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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.

Moving particle semi-implicit (MPS) method is a mesh-free method to perform computational fluid dynamics (CFD). The purpose of this study was to calculate the simulated fractional flow reserve (sFFR) using a coronary stenosis model, and to validate the MPS-derived sFFR against invasive FFR using clinical coronary CT data. Coronary flow simulation included 21 stenosis models with stenosis ranging 30–70%. Patient coronary analysis was performed in 76 consecutive patients (100 vessels) who underwent coronary CT angiography and subsequent invasive FFR between November 2016 and March 2020. Accuracy of sFFR and CT angiography for diagnosis of invasive FFR ≤ 0.80 was compared. Quantitative morphological stenosis data of CT angiography were also obtained. Area stenosis showed a good correlation to sFFR (R2= 0.996, p < 0.001) in coronary stenosis models. In the patient study, the mean FFR value was 0.82 ± 0.10, and 37 out of 100 vessels showed FFR ≤ 0.80. FFR and sFFR values showed a good correlation (R2= 0.59, p < 0.001) with a slight underestimation of sFFR as compared with FFR (mean difference − 0.015 ± 0.096, p = 0.12). The sensitivity, specificity, positive predictive value, and negative predictive value of sFFR to predict FFR ≤ 0.80 was 86%, 89%, 82%, 92%, respectively. The accuracy to predict FFR ≤ 0.80 using sFFR was greater than using diameter stenosis and minimum lumen area (88% vs. 74%, p = 0.008). CFD using the MPS method showed feasible results validated against invasive FFR. The accuracy to predict significant stenosis was higher than morphological stenosis.

Lysophosphatidic acids (LysoPAs) and lysophosphatidylserine (LysoPS) are emerging lipid mediators proposed to be involved in the pathogenesis of acute coronary syndrome (ACS). In this study, we attempted to elucidate how LysoPA and LysoPS become elevated in ACS using human blood samples collected simultaneously from culprit coronary arteries and peripheral arteries in ACS subjects. We found that: 1) the plasma LysoPA, LysoPS, and lysophosphatidylglycerol levels were not different, while the lysophosphatidylcholine (LysoPC), lysophosphatidylinositol, and lysophosphatidylethanolamine (LysoPE) levels were significantly lower in the culprit coronary arteries; 2) the serum autotaxin (ATX) level was lower and the serum phosphatidylserine-specific phospholipase A1(PS-PLA1) level was higher in the culprit coronary arteries; 3) the LysoPE and ATX levels were significant explanatory factors for the mainly elevated species of LysoPA, except for 22:6 LysoPA, in the peripheral arteries, while the LysoPC and LysoPE levels, but not the ATX level, were explanatory factors in the culprit coronary arteries; and 4) 18:0 and 18:1 LysoPS were significantly correlated with PS-PLA1only in the culprit coronary arteries. In conclusion, the origins of LysoPA and LysoPS might differ between culprit coronary arteries and peripheral arteries, and substrates for ATX, such as LysoPC and LysoPE, might be important for the generation of LysoPA in ACS.

This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre–percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS.

Glycero-lysophospholipids (glycero-LPLs), which are known to exert potent biological activities, have been demonstrated to be secreted from activated platelets in vitro; however, their association with platelet activation in vivohas not been yet elucidated. In this study, we investigated the correlations between the blood levels of each glycero-LPL and serotonin, a biomarker of platelet activation, in human subjects to elucidate the involvement of platelet activation in glycero-LPLs in vivo.

Introduction:Treatment for Multiple Myeloma (MM) with new therapeutic agents has dramatically improved outcomes and increased the number of survivors. Although venous thromboembolism (VTE) is common in MM, the pathophysiological interplay between VTE and MM, including risk factors related to the patient, disease, and modern treatments, is complex and incompletely understood.Objectives:To evaluate real-world data on the risk factors of VTE and outcomes of patients with MM using a nationwide claims database.Methods:This study involved the retrospective observational analysis of the Japan Medical Data Center (JMDC, Tokyo, Japan) database, an anonymized patient-level claims database younger than 75 years old. We identified cases with diagnosis and treatment of MM with codes provided by JMDC. Patients with a tentative diagnosis code of MM [C90] were included. Cases with a history of VTE or a pre-diagnostic history of fewer than six months were excluded. Propensity score (PS) was calculated using logistic regression based on age, gender, and cardiovascular risk factors.Results:We identified 2,023 eligible cases (mean age 53.6 ± 11.8 years) between January 2015 and December 2020. After 1:1 PS matching, the number of patients, mean age (years), follow-up (months) were as follows: MM group (n=280, 58.7 ± 8.1, 18.6 ± 14.8), Control group (n=280, 58.5 ± 8.1, 24.4 ± 18.4). Kaplan-Meier analysis indicated that the rate of VTE within 60 months was significantly higher among MM than in Control (25.7% vs 2.5%, Log-rank p<.001). Within the MM group, multivariable Cox proportional hazard model showed that lenalidomide had a risk of VTE (Hazard Ratio 1.16 [95% Confidence Interval: 1.19-7.69]) among modern therapies (stem cell transplantation 37.1%, elotuzumab 6.4%, daratumumab 16.8%, bortezomib 88.9%, carfilzomib 21.8%, ixazomib 11.8%, thalidomide 3.9%, lenalidomide 78.9%, and pomalidomide 15.4%).Conclusions:Patients who underwent modern MM therapies, including immunomodulatory agents, had significantly higher VTE risk than PS-matched Control. Therefore, further studies using real-world data to improve prevention, early detection, and treatment of MM-related VTE are warranted.

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The aim of this study was to investigate whether effective suppression of central sleep apnea (CSA) by adaptive servo-ventilation (ASV) improves underlying cardiac dysfunction among patients with heart failure (HF) in whom CSA was not effectively suppressed by continuous positive airway pressure (CPAP).

The metabolic syndrome is associated with high risk for long-term coronary artery disease mortality. However, few studies have examined the prognostic importance of the metabolic syndrome with and without hypertension.

Therapy with continuous positive airway pressure (CPAP) provides several benefits for patients with heart failure (HF) complicated by obstructive sleep apnea (OSA). However, the effect on the prognosis of such patients remains unknown.

Background:Little is known about the long-term impact of apolipoprotein E (apoE) on residual cardiovascular risk in the patients with chronic coronary syndrome (CCS) receiving statin treatment.Methods:A total of 1109 consecutive patients (mean age, 67±10 years; 83% men) with CCS who underwent their first intervention between 2000 and 2016 were included in this study. All patients had achieved LDL-C <100 mg/dL on statin treatment, as target value recommended by the guidelines at that time, and were divided into two groups based on median serum apoE value. We evaluated the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, and target vessel revascularization.Results:A total of 552 and 557 patients were categorized to the higher, and lower apoE groups, respectively. There were significant relationships between apoE levels and total cholesterol levels, triglyceride levels, high-density lipoprotein cholesterol levels and estimated remnant cholesterol except for LDL-C levels. During the median follow-up period of 5.1 years, 195 patients (17.6%) developed MACEs. Kaplan-Meier analysis revealed that the cumulative incidence of MACEs in the higher apoE group was significantly higher than in the lower apoE group (29.5% vs.23.8% log-rank test, p =0.019). On multivariable Cox hazard analysis, serum apoE level (1-mg/dL increase) (hazard ratio 1.15; 95% confidence interval 1.03-1.29, p=0.013) was a most strongly independent predictor of MACEs. Furthermore, after adjustment for various confounders including TG, HDL-C, LDL-C, and traditional cardiovascular risk factors, the higher apoE group was significantly associated with an increased risk of MACEs compared with the lower apoE group (p =0.008).Conclusions:Serum ApoE level could be a strong predictor and residual cardiovascular risk in patients with CCS on long-term, even if controlled LDL-C levels with statin treatment.

Background and Objective:Living alone is reported as an independent risk factor for worse clinical outcomes after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Manifestations of psychological stress in patients living alone is reported to be associated with subsequent cardiovascular events. The impact of living alone on the psychological factors of patients may be differ depending on their living environment. However, comparison of the effects of living alone in different living environment on the prognosis of patients with ACS has not been reported.Purpose:The aim of the study was to compare the effect of living alone on clinical outcomes in patients with ACS between urban and rural area.Methods:Data from a multi-center, observational study of consecutive ACS patients who underwent emergency PCI between January 2012 and December 2016 were analyzed. The clinical endpoint was major adverse cardiovascular events (MACE) which defined as composite of cardiovascular death, ACS, and stroke.Results:In this study, 1349 patients were enrolled and divided into two population according to their living environment; urban area (n=417), and rural area (n=932). 87 patients (20.9 %) in urban area, and 169 patients (18.1 %) in rural were living alone. There were no significant differences in baseline characteristics between the living alone and the living together group in both urban and rural area. During a median follow-up period of 2.1 years, Kaplan-Meier curves showed the living alone group had higher risk of MACE than the living together group in urban area (log-rank, p=0.01). On the other hands, no significant differences were shown in the incidences of MACE between two groups in rural area (p=0.86). After adjustment for other covariates, the living alone was significantly associated with MACE (hazard ratio [HR], 2.83; 95 % confidential interval [CI], 1.16-6.91; p=0.02) compared with the living together in urban area. However, in rural area, the living alone group was not significantly associated with MACE (HR, 1.02; 95 % CI, 0.66-1.57; p=0.92) compared with the living together group.Conclusion:Living alone was significantly associated with worse clinical outcomes after emergency PCI of ACS in urban area but not in rural area.

Introduction:The evidence-based optimal medical therapy has been encouraged in the treatment of patients with coronary artery disease. However, as follow-up periods are limited (-5 years) in the most of randomized trials, prognostic efficacy of drugs in longer time period has not been fully evaluated. Therefore, this registry-based study aimed to simultaneously address the long-term prognostic impact of 6 major classes of cardiovascular (CV) drugs, beta-blockers (BBs), calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), Statins and Non-aspirin antiplatelets following percutaneous coronary intervention (PCI).Methods and Results:This is an analyses of single center prospective registry with lengthy history launched in 1984. Consecutive 6,299 patients underwent first PCI between 1984 and 2018 were included and CV mortality was set as the endpoint. Median and the range of follow-up period is 8.8, 0-28.9 years, respectively. Cox proportional hazard analyses adjusted by age, gender, BMI, diabetes and cardiac and renal function simultaneously evaluated the prognostic impacts of 6 major CV drugs in the entire population and patients with acute coronary syndrome (ACS). Among 6 drugs, ARBs (Hazard Ratio (HR): 0.72, 95% confidence interval (95% CI): 0.55-0.93, p=0.01), Non-aspirin antiplatelets (0.67, 0.53-0.86, p=0.002) and Statins (0.56, 0.44-0.7, p<0.001) were significantly associated with reduced risk of CV mortality in the entire PCI population (Figure A). In ACS patients (n=1,790), only Statins at PCI predicted the reduced risk of CV mortality (HR: 0.44, 95%CI 0.28-0.68 p<0.001) (Figure B).Conclusions:This long-term PCI registry-based analyses demonstrated the significant prognostic efficacy of ARBs, antiplatelets other than aspirin and statins. In ACS patients, only Statins, not other 5 classes of major CV drugs, were associated with reduced risk of CV mortality.

Background:Anemia is one of the most common complications of chronic kidney disease (CKD), renal anemia, which has a significant link with increased risk of the morbidity, as well as the mortality of cardiovascular disease. However, the prognostic implication of the temporal change of anemia status has been rarely addressed, especially in secondary prevention of coronary artery disease (CAD).Methods and Results:This long-term (median follow-up range: 5.7 years) single center observational study involved consecutive 416 patients with CKD over stage 3 (defined by eGFR<60 ml/1.72/m2) who underwent percutaneous coronary intervention (PCI) for the first time since 2003 to 2018. All-cause death was set as an endpoint. Participants were divided into 4 groups by the median of hemoglobin (Hb) at PCI (baseline, 12.0 mg/dl) and 8.1±2.1 months after PCI (follow-up, 12.7 mg/dl), respectively: Groups of Continuously high-Hb (n=146), Increased-Hb (n=51), Attenuated-Hb (n=61) and Persistently low-Hb (n=158). Categorized Cox proportional hazard analysis with setting Continuously high-Hb group as a reference showed a significantly increased risk of all-cause death in groups of Attenuated- (Hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.2, p=0.01) and Persistently low-Hb (HR 2.6, 95%CI 1.4-4.8, p=0.002), respectively, while similar in Increased-Hb group (HR 1.1, 95%CI 0.3-3.2, p>0.5) (Figure).Conclusion:This study showed a significant association between the reduced Hb overtime and increased mortality risk in patients with CKD and CAD, which might potentially indicate a prognostic merit of the intervention for renal anemia in this population.

Hypertension and constipation are major hemodialysis complications. Salt restriction is one of the most important nonpharmacological interventions in managing hypertension. In patients undergoing hemodialysis, nonpharmacological strategies to manage constipation are extremely difficult to develop owing to the presence of excess dietary potassium and fluids. Frugra®, which is a cereal food that has a low salt content of 0.5 g per serving, may help reduce salt intake. Additionally, Frugra is rich in dietary fiber, thereby beneficial for such patients. In this study, we evaluated the safety and efficacy of Frugra in patients undergoing hemodialysis, focusing mainly on blood pressure and bowel health by changing the usual breakfast meal to Frugra for 8 weeks. We enrolled 11 patients undergoing hemodialysis. Despite the absence of changes in the patients’ dry weight levels, their systolic blood pressure levels decreased from 155.5 ± 20.9 mmHg to 137.9 ± 10.3 mmHg after 2 months (P < 0.05). All participants reported improvements in bowel movement, and the levels of indoxyl sulfate, a representative gut-derived uremic toxin, were decreased from 49.3 μg/ml to 33.4 μg/ml. Furthermore, adverse events including electrolyte abnormalities were not observed. Therefore, Frugra may be useful to manage the health of patients undergoing hemodialysis.

Background:Serum levels of Lipoprotein(a) [Lp(a)] have been reported as a residual risk marker for adverse events in patient coronary artery disease (CAD). However, the prognostic impact of Lp(a) on long-term clinical outcomes in diabetic patients with CAD underwent percutaneous coronary intervention (PCI) remains unclear.Methods:The present investigation was a single-center, observational, retrospective cohort study. Among consecutive patients with CAD who underwent first PCI in our institution from 2000 to 2016, we enrolled diabetic patients on statin treatment. As results, 927 patients (81% men; mean age 66 years) were enrolled and divided into 2 groups according to the median Lp(a) level of 19.5 mg/dL. The incidence of major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI) and non-fatal cerebral infarction (CI), was evaluated.Result:No significant differences were seen in age, sex, smoking habits, hypertension, chronic kidney disease or body mass index between the high and low Lp(a) groups. During a median follow-up period of 5.0 years (interquartile range, 1.9-9.7), MACE occurred 90 cases (17.6%) including 40 (7.9%) cardiac deaths, 18 (3.6%) non-fatal MI, and 37 (7.9%) non-fatal CI. The incidence of MACE was significantly higher in the high Lp(a) group than the low Lp(a) group (log-rank test, p = 0.002). Higher Lp(a) levels at the time of PCI was significantly associated with higher rate of adverse cardiac events even after adjustment for other covariates including other lipid profiles (HR 1.96, 95%CI 1.26-3.12, p = 0.003).Conclusion:Our results have demonstrated that in diabetic patients with CAD on statin treatment increased Lp(a) levels could be good residual lipid risk marker. Assessing Lp(a) levels may be useful for risk stratification on long-term clinical outcomes after PCI.

Background:Although a recent clinical research shows the impact of Residual inflammatory risk (RIR) after percutaneous coronary intervention (PCI) in Western population, some differences in high sensitive C-reactive protein (hsCRP) levels have been reported between ethnicities. The aim of this study was to investigate the long-term clinical impact of RIR evaluating serial hsCRP in Asian patients with coronary artery disease (CAD).Methods:This is a single-center, observational, retrospective cohort study assessing 2,032 Japanese patients with stable CAD who underwent first PCI with serial hsCRP measurements (2 measurements 6-9 months apart) from 2000 to 2016. High RIR was defined as hsCRP > 0.9 mg/l according to the median value. Patients were assigned to four groups as persistent high RIR, increased RIR (first low- then high hsCRP), attenuated RIR (first high- then low hsCRP), or persistent low RIR. The incidence of major adverse cardiac events (MACE) and all-cause death were evaluated (median follow-up period: 4.9 years).Results:Of patients (83% men; mean age 66 years), 584 patients (28.7%) had persistent high RIR, 162 patients (8.2%) had increased RIR, 425 patients (20.9%) had attenuated RIR, and persistent low RIR was seen in 857 (42.2%). The rate of MACE in patients with persistent high, increased and attenuated RIR were significantly higher than that with persistent low RIR (p<0.001). In addition, the rate of all-cause death in patients with persistent high and increased RIR was significantly higher than those with attenuated and persistent low RIR (p <0.001). After adjustment, the presence of persistent high RIR were associated with higher incidence of MACE and higher all-cause mortality (both p = 0.001) (shown on figure).Conclusion:High RIR was significantly associated with MACE and all-cause death in Asian patients after PCI. Evaluation of change in inflammation carries important prognostic information and may guide the therapeutic approach.

Background:Red cell distribution width (RDW) has been shown to be an independent risk factor for increased cardiovascular mortality, heart failure or cardiovascular disease. However, the association between RDW and long-term clinical outcomes in patients with stable coronary artery disease (CAD) remains uncertain. Purpose:The purpose of this study is to examine the predictive value of RDW levels in patients with stable CAD.Methods:We enrolled 2,881 stable CAD patients who underwent their first percutaneous coronary intervention (PCI) and who had available data on pre-procedural RDW between 2002 and 2016. Among these, 1,827 patients without anemia and severe renal dysfunction were divided into quartiles based on their RDW values. The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction, were evaluated.Results:The median RDW was 13.0 % (interquartile range: 12.7-13.5). During a median follow-up of 6.2 years, 209 (11.4%) MACE were identified. Kaplan-Meier curves showed the highest RDW quartile group had clearly higher incidence of MACE (log-rank p=0.0002, Figure). After adjustment for other risk factors, the highest RDW group had a significantly higher risk of MACE compared with the lowest RDW group (HR 1.54, 95%CI 1.03-2.32, p=0.03). Increasing RDW as a continuous variable was also associated with the incidence of MACE (HR 1.37 per 1% increase, 95%CI 1.20-1.58, p<0.0001).Conclusions:Increased RDW was associated with worse clinical outcomes after elective PCI. Assessing pre-PCI RDW may be useful for risk stratification of stable CAD.

Previous studies demonstrated no significant effect of statins to reduce risk of cardiovascular events in patients with chronic hemodialysis (HD) and current guidelines recommend avoid initiation of statin in such population. Furthermore, it has been rarely addressed whether statins have beneficial effect on secondary prevention in patients with hemodialysis and established coronary artery disease (CAD). In this study, we evaluated the efficacy of statins on the prognosis in hemodialysis patients (HD+) and compared with those who without hemodialysis (HD-) underwent percutaneous coronary intervention (PCI).Methods:A single center registry database launched since 1984 enrolled consecutive patients who underwent PCI at Juntendo University Hospital for the first time between January 2000 and December 2016 (n=4542). Patients were divided into two groups as with and without chronic hemodialysis (HD(-) (n=4341) and HD(+) (n=201), respectively). Patients underwent just temporary hemodiafiltration and peritoneal dialysis were not included in HD(+) group. Primary endpoint was cardiovascular (CV) mortality. Median and range follow-up period was 5.8 (0-17.8) years, respectively.Results:Kaplan-Meier analysis showed significantly lower cumulative incidence of CV death in patients receiving statins in both groups (Figure). Multivariate Cox proportional hazards analysis adjusted by age, gender and diabetes identified statins as an independent predictor of reduced risk of CV death, and hazard ratios were comparable in both groups. (HD(-): Hazard ratio (HR): 0.60, 95% confidence interval (CI): 0.47-0.76, p<0.001, HD(+): HR: 0.38, 95%CI: 0.17-0.79, p=0.008), interaction P>0.05).Conclusions:Statin therapy may be associated with reduced risk of CV death in secondary prevention of patients with chronic hemodialysis.

Background:A low 1,5-anhydro-d-glucitol (AG) blood level is considered a clinical marker of postprandial hyperglycemia. Previous studies reported that 1,5-AG levels were associated with vascular endothelial dysfunction and coronary artery disease (CAD). However, the association between 1,5-AG levels and coronary artery plaque in patients with CAD is unclear.Methods:This study included 161 patients who underwent percutaneous coronary intervention for CAD. The culprit plaque characteristics and the extent of coronary calcification, which was measured by the angle of its arc, were assessed by preintervention intravascular ultrasound (IVUS). Patients with chronic kidney disease or glycosylated hemoglobin ?7.0 were excluded. Patients were divided into 2 groups according to serum 1,5-AG levels (<14.0 ?g/mL vs. ?14 ?g/mL).Results:The total atheroma volume and the presence of IVUS-attenuated plaque in the culprit lesions were similar between groups. Calcified plaques were frequently observed in the low 1,5-AG group (p = 0.06). Compared with the high 1,5-AG group, the low 1,5-AG group had significantly higher median maximum calcification (144? vs. 107?, p = 0.03) and more frequent calcified plaques with a maximum calcification angle of ?180? (34.0% vs. 13.2%, p = 0.003). Multivariate logistic regression analysis showed that a low 1,5-AG level was a significant predictor of a greater calcification angle (>180?) (OR 2.64, 95% CI 1.10-6.29, p = 0.03).Conclusions:Low 1,5-AG level, which indicated postprandial hyperglycemia, was associated with the severity of coronary artery calcification. Further studies are needed to clarify the effects of postprandial hyperglycemia on coronary artery calcification.

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