Integrating mitochondrial and nuclear genomic data to decipher the evolutionary history of Eubranchipus species in Japan.

Understanding the genetic diversity and evolutionary history of species is crucial for their conservation and management. In this study, we investigated the genetic diversity and phylogenetic relationships among Eubranchipus species occurring in Japan. Phylogenetic analyses revealed that nuclear and mitochondrial data yield incompatible results. In E. uchidai, nuclear data support the monophyly of the Shimokita area, while mitochondrial data indicate a clustering of Higashidori2 individuals with Hokkaido (Ishikari and Wakkanai) E. uchidai. Similar incongruences were observed in E. hatanakai, where nuclear data favor the monophyly of the Chokai area, while mitochondrial data cluster some Chokai pool 3 individuals with Aizu individuals. These incompatibilities might be caused by mitochondrial gene flow. The findings emphasize the importance of considering both nuclear and mitochondrial data during phylogenetic studies and provide valuable insights into the complex dynamics of migration and genetic exchange in Eubranchipus species.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: 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. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Impact of Low-Dose Prasugrel on Platelet Reactivity in Chronic Phase of Post-Percutaneous Coronary Intervention (CHAPERON): a Prospective Cohort Study.

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 ).

Design and synthesis of 14 and 15-membered macrocyclic scaffolds exhibiting inhibitory activities of hypoxia-inducible factor 1α.

Inspired by the privileged molecular skeletons of 14- and 15-membered antibiotics, we adopted a relatively unexplored synthetic approach that exploits alkaloidal macrocyclic scaffolds to generate modulators of protein-protein interactions (PPIs). As mimetics of hot-spot residues in the α-helices responsible for the transcriptional regulation, three hydrophobic sidechains were displayed on each of the four distinct macrocyclic scaffolds generating diversity of their spatial arrangements. Modular assembly of the building blocks followed by ring-closing olefin metathesis reaction and subsequent hydrogenation allowed concise and divergent synthesis of scaffolds 1-4. The 14-membered alkaloidal macrocycles 2-4 demonstrated similar inhibition of hypoxia-inducible factor (HIF)-1α transcriptional activities (IC50 between 8.7 and 10 µM), and 4 demonstrated the most potent inhibition of cell proliferation in vitro (IC50 = 12 µM against HTC116 colon cancer cell line). A docking model suggested that 4 could mimic the LLxxL motif in HIF-1α, in which the three sidechains are capable of matching the spatial arrangements of the protein hot-spot residues. Unlike most of the stapled peptides, the 14-membered alkaloidal scaffold has a similar size to the α-helix backbone and does not require additional atoms to induce α-helix mimetic structure. These experimental results underscore the potential of alkaloidal macrocyclic scaffolds featuring flexibly customizable skeletal, stereochemical, substitutional, and conformational properties for the development of non-peptidyl PPI modulators targeting α-helix-forming consensus sequences responsible for the transcriptional regulation.

Long-term impact of high-sensitivity C-reactive protein in patients with intermittent claudication due to peripheral artery disease following endovascular treatment.

Little is known about the prognostic impact of high-sensitivity C-reactive protein (hs-CRP) levels on causes of death during long-term follow-up. We, therefore, investigated the associations between hs-CRP and clinical outcomes in the patients with intermittent claudication. Three hundred thirty-five consecutive patients (mean age, 72 ± 8 years, 82% men) undergoing first intervention for de novo iliac and/or femoropopliteal artery lesions from 2009 to 2020 were studied. Patients were divided into 2 groups based on the optimal cutoff value of hs-CRP (> or ≤ 0.15 mg/dL). The median follow-up duration was 3.6 years (interquartile range, 1.0-6.2 years). Although the cumulative incidence rate of major adverse cardiovascular limb events was not significantly different between the higher and lower hs-CRP groups (29.0 and 22.1%, respectively; log-rank test, p = 0.410), that of all-cause death was significantly higher in the higher hs-CRP group than in the lower hs-CRP group (18.7 vs. 5.8%, log-rank test, p = 0.007), even in cardiovascular-related death and malignancy-related death (log-rank test, p = 0.030 and 0.046, respectively). Higher hs-CRP levels at the time of intervention were significantly associated with higher frequency of all-cause death, even after adjusting for other risk factors (hazard ratio 2.79; 95% confidence interval 1.66-7.17, p = 0.024). In addition, malignancy-related death was most frequent as high as 60% (21/35 deaths), and elevated hs-CRP levels and the Brinkman index were strongly independent predictors of malignancy-related death. In conclusion, elevated hs-CRP levels were significantly associated with cardiovascular-related and malignancy-related deaths in patients with intermittent claudication. Furthermore, the result that cancer mortality exceeds cardiovascular mortality is different from previous reports, so the present findings warrant further investigation.

The prognostic implications of chronic kidney disease and anemia on long-term outcomes in patients undergoing percutaneous coronary intervention.

Chronic kidney disease (CKD) and anemia are each individually associated with worse clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic impact of both CKD and anemia on clinical outcomes, when they coexist, remains unclear in CAD patients after percutaneous coronary intervention (PCI). We studied 2484 CAD patients who underwent their first PCI and had available date on preprocedural hemoglobin between 2000 and 2016. The patients were divided into four groups according to the presence of CKD and/or anemia. We evaluated the incidences of all-cause death and major adverse cardiac and cerebrovascular events (MACCEs), including cardiovascular death, non-fatal myocardial infarction, and stroke. Among the patients, 310 patients (12.5%) had both CKD and anemia (CKD with anemia group), 309 (12.4%) had CKD only, 461(18.6%) had anemia only, and 1404 (56.5%) had neither CKD nor anemia. Patients in the CKD with anemia group were older and had a higher incidence of hypertension and diabetes mellitus. During a median follow-up period of 3.7 years, Kaplan-Meier curves showed that patients in the CKD with anemia group had significantly higher incidences of MACCE and all-cause death than the CKD only and anemia only group (both log-rank p < 0.001). Using patients with the no CKD or anemia group as a reference, the adjusted hazard ratios (HRs), 95% confidence interval for MACCE were 1.51 (0.92-2.47) for the CKD only, 1.48 (0.94-2.32) for the anemia only and 2.00 (1.18-3.38) for the CKD with anemia group. Moreover, the adjusted HR for all-cause death were 1.42 (0.96-2.10) for the CKD only, 1.79 (1.28-2.51) for the anemia only, and 1.92 (1.30-2.84) for the CKD with anemia group. In conclusion, the combined effects of both CKD and anemia on outcomes after PCI were worse than either of their individual effects.

High Apolipoprotein E Levels Predict Adverse Limb Events in Patients with Peripheral Artery Disease Due to Peripheral Artery Disease Undergoing Endovascular Treatment and On-Statin Treatment.

Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.

Clinical Characteristics and Long-Term Outcomes of Patients with Acute Coronary Syndrome During Travel.

Cardiovascular disease is a major cause of death among travelers, but the clinical characteristics and clinical outcomes of patients who develop acute coronary syndrome (ACS) while traveling have not been assessed. We evaluated 2548 patients with ACS who underwent primary percutaneous coronary intervention (PCI) between 1999 and 2015 and compared the incidences of all-cause and cardiac death during follow-up between travelers and locals. We assessed 192 (7.5%) patients who developed ACS while traveling. These patients were younger and had a higher prevalence of ST-elevation myocardial infarction than local patients. During a median follow-up period of 5.3 years, 632 (24.8%) all-cause deaths were identified, including 310 cardiac deaths (12.2%). Kaplan-Meier analysis revealed that the cumulative incidence of all-cause death was significantly lower among the travelers than locals (P = 0.001, log-rank test). Multivariate Cox hazard analysis revealed that travel was significantly associated with a lower rate of all cause death (hazard ratio, 0.53; 95% confidence interval, 0.33-0.80; P = 0.002). Cardiac mortality did not significantly differ between travelers and locals (P = 0.29). Patients with ACS treated with primary PCI while traveling had more favorable long-term clinical outcomes than local patients. Appropriate initial treatments and secondary preventions might improve the prognosis of travelers.

Rapid and Systematic Exploration of Chemical Space Relevant to Artemisinins: Anti-malarial Activities of Skeletally Diversified Tetracyclic Peroxides and 6-Aza-artemisinins.

To achieve both structural changes and rapid synthesis of the tetracyclic scaffold relevant to artemisinins, we explored two kinds of de novo synthetic approaches that generate both skeletally diversified tetracyclic peroxides and 6-aza-artemisinins. The anti-malarial activities of the tetracyclic peroxides with distinct skeletal arrays, however, were moderate and far inferior to artemisinins. Given the privileged scaffold of artemisinins, we next envisioned element implantation at the C6 position with a nitrogen without the trimmings of substituents and functional groups. This molecular design allowed the deep-seated structural modification of the hitherto unexplored cyclohexane moiety (C-ring) while keeping the three-dimensional structure of artemisinins. Notably, this approach induced dramatic changes of retrosynthetic transforms that allow an expeditious catalytic asymmetric synthesis with generation of substitutional variations at three sites (N6, C9, and C3) of the 6-aza-artemisinins. These de novo synthetic approaches led to the lead discovery with substantial intensification of the in vivo activities, which undermine the prevailing notion that the C-ring of artemisinins appears to be merely a structural unit but to be a functional area as the anti-malarial pharmacophore. Furthermore, we unexpectedly found that racemic 6-aza-artemisinin (33) exerted exceedingly potent in vivo efficacies superior to the chiral one and the first-line drug, artesunate.

A fully synthetic 6-aza-artemisinin bearing an amphiphilic chain generates aggregates and exhibits anti-cancer activities.

Installation of a nitrogen at the C6 position of artemisinin facilitates the addition of a functional unit on the cyclohexane moiety (C-ring). In this study, conjugation of an amphiphilic chain, composed of sequentially connected hydrophilic oligoethylene glycol, hydrophobic alkyl chain, urea, and 4,4'-disubstituted biphenyl linker, imparted self-assembling properties. The fully synthetic mid-molecular weight 6-aza-artemisinin 6 bearing the amphiphilic moiety formed aggregates (approx. 200 nm) at ambient temperature and exhibited increased in vitro anti-cancer activities compared to the N-benzylated aza-artemisinin 5.

Impact of LR11 as Residual Risk on Long-Term Clinical Outcomes in Patients with Coronary Artery Disease Treated with Statins after First Percutaneous Coronary Intervention.

Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.

Neutrophil to Lymphocyte Ratio and Long-Term Cardiovascular Outcomes in Coronary Artery Disease Patients with Low High-Sensitivity C-Reactive Protein Level.

Although an elevated neutrophil to lymphocyte ratio (NLR) has been associated with the adverse outcomes of coronary artery disease (CAD), less is known about its prognostic value among patients with low high-sensitivity C-reactive protein (hs-CRP) levels. We enrolled 2,591 consecutive patients with stable CAD who underwent elective percutaneous coronary intervention (PCI) and had available data on preprocedural hs-CRP and NLR between 2000 and 2016. Of these patients, 1,951 with low-grade hs-CRP levels (< 2.0 mg/L) were divided into quartiles based on the NLR values. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke after the index PCI. Clinical follow-up data were obtained up to 5 years. The median NLR was 1.9 (interquartile range: 1.5-2.5). During the follow-up, 102 events occurred (5.2%), with a cumulative incidence that was significantly higher in the highest NLR group than in the other groups (log-rank, P = 0.02). After adjusting for the other cardiovascular risk factors, the risk for the primary endpoint was significantly higher for the highest than in the lowest NLR group (HR 1.97, 95% CI 1.09-3.54, P = 0.02). Increasing NLR as a continuous variable was associated with the incidence of adverse cardiovascular events (HR 1.85 per log 1 NLR increase, 95% CI 1.19-2.88, P = 0.007). In conclusion, the adverse long-term clinical outcomes of CAD patients with low-grade hs-CRP levels has been independently predicted by increased NLR level. NLR could be useful for risk stratification of CAD patients with increased inflammatory marker levels.

Prognostic Impact of B-Type Natriuretic Peptide on Long-Term Clinical Outcomes in Patients with Non-ST-Segment Elevation Acute Myocardial Infarction Without Creatine Kinase Elevation.

Although B-type natriuretic peptide (BNP) has gradually gained recognition as an indicator in risk stratification for patients with acute myocardial infarction (AMI), the prognostic impact on long-term clinical outcomes in patients with non-ST-segment elevation acute myocardial infarction (NSTEMI) without creatine kinase (CK) elevation remains unclear.This prospective multicenter study assessed 3,283 consecutive patients with AMI admitted to 28 institutions in Japan between 2012 and 2014. We analyzed 218 patients with NSTEMI without CK elevation (NSTEMI-CK) for whom BNP was available. In the NSTEMI-CK group, patients were assigned to high- and low-BNP groups according to BNP values (cut-off BNP, 100 pg/mL). The primary endpoint was defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, cardiac failure, and urgent revascularization for unstable angina up to 3 years. Primary endpoints were observed in 60 (33.3%) events among patients with NSTEMI-CK. Kaplan-Meier analysis revealed a significantly higher event rate for primary endpoints among patients with high BNP (log-rank P < 0.001). After adjusting for covariates, a higher BNP level was significantly associated with long-term clinical outcomes in NSTEMI-CK (adjusted hazard ratio, 4.86; 95% confidence interval, 2.18-12.44; P < 0.001).The BNP concentration is associated with adverse long-term clinical outcomes among patients with NSTEMI-CK who are considered low risk. Careful clinical management may be warranted for secondary prevention in patients with NSTEMI-CK with high BNP levels.

Impact of serum 1,5-anhydro-D-glucitol level on the prediction of severe coronary artery calcification: an intravascular ultrasound study.

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 µg/mL vs. ≥ 14 µg/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.

Outcome after primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction complicated by cardiogenic shock.

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 0 day to 1 year and from 1 to 10 years. RESULTS: Among the 1758 STEMI patients in the cohort, 212 (12.1 %) patients with CS showed significantly higher 30-day CVD rate on admission than those without (26.4 % vs 2.9 %). Landmark Kaplan-Meier analysis showed that CVD from day 0 to year 1 was significantly higher in the patients with CS (log-rank p < 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; p < 0.0001), but the mortality rates from 1 to 10 years were comparable (log-rank p = 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 >1 year were comparable. Surviving the early phase is essential for patients with STEMI and CS to improve long-term outcomes.

Long-Term Impact of Renin-Angiotensin System Inhibitors for Secondary Prevention in Patients with Chronic Kidney Disease Who Underwent Percutaneous Coronary Intervention.

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.

Impact of simple equation for estimating appendicular skeletal muscle mass in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

Background: Sarcopenia, which is evaluated based on appendicular skeletal muscle mass (ASM) using dual-energy X-ray absorptiometry and bioelectrical impedance analysis, is a prognostic predictor for adverse outcomes in patients with coronary artery disease (CAD). However, a simple equation for estimating ASM is yet to be validated in clinical practice. Methods: We enrolled 2211 patients with CAD who underwent percutaneous coronary intervention at our hospital between 2010 and 2017. The mean age was 68 years and 81.5 % were men. Patients were divided into 2 groups based on each ASM index (ASMI): low; male < 7.3 and female < 5.0 and high; male ≥ 7.3 and female ≥ 5.0. ASM was calculated using the following equation: 0.193 × bodyweight + 0.107 × height - 4.157 × gender - 0.037 × age - 2.631. Primary endpoints were major adverse cardiac events (MACE, which includes cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure), and all-cause mortality. Results: During the median follow-up period of 4.8 years, cumulative incidence of events were significantly higher in the low ASMI group. Cox proportional hazards model revealed that the low ASMI group had a significantly higher risk of primary endpoints than the high ASMI group (all-cause mortality; hazard ratio (HR): 2.13, 95 % confidence interval [CI]: 1.40-3.22, p < 0.001 and 4-point MACE; HR: 1.72, 95 % CI: 1.12-2.62, p = 0.01). Similar trends were observed after stratification by age of 65 years. Conclusion: Low ASMI, evaluated using the aforementioned equation, is an independent predictor of MACE and all-cause mortality in patients with CAD.

Paradoxical Long-Term Impact Between Serum Apolipoprotein E and High-Density Lipoprotein Cholesterol in Patients Undergoing Percutaneous Coronary Intervention.

AIM: Apolipoprotein E (ApoE) strongly affects arteriosclerosis but has atheroprotective effects in combination with high-density lipoprotein cholesterol (HDL-C). The impact of the quantitative relationship between serum ApoE and HDL-C levels in patients with coronary artery disease (CAD) remains unclear. METHODS: A total of 3632 consecutive patients who underwent their first intervention between 2000 and 2016 were included. They were categorized into normal and abnormal HDL-C groups based on the normal HDL-C value, and each group was subdivided into high and low ApoE subgroups based on the group-specific median ApoE value. We evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and all-cause deathResults: During a 6.4-year follow-up, 419 patients developed MACCE and 570 patients died. The interaction term between ApoE levels and HDL-C status in MACCE and all-cause death proved to be statistically significant. Kaplan-Meier analysis revealed that the cumulative incidence of MACCE was significantly higher for elevated pre-procedural ApoE levels than for reduced preprocedural ApoE levels in the normal HDL-C group. Conversely, the cumulative incidence of MACCE was significantly higher for reduced pre-procedural ApoE levels than for elevated pre-procedural ApoE levels in the abnormal HDL-C group. After adjustment for important covariates, multivariable Cox hazard analysis revealed that the serum ApoE level was a strongly independent predictor of MACCE; this was inversely related in both groups. CONCLUSIONS: Serum ApoE levels may have a paradoxical impact on the future cardiovascular risk depending on the HDL-C status in patients with CAD.

Complete mitochondrial genomes of three fairy shrimps from snowmelt pools in Japan.

BACKGROUND: Fairy shrimps belong to order Anostraca, class Branchiopoda, subphylum Crustacea, and phylum Arthropoda. Three fairy shrimp species (Eubranchipus uchidai, E. asanumai, and E. hatanakai) that inhabit snowmelt pools are currently known in Japan. Whole mitochondrial genomes are useful genetic information for conducting phylogenetic analyses. Mitochondrial genome sequences for Branchiopoda members are gradually being collated. RESULTS: Six whole mitochondrial genomes from the three Eubranchipus species are presented here. Eubranchipus species share the anostracan pattern of gene arrangement in their mitochondrial genomes. The mitochondrial genomes of the Eubranchipus species have a higher GC content than those of other anostracans. Accelerated substitution rates in the lineage of Eubranchipus species were observed. CONCLUSION: This study is the first to obtain whole mitochondrial genomes for Far Eastern Eubranchipus species. We show that the nucleotide sequences of cytochrome oxidase subunit I and the 16S ribosomal RNA of E. asanumai presented in a previous study were nuclear mitochondrial DNA segments. Higher GC contents and accelerated substitution rates are specific characteristics of the mitochondrial genomes of Far Eastern Eubranchipus. The results will be useful for further investigations of the evolution of Anostraca as well as Branchiopoda.

Combined impacts of low apolipoprotein A-I levels and reduced renal function on long-term prognosis in patients with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: The relationship of apolipoprotein A-I (ApoA-I) and renal function in patients after intervention remain unclear, thus, we aimed to evaluate the combined impacts of ApoA-I and kidney disease (KD). MATERIAL AND METHODS: Altogether, 4101 consecutive patients who underwent intervention between 2000 and 2016 were included. The patients were divided into four groups based on the median ApoA-I values and presence of KD. We evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCE), including cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke, and all-cause death. RESULTS: During the median follow-up period of 6.2 years, 618 patients (15.1%) developed MACCE, and 627 patients (15.3%) died. ApoA-I level was significantly related to estimated glomerular filtration rate, and ApoA-I levels and KD status interaction term was statistically significant. Kaplan-Meier analysis revealed that the low ApoA-I with KD had the significantly highest cumulative incidence rate of MACCE and all-cause death compared to the other three groups. Additionally, ApoA-I levels and KD status were independent predictors of MACCE and all-cause death in multivariable Cox hazard analysis. CONCLUSION: The combined impacts of ApoA-I and renal function could be useful for evaluating cardiovascular and life prognoses in patients undergoing intervention.