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.

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.

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.

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 ).

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 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.

Relationship Between Optical Coherence Tomography-Derived In-Stent Neoatherosclerosis and the Extent of Lipid-Rich Neointima by Near-Infrared Spectroscopy and Intravascular Ultrasound: A Multimodal Imaging Study.

Background In-stent restenosis, especially for neoatherosclerosis, is a major concern following percutaneous coronary intervention. This study aimed to elucidate the association of features of in-stent restenosis lesions revealed by optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) and the extent of lipid-rich neointima (LRN) assessed by near-infrared spectroscopy (NIRS) and intravascular ultrasound, especially for neoatherosclerosis. Methods and Results We analyzed patients undergoing percutaneous coronary intervention for in-stent restenosis lesions using both OCT/OFDI and NIRS-intravascular ultrasound. OCT/OFDI-derived neoatherosclerosis was defined as lipid neointima. The existence of large LRN (defined as a long segment with 4-mm maximum lipid core burden index ≥400) was evaluated by NIRS. In 59 patients with 64 lesions, neoatherosclerosis and large LRN were observed in 17 (26.6%) and 21 lesions (32.8%), respectively. Naturally, large LRN showed higher 4-mm maximum lipid core burden index (median [interquartile range], 623 [518-805] versus 176 [0-524]; P<0.001). In OCT/OFDI findings, large LRN displayed lower minimal lumen area (0.9±0.4 versus 1.3±0.6 mm2; P=0.02) and greater max lipid arc (median [interquartile range], 272° [220°-360°] versus 193° [132°-247°]; P=0.004). In the receiver operating characteristic curve analysis, 4-mm maximum lipid core burden index was the best predictor for neoatherosclerosis, with a cutoff value of 405 (area under curve, 0.92 [95% CI, 0.83-1.00]). In multivariable logistic analysis, only low-density lipoprotein cholesterol (odds ratio, 1.52 [95% CI, 1.11-2.08]) was an independent predictor for large LRNs. Conclusions NIRS-derived large LRN was significantly associated with neoatherosclerosis by OCT/OFDI. The neointimal characterization by NIRS-intravascular ultrasound has potential as an alternative method of OCT/OFDI for in-stent restenosis lesions.

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.

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.

Comparison of clinical outcomes between percutaneous coronary intervention for de novo lesions versus in-stent restenosis lesions.

In-stent restenosis (ISR) remains the primary concern after a percutaneous coronary intervention (PCI) and is considered to be associated with worse clinical outcomes. However, comparative data on ISR and de novo lesions are rare. Therefore, we aimed to compare PCI-related clinical outcomes between patients with de novo lesions and those with ISR lesions. We undertook a retrospective analysis of patients who had undergone a PCI between 2013 and 2020. The incidences of major adverse cardiac and cerebrovascular events (MACCE) and all-cause death over a 2-year follow-up period were evaluated. In total, 1538 patients were enrolled and divided into two groups: a de novo lesions group (n = 1258, 81.8%) and an ISR lesions group (n = 280, 18.2%). Patients in the ISR lesions group were significantly older, with a higher prevalence of hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease than those in the de novo lesions group. Kaplan-Meier curves showed no significant between-group differences in the incidence of MACCE (log-rank, p = 0.93) and all-cause death (p = 0.09). After adjustment for other covariates, PCIs for ISR lesions were not found to be significantly associated with MACCE (hazard ratio [HR], 1.10; 95% confidential interval [CI] 0.49-2.49; p = 0.81) and all-cause death (HR, 0.58; 95% CI 0.26-1.31; p = 0.19). PCIs for ISR lesions were not associated with worse clinical outcomes compared with PCIs for de novo lesions.

Combined impact of residual inflammatory risk and chronic kidney disease on long-term clinical outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Inflammatory status is associated with cardiovascular events in patients with coronary artery disease (CAD) and renal function impairment. Chronic kidney disease (CKD) increases the incidence of cardiovascular events. However, whether the presence of residual inflammatory risk (RIR) and CKD together has a synergistic effect on the long-term clinical outcomes of patients with stable CAD undergoing percutaneous coronary intervention (PCI) remains unclear. METHODS: We assessed 2,948 consecutive patients with stable CAD who underwent the first PCI from 2000 to 2016. Of these, we analyzed the data of patients (2,087) with measurements of high-sensitivity C-reactive protein (hs-CRP) available at follow-up (6-9 months later). High RIR was defined as hs-CRP of >0.6 mg/L according to the median value at follow-up. Patients were classified into four groups: Group 1 (low RIR, non-CKD), Group 2 (high RIR, non-CKD), Group 3 (low RIR, CKD), and Group 4 (high RIR, CKD). We evaluated all-cause mortality and major adverse cardiac events (MACE). The median follow-up period was 5.2 (interquartile range, 1.9-9.9) years. RESULTS: In total, 189 (16.1%) and 128 (11.2%) cases of all-cause mortality and MACE, respectively, were identified during follow-up. The rates of all-cause mortality and MACE were significantly higher in Group 4 than those in the other groups (p<0.001). There was a stepwise increase in the incidence of all-cause mortality and MACE. Upon adjustment for important covariates, the presence of high RIR and/or CKD showed an independent association with a high incidence of MACE and all-cause mortality. CONCLUSIONS: The presence of high RIR and CKD conferred a synergistic adverse effect on the long-term clinical outcomes of patients undergoing PCI.

Long-term impact of ß-blocker in elderly patients without myocardial infarction after percutaneous coronary intervention.

AIMS: Little is known about the long-term outcomes of ß-blockers use in patients with coronary artery disease (CAD) without myocardial infarction (MI) and reduced ejection fraction (rEF). However, more attention should be paid to the oral administration of ß-blockers in elderly patients who are susceptible to heart failure (HF), sinus node dysfunction, or rate response insufficiency. We aimed to evaluate the long-term impact of ß-blockers in elderly patients with CAD without MI or systolic HF who have undergone percutaneous coronary intervention. METHODS AND RESULTS: A total of 1018 consecutive elderly patients with CAD (mean age, 72 ± 7 years; 77% men) who underwent their first intervention between 2010 and 2018 were included in this study. According to the presence or absence of the use of ß-blockers, 514 patients (50.5%) were allocated to the ß-blocker group, and 504 (49.5%) to the non-ß-blocker group. We evaluated the incidence of 4-point major adverse cardiovascular events (4P-MACE), including cardiovascular death, non-fatal MI, non-fatal stroke, admission for HF, target vessel revascularization (TVR), and all-cause death. We focused on the association between chronotropic incompetence of ß-blockers and incidence of a new HF and analysed the results using an exercise electrocardiogram regularly performed in the outpatient department after percutaneous coronary intervention. During a median follow-up duration of 5.1 years, 83 patients (8.3%) developed 4P-MACE, including cardiovascular death in 17, non-fatal MI in 13, non-fatal stroke in 25, and admission for HF in 39 patients. Additionally, 124 patients (12.2%) had a TVR and 104 (10.2%) died of other causes. Kaplan-Meier analysis showed that the cumulative incidence rate of 4P-MACE in the ß-blocker group was significantly higher than that in the non-ß-blocker group (15.4% vs. 10.0%, log-rank test, P = 0.015). Above all, the cumulative incidence rate of admission for HF in the ß-blocker group was significantly higher (8.8% vs. 3.2%, log-rank test, P < 0.001). The ß-blocker group had significantly lower resting heart rate, stress heart rate, and stress-rest Δ heart rate on exercise electrocardiogram. Multivariate Cox hazard analysis revealed that EF, ß-blocker use, stress-rest Δ heart rate, and CKD were strong independent predictors of admission for HF. CONCLUSIONS: Long-term ß-blocker use was significantly associated with an increased risk of adverse cardiovascular events in elderly patients with CAD without MI or systolic HF. In particular, the chronotropic incompetence action of ß-blockers could increase the risk of admission for HF in elderly patients with CAD without MI and systolic HF, and the present findings warrant further investigation.

Serum apolipoprotein E levels predict residual cardiovascular risk in patients with chronic coronary syndrome undergoing first percutaneous coronary intervention and on-statin treatment.

BACKGROUND AND AIMS: Little is known about the long-term impact of apolipoprotein E (apoE) on residual cardiovascular risk in 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 low-density lipoprotein cholesterol (LDL-C) <100 mg/dL on statin treatment and were divided into two groups based on median serum apoE values. 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). Using 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 the strongest independent predictor of MACEs. CONCLUSIONS: Serum apoE level could be a strong predictor of residual cardiovascular risk in patients with CCS long-term, even if LDL-C levels are controlled with statin treatment.

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.

Stepwise regression of non-culprit lipid-rich plaque observed using serial near-infrared spectroscopy-intravascular ultrasound and optical coherence tomographic measurements after aggressive cholesterol-lowering treatment: a case report.

BACKGROUND: Lipid-rich plaques (LRP) in the non-culprit lesions (NCL) in patients with the acute coronary syndrome may trigger lesion-related, adverse cardiovascular events. Aggressive lipid-lowering therapy may stabilize LRP; however, the times of stabilization remain undefined. CASE SUMMARY: A 60-year-old man presented with unstable angina. Coronary angiography revealed a severely stenotic lesion (culprit lesion) in the left descending artery, and another non-obstructive lesion in the distal left main trunk artery. Near-infrared spectroscopy (NIRS) imaging showed LRP with a maximum lipid core burden index (LCBI)4mm of 422. Optical coherence tomographic (OCT) imaging showed the vulnerable plaque as a thin cap fibroatheroma with a thickness of 50 µm. We prescribed aggressive lipid-lowering treatment with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, and serially observed this lesion for 24 months. The NIRS imaging showed that the LCBI gradually decreased over time (max LCBI4mm of 422, 417, 318, 265, and 106 conducted at index percutaneous coronary intervention, 3, 8, 12, and 24 months, respectively). As plaque regression and stabilization of high-risk LRP were observed, we promptly discontinued treatment with the PCSK9i inhibitor. DISCUSSION: During the long-term, 24-month, follow-up using serial NIRS-IVUS imaging, we observed the gradual decrease in LCBI over time, due to aggressive lipid-lowering therapy. Compared with the lowering of low-density lipoprotein cholesterol, the stabilization of vulnerable plaques may require longer times of about 2 years. Evaluation of NCL-related adverse cardiac events by serial intravascular imaging over time, using NIRS-IVUS or OCT, may be warranted in such cases.

Impact of Prior Stroke on Long-Term Outcomes in Patients With Acute Coronary Syndrome.

Background: Cerebrovascular disease often coexists with coronary artery disease (CAD), and it has been associated with worse clinical outcomes in CAD patients. However, the prognostic effect of prior stroke on long-term outcomes in patients with acute coronary syndrome (ACS) is still unclear. Methods and Results: An observational cohort study of ACS patients who underwent emergency percutaneous coronary intervention (PCI) between January 1999 and May 2015 was conducted. Patients were divided into 2 groups according to their history of stroke. We evaluated both all-cause death and cardiac death. Of the 2,548 consecutive ACS patients in the current cohort, 268 (10.5%) had a history of stroke at the onset of ACS. Patients with a history of stroke were older and had a higher prevalence of comorbidities such as hypertension or renal deficiency. The cumulative incidences of all-cause death and cardiac death were significantly higher in patients with a history of stroke (both log-rank P<0.0001). Multivariate Cox hazard regression analysis showed that a history of stroke was significantly associated with the incidences of all-cause death (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.20-1.85, P=0.0004) and cardiac death (HR 1.41, 95% CI 1.03-1.93, P=0.03). Conclusions: About 10% of the ACS patients had a history of stroke and had worse clinical outcomes.

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.

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.

Coronary lipid-rich plaque characteristics in Japanese patients with acute coronary syndrome and stable angina: A near infrared spectroscopy and intravascular ultrasound study.

BACKGROUND: Asians have a much lower incidence of adverse coronary events than Caucasians. We sought to evaluate the characteristics of coronary lipid-rich plaques (LRP) in Asian patients with acute coronary syndrome (ACS) and stable angina (SA). We also aimed to identify surrogate markers for the extent of LRP. METHODS: We evaluated 207 patients (ACS, n = 75; SA, n = 132) who underwent percutaneous coronary intervention under near infrared spectroscopy intravascular ultrasound (NIRS-IVUS). Plaque characteristics and the extent of LRP [defined as a long segment with a 4-mm maximum lipid-core burden index (maxLCBI4mm)] on NIRS in de-novo culprit and non-culprit segments were analyzed. RESULTS: The ACS culprit lesions had a significantly higher maxLCBI4mm (median [interquartile range (IQR)]: 533 [385-745] vs. 361 [174-527], p < 0.001) than the SA culprit lesions. On multivariate logistic analysis, a large LRP (defined as maxLCBI4mm ≥ 400) was the strongest independent predictor of the ACS culprit segment (odds ratio, 3.87; 95% confidence interval, 1.95-8.02). In non-culprit segments, 19.8% of patients had at least one large LRP without a small lumen. No significant correlation was found between the extent of LRP and systematic biomarkers (hs-CRP, IL-6, TNF-α), whereas the extent of LRP was positively correlated with IVUS plaque burden (r = 0.24, p < 0.001). CONCLUSIONS: We confirmed that NIRS-IVUS plaque assessment could be useful to differentiate ACS from SA culprit lesions, and that a threshold maxLCBI4mm ≥ 400 was clinically suitable in Japanese patients. No surrogate maker for a high-risk LRP was found; consequently, direct intravascular evaluation of plaque characteristics remains important.