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).

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

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

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

PURPOSE: Asians often face the problems of clopidogrel resistance and East Asian paradox. This study aimed to evaluate the effects of P2Y12 inhibitors, including low-dose prasugrel 2.5 mg, on the P2Y12 reaction unit (PRU) in the chronic phase after percutaneous coronary intervention (PCI). METHODS: A total of 348 patients were studied. PRU was measured 6-12 months after PCI and subsequently, 6 months later using a P2Y12 assay, respectively. This study evaluated the proportion of bleeding risk (PRU ≤ 85) and ischemic risk (PRU ≥ 239) as primary endpoints, and the prediction of bleeding risk and ischemic risk using multivariable logistic regression analysis. RESULTS: At baseline, 136 patients (39%) received prasugrel 3.75 mg, 48 patients (14%) received prasugrel 2.5 mg, and 164 patients (47%) received clopidogrel 75 mg. Clopidogrel 75 mg had a significantly higher proportion of ischemic risk within one year after PCI than the other groups, and was an independent predictor for ischemic risk with reference of prasugrel 3.75 mg. In addition, switching from clopidogrel 75 mg to prasugrel 2.5 mg significantly lowered and aggregated the PRU value. Whereas, dose reduction of prasugrel had a significantly lower proportion of bleeding risk over one year after PCI than the continuation of prasugrel 3.75 mg, and was an independent predictor for bleeding risk with reference of continuation of prasugrel 3.75 mg. CONCLUSIONS: Prasugrel 2.5 mg has a lower ischemic risk and a more stable PRU value compared with clopidogrel treatment. Prasugrel also contributes to a decline in bleeding risk with concomitant dose reduction. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN), ID: UMIN000029541, Date: October 16, 2017 ( https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033395 ).

Impact of periprocedural bleeding on mid-term outcome in nonagenarians who underwent transcatheter aortic valve implantation: insights from LAPLACE registry.

Data from several recent studies have demonstrated the safety and efficacy of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) even in nonagenarians. However, the impact of periprocedural bleeding following TAVI on their outcome remains unclear. In the aLliAnce for exPloring cLinical prospects of AortiC valvE disease (LAPLACE) registry, we compared outcomes between the bleeding and no-bleeding groups among 1953 patients < 90 years old (mean age, 83.0 ± 4.6 years old) and 316 nonagenarians (mean age, 91.7 ± 1.9 years old) who underwent TAVI with a median follow-up period of 628 days. The group with any periprocedural bleeding showed a higher 30-day mortality than the no-bleeding group in patients < 90 years old (3.3% vs. 0.5%, p = 0.001) and nonagenarians (7.9% vs. 0.7%, p = 0.001). In patients < 90 years old, severe periprocedural bleeding (n = 85) was associated with a higher mid-term all-cause mortality rate than no severe bleeding (n = 1,868), even after adjusting for covariates (hazard ratio [HR], 1.994; 95% confidence interval [CI] 1.287-2.937; p = 0.002). On the other hand, in nonagenarians, any periprocedural bleeding (n = 38) was associated with a higher mid-term cardiovascular (CV) mortality rate (21.1% vs. 4.3%, log-rank p = 0.014) than no bleeding (n = 278), even after adjusting for covariates (HR, 3.104; 95% CI 1.140-8.449; p = 0.027). In conclusion, any periprocedural bleeding after TAVI was associated with mid-term CV mortality in nonagenarians, whereas severe bleeding was associated with mid-term all-cause mortality in patients < 90 years old.

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.

Coronary flow disturbance assessed by vorticity as a cause of functionally significant stenosis.

OBJECTIVES: Vorticity calculated using computational fluid dynamics (CFD) could assess the flow disturbance generated by coronary stenosis. The purpose of this study was to investigate whether vorticity would be an underlying cause of functionally significant stenosis assessed by invasive fractional flow reserve (FFR). METHODS: This retrospective study included 113 patients who underwent coronary CT angiography showing intermediate stenosis and subsequent invasive FFR between December 2015 and March 2020. Vorticity at the stenosis site was calculated using a mesh-free CFD method. We also evaluated the minimum lumen area (MLA) and diameter stenosis (DS) of the lesion. Invasive FFR of ≤ 0.80 was considered functionally significant. Data were compared using Student's t-test and logistic regression analysis was performed. RESULTS: Of the evaluated 144 vessels, 53 vessels (37%) showed FFR ≤ 0.80. Vorticity of significant stenosis was significantly higher than non-significant stenosis (569 ± 78 vs. 328 ± 34 s-1, p < 0.001). A significant negative relationship was present between vorticity and invasive FFR (R2 = 0.31, p < 0.001). Multivariate logistic regression analysis including MLA and DS showed that vorticity (per 100 s-1, odds ratio: 1.36, 95% confidence interval: 1.21-1.57, p < 0.001) was a statistically significant factor to detect functional significance. The area under the receiver operating characteristic curve statistically significantly increased when vorticity was combined with DS and MLA (0.76 vs. 0.87, p = 0.001). CONCLUSIONS: Vorticity had a statistically significant negative relationship with invasive FFR independent of geometric stenosis. KEY POINTS: • Flow disturbance caused by coronary stenosis could be evaluated by calculating vorticity which is defined as the norm of the rotation of the velocity vector. • Vorticity was statistically significantly higher in stenosis with functional significance than stenosis without. • Vorticity has an additive value to detect functionally significant stenosis over geometrical stenosis.

Red Cell Distribution Width Predicts Long-Term Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

Red cell distribution width (RDW) has been shown to be an independent risk factor for increased cardiovascular mortality, heart failure, and cardiovascular disease. However, the association between RDW and long-term clinical outcomes in patients with chronic coronary syndrome (CCS) remains uncertain. In this study, a total of 2,881 CCS patients who underwent their first percutaneous coronary intervention (PCI) and who had available data on pre-procedural RDW between 2002 and 2016 were enrolled. Of these, 1,827 without anemia and severe renal dysfunction were divided into quartiles based on their RDW values. The primary endpoint was a composite of all-cause death and non-fatal myocardial infarction. As a result, patients in the higher RDW quartile groups were more likely to be older and have chronic kidney disease. During a median follow-up of 6.2 years, 209 (11.4%) events were identified. Kaplan-Meier curves showed the highest RDW quartile group had a clearly higher incidence of the primary endpoint (log-rank P = 0.0002). The highest RDW group had a significantly higher risk of cardiovascular events compared with the lowest RDW group, even after adjustment for other risk factors (hazard ratio 1.95, 95% confidence interval 1.04-3.67, P = 0.04). Increasing RDW as a continuous variable was also associated with the incidence of the primary endpoint (hazard ratio 1.46 per 1% increase, 95% confidence interval 1.24-1.69, P < 0.0001). In conclusion, this study demonstrated that increased RDW was associated with worse clinical outcomes after elective PCI. Assessing pre-PCI RDW may be useful for risk stratification of CCS.

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.

Differing effects of beta-blockers on long-term clinical outcomes following percutaneous coronary intervention between patients with mid-range and reduced left ventricular ejection fraction.

BACKGROUND: The aim of this study was to determine the difference in effects of beta-blockers on long-term clinical outcomes between ischemic heart disease (IHD) patients with mid-range ejection fraction (mrEF) and those with reduced ejection fraction (rEF). METHODS: Data were assessed of 3508 consecutive IHD patients who underwent percutaneous coronary intervention (PCI) between 1997 and 2011. Among them, 316 patients with mrEF (EF = 40-49%) and 201 patients with rEF (EF < 40%) were identified. They were assigned to groups according to users and non-users of beta-blockers and effects of beta-blockers were assessed between mrEF and rEF patients, separately. The primary outcome was a composite of all-cause death and non-fatal acute coronary syndrome. RESULTS: The median follow-up period was 5.5 years in mrEF patients and 4.3 years in rEF patients. Cumulative event-free survival was significantly lower in the group with beta-blockers than in the group without beta-blockers in rEF (p = 0.003), whereas no difference was observed in mrEF (p = 0.137) between those with and without beta-blockers. In the multivariate analysis, use of beta-blockers was associated with reduction in clinical outcomes in patients with rEF (hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; p = 0.036), whereas no association was observed among those with mrEF (HR 0.74; 95% CI 0.49-1.10; p = 0.137). CONCLUSIONS: Our observational study showed that use of beta-blockers was not associated with long-term clinical outcomes in IHD patients with mrEF, whereas a significant association was observed in those with rEF.

Plaque characteristics on coronary CT angiography associated with the positive findings of fractional flow reserve and instantaneous wave-free ratio.

BACKGROUND: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are useful in determining indications for revascularization of coronary artery disease (CAD). Although the discordance of FFR and iFR was noted in approximately 20%, this cause has not been well established. We investigated patient background and features on coronary CT angiography (CCTA) showing not only FFR- and iFR-positive findings but also discordance between FFR ≤ 0.8 and iFR ≤ 0.89. METHODS: Subjects were consecutively treated in 83 cases with 105 vessels in which stenosis of 30-90% was detected at one vessel of at least 2 mm or more in the major epicardial vessels and FFR and iFR was performed within subsequent 90 days, among suspected CAD which underwent CCTA. The factors affecting not only FFR- and iFR-positive findings, respectively, but also discordance between FFR and iFR was evaluated using logistic regression analysis on per-patient and per-vessel basis. RESULTS: FFR- and iFR-positive findings were observed in 42 vessels (40.0%) and 34 vessels (32.3%), respectively. Discordance between FFR ≤ 0.8 and iFR ≤ 0.89 was observed in 22 vessels (21.0%) of 21 patients. In multivariate logistic analysis, LAD (OR 3.55; 95%CI 1.20-11.71; p = 0.0217) and lumen volume/myocardial weight (L/M) ratio (OR 0.93; 0.86-0.99, p = 0.0290) were significant predictors for FFR-positive findings. For iFR-positive findings, LAD (OR 3.86; 95%CI 1.12-13.31; p = 0.0236) was only significant predictor. In FFR ≤ 0.8 and iFR > 0.89 group (15 vessels, 14.3%), positive remodeling (PR) (OR 5.03, 95%CI 1.23-20.48, p = 0.0205) was significant predictor. In FFR > 0.8 and iFR ≤ 0.89 group (7 vessels, 6.7%), there were no significant predictors. CONCLUSION: On CCTA characteristics, a relevant predictor for FFR-positive findings included low L/M ratio. PR was significant predictor in FFR-positive, iFR-negative patients among those with discordance between the FFR and iFR.

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

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

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

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

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

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

Increased risk of cardiovascular mortality by strict glycemic control (pre-procedural HbA1c < 6.5%) in Japanese medically-treated diabetic patients following percutaneous coronary intervention: a 10-year follow-up study.

BACKGROUND: In the secondary prevention of cardiovascular (CV) disease in patients with diabetes, an optimal level of HbA1c, the most widely-used glycemic control indicator, for favorable clinical consequences still remains to be established. This study assessed the association between preprocedural HbA1c level and CV mortality in Japanese diabetic patients undergoing percutaneous coronary intervention (PCI). METHODS: This is a retrospective observational study using a single-center prospective PCI database involving consecutive 4542 patients who underwent PCI between 2000 and 2016. Patients with any antidiabetic medication including insulin at PCI were included in the analysis (n = 1328). We divided the patients into 5 and 2 groups according to HbA1c level; HbA1c: < 6.5% (n = 267), 6.5-7.0% (n = 268), 7.0-7.5% (n = 262), 7.5-8.5% (n = 287) and ≥ 8.5% (n = 244), and 7.0% > and ≤ 7.0%, respectively. The primary outcome was CV mortality including sudden death. The median follow-up duration was 6.2 years. RESULTS: In the follow-up period, CV and sudden death occurred in 81 and 23 patients, respectively. While unadjusted Kaplan-Meier analysis showed no difference in cumulative CV mortality rate between patients binarized by preprocedural HbA1c 7.0%, analysis of the 5 groups of HbA1c showed significantly higher cumulative CV death in patients with HbA1c < 6.5% compared with those with 7.0-7.5% (P = 0.042). Multivariate Cox hazard analysis revealed a U-shaped relationship between preprocedural HbA1c level and risk of CV death, and the lowest risk was in the HbA1c 7.0-7.5% group (Hazard ratio of HbA1c < 6.5% compared to 7.0-7.5%: 2.97, 95% confidence interval: 1.33-7.25, P = 0.007). Similarly, univariate analysis revealed the lowest risk of sudden death was in the HbA1c 7.0-7.5% group. CONCLUSION: The findings indicate an increased risk of CV mortality by strict glycemic control (HbA1c < 6.5%) in the secondary prevention of CV disease in Japanese patients with medically-treated diabetes. Trial registration This study reports the 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).

Adjustment of CT-fractional flow reserve based on fluid-structure interaction underestimation to minimize 1-year cardiac events.

The purpose of the study was to evaluate the optimal cut-off value of CT-Fractional Flow Reserve (CT-FFR) using fluid-structure interaction and how to adjust the CT-FFR's underestimation from a standpoint of minimize 1-year cardiac events. Subjects were 38 cases with 44 vessels in which stenosis of 30-90% was detected using one-rotation scanning by 320-row coronary CT angiography (CCTA) and invasive FFR (i-FFR) was performed within subsequent 90 days. CT-FFR was calculated using on-site from the multiple cardiac phases. A hypothetical 1-year cardiac event incidence was estimated using previous evidences when revascularization was decided based on CT-FFR. We assessed the optimal cut-off value of CT-FFR and how to correct the CT-FFR to minimize hypothetical cardiac events under four different disease prevalence (20%, 25%, 30%, 35%, and 40%). A total of 16 vessels had i-FFR ≤ 0.8. On per-patient basis, the sensitivity, specificity, positive predict value, negative predict value, and diagnostic accuracy of CT-FFR â‰¦ 0.8 vs CCTA > 50% to detect functional stenosis defined as invasive FFR â‰¦ 0.80 were 93.3% vs 73.3%, 73.9% vs 26.1%, 70.0% vs 39.3%, 94.4% vs 60.0%, and 81.6% vs 44.7%, respectively. For minimize 1-year cardiac events, the optimal cut-off value for more than 30% of disease prevalence was 0.80. However, the optimal cut-off value for 20, 25, and 30% was 0.54 in any cases. After the adjustment of CT-FFR using a formula of 0.3X + 0.634 for CT-FFR < 0.7 to counteract its underestimation, the % reduction of the events for 20, 25, 30, 35, and 40% at a 0.80 cut-off were 19.0%, 15.6%, 12.6%, 10.0%, and 7.7% respectively. It was reasonable to support that the optimal cut-off value was 0.80 in disease prevalence of more than 30% for minimize 1-year cardiac events. However, underestimation should be adjusted to reduce cardiac events, especially when disease prevalence is low.

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

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

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

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

Reduced Number of Platelets During Intra-Aortic Balloon Pumping Counterpulsation Predicts Higher Cardiovascular Mortality After Device Removal in Association with Systemic Inflammation.

Thrombocytopenia is a frequent complication in patients requiring intra-aortic balloon pumping (IABP) counterpulsation. However, its prognostic impact has not been fully addressed. The objective of this study is to evaluate the impact of the change in the platelet number during IABP use on the prognosis after device removal.This is a retrospective observational study. Patients in the intensive cardiac care unit at three Juntendo University hospitals who underwent percutaneous implantation of IABP with or without veno-arterial extracorporeal membrane oxygenation (V-A ECMO), since 2012-2016, were enrolled in the study (n = 439). Patients who died during mechanical circulatory support (n = 47) were excluded. We evaluated the prognostic impact of the ratio of platelet reduction from the baseline (% PLT reduction) during IABP use on cardiovascular mortality after device removal.The median and the range of follow-up period were 298 days and 0-1,869 days, respectively. Unadjusted Kaplan-Meier analysis demonstrated that patients with a higher % PLT reduction had higher cardiovascular (CV) mortality. An adjusted Cox proportional hazard analysis demonstrated that a 10% higher % PLT reduction was associated with higher cardiovascular (CV) mortality (Hazard ratio: 1.3, 95% Confidence interval: 1.1-1.6, P < 0.001). Moreover, % PLT reduction and the maximum C-reactive protein (CRP) level during IABP use were positively correlated (r = 0.326, P < 0.001).The reduced number of platelets during IABP use was associated with an increased risk of CV mortality.

Common variants in the COL2A1 gene are associated with lattice degeneration of the retina in a Japanese population.

Purpose: Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion that predisposes the patient to retinal detachment. It has been suggested that collagen type II alpha 1 (COL2A1) gene variants may contribute to the development of disorders associated with retinal detachment. Here we investigated whether COL2A1 gene variants were associated with the risk of lattice degeneration of the retina. Methods: We recruited 634 Japanese patients with lattice degeneration of the retina and 1694 Japanese healthy controls. We genotyped 13 tagging single-nucleotide polymorphisms (SNPs) in COL2A1. We also performed imputation analysis to evaluate the potential association of un-genotyped COL2A1 SNPs, involving the imputation of 65 SNPs. Results: Two intronic SNPs-rs1793954 and rs1635533-were significantly associated with lattice degeneration of the retina. The SNP rs1793954 showed the strongest association, with its C allele carrying an increased disease risk (p = 0.0016, corrected p = 0.021, OR = 1.25). The rs1793954 and rs1635533 SNPs were in strong linkage disequilibrium with each other (r 2 = 0.99), and conditional analysis revealed that rs1793954 could account for the association between rs1635533 and the disease. Conclusions: Our results suggested that COL2A1 gene variants may contribute to the development of lattice degeneration of the retina. Further genetic and functional analyses of COL2A1 variants are needed to clarify the present findings.

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

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