Elevated levels of plasma inactive stromal cell derived factor-1α predict poor long-term outcomes in diabetic patients following percutaneous coronary intervention.

BACKGROUND: Since the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI. METHODS: This single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α. RESULTS: Unadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively). CONCLUSION: The study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI. TRIAL REGISTRATION: This study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

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 ).

A case of adult patent ductus arteriosus-associated infective endarteritis who was successfully treated with only antibiotics.

Patent ductus arteriosus-associated infective endarteritis (PDA-IE) is an extremely rare complication of PDA in recent years. In this report, we describe a case of PDA-IE complicated by septic pulmonary embolism who was successfully treated with only antibiotics.

Favorable Prognosis in Patients with Recovered Pulmonary Hypertension after TAVI: An Analysis of the LAPLACE-TAVI Registry.

Pulmonary hypertension (PH) is a common complication of aortic stenosis (AS). Despite the established association between PH and poor outcomes in patients with AS, the prognostic implication of a change in PH after transcatheter aortic valve implantation (TAVI) has been rarely evaluated. This study analyzed a prospective multi-center TAVI registry database involving six Japanese centers and used the transtricuspid pressure gradient (TRPG) obtained by echocardiography to estimate pulmonary artery systolic pressure. The participants (n = 2056) were first divided into two groups by TRPG before TAVI, a PH (−) group (TRPG < 30 mmHg) (n = 1407, 61.9%) and a PH (+) group (TRPG ≥ 30 mmHg) (n = 649, 28.6%). Next, by TRPG after (4.1 ± 5.3 days) TAVI, the PH (+) group was further subdivided into two groups, Recovered PH (TRPG < 30 mmHg, n = 253) and Persistent PH (TRPG after TAVI ≥ 30 mmHg, n = 396). The median follow-up duration was 1.8 years. The primary and secondary endpoints were the composite and each of cardiovascular (CV) death and heart failure hospitalization, respectively. Unadjusted Kaplan-Meier estimates with log-rank comparisons showed significantly higher cumulative incidences of primary and secondary endpoints in the Persistent PH group compared to other groups. Moreover, adjusted multivariate Cox-proportional hazard analyses showed that a decreased (−10 mmHg) TRPG after TAVI was linearly associated with a reduced risk of the primary endpoint (hazard ratio (HR): 0.76, 95% confidence interval (CI): 0.64−0.90, p = 0.0020). The findings in the present study indicate that the recovery of PH may partly contributes to the prognostic benefit of TAVI procedure in patients with AS and elevated pulmonary artery systolic pressure.

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).

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.

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.

Dipeptidyl peptidase-4 inhibitors reduced long-term cardiovascular risk in diabetic patients after percutaneous coronary intervention via insulin-like growth factor-1 axis.

Dipeptidyl-peptidase-4 inhibitors (DPP4i) have been the most used antidiabetic medications worldwide due to their good safety profiles and tolerability with a low risk of hypoglycemia, however, large cardiovascular outcome trials (CVOTs) have not shown any significant the prognostic superiority. On the contrary, since observational studies have suggested the effects of DPP4i are enhanced some populations, such as Asians and those who without overweight, their prognostic benefit is still under debate. The aim of this study was thus to assess the prognostic impact of DPP4i in patients with both diabetes and coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) through the insulin-like growth factor-1 (IGF-1) axis, a substrate of DPP4. This single-center analysis involved consecutive Japanese diabetic patients who underwent PCI for the first time between 2008 and 2018 (n = 885). Primary and secondary endpoints were set as cardiovascular (CV) death and the composite of CV death, non-fatal myocardial infarction and ischemic stroke (3P-MACE). Serum levels of IGF-1 and its main binding protein (insulin-like growth factor binding protein-3: IGFBP-3) were measured. In consequences, unadjusted Kaplan-Meier analyses revealed reduced incidences of CV-death and 3P-MACE by DPP4i, which was particularly enhanced in patients who were not overweight (BMI ≤ 25). Multivariate Cox hazard analyses consistently indicated reduced risks of CV death by DPP4i at PCI (hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.16-0.82, p = 0.01) and 3P-MACE (HR 0.47, 95% CI 0.25-0.84, p = 0.01), respectively. Moreover, elevated IGF-1 activity indicated by the IGF-1/IGFBP-3 ratio was associated with decreased risks of both endpoints and it was significantly higher in patients with DPP4i (p < 0.0001). In conclusion, the findings of the present study indicate beneficial effects of DPP4i to improve outcomes in Japanese diabetic patients following PCI, which might be mediated by DPP4-IGF-1 axis.

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.

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.

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.

Predictors of discordance between fractional flow reserve and resting full-cycle ratio in patients with coronary artery disease: Evidence from clinical practice.

BACKGROUND: Fractional flow reserve (FFR) is an established method for assessing functional myocardial ischemia. Recently, the resting full-cycle ratio (RFR) has been introduced as a non-hyperemic index of functional coronary stenosis. However, the effects of clinical characteristics on discordance between RFR and FFR have not been fully evaluated. We aimed to identify clinical characteristics that influence FFR-RFR concordance. METHODS: We included 410 patients with 573 intermediate coronary lesions who underwent clinically indicated invasive coronary angiography, as well as assessments of FFR and RFR. Receiver-operating characteristic (ROC) curves were created to assess the optimal cut-off values of RFR for predicting FFR ≤0.80. RESULTS: RFR exhibited a strong correlation with FFR (r = 0.66, p < 0.0001). ROC analysis identified an optimal RFR cut-off value of 0.92 for categorization based on an FFR cut-off value of 0.8. The discordance of FFR >0.8 and RFR ≤0.92 (high FFR/low RFR) was observed in 112 lesions (20.9%), whereas the discordance of FFR ≤0.8 and RFR >0.92 (low FFR/high RFR) was observed in 35 lesions (6.5%). Higher rate of hemodialysis and lower hemoglobin levels were observed in the high FFR/low RFR group. Multivariate analyses identified female sex, left anterior descending artery (LAD) lesions, and hemodialysis as significant predictors of high FFR/low RFR. Conversely, body surface area and non-LAD lesions were significantly associated with low FFR/high RFR. Hemodialysis [odds ratio (OR): 2.41, 95% confidence interval (CI) 1.31-4.41; p = 0.005] and LAD lesions (OR: 1.86, 95% CI: 1.25-2.79; p = 0.002) were identified as independent predictors of overall FFR-RFR discordance. CONCLUSIONS: RFR exhibited good diagnostic performance in the identification of functionally significant stenosis. However, RFR may overestimate functional severity in patients undergoing hemodialysis or in those with LAD lesions. Further prospective trials are required to demonstrate the non-inferiority of RFR to FFR.

Long-term clinical outcomes and cause of death after endovascular treatment for femoropopliteal artery lesions.

BACKGROUND: Endovascular treatment (EVT) for femoropopliteal artery disease is common in clinical practice. However, little is known about its prognostic factors, causes of death, and long-term clinical outcomes. METHODS: Two hundred eighty-five consecutive patients (mean age, 72±8 years, 73% men) undergoing their first EVT for de-novo femoropopliteal artery disease from 2009 to 2018 were studied. Patients were divided in two groups according to the presence of critical limb ischemia (CLI). We evaluated the incidence of major adverse limb events (MALE) including clinically driven target vessel revascularization and target limb major amputation, and all-cause death. RESULTS: The procedure was successful in 97.9% of cases. The non-CLI group comprised 205 patients (72%), and the CLI group comprised 80 patients (28%). The CLI group exhibited higher high-sensitivity C-reactive protein (hs-CRP) levels and a higher rate of hemodialysis than the non-CLI group. During the median follow-up period of 3.5 years, there were 62 deaths (21.8%) including cardiovascular (32.3%), infection (32,3%), and malignancy-related (22.6%) deaths. Kaplan-Meier analysis revealed that the CLI group had a significantly higher incidence of MALE and all-cause death (log-rank, both p<0.001, respectively). The leading causes of death in the CLI group were cardiovascular- and infection-related death; the leading cause of death in the non-CLI group was malignancy-related. On multivariate Cox hazard analysis, hemodialysis, TASC II classification C/D lesions, and CLI were significant predictors of MALE (p<0.001, p=0.005, and p=0.012, respectively). Hemodialysis, age, higher hs-CRP levels, and CLI were significant predictors of all-cause death (p<0.001, p=0.003, p=0.009, and p=0.021, respectively). CONCLUSIONS: Although EVT for femoropopliteal artery disease appears feasible with a high rate of procedural success, a high incidence of MALE and all-cause death was observed. Further studies are needed to improve the outcomes in patients with CLI.

Simultaneous Estimation of Gender Male and Atrial Fibrillation as Risk Factors for Adverse Outcomes Following Transcatheter Aortic Valve Implantation.

Accurate outcome prediction following transcatheter aortic valve implantation (TAVI) has gained further importance along with expanding its indication to patients with a lower surgical risk. Although previous studies have evaluated the prognostic impacts of gender and atrial fibrillation (AF) in TAVI patients, these two factors have rarely been addressed simultaneously. This retrospective observational study based on a multicenter TAVI registry involved 1088 patients who underwent TAVI between May, 2010 and February, 2020 at 3 hospitals in Japan. Participants were divided into 4 groups by gender and pre-existing AF, such as Female AF(-) (n = 559), Male AF(-) (n = 266), Female AF(+) (n = 187) and Male AF(+) (n = 76). Primary and secondary endpoints were death due to any and cardiovascular cause, and the composite of all-cause death and heart failure hospitalization, respectively. The median follow-up period was 538 days. Cumulative incidences of primary and secondary endpoints were lower in the Female AF(-) group compared to the other 3 groups. Adjusted multivariate Cox proportional hazard analyses showed an independent association of either or both of male gender and AF with adverse outcomes, when compared to the group with none of these (hazard ratios and 95% confidence intervals vs. Female AF(-) (reference) for all-cause death of Male AF(-): 2.7, 1.6-4.6, p < 0.001, Female AF(+): 3.5, 2.1-6.0, p < 0.001, and Male AF(+): 3.9, 1.9-7.8, p < 0.001), while there was no evidence of their synergistic prognostic impact. Male gender and being complicated by AF independently, but not synergistically, predicted poor long-term outcomes in patients undergoing TAVI.

Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation.

BACKGROUND AND AIMS: Pathophysiological roles of monocytes in atrial fibrillation (AF), particularly for the progression of structural remodeling of the left atrium (LA), remain elusive. This study examined the association between the characteristics of circulating and local monocytes and extent of structural remodeling in LA, gauged by LA size, in AF patients. METHODS: First, 161 AF patients who were referred for catheter ablation were enrolled and divided into two groups according to the median of LA diameter (≤39 mm: normal LA group, >39 mm: enlarged LA group). As a control group, 22 patients underwent catheter ablation for paroxysmal supraventricular tachycardia (PSVT) without history of AF were analyzed. Blood samples were collected for flow cytometric analyses to evaluate monocyte subsets based on the levels of CD14 and CD16. Moreover, monocytes were isolated from blood to measure CC chemokine receptor 2 (CCR2) transcripts and protein levels, and migratory activity toward monocyte chemoattractant protein 1 (MCP-1). Second, to characterize the local monocytes in the atrial wall in AF, the resected left atrial appendages (LAA) in AF patients underwent cardiac surgery were histologically evaluated (n = 20). RESULTS: The proportions of monocyte subsets based on CD14 and CD16 expressions were not significantly different between the normal and enlarged LA group. Both transcripts and total protein levels of CCR2 in monocytes were higher in the enlarged LA group compared to those in the normal LA group. In the enlarged LA group, monocytes exhibited more enhanced migratory activity than the normal LA group. Moreover, we found a significantly higher number of CCR2-positive monocytes/macrophages in the LAA in the enlarged LA group. CONCLUSION: Enhanced migratory activity in circulating and local monocytes may play a pivotal role in the pathogenesis of progression in atrial remodeling in AF patients.