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 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.

Low apolipoprotein A1 was associated with increased risk of cancer mortality in patients following percutaneous coronary intervention: A 10-year follow-up study.

Previous studies showed that elevated apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-C) predicted reduced risk of cardiovascular-related (CV) mortality in patients following percutaneous coronary intervention (PCI). Nevertheless, as the association between ApoA1 and cancer mortality in this population has been rarely addressed, our study aimed to evaluate prognostic impact of ApoA1 on multiple types of cancer mortality after PCI. This is a retrospective analysis of a single-center prospective registry database of patients who underwent PCI between 2000 and 2018. The present study enrolled 3835 patients whose data of serum ApoA1 were available and they were divided into three groups according to the tertiles of the preprocedural level of ApoA1. The outcome measures were total, gastrointestinal, and lung cancer mortalities. The median and range of the follow-up period between the index PCI and latest follow-up were 5.9 and 0-17.8 years, respectively. Consequently, Kaplan-Meier analyses showed significantly higher rates of the cumulative incidences of total, gastrointestinal, and lung cancer mortality in the lowest ApoA1 tertile group compared to those in the highest. In contrast, there were no significant differences in all types of cancer mortality rates in the groups divided by the tertiles of HDL-C. Multivariable Cox proportional hazard regression analysis adjusted by cancer-related prognostic factors, such as smoking status, identified the elevated ApoA1 as an independent predictor of decreased risk of total and gastrointestinal cancer mortalities. Our study demonstrates the prognostic implication of preprocedural ApoA1 for predicting future risk of cancer mortality in patients undergoing PCI.

A Prognostic Merit of Statins in Patients with Chronic Hemodialysis after Percutaneous Coronary Intervention-A 10-Year Follow-Up Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) on chronic hemodialysis who are complicated by coronary artery disease (CAD) are at very high risk of cardiovascular (CV) events and mortality. However, the prognostic benefit of statins, which is firmly established in the general population, is still under debate in this particular population. METHODS: As a part of a prospective single-center percutaneous coronary intervention (PCI) registry database, this study included consecutive patients on chronic hemodialysis who underwent PCI for the first time between 2000 and 2016 (n = 201). Participants were divided into 2 groups by following 2 factors, such as (1) with or without statin, and (2) with or without high LDL-C (> and ≤LDL-C = 93 mg/dL, median) at the time of PCI. The primary endpoint was defined as CV death, and the secondary endpoints included all-cause and non-CV death, and 3 point major cardiovascular adverse events (3P-MACE) which is the composite of CV death, non-fatal myocardial infarction and stroke. The median and range of the follow-up period were 2.8, 0-15.2 years, respectively. RESULTS: Kaplan-Meier analyses showed significantly lower cumulative incidences of primary and secondary endpoints other than non-CV deaths in patients receiving statins. Conversely, no difference was observed when patients were divided by the median LDL-C at the time of PCI (p = 0.11). Multivariate Cox proportional hazard analysis identified statins as an independent predictor of reduced risk of CV death (Hazard ratio of statin use: 0.43, 95% confidence interval 0.18-0.88, p = 0.02), all-cause death (HR: 0.50, 95%CI 0.29-0.84, p = 0.007) and 3P-MACE (HR: 0.50, 95%CI 0.25-0.93, p = 0.03). CONCLUSIONS: Statins were associated with reduced risk of adverse outcomes in patients with ESRD following PCI.

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.

Incremental Diagnostic Value of CT Fractional Flow Reserve Using Subtraction Method in Patients with Severe Calcification: A Pilot Study.

Although on-site workstation-based CT fractional flow reserve (CT-FFR) is an emerging method for assessing vessel-specific ischemia in coronary artery disease, severe calcification is a significant factor affecting CT-FFR's diagnostic performance. The subtraction method significantly improves the diagnostic value with respect to anatomic stenosis for patients with severe calcification in coronary CT angiography (CCTA). We evaluated the diagnostic capability of CT-FFR using the subtraction method (subtraction CT-FFR) in patients with severe calcification. This study included 32 patients with 45 lesions with severe calcification (Agatston score >400) who underwent both CCTA and subtraction CCTA using 320-row area detector CT and also received invasive FFR within 90 days. The diagnostic capabilities of CT-FFR and subtraction CT-FFR were compared. The sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) of CT-FFR vs. subtraction CT-FFR for detecting hemodynamically significant stenosis, defined as FFR ≤ 0.8, were 84.6% vs. 92.3%, 59.4% vs. 75.0%, 45.8% vs. 60.0%, and 90.5% vs. 96.0%, respectively. The area under the curve for subtraction CT-FFR was significantly higher than for CT-FFR (0.84 vs. 0.70) (p = 0.04). The inter-observer and intra-observer variabilities of subtraction CT-FFR were 0.76 and 0.75, respectively. In patients with severe calcification, subtraction CT-FFR had an incremental diagnostic value over CT-FFR, increasing the specificity and PPV while maintaining the sensitivity and NPV with high reproducibility.

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.

Comparison of 6-month vascular healing response after bioresorbable polymer versus durable polymer drug-eluting stent implantation in patients with acute coronary syndromes: A randomized serial optical coherence tomography study.

OBJECTIVES: This study was conducted to use optical coherence tomography (OCT) to compare vascular healing between bioresorbable polymer (BP) and durable polymer (DP) everolimus-eluting stents (EES) in patients with acute coronary syndromes (ACS). BACKGROUND: Whether BP-EES induce better vascular healing compared to contemporary DP-EES remains controversial, especially for ACS. METHODS: In this prospective, randomized, non-inferiority trial, we used OCT to compare 6-month vascular healing in patients with ACS randomized to BP versus DP-EES: percent strut coverage (primary endpoint, non-inferiority margin of 2.0%) and neointimal thickness and percent neointimal hyperplasia (NIH) volume. As an exploratory analysis, morphological factors related to the endpoints and the effect of underlying lipidic plaque on stent healing were evaluated. RESULTS: A total of 104 patients with ACS were randomly assigned to BP-EES (n = 52) versus DP-EES (n = 52). Of these, 86 patients (40 BP-EES and 46 DP-EES) were included in the final OCT analyses. Six-month percent strut coverage of BP-EES (83.6 ± 11.4%) was not non-inferior compared to those of DP-EES (81.6 ± 13.9%), difference 2.0% (lower 95% confidence interval-2.6%), pnon-inferiority  = 0.07. There were no differences in neointimal thickness 70.0 ± 33.9 µm versus 67.2 ± 33.9 µm, p = 0.71; and percent NIH volume 7.5 ± 4.7% versus 7.3 ± 5.3%, p = 0.85. By multivariable linear regression analysis, stent type was not associated with percent strut coverage or percent NIH volume; however, percent baseline embedded struts or stent expansion was positively associated with percent NIH volume. Greater NIH volume was observed in lipidic compared with non-lipidic segments (8.7 ± 5.6% vs. 6.1 ± 5.2%, p = 0.005). CONCLUSIONS: Six-month strut coverage of BP-EES was not non-inferior compared to those of DP-EES in ACS patients. Good stent apposition and expansion were independently associated with better vascular healing.

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.

Comparison of diagnostic performance in on-site based CT-derived fractional flow reserve measurements.

BACKGROUND: Computed tomography fractional flow reserve (CT-FFR), which can be acquired on-site workstation using fluid structure interaction during the multiple optimal diastolic phase, has an incremental diagnostic value over conventional coronary computed tomography angiography (CCTA). However, the appropriate location for CT-FFR measurement remains to be clarified. METHOD: A total of 115 consecutive patients with 149 vessels who underwent CCTA showing 30-90% stenosis with invasive FFR within 90 days were retrospectively analyzed. CT-FFR values were measured at three points: 1 and 2 cm distal to the target lesion (CT-FFR1cm, 2cm) and the vessel terminus (CT-FFRlowest). The diagnostic accuracies of CT-FFR ≤ 0.80 for detecting hemodynamically significant stenosis, defined as invasive FFR ≤ 0.80, were compered. RESULT: Fifty-five vessels (36.9%) had invasive FFR ≤ 0.80. The accuracy and AUC for CT-FFR1cm and 2cm were comparable, while the AUC for CT-FFRlowest was significantly lower than CT-FFR1cm and 2cm. (lowest/1cm, 2 cm = 0.68 (95 %CI 0.63-0.73) vs 0.79 (0.72-0.86, p = 0.006), 0.80 (0.73-0.87, p = 0.002)) The sensitivity and negative predictive value of CT-FFRlowest were 100%. The reclassification rates from positive CT-FFRlowest to negative CT-FFR1cm and 2cm were 55.7% and 54.2%, respectively. CONCLUSION: The diagnostic performance of CT-FFR was comparable when measured at 1-to-2 cm distal to the target lesion, but significantly higher than CT-FFRlowest. The lesion-specific CT-FFR could reclassify false positive cases in patients with positive CT-FFRlowest, while all patients with negative CT-FFRlowest were diagnosed as negative by invasive FFR.

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.

Sex differences in clinical outcomes after rotational atherectomy of calcified coronary stenoses: from multicenter registry.

BACKGROUND: Recent improvements in devices and medications may diminish the risk of adverse events following percutaneous coronary intervention (PCI) in women. However, complex calcified coronary lesions are increasingly being encountered in clinical practice, which remain challenging for contemporary PCI. Rotational atherectomy (RA) of severely calcified lesions is an option that facilitates the technical success of PCI. We aimed to examine sex differences in long-term clinical prognoses after PCI with RA in the drug-eluting stent (DES) era. METHODS AND RESULTS: We evaluated J2T ROTA registry data from 1,090 patients with severely calcified de novo coronary artery stenoses who underwent PCI using RA at 3 hospitals between 2004 and 2015. After excluding patients who received regular hemodialysis, 788 patients, including 570 men and 218 women, were ultimately analyzed. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), which included death, acute coronary syndrome (ACS), and stroke. The women were significantly older, and presented more frequently with chronic kidney disease, ACS, atrial fibrillation, lower body mass indexes, and worse lipid profiles than the men. During the observation period, MACCE occurred in 197 patients (25%) (118 deaths, 29 strokes, and 50 ACS). In the unmatched population, women had a higher MACCE rate than men (hazard ratio: 1.48, [95% confidence interval: 1.07-2.06]). However, sex was not associated with MACCE in the propensity score-matched population. CONCLUSION: In the DES era, differences between sexes were not observed in relation to long-term MACCE in patients undergoing PCI with RA for severely calcified coronary artery stenoses.