis for the incidence of CVD from 0â¯day to 1â¯year and from 1 to 10â¯years. RESULTS: Among the 1758 STEMI patients in the cohort, 212 (12.1â¯%) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4â¯% vs 2.9â¯%). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank pâ¯<â¯0.0001). Multivariate Cox regression analysis showed that CS was significantly associated with higher cardiovascular mortality (adjusted hazard ratio, 11.8; 95%confidence intervals, 7.78-18.1; pâ¯<â¯0.0001), but the mortality rates from 1 to 10â¯years were comparable (log-rank pâ¯=â¯0.68). CONCLUSION: The cardiovascular 1-year mortality rate for patients with STEMI was higher for those with CS on admission than without, but the mortality rates of >1â¯year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Choque Cardiogênico , Humanos , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Seguimentos , Estudos de Coortes , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Incidência , Fatores de RiscoRESUMO
Introduction: The long-term impact of renin-angiotensin system (RAS) inhibitors for secondary prevention in patients with chronic kidney disease (CKD) and coexisting coronary artery disease remains unclear. Methods: Altogether, 1,160 consecutive patients with CKD (mean age, 70 ± 9 years; 78% men) who underwent their first percutaneous coronary intervention (PCI) between 2000 and 2018 were included and analyzed. Based on their RAS inhibitor use, 674 patients (58%) were allocated to the RAS inhibitor group, and 486 patients (42%) were allocated to the non-RAS inhibitor group. This study evaluated the incidence of 3-point major adverse cardiovascular events (3P-MACE), including cardiovascular death, nonfatal acute coronary syndrome and nonfatal stroke, admission for heart failure (HF), target vessel revascularization (TVR), and all-cause death. Results: During a median follow-up duration of 7.8 years, 280 patients (24.1%) developed 3P-MACE, 134 patients (11.6%) were hospitalized for HF, 171 patients (14.7%) underwent TVR, and 348 patients (30.0%) died of any causes. The cumulative incidence rate of 3P-MACE in the RAS inhibitor group was significantly lower than in the non-RAS inhibitor group (31.7% vs. 39.0%, log-rank test, p = 0.034); however, that of admission for HF in the RAS inhibitor group was significantly higher than in the non-RAS inhibitor group (28.1% vs. 13.3%, log-rank test, p < 0.001). The subgroup of preserved ejection fraction, non-acute myocardial infarction, and non-proteinuria tended to promote the onset of HF rather than cardiovascular prevention by RAS inhibitors. Conclusion: The long-term RAS inhibitor use for patients with CKD after PCI might prevent cardiovascular events but increase the risk of HF.
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AIM: This study aimed to clarify the prevalence, predictors, and prognosis of frailty and sarcopenia in both cross-sectional and longitudinal study of the real world. METHODS: The JUSTICE-TOKYO study is a single-center, prospective observational study of elderly patients. Patients aged ≥65 years who regularly visited our center were enrolled and followed up for 4 years (n = 1042). The diagnosis of sarcopenia and frailty in the enrolled patients was based on the criteria established by the Asian Working Group for Sarcopenia and Japanese version of the Cardiovascular Health Study criteria, respectively. The primary end point is the incidence of all-cause mortality and hospitalization for treatment. The secondary end points are clinically significant bleeding, cardiovascular events, strokes, malignancies, incidence of falling, fractures, pneumonia, and the onset of new dementia cases. RESULTS: A total of 1042 patients were enrolled in this study. The mean age of the cohort at baseline was 78.2 years, with 56% being women. Among the enrolled patients, 223 (21.4%) diagnosed with sarcopenia, 172 (16.5%) exhibited frailty, and 541 (51.9%) fell into the prefrailty category. CONCLUSIONS: The JUSTICE-TOKYO study provides valuable insights into the prevalence of sarcopenia and frailty among older adult outpatients in a real-world context and contributes to measures aimed at extending healthy life expectancy. Geriatr Gerontol Int 2024; 24: 168-172.
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Fragilidade , Sarcopenia , Idoso , Humanos , Feminino , Masculino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/complicações , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/complicações , Tóquio/epidemiologia , Estudos Longitudinais , Estudos Transversais , Prognóstico , Idoso Fragilizado , Avaliação GeriátricaRESUMO
BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes mellitus, dyslipidemia, and smoking) are widely recognized as risk factors for coronary artery disease. However, the associations between absence of SMuRFs and long-term clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients are unclear. METHODS: Consecutive STEMI patients who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 were retrospectively analyzed. The primary endpoint was up to 5-year all-cause mortality. Clinical characteristics and outcomes were compared between patients with at least one of the SMuRFs and those without any SMuRFs. RESULTS: Of 1963 STEMI patients, 126 (6.4â¯%) did not have any SMuRFs. Patients without SMuRFs were significantly older, had lower body mass index, and were more likely to be female. During a median follow-up period of 4.9â¯years, the cumulative incidence of death was significantly higher in patients without SMuRFs than in those with SMuRFs (log-rank pâ¯<â¯0.0001). Landmark analysis showed that patients without SMuRFs had higher mortality within 30â¯days of STEMI onset (log-rank pâ¯=â¯0.0045) and >30â¯days after STEMI onset (log-rank pâ¯=â¯0.0004). Multivariable Cox hazards analysis showed that absence of SMuRFs was associated with a higher risk of mortality (hazard ratio, 1.59; 95â¯% confidence interval, 1.14-2.21; pâ¯=â¯0.006). CONCLUSIONS: Of STEMI patients undergoing primary PCI, patients without any SMuRFs had higher mortality than those with at least one of the SMuRFs. Patients without any SMuRFs have a poor prognosis and require more attention.
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Sarcopenia is a poor prognostic factor in patients with chronic kidney disease (CKD). Adequate dietary patterns are important for preventing sarcopenia; however, evidence regarding the underlying association between sarcopenia and diet is insufficient. Therefore, in this study, we aimed to investigate the association between sarcopenia and dietary patterns in CKD patients receiving conservative treatment. In this cross-sectional study, 441 patients with conservative CKD were examined using the Asian Working Group for Sarcopenia diagnostic criteria. CKD was defined as an eGFR of <60 mL/min/1.73 m2 present for >3 months. The participants were divided into sarcopenia and non-sarcopenia groups, and dietary patterns were compared between the two groups using the dietary variety score, a simple dietary survey method that investigates the weekly frequency of consumption of 10 food groups. Logistic regression analysis for CKD G3 showed that female sex (odds ratio (OR): 0.166, 95% confidence interval (CI): 0.086-0.320), increased body mass index (OR: 0.663, 95% CI: 0.590-0.745), and almost daily consumption of green/yellow vegetables (OR: 0.350, 95% CI: 0.176-0.695) were positively associated with non-sarcopenia. Although further prospective studies are required, the results suggest that low frequent consumption of vegetables is associated with sarcopenia in patients with CKD.
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Insuficiência Renal Crônica , Sarcopenia , Humanos , Feminino , Idoso , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Estudos Transversais , Tratamento Conservador , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , VerdurasRESUMO
Background Thrombocytopenia poses a risk of bleeding in patients with chronic coronary syndrome after coronary intervention. However, whether thrombocytopenia also increases the bleeding risk in patients with atrial fibrillation and chronic coronary syndrome remains unclear. Methods and Results This study evaluated the AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial. Thrombocytopenia was defined as platelet count <100 000/mm3 level at enrollment. Primary end points included incidence of major bleeding based on the International Society on Thrombosis and Hemostasis criterion and major adverse cardiovascular ischemic events (cardiac death, myocardial infarction, and stroke). A total of 2133 patients were classified into the thrombocytopenia (n=70) and nonthrombocytopenia (n=2063) groups. Major bleeding was significantly higher in the thrombocytopenia group than in the nonthrombocytopenia group (10.0% versus 4.1%, P=0.027). The thrombocytopenia group tended to have a higher risk of major adverse cardiovascular ischemic events (11.4% versus 6.2%, P=0.08). The bleeding incidence was significantly higher in patients with thrombocytopenia receiving combination therapy with rivaroxaban and a single antiplatelet drug (thrombocytopenia group, 14.3%, versus nonthrombocytopenia group, 5.0%; hazard ratio, 3.18 [95% CI, 1.27-7.97], P=0.014). Thrombocytopenia was an independent predictor of major bleeding (hazard ratio, 2.57 [95% CI, 1.19-5.56], P=0.017). Conclusions Among patients with atrial fibrillation and chronic coronary syndrome, thrombocytopenia was significantly associated with increased risk of major bleeding. Selecting drugs for patients with thrombocytopenia continuing antithrombotic therapy should be given special consideration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02642419. https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000016612.
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Fibrilação Atrial , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Trombocitopenia , Humanos , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/tratamento farmacológico , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Fatores de Risco , Rivaroxabana/efeitos adversos , Trombocitopenia/epidemiologia , Trombocitopenia/complicações , Resultado do TratamentoRESUMO
BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.MethodsâandâResults: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.
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Fibrilação Atrial , Acidente Vascular Cerebral , Idoso , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , População do Leste Asiático , Medição de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/induzido quimicamente , Sistema de Registros , Fatores de Risco , Anticoagulantes/efeitos adversosRESUMO
BACKGROUND: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin. METHODS: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline. RESULTS: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001). CONCLUSIONS: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.
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Doença da Artéria Coronariana , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Biomarcadores , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Troponina IRESUMO
BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 Assuntos
Doenças Cardiovasculares
, Doença da Artéria Coronariana
, Inibidores de Hidroximetilglutaril-CoA Redutases
, Infarto do Miocárdio
, Hormônios Peptídicos
, Humanos
, Proteína 3 Semelhante a Angiopoietina
, Proteína 8 Semelhante a Angiopoietina
, Doenças Cardiovasculares/sangue
, Doenças Cardiovasculares/induzido quimicamente
, Doenças Cardiovasculares/diagnóstico
, Doenças Cardiovasculares/epidemiologia
, Doença da Artéria Coronariana/sangue
, Doença da Artéria Coronariana/tratamento farmacológico
, Doença da Artéria Coronariana/epidemiologia
, População do Leste Asiático
, Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos
, Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico
, Lipídeos
, Infarto do Miocárdio/tratamento farmacológico
, Resultado do Tratamento
RESUMO
OBJECTIVES: Atrial fibrillation (AF) is a heterogeneous condition. We performed a cluster analysis in a cohort of patients with AF and assessed the prognostic implication of the identified cluster phenotypes. METHODS: We used two multicentre, prospective, observational registries of AF: the SAKURA AF registry (Real World Survey of Atrial Fibrillation Patients Treated with Warfarin and Non-vitamin K Antagonist Oral Anticoagulants) (n=3055, derivation cohort) and the RAFFINE registry (Registry of Japanese Patients with Atrial Fibrillation Focused on anticoagulant therapy in New Era) (n=3852, validation cohort). Cluster analysis was performed by the K-prototype method with 14 clinical variables. The endpoints were all-cause mortality and composite cardiovascular events. RESULTS: The analysis subclassified derivation cohort patients into five clusters. Cluster 1 (n=414, 13.6%) was characterised by younger men with a low prevalence of comorbidities; cluster 2 (n=1003, 32.8%) by a high prevalence of hypertension; cluster 3 (n=517, 16.9%) by older patients without hypertension; cluster 4 (n=652, 21.3%) by the oldest patients, who were mainly female and with a high prevalence of heart failure history; and cluster 5 (n=469, 15.3%) by older patients with high prevalence of diabetes and ischaemic heart disease. During follow-up, the risk of all-cause mortality and composite cardiovascular events increased across clusters (log-rank p<0.001, p<0.001). Similar results were found in the external validation cohort. CONCLUSIONS: Machine learning-based cluster analysis identified five different phenotypes of AF with unique clinical characteristics and different clinical outcomes. The use of these phenotypes may help identify high-risk patients with AF.
Assuntos
Fibrilação Atrial , Hipertensão , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Estudos Prospectivos , Fatores de Risco , Anticoagulantes , Análise por Conglomerados , Hipertensão/tratamento farmacológico , Sistema de RegistrosRESUMO
OBJECTIVE: Antithrombotic therapy is essential for patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) because of the high risk of thrombosis, whereas a combination of antiplatelets and anticoagulants is associated with a high risk of bleeding. We sought to develop and validate a machine-learning-based model to predict future adverse events. METHODS: Data from 2215 patients with AF and stable CAD enrolled in the Atrial Fibrillation and Ischaemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease trial were randomly assigned to the development and validation cohorts. Using the random survival forest (RSF) and Cox regression models, risk scores were developed for net adverse clinical events (NACE) defined as all-cause death, myocardial infarction, stroke or major bleeding. RESULTS: Using variables selected by the Boruta algorithm, RSF and Cox models demonstrated acceptable discrimination and calibration in the validation cohort. Using the variables weighted by HR (age, sex, body mass index, systolic blood pressure, alcohol consumption, creatinine clearance, heart failure, diabetes, antiplatelet use and AF type), an integer-based risk score for NACE was developed and classified patients into three risk groups: low (0-4 points), intermediate (5-8) and high (≥9). In both cohorts, the integer-based risk score performed well, with acceptable discrimination (area under the curve 0.70 and 0.66, respectively) and calibration (p>0.40 for both). Decision curve analysis showed the superior net benefits of the risk score. CONCLUSIONS: This risk score can predict the risk of NACE in patients with AF and stable CAD. TRIAL REGISTRATION NUMBERS: UMIN000016612, NCT02642419.
Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Fatores de RiscoRESUMO
PURPOSE: Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5 mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). METHODS: A total of 348 patients were studied. PRU was measured 6-12 months after PCI and subsequently, 6 months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. RESULTS: At baseline, 136 patients (39%) received prasugrel 3.75 mg, 48 patients (14%) received prasugrel 2.5 mg, and 164 patients (47%) received clopidogrel 75 mg. Clopidogrel 75 mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75 mg. In addition, switching from clopidogrel 75 mg to prasugrel 2.5 mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75 mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75 mg. CONCLUSIONS: Prasugrel 2.5 mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).
RESUMO
BACKGROUND: Recent clinical trials have shown that percutaneous coronary intervention (PCI) for non-culprit lesions (NCLs) reduces the risk of adverse events in patients with ST-segment elevation myocardial infarction (STEMI), but the effect on long-term outcomes remains unclear in acute coronary syndrome (ACS) patients and a real-world clinical setting. METHODS: A retrospective observational cohort study of ACS patients who underwent primary PCI between April 2004 and December 2017 at Juntendo University Shizuoka Hospital, Japan, was performed. The primary endpoint was the composite of cardiovascular disease death (CVD death) and non-fatal myocardial infarction (MI) during the mean follow-up period of 2.7 years, and a landmark analysis for the incidence of the primary endpoint from 31 days to 5 years between the multivessel PCI group and the culprit only PCI group was performed. Multivessel PCI was defined as PCI including non-infarct-related coronary arteries within 30 days after the onset of ACS. RESULTS: Of the 1109 ACS patients with multivessel coronary artery disease of the current cohort, multivessel PCI was performed in 364 (33.2 %) patients. The incidence of the primary endpoint from 31 days to 5 years was significantly lower in the multivessel PCI group (4.0 % vs. 9.6 %, log-rank p = 0.0008). Multivariate Cox regression analysis showed that multivessel PCI was significantly associated with fewer cardiovascular events (HR 0.37, 95 % CI 0.19-0.67, p = 0.0008). CONCLUSION: In ACS patients with multivessel coronary artery disease, multivessel PCI may reduce the risk of CVD death and non-fatal MI compared to culprit-lesion-only PCI.