Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Advance online publication
Showing 51-100 articles out of 143 articles from Advance online publication
  • Naotaka Akutsu, Koichiro Hori, Saki Mizobuchi, Akihito Ogaku, Yutaka K ...
    Type: Original Article
    Article ID: 60954
    Published: 2021
    [Advance publication] Released: March 21, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation.

    Methods: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n=53) and LDL-C/Apo B >1.2 group (high LDL-C/Apo B group, n=47).

    Results: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm3, p=0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) (p=0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) (p=0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p=0.017) than the high LDL-C/Apo B group.

    Conclusions: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.

    Download PDF (3320K)
  • Hao-Yu Wang, Dong Yin, Yan-Yan Zhao, Rui Zhang, Yue-Jin Yang, Bo Xu, K ...
    Type: Original Article
    Article ID: 60129
    Published: 2021
    [Advance publication] Released: March 20, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: The ESC/EACTS myocardial revascularization guidelines recently standardized the definition of patients at high ischemic risk (HIR). However, the ability of ESC/EACTS-HIR criteria to stratify ischemic and bleeding risk in a contemporary real-world East Asian cohort remains unexplored.

    Methods: A total of 10,167 consecutive patients undergoing PCI from prospective Fuwai PCI Registry (January 2013 to December 2013) were reviewed. ESC/EACTS-HIR features was defined as having at least one of the eight clinical and angiographic characteristics. The primary ischemic endpoint was target vessel failure (cardiac death, target vessel myocardial infarction [MI], or target vessel revascularization [TVR]); bleeding outcome was assessed using the BARC type 2, 3, or 5 bleeding. Median follow-up was 29 months.

    Results: Compared with non-HIR patients, HIR patients (n=5,149, 50.6%) were associated with increased risk for target vessel failure (adjusted hazard ratio [HRadjust]: 1.48 [1.25-1.74]) and patient-oriented composite outcome (HRadjust: 1.44 [1.28-1.63]), as well as cardiac death, MI, and TVR. By contrast, the risk of clinically relevant bleeding was not significantly different between the two groups. (HRadjust: 0.84 [0.66-1.06]). Greater than or equal to three implanted stents and diabetic patients with diffuse multivessel coronary disease emerged as independent predictors for long-term adverse outcomes. There was no significant interaction between high bleeding risk (HBR) status and clinical outcomes associated with ESC/EACTS-HIR criteria (all Pinteraction >0.05).

    Conclusion: The ESC/EACTS-HIR features identified patients at increased risk of thrombotic events, including cardiac death, but not for clinically relevant bleeding. Importantly, HBR did not modify cardiovascular risk subsequent to patients with ESC/EACTS-HIR features, suggesting its potential clinical applicability in tailoring antithrombotic therapy.

    Download PDF (2606K)
  • Yuko Horikoshi, Shin-ichiro Katsuda, Yuko Fujikura, Akihiro Hazama, Hi ...
    Type: Original Article
    Article ID: 60848
    Published: 2021
    [Advance publication] Released: March 20, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The cardio-ankle vascular index (CAVI) consists of intrinsic and functional arterial stiffness mainly regulated by vasoactive compounds. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was determined by applying the CAVI theory to the whole aorta and iliac-femoral arteries. We investigated the changes in aBeta and ifBeta in response to decreased blood pressure (BP) induced by the Ca2+ channel blocker nicardipine to elucidate the involvement of Ca2+ in aBeta and ifBeta.

    Methods: Pressure waves at the origin of the aorta (oA), distal end of the abdominal aorta (dA), and left femoral artery (fA) as well as flow waves at the oA were simultaneously recorded before and after the infusion of nicardipine (50 µg/kg/min) for 2 min in 12 male rabbits under pentobarbital anesthesia. Beta was calculated using the following formula: Beta=2ρ / PP×ln (SBP / DBP)×PWV2, where ρ, SBP, DBP, and PP denote blood density and systolic, diastolic, and pulse pressures, respectively. aBeta, ifBeta, and aortic-iliac-femoral Beta (aifBeta) were calculated using aPWV, ifPWV, and aifPWV, respectively.

    Results: SBP, mean arterial pressure (MAP), DBP, and total peripheral vascular resistance significantly decreased during the administration of nicardipine, whereas cardiac output significantly increased. aBeta and ifBeta significantly increased and decreased, respectively, whereas aifBeta did not change despite the decrease in BP. ifBeta and aBeta positively and negatively correlated with BP, respectively, whereas aifBeta did not correlate with SBP.

    Conclusions: There were contradictory arterial responses to nicardipine between the elastic and muscular arteries. Unknown vasoconstriction mechanisms that are not involved in Ca2+ influx may function in the aorta in response to decreased BP.

    Download PDF (480K)
  • Pingting Zhong, Jie Qin, Zhixi Li, Lei Jiang, Qingsheng Peng, Manqing ...
    Type: Original Article
    Article ID: 62059
    Published: 2021
    [Advance publication] Released: March 19, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: To develop and validate a nomogram using retinal vasculature features and clinical variables to predict coronary artery disease (CAD) in patients with suspected angina.

    Methods: The prediction model consisting of 795 participants was developed in a training set of 508 participants with suspected angina due to CAD, and data were collected from January 2018 to June 2019. The held-out validation was conducted with 287 consecutive patients from July 2019 to November 2019. All patients with suspected CAD received optical coherence tomography angiography (OCTA) examination before undergoing coronary CT angiography. LASSO regression model was used for data reduction and feature selection. Multivariable logistic regression analysis was used to develop the retinal vasculature model for predicting the probability of the presence of CAD.

    Results: Three potential OCTA parameters including vessel density of the nasal and temporal perifovea in the superficial capillary plexus and vessel density of the inferior parafovea in the deep capillary plexus were further selected as independent retinal vasculature predictors. Model clinical electrocardiogram (ECG) OCTA (clinical variables+ECG+OCTA) was presented as the individual prediction nomogram, with good discrimination (AUC of 0.942 [95% CI, 0.923–0.961] and 0.897 [95% CI, 0.861–0.933] in the training and held-out validation sets, respectively) and good calibration. Decision curve analysis indicated the clinical applicability of this retinal vasculature nomogram.

    Conclusions: The presented retinal vasculature nomogram based on individual probability can accurately identify the presence of CAD, which could improve patient selection and diagnostic yield of aggressive testing before determining a diagnosis.

    Download PDF (2426K)
  • Takumi Matsumura, Tomoko Sankai, Kazumasa Yamagishi, Yasuhiko Kubota, ...
    Type: Original Article
    Article ID: 60103
    Published: 2021
    [Advance publication] Released: March 16, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: We aimed to examine the impact of high-risk levels of cardiovascular risk factors on the incidence of cardiovascular disease (CVD) in overweight and non-overweight individuals without treatment for the risk factors.

    Methods: A total of 8,051 individuals aged 40–74 years without a history of CVD and/or without treatment for hypertension, diabetes, hyperlipidemia, and kidney disease at baseline in 1995–2000 were followed up for a median of 14.1 years. We classified the participants into three risk categories (low-, intermediate-, and high-risk groups) on the basis of individual risk factors (blood pressure, serum glucose, low-density lipoprotein cholesterol [LDL-C], and urinary protein) according to the guidelines of Japanese clinical societies. The high-risk group (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg, fasting serum glucose ≥ 130 mg/dL or non-fasting serum glucose ≥ 180 mg/dL, LDL-C ≥ 180 mg/dL, proteinuria ≥ 2+) needed to refer to physicians or start treatment immediately. Overweight was defined as a body mass index of ≥ 25 kg/m2.

    Results: Compared with those in the non-overweight low-risk group, the hazard ratios (HRs) (95% confidence intervals, population-attributable fractions [PAFs]) of CVD in the high-risk categories of blood pressure were 2.0 (1.4–2.9, 7.0%) in the non-overweight high-risk group and 2.9 (1.9–4.3, 6.8%) in the overweight high-risk group. The corresponding HRs (95% confidence intervals, PAFs) of serum glucose were 2.0 (1.2–3.4, 2.5%) and 2.2 (1.1–4.3, 1.5%) in the non-overweight and overweight high-risk groups, respectively. Such associations were not observed for the high-risk group of LDL-C and proteinuria.

    Conclusions: The present long-term observational study implies that targeting persons with non-treated severe hypertension and diabetes is prioritized to prevent CVD regardless of overweight status.

    Download PDF (449K)
  • Mizuki Sata, Tomonori Okamura, Sei Harada, Daisuke Sugiyama, Kazuyo Ku ...
    Type: Original Article
    Article ID: 58719
    Published: 2021
    [Advance publication] Released: March 06, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness.

    Methods: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35–74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: “Category I (Low risk),” “Category II (Middle risk),” and “Category III (High risk).”

    Results: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61–5.43) and 7.33 (4.03–13.3) for males and 3.99 (2.55–6.24) and 3.34 (2.16–5.16) for females, respectively.

    Conclusions: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

    Download PDF (215K)
  • Korehito Iida, Takafumi Hiro, Daisuke Fukamachi, Mitsumasa Sudo, Toshi ...
    Type: Original Article
    Article ID: 60509
    Published: 2021
    [Advance publication] Released: March 02, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Coronary plaque rupture is the main cause of acute coronary syndrome (ACS), but the role of blood flow features around plaque rupture for ACS is still unknown. The present study aimed to assess the relationship between the geometric configuration of ruptured plaque and ACS occurrence using computational fluid dynamics (CFD) by moving particle method in patients with coronary artery disease.

    Methods: In this study, 45 patients with coronary artery disease who underwent three-dimensional intravascular ultrasound (IVUS) and had a coronary ruptured plaque (24 plaques with provoked ACS, 21 without) were included. To compare the difference in blood flow profile around ruptured plaque between the patients with and without ACS, the IVUS images were analyzed via the novel CFD analysis.

    Results: There were no significant differences in localized flow profile around ruptured plaque between the two groups when the initial particle velocity was 10.0 cm/s corresponded to a higher coronary flow velocity at ventricular diastole. However, when it was 1.0 cm/s corresponded to lower coronary flow velocity at ventricular systole, particles with lower velocity (0 ≤ V ≤ 5 cm/s) were more prevalent around ACS-PR (p=0.035), whereas particles with higher velocity (10 ≤ V ≤ 20 cm/s) were more often detected in silent plaque ruptures (p=0.018).

    Conclusions: Three-dimensional IVUS revealed that coronary plaque rupture was a complex one with a wide variety of its stereoscopic configuration, leading to various patterns of the local coronary flow profile. A novel CFD analysis suggested that the local flow was more stagnant around ACS-provoked ruptures than in silent ones.

    Download PDF (1425K)
  • Ryo Nishikawa, Masato Furuhashi, Mika Hori, Masatsune Ogura, Mariko Ha ...
    Type: Case Report
    Article ID: 58909
    Published: 2021
    [Advance publication] Released: February 27, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    A 56-year-old postmenopausal woman with out-of-hospital cardiac arrest caused by acute myocardial infraction was successfully resuscitated by intensive treatments and recovered without any neurological disability. She was diagnosed as having familial hypercholesterolemia (FH) based on a markedly elevated low-density lipoprotein cholesterol (LDL-C) level and family history of premature coronary artery disease. Genetic testing in her family members showed that a variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.2004C>A, p.S668R), which had been previously reported as having uncertain significance, was associated with FH, indicating that the variant is a potential candidate for the FH phenotype. Next-generation sequencing analysis for the proband also showed that there was a heterozygous mutation of the ATP-binding cassette sub-family G member 5 (ABCG5) gene (c.1166G>A, R389H), which has been reported to increase LDL-C level and the risk of cardiovascular disease. She was also diagnosed as having type 1 CD36 deficiency based on a lack of myocardial uptake of 123 I-labeled 15-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid in scintigraphy and the absence of CD36 antigen in both monocytes and platelets in flow cytometry. She had a homozygous mutation of the CD36 gene (c.1126-5_1127delTTTAGAT), which occurs in a canonical splice site (acceptor) and is predicted to disrupt or distort the normal gene product. To our knowledge, this is the first report of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction in the present case.

    Download PDF (1968K)
  • Jianwei Zhang, Yu Du, Chengping Hu, Yan Liu, Jinxing Liu, Ang Gao, Yin ...
    Type: Original Article
    Article ID: 61358
    Published: 2021
    [Advance publication] Released: February 27, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: The associations between increased glycated albumin (GA) in the serum and diabetic complications and mortality have been revealed in the general population. However, less is known regarding the prognostic value of GA in patients diagnosed with acute coronary syndrome (ACS).

    Methods: In this study, all patients admitted for ACS who underwent a successful percutaneous coronary intervention (PCI) at our center from January 2018 to February 2019 were retrospectively examined. Clinical characteristics, laboratory results (e.g., serum GA levels), and procedural details were collected. The primary outcome included a composite of major adverse cardio-cerebral events (MACCE), such as death, myocardial infarction, stroke, and unplanned revascularization. The association between serum GA levels and clinical outcomes was tested in three multivariable models using Cox proportional hazard analysis. Subgroup analysis was performed in patients who were diagnosed with diabetes versus patients without diabetes.

    Results: A total of 1,806 ACS patients (mean age of 59.4 years; 77.8% were men; 44.9% were diagnosed with diabetes) were enrolled in this study, where the majority exhibited unstable angina (81.6%) and showed preserved left ventricular systolic function. Patients in the high GA level group were commonly female and were more likely to have metabolic disorders and to exhibit severe CAD (all p<0.05). MACCE occurred in 126 patients (7.0%) during a mean follow-up time of 17.2 months. The cumulative risk of MACCE at the 18-month follow-up visit significantly increased in a stepwise fashion along with increased GA levels (log-rank p=0.018) in the serum. The association between serum GA levels and MACCE was further determined after adjusting traditional risk factors and hemoglobin A1c (HbA1c) (GA, per 1% increase: hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.06–1.13; GA, higher vs. lower tertial: HR 1.92, 95% CI 1.01–3.67). In a subgroup analysis, the prognostic role of serum GA only existed in diabetic patients, even when adjusting for traditional risk factors and HbA1c levels.

    Conclusions: Elevated GA levels in the serum were associated with poor intermediate-term outcomes in low-risk ACS patients who underwent PCI, especially in patients with preexisting diabetes.

    Download PDF (512K)
  • Daiji Nagayama, Atsuhito Saiki, Yasuhiro Watanabe, Takashi Yamaguchi, ...
    Type: Original Article
    Article ID: 62141
    Published: 2021
    [Advance publication] Released: February 27, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: To clarify the mechanism by which pitavastatin reduced cardiovascular (CV) events more effectively than atorvastatin in the TOHO Lipid Intervention Trial Using Pitavastatin (TOHO-LIP), the changes in (Δ) non-heparinized serum level of lipoprotein lipase mass (LPL mass) during administration of the respective statins were investigated.

    Methods: From TOHO-LIP data, 223 hypercholesterolemic patients with any CV risks followed at Toho University Sakura Medical Center were analyzed. The patients were randomized to pitavastatin (2 mg/day) group (n=107) or atorvastatin (10 mg/day) group (n=116), and followed for 240 weeks. In this subgroup study, the primary and secondary end points were the same as those in TOHO-LIP, and 3-point major adverse cardiovascular events (3P-MACE) was added. The relationship between ΔLPL mass during the first year and the incidences of each end point was analyzed.

    Results: The lipid-lowering effect was not different between the two statins. Cumulative 240-week incidence of each end point was significantly lower in pitavastatin group (primary: 1.9% vs. 10.3%, secondary: 4.7% vs. 18.1%, 3P-MACE: 0.9% vs. 6.9%). Mean LPL mass (64.9 to 69.0 ng/mL) and eGFR (70.1 to 73.6 ml/min/1.73m2) increased in pitavastatin group, but not in atorvastatin group during the first year. Cox proportional-hazards model revealed that ΔLPL mass (1 ng/mL or 1SD) contributed to almost all end points.

    Conclusions: Pitavastatin administration reduced CV events more efficaciously than atorvastatin despite similar LDL cholesterol-lowering effect of the two statins. Increased LPL mass during the first year by pitavastatin treatment may be associated with this efficacy.

    Download PDF (257K)
  • Mitsuyoshi Takahara, Yoshimitsu Soga, Masahiko Fujihara, Daizo Kawasak ...
    Type: Original Article
    Article ID: 62356
    Published: 2021
    [Advance publication] Released: February 27, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: This study aimed to reveal the mortality risk by age in patients undergoing femoropopliteal endovascular therapy for intermittent claudication, in comparison to the national age-specific standard value.

    Methods: We analyzed 2056 patients undergoing endovascular therapy for moderate to severe intermittent claudication between 2010 and 2018, performed at five cardiovascular centers in Japan. The 3-year mortality risk by age was compared with the data from year- and sex-matched Japanese citizens, which were obtained from Japan's national life table data. Clinical characteristics associated with age in the study patients were also explored.

    Results: The mean age was 73±9 years. The 3-year mortality risk was increased with age in the patient population, from 6.4% for patients aged <65 years to 21.2% for those aged ≥ 85 years. On the contrary, its risk ratio relative to the matched citizens of the same age was decreased with age; the relative risk ratio was 3.08 for patients aged <65 years (P=0.001) and 0.60 for those aged ≥ 85 years (P=0.016). Current smoking, body mass index ≥ 25 kg/m2, hyperlipidemia, diabetes mellitus, and dialysis dependence were inversely associated with age (all P<0.05).

    Conclusion: Mortality risk increased with age, but the risk ratio relative to the matched citizens decreased with age. Younger patients had a higher mortality risk relative to the matched citizens, whereas patients aged ≥ 85 years had a lower mortality risk relative to the matched citizens. Younger patients were more likely to accumulate cardiovascular risk factors.

    Download PDF (509K)
  • Jiali Sun, Guoqiang Liu, Dingyue Zhang, Zhigang Wu, Jingyao Liu, Wei ...
    Type: Original Article
    Article ID: 62448
    Published: 2021
    [Advance publication] Released: February 27, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: This study aims to evaluate the differences in the characteristics of atherosclerotic plaques in the proximal, curved, and distal segments of the curved basilar artery (BA) through high-resolution magnetic resonance imaging(HR-MRI).

    Methods: The imaging and clinical data of 146 patients were retrospectively analyzed. On the basis of three-dimensional (3D) time -of -flight magnetic resonance angiography (3D-TOF-MRA), 51 patients with BA curvature were selected for the study. The BA plaque is divided into three groups: proximal, curved, and distal. Plaques were identified and analyzed according to spin echo acquisition imaging via T1-weighted 3D volumetric isotropic Tse acquisition (T1W-3D -VISTA), and compare the differences in clinical related factors and plaque characteristics between groups. Diffusion-weighted imaging (DWI) and/or T2WI identified brainstem infarction. The patients were divided into symptomatic and asymptomatic groups. The correlation between plaque location and symptoms was identified and analyzed.

    Results: Among 51 patients, a total of 376 plaques were detected. Plaques in the proximal and curved segments are more common than those in the distal segments. Proximal plaques are more likely to have intraplaque hemorrhage (P=0.002 <0.05). There was no significant difference in the distribution of criminal plaques and non-criminal plaques between each group (P=0.36 >0.05).

    Conclusion: Plaques in the proximal and curved segments of the BA are more common than those in the distal segments. The proximal plaque is more prone to intraplaque hemorrhage.

    Download PDF (1633K)
  • Masato Nakamura, Junya Ako, Hidenori Arai, Atsushi Hirayama, Atsushi N ...
    Type: Original Article
    Article ID: 59543
    Published: 2021
    [Advance publication] Released: February 21, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The prevalence of atherosclerotic cardiovascular (CV) disease has risen in Japan due to increasing metabolic risk factors, including dyslipidemia. A positive linear correlation between low-density lipoprotein cholesterol (LDL-C) levels, incidence of CV events, and preventive effects of lipid-lowering therapy (LLT) is well established; however, data in Japan are limited. This analysis evaluated current lipid management practices and risk of recurrent CV events in Japanese post-acute coronary syndrome (ACS) patients.

    Methods: EXPLORE-J is a multicenter, 2-year observational study of hospitalized ACS patients in Japan.

    Results: At 2-year follow-up (n=1944, mean age 66 years, 80.3% male), the cumulative incidence of major adverse cardiovascular events (MACE; death associated with myocardial infarction/cerebrovascular accident [CVA] and other CV death, non-fatal ACS, and non-fatal CVA requiring hospitalization during the observation period) was 6.2%; respective incidences of CV death, non-fatal ACS, and CVA were 0.7%, 4.5%, and 1.7%. Statin, intensive statin, and ezetimibe were prescribed for 93.6%, 8.2%, and 3.9% at visit (V)1 (Day[D]1+14), and 92.3%, 10.5%, and 11.6% of patients at V5 (D730±30 days), respectively. Mean LDL-C was reduced from first post-ACS measurement (121.3 mg/dL) to V5 (79.8 mg/dL). A limited number of patients achieved LDL-C <70 mg/dL from V1–V5 (14.4%–34.6%); those with a greater LDL-C reduction by V1 had a lower probability of MACE, indicating the benefits of early LDL-C reduction post ACS.

    Conclusions: Guideline-recommended LDL-C target achievement post ACS in Japan is suboptimal, suggesting the need for LLT intensification. Additional analyses by risk stratification of the study population and the benefits of lipid management are planned.

    Download PDF (1103K)
  • Kazushige Dobashi
    Type: Editorial
    Article ID: ED163
    Published: 2021
    [Advance publication] Released: February 21, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (275K)
  • Masatsune Ogura
    Type: Editorial
    Article ID: ED164
    Published: 2021
    [Advance publication] Released: February 21, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (213K)
  • Nahoko Kato-Kogoe, Shoichi Sakaguchi, Kuniyasu Kamiya, Michi Omori, Ya ...
    Type: Original Article
    Article ID: 60608
    Published: 2021
    [Advance publication] Released: February 19, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Oral bacteria have been reported to be associated with the pathogenesis of atherosclerosis; however, the relationship between the oral microbiota and atherosclerosis remains unclear. The present study aimed to investigate whether or not salivary microbiota of patients with atherosclerotic cardiovascular disease (ACVD) differs from that of subjects without ACVD, and to characterize the salivary microbiota of patients with ACVD.

    Methods: This study included 43 patients with ACVD and 86 age- and sex-matched non-ACVD individuals. 16S rRNA metagenomic analysis were performed using DNA isolated from the saliva samples of the participants. To select unique operational taxonomic unit (OTU) sets of ACVD, we conducted the random forest algorithm in machine learning, followed by confirmation via 10-fold cross-validation

    Results: There was no difference in richness or evenness between the ACVD and non-ACVD groups (alpha diversity; observed OTU index, p=0.503; Shannon's index, p=0.478). However, significant differences were found in the overall salivary microbiota structure (beta diversity; unweighted UniFrac distances, p=0.001; weighted UniFrac distances, p=0.001). The Actinobacteria phylum was highly abundant in patients with ACVD, while the Bacteroidetes phylum was less abundant. The random forest classifier identified 43 OTUs as an optimal marker set of ACVD. In a 10-fold cross validation using the validation data, an area under the curve (AUC) of 0.933 (95% CI, 0.855–1.000) was obtained.

    Conclusions: The salivary microbiota in patients with ACVD was distinct from that of non-ACVD individuals, indicating that the salivary microbiota may be related to ACVD.

    Download PDF (2362K)
  • Yusuke Akiyama, Tetsuya Matoba, Shunsuke Katsuki, Susumu Takase, Soich ...
    Type: Original Article
    Article ID: 61366
    Published: 2021
    [Advance publication] Released: February 19, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Previous studies suggested that implantation with a 1st-generation DES was associated with coronary endothelial dysfunction, which was associated with Rho-kinase activation. Second-generation drug-eluting stents (DESs) may preserve coronary endothelial function in stented coronary arteries; however, because of methodological limitations, further study is needed to clarify the association between 2nd-generation DESs and coronary endothelial dysfunction.

    Methods: We retrospectively analysed the CuVIC trial database, where we identified 112 patients who underwent coronary stenting in the left coronary arteries with either a bare metal stent (BMS, n=53) or 2nd-generation DES (n=59). We compared vasomotions of target vessels with stents and non-target vessels without stents. Furthermore, we measured the Rho-kinase activation detected in mononucleocytes from aortic and coronary sinus blood.

    Results: ACh-induced vasoconstrictive responses of target vessels were not enhanced with a 2nd-generation DES (45±21% vs. 44±20%, P=0.56, paired t-test), but significantly enhanced in the coronary arteries with a BMS (50±18% vs. 42±20%, P=0.002). Rho-kinase activation did not differ between patients with a BMS and 2nd-generation DES. In the target vessels with a BMS, large late lumen loss and acute coronary syndrome (ACS) at the index percutaneous coronary intervention (PCI) were associated with ACh-induced enhanced coronary vasoconstrictive responses.

    Conclusions: Evaluation of ACh-induced vasomotion of target vessels comparing with non-target vessels revealed that 2nd-generation DESs were not associated with coronary endothelial dysfunction in target vessels, nor activation of Rho-kinase in the coronary sinus blood 6-8 months after stenting.

    Download PDF (819K)
  • Ho-Ming Su, Wen-Hsien Lee, Wei-Chung Tsai, Tzu-Chieh Lin, Ye-Hsu Lu, C ...
    Type: Original Article
    Article ID: 60806
    Published: 2021
    [Advance publication] Released: February 18, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Abnormal ankle-brachial index (ABI) is regarded as peripheral artery disease and can be used to predict cardiovascular (CV) outcomes. However, the usefulness of ABI for the prediction of CV outcome in patients with normal ABI is limited. Upstroke time per cardiac cycle (UTCC) is recently reported to be associated with mortality in patients with acute myocardial infarction and the elderly. Therefore, we aimed to evaluate UTCC, left ventricular ejection fraction (LVEF), brachial-ankle pulse wave velocity (baPWV), and ABI for the prediction of mortality in patients with normal ABI.

    Methods: Patients arranged for echocardiographic examinations were enrolled, and 1076 patients with normal ABI were included. ABI, baPWV, and UTCC were measured by an ABI-form device.

    Results: The median follow-up to mortality was 95 months. There were 88 CV and 244 all-cause deaths. After multivariate analysis, UTCC was associated with increased CV and all-cause mortality (P ≤ 0.004). Age, diabetes, heart failure, left ventricular hypertrophy, baPWV, and LVEF were also independent predictors of CV and all-cause mortality, but ABI was not. Furthermore, UTCC had a better additive predictive value than ABI, baPWV, and LVEF for CV mortality (P ≤ 0.012). It also had a better additive predictive value than ABI and LVEF for all-cause mortality (P ≤ 0.013).

    Conclusions: UTCC is an independent predictor for CV and all-cause mortality in patients with normal ABI. It also has a better additive predictive value of CV and all-cause mortality than ABI and LVEF. Therefore, UTCC is a simple, novel, and useful parameter for identifying high-risk patients with normal ABI.

    Download PDF (382K)
  • Haruka Chichibu, Kazumasa Yamagishi, Rie Kishida, Koutatsu Maruyama, M ...
    Type: Original Article
    Article ID: 61390
    Published: 2021
    [Advance publication] Released: February 18, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Seaweed contains soluble dietary fibers, potassium, and flavonoids and was recently reported to be inversely associated with the risk of coronary heart disease and mortality from stroke. However, epidemiological evidence on this issue has remained scarce.

    Methods: At the baseline survey of four Japanese communities between 1984 and 2000, we enrolled 6,169 men and women aged 40–79 years who had no history of cardiovascular disease. We assessed their seaweed intake using the data from a 24 h dietary recall survey and categorized the intake into four groups (0, 1–5.5, 5.5–15, and ≥ 15 g/day). We used sex-specific Cox proportional hazards models to examine the association between seaweed intake and risk of cardiovascular disease (stroke, stroke subtypes, and coronary heart disease).

    Results: During the 130,248 person-year follow-up, 523 cases of cardiovascular disease occurred: 369 cases of stroke and 154 cases of coronary heart disease. Seaweed intake levels were inversely associated with the risk of total stroke and cerebral infarction among men but not among women. Adjustment for cardiovascular risk factors did not change the associations: the hazard ratios (95% confidence intervals; P for trend) for the highest versus lowest categories of seaweed intake were 0.63 (0.42–0.94; 0.01) for total stroke and 0.59 (0.36–0.97; 0.03) for cerebral infarction. No associations were observed between seaweed intake and risks of intraparenchymal hemorrhage, subarachnoid hemorrhage, or coronary heart disease among men or women.

    Conclusions: We found an inverse association between seaweed intake and risk of total stroke, especially that from cerebral infarction, among Japanese men.

    Download PDF (267K)
  • Sono Toi, Yuka Shirai, Kentaro Ishizuka, Megumi Hosoya, Misa Seki, Eik ...
    Type: Original Article
    Article ID: 61895
    Published: 2021
    [Advance publication] Released: February 18, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: This study aimed at clarifying the incidence of recurrent stroke and its etiology in patients with embolic stroke of undetermined source (ESUS) and other stroke subtypes in both the acute and chronic periods.

    Methods: A total of 645 patients who were admitted with acute ischemic stroke (IS) between March 2015 and August 2019 were enrolled. Among them, 511 patients with ESUS, cardioembolism (CE), large artery atherosclerosis (LAA), or small vessel disease (SVD) were analyzed in this study. After discharge, 391 patients who visited the outpatient clinic were followed up until August 2020. The outcome was stroke recurrence.

    Results: In the acute admission, recurrence rates were 7.6%, 8.1%, 18.8%, and 2.2% in patients with ESUS, CE, LAA, and SVD, respectively, and there were significant differences between the groups. The subtype of recurrence was almost identical to that of the index stroke. In the outpatient clinic, the annual recurrence rates were 4.4%, 4.3%, 6.0%, and 2.9% in ESUS, CE, LAA, and SVD, respectively, and no difference was observed. Subtypes of recurrence in outpatients with ESUS included ESUS, intracerebral hemorrhage (ICH), and SVD. Patients with ESUS and SVD had a higher risk of ICH during follow-up.

    Conclusions: Although the risk of recurrence was comparable between patients with ESUS and CE and intermediate between patients with LAA and SVD, in the acute admission unit, the risk in outpatients was similar among all subtypes. ESUS was the most recurrent stroke subtype in outpatients with ESUS. The risk of hemorrhagic stroke was significant in patients with SVD and ESUS.

    Download PDF (400K)
  • Naoko Higashino, Osamu Iida, Yosuke Hata, Mitsutoshi Asai, Masaharu Ma ...
    Type: Original Article
    Article ID: 60095
    Published: 2021
    [Advance publication] Released: February 14, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Hemodialysis vintage and serum phosphorus levels adversely affect outcomes in patients on hemodialysis. Whether these factors have a similar prognostic impact on patients who are on hemodialysis and have chronic limb-threatening ischemia (CLTI) has not been systematically studied. We aimed to explore the risk factors, including hemodialysis vintage and serum phosphorus levels, on clinical outcomes after endovascular therapy (EVT) in hemodialysis patients with CLTI.

    Methods: The current study rerospectively analyzed 374 hemodialysis patients with CLTI presenting with ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 68.2%, Rutherford 5: 75.9%, 6: 24.1%, WIfI stage 4: 50.0%) primarily treated with EVT between April 2007 and December 2016. The primary outcome measure was 1-year amputation-free survival (AFS), while the secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model.

    Results: Multivariate analysis significantly associated longer hemodialysis vintages with higher serum phosphorus levels (hazard ratio [HR], 0.599; 95% confidence interval [CI], 0.394-0.910; p=0.016) with 1-year AFS. Longer vintages for hemodialysis with higher serum phosphorus levels were marginally, but not significantly, associated with 1-year wound healing. (HR, 0.684; 95% CI, 0.467–1.000; p=0.050).

    Conclusion: Longer hemodialysis vintages with higher serum phosphorus levels adversely affect outcomes after EVT for hemodialysis patients with CLTI presenting with ischemic tissue loss.

    Download PDF (498K)
  • Yoshito Kadoya, Kan Zen, Osamu Iida, Yoshito Yamamoto, Daizo Kawasaki, ...
    Type: Original Article
    Article ID: 61150
    Published: 2021
    [Advance publication] Released: February 10, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The post-endovascular treatment outcomes of thrombotic lesions remain unclear. This study aimed to investigate the effects of thrombotic lesions on post-endovascular treatment outcomes in patients with non-acute aortoiliac total occlusions.

    Methods: This subanalysis of a multicenter prospective observational registry study included patients from 64 institutions in Japan between April 2014 and April 2016. A total of 346 patients (394 limbs; median age, 72 years), including 186 men, underwent endovascular treatment for non-acute aortoiliac total occlusions and were included. The patients were classified as having thrombotic or non-thrombotic lesions. The primary (1-year primary patency rate) and secondary (1-year overall survival rate) endpoints were evaluated.

    Results: Thrombotic lesions were identified in 18.5% (64/346) of the patients. The 1-year primary patency (85.9% versus 95.4%, log-rank p<.001) and overall survival (90.6% versus 97.9%, log-rank p=.003) rates were significantly lower in the thrombotic group than in the non-thrombotic group. Thrombotic lesions had significant effects on the post-endovascular treatment outcomes, with adjusted hazard ratios of 3.91 (95% confidence interval, 1.64–9.34, p=.002) for primary patency and 4.93 (95% confidence interval, 1.59–15.3, p=.006) for all-cause mortality.

    Conclusions: Thrombotic lesions were associated with 1-year restenosis and all-cause mortality after endovascular treatment for non-acute aortoiliac total occlusions. Endovascular treatment strategies should be carefully planned for patients with thrombotic lesions.

    Download PDF (631K)
  • Tianqi Xu, Yulan Feng, Weiwen Wu, Fanxia Shen, Xiaodong Ma, Weiping De ...
    Type: Original Article
    Article ID: 61267
    Published: 2021
    [Advance publication] Released: February 06, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: To explore the predictive values of different small vessel disease (SVD) scores on functional recoveries and the clinical cerebrovascular events in mild intracerebral hemorrhage (ICH).

    Methods: In this study, we enrolled conscious and mild ICH patients without surgery and further divided them into the cerebral amyloid angiopathy (CAA)-ICH group and hypertension (HTN)-ICH group. The severity of individual SVD markers, including lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), white matter hyperintensity (WMH), and cortical superficial siderosis (cSS), was evaluated. The original SVD score, modified SVD score, refined SVD score, and CAA-SVD score and the total number of SVD markers were further calculated. Functional recoveries were evaluated using the modified Rankin scale. Recurrences of stroke were defined as readmission to the hospital with a definite diagnosis of stroke.

    Results: A total of 163 ICH patients (60 CAA-ICH and 103 HTN-ICH) were included in the study. The CAA-SVD score (OR=3.429; 95% confidence interval (CI)=1.518–7.748) had the best predictive effect on functional dependence in the CAA-ICH group, among which cSS severities probably played a vital role (OR=4.665; 95% CI=1.388–15.679). The total number of SVD markers [hazard ratio (HR)=3.765; 95% CI=1.467–9.663] can better identify stroke recurrences in CAA-ICH. In HTN-ICH, while the total number of SVD markers (HR=2.136; 95% CI=1.218–3.745) also demonstrated association with recurrent stroke, this effect seems to be related with the influence of lacunes (HR=5.064; 95% CI=1.697–15.116).

    Conclusions: The CAA-SVD score and the total number of SVD markers might identify mild CAA-ICH patients with poor prognosis. However, it would be better to focus on lacunes rather than on the overall burden of SVD to predict recurrent strokes in HTN-ICH.

    Download PDF (404K)
  • Makoto Utsunomiya
    Type: Editorial
    Article ID: ED161
    Published: 2021
    [Advance publication] Released: February 06, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (139K)
  • Hayato Tada
    Type: Editorial
    Article ID: ED162
    Published: 2021
    [Advance publication] Released: February 06, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (326K)
  • Qinyao Zhang, Meirong Hu, Shumei Ma
    Type: Original Article
    Article ID: 59832
    Published: 2021
    [Advance publication] Released: February 05, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Soluble suppression of tumorigenicity 2 (sST2) was validated to independently predict prognosis for heart failure (HF) and ST-segment elevation myocardial infarction (STEMI). In this study, we aimed to evaluate the relation between sST2 and coronary artery stenosis, and no-reflow phenomenon and one-year prognosis in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

    Methods: This prospective study consecutively enrolled 205 patients who were diagnosed with NSTE-ACS and underwent percutaneous coronary intervention (PCI). sST2 was measured for all patients during admission. Patients were divided into two groups based on the optimal cutoff value: sST2 >34.2 ng/ml and sST2 ≤ 34.2 ng/ml groups.

    Results: Patients in the sST2 >34.2 ng/ml group was associated with higher Gensini scores and multivessel disease. sST2 had weak predictive value for no-reflow phenomenon (area under the curve [AUC], 0.662; 95% confidence interval [CI], 0.53–0.79; P=0.015) with 66.7% sensitivity and 65.2% specificity, and it also had independent predictive value of no-reflow phenomenon after adjusting for confounding factors (odds ratio [OR], 3.802; 95% CI, 1.03–14.11; P=0.046). sST2 >34.2 ng/ml had a commendable predictive value for the one-year prognosis (AUC, 0.84; 95% CI, 0.75–0.93; P<0.001) with 72% sensitivity and 84% specificity , and it independently predicted one-year major cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR], 10.22;95% CI, 4.05–25.7; P<0.001).

    Conclusion: The sST2 concentration on admission is correlated with the degree of coronary artery stenosis. sST2 can predict both no-reflow and MACCE in patients with NSTE-ACS after PCI and was an independent predictor of MACCE and no-reflow phenomenon.

    Download PDF (349K)
  • Teruo Sekimoto, Shinji Koba, Hiroyoshi Mori, Rikuo Sakai, Taito Arai, ...
    Type: Original Article
    Article ID: 60152
    Published: 2021
    [Advance publication] Released: February 05, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: This study investigated whether the small dense low-density lipoprotein cholesterol (sd-LDL-c) level is associated with the rapid progression (RP) of non-culprit coronary artery lesions and cardiovascular events (CE) after acute coronary syndrome (ACS).

    Methods: In 142 consecutive patients with ACS who underwent primary percutaneous coronary intervention for the culprit lesion, the sd-LDL-c level was measured using a direct homogeneous assay on admission for ACS and at the 10-month follow-up coronary angiography. RP was defined as a progression of any pre-existing coronary stenosis and/or stenosis development in the initially normal coronary artery. CEs were defined as cardiac death, myocardial infarction, stroke, or coronary revascularization.

    Results: Patients were divided into two groups based on the presence (n=29) or absence (n=113) of RP after 10 months. The LDL-c and sd-LDL-c levels at baseline were equivalent in both the groups. However, the sd-LDL-c, triglyceride, remnant lipoprotein cholesterol (RL-c), and apoC3 levels at follow-up were significantly higher in the RP group than in the non-RP group. The optimal threshold values of sd-LDL-c, triglyceride, RL-c, and apoC3 for predicting RP according to receiver operating characteristics analysis were 20.9, 113, 5.5, and 9.7 mg/dL, respectively. Only the sd-LDL-c level (≥ 20.9 mg/dL) was significantly associated with incident CEs at 31±17 months (log-rank: 4.123, p=0.043).

    Conclusions: The sd-LDL-c level on treatment was significantly associated with RP of non-culprit lesions, resulting in CEs in ACS patients. On-treatment sd-LDL-c is a residual risk and aggressive reduction of sd-LDL-c might be needed to prevent CEs.

    Download PDF (289K)
  • Maryam Zaid, Akira Fujiyoshi, Takashi Hisamatsu, Aya Kadota, Sayaka Ka ...
    Type: Original Article
    Article ID: 61283
    Published: 2021
    [Advance publication] Released: February 05, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium.

    Methods: Japanese men aged 40-79y (n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCAmean), internal carotid artery (ICAmean) and bifurcation (Bifmean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles.

    Results: All cIMT measures had positive associations with CAC (p<0.001): [OR, 95% Confidence Interval]: ICAmean [1.23, 1.07-1.42], CCAmean [1.27, 1.08-1.49], Bifmean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p<0.05), while CCAmean had some of the weakest associations among age quartiles.

    Conclusions: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCAmean, was no longer associated with coronary calcium after age-adjustment and stratification.

    Download PDF (719K)
  • Tetsuya Matoba
    Type: Editorial
    Article ID: ED160
    Published: 2021
    [Advance publication] Released: February 05, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (1704K)
  • Xiaomei Lu, Bin Yang, Huijun Yang, Laiyuan Wang, Hongfan Li, Shufeng C ...
    Type: Original Article
    Article ID: 57125
    Published: 2021
    [Advance publication] Released: February 03, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: ATP-binding cassette (ABC) transporters and endonuclease-exonuclease-phosphatase family domain containing 1 (EEPD1) are reported to regulate cellular cholesterol efflux in macrophages. Bioinformatics analysis has revealed that ABCG1 and EEPD1 might be potential targets of microRNA (miR)-320b. This study aimed to elucidate the roles of miR-320b in cholesterol efflux from macrophages and the pathogenesis of atherosclerosis.

    Methods: Microarray was conducted to profile microRNA (miRNA) expression, and quantitative real-time PCR (qPCR) was used to validate the differentially expressed miRNAs in peripheral blood mononuclear cells of coronary artery disease (CAD) patients and healthy controls. Luciferase assay was conducted to evaluate the activity of reporter construct containing the 3´-untranslated region (3´-UTR) of target genes. Besides, NBD-cholesterol efflux induced by high-density lipoprotein (HDL) and lipid-free apolipoprotein A1 (apoA1) was detected using fluorescence intensity, respectively. Apoe-/- mice were injected with adeno-associated virus (AAV)2-miR-320b or control via tail vein, thereafter fed with 14 week atherogenic diet to study the roles of miR-320b in vivo.

    Results: MiR-320b was highly expressed in CAD patients compared with that in the healthy controls in both the microarray analysis and qPCR analysis. In vitro study showed that miR-320b decreased HDL- and apoA1- mediated cholesterol efflux from macrophages partly by directly targeting ABCG1 and EEPD1 genes and partly via suppressing the LXRα-ABCA1/G1 pathway. Consistently, in vivo administration of AAV2-miR-320b into Apoe-/- mice attenuated cholesterol efflux from peritoneal macrophages, which showed reduced expression of ABCA1/G1 and EEPD1, and increased lipid LDL-C level, with a down-regulation of hepatic LDLR and ABCA1. AAV2-miR-320b treatment also increased atherosclerotic plaque size and lesional macrophage content and enhanced pro-inflammatory cytokines levels through the elevated phosphorylation level of nuclear factor-κB p65 in macrophages.

    Conclusion: We identify miR-320b as a novel modulator of macrophage cholesterol efflux and that it might be a promising therapeutic target for atherosclerosis treatment.

    Download PDF (3248K)
  • Yue Zhang, Xiaosong Ding, Bing Hua, Qingbo Liu, Hui Gao, Hui Chen, Xue ...
    Type: Original Article
    Article ID: 61119
    Published: 2021
    [Advance publication] Released: February 03, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L.

    Methods: A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2].

    Results: Compared with the TyG index <8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index <8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02–2.75; p=0.043].

    Conclusions: In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

    Download PDF (1611K)
  • Yingying Ma, Xiurui Liang, Chen Li, Ruoming Li, Xin Tong, Rui Zhang, X ...
    Type: Original Article
    Article ID: 58305
    Published: 2021
    [Advance publication] Released: February 02, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Previously, we found that diabetes-related liver dysfunction is due to activation of the 5-HT2A receptor (5-HT2AR) and increased synthesis and degradation of 5-HT. Here, we investigated the role of 5-HT in the development of atherosclerosis.

    Methods: The study was conducted using high-fat diet-fed male ApoE-/- mice, THP-1 cell-derived macrophages, and HUVECs. Protein expression and biochemical indexes were determined by Western blotting and quantitative analysis kit, respectively. The following staining methods were used: oil red O staining (showing atherosclerotic plaques and intracellular lipid droplets), immunohistochemistry (showing the expression of 5-HT2AR, 5-HT synthase, and CD68 in the aortic wall), and fluorescent probe staining (showing intracellular ROS).

    Results: In addition to improving hepatic steatosis, insulin resistance, and dyslipidemia, co-treatment with a 5-HT synthesis inhibitor and a 5-HT2AR antagonist significantly suppressed the formation of atherosclerotic plaques and macrophage infiltration in the aorta of ApoE-/- mice in a synergistic manner. Macrophages and HUVECs exposed to oxLDL or palmitic acid in vitro showed that activated 5-HT2AR regulated TG synthesis and oxLDL uptake by activating PKCε, resulting in formation of lipid droplets and even foam cells; ROS production was due to the increase of both intracellular 5-HT synthesis and mitochondrial MAO-A-catalyzed 5-HT degradation, which leads to the activation of NF-κB and the release of the inflammatory cytokines TNF-α and IL-1β from macrophages and HUVECs as well as MCP-1 release from HUVECs.

    Conclusion: Similar to hepatic steatosis, the pathogenesis of lipid-induced atherosclerosis is associated with activation of intracellular 5-HT2AR, 5-HT synthesis, and 5-HT degradation.

    Download PDF (5049K)
  • Shizuya Yamashita, Mitsuyo Okazaki, Takeshi Okada, Daisaku Masuda, Kou ...
    Type: Original Article
    Article ID: 60764
    Published: 2021
    [Advance publication] Released: February 02, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: We established a method to evaluate the lipid concentrations, size and particle numbers (PNs) of lipoprotein subclasses by gel permeation chromatography (GP-HPLC). Nuclear magnetic resonance (NMR) is widely used to analyze these parameters of lipoprotein subclasses, but differences of the two methods are unknown. Current study compared the PNs of each lipoprotein subclass measured by GP-HPLC and NMR, and assessed the effect of a selective PPARα modulator, pemafibrate.

    Methods: Lipoprotein profiles of 212 patients with dyslipidemia who participated in the phase 2 clinical trial of a selective PPARα modulator, pemafibrate, were analyzed by two methods, GP-HPLC and NMR, which were performed with LipoSEARCH (Skylight Biotech) and LipoProfile 3 (LabCorp), respectively. GP-HPLC evaluated the PNs of 18 subclasses, consisting of CM, VLDL1-5, LDL1-6, and HDL1-6. NMR evaluated the PNs of 9 subclasses, consisting of large VLDL & CM, medium VLDL, small VLDL, IDL, large LDL, small LDL, large HDL, medium HDL and small HDL.

    Results: Three major classes, total CM&VLDL, total LDL and total HDL were obtained by grouping of corresponding subclasses in both methods and PNs of these classes analyzed by GP-HPLC were correlated positively with those by NMR. The correlation coefficients in total CM&VLDL, total LDL and total HDL between GP-HPLC and NMR was 0.658, 0.863 and 0.798 (all p<0.0001), respectively. The PNs of total CM&VLDL, total LDL and total HDL analyzed by GP-HPLC was 249.5±51.7nM, 1,679±359 nM and 13,273±1,564 nM, respectively, while those by NMR was 124.6±41.8 nM, 1,514±386 nM and 31,161±4,839 nM, respectively. A marked difference in the PNs between the two methods was demonstrated especially in total HDL.

    The number of apolipoprotein (Apo) B molecule per one ApoB-containing lipoprotein particle, total CM&VLDL plus total LDL, was 1.10±0.05 by GP-HPLC, while 1.32±0.18 by NMR. The number of ApoA-I per one HDL particle was 3.40±0.17 by GP-HPLC, but only 1.46±0.15 by NMR, much less than reported previously.

    From the phase 2 clinical trial, randomizing 212 patients to pemafibrate 0.025-0.2 mg BID, fenofibrate 100 mg QD, or placebo groups, pemafibrate reduced the PNs of CM, large VLDL1-VLDL3 and medium VLDL4, but not small VLDL5 by GP-HPLC. It significantly decreased the PNs of smaller LDL and larger HDL particles, but increased those of larger LDL and smaller HDL particles. In contrast, NMR showed marked variations in the effect of pemafibrate on lipoprotein PNs, and no significant size-dependent changes.

    Conclusions: GP-HPLC evaluates the lipoprotein PNs more accurately than NMR and can be used for assessing the effects of lipid-lowering drugs on lipoprotein subclasses.

    Download PDF (2150K)
  • Mitsuyoshi Takahara, Osamu Iida, Yoshimitsu Soga, Nobuyoshi Azuma, Shi ...
    Type: Original Article
    Article ID: 61481
    Published: 2021
    [Advance publication] Released: January 30, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: This study aimed to demonstrate the clinical impact of various frailty-related aspects in poor-risk patients undergoing revascularization for chronic limb-threatening ischemia (CLTI).

    Methods: We analyzed a clinical database of a prospective multicenter observational study. A total of 562 CLTI patients who required assistance for their daily lives and were candidates for revascularization were included. We examined various measures of frailty severity, including activities of daily living (ADL)/mobility, physical performance, nutritional status, cognitive function, and cardiac function at baseline (before revascularization). Data on inflammatory markers at baseline and ADL/mobility before CLTI onset were also collected.

    Results: The patients were aged 77±10 years, 65% were non-ambulatory, and 38% were categorized as mild dementia or severer. The correlation coefficients between the frailty measures ranged from 0.00 to 0.91. The random forest analysis for one-year mortality risk showed that these frailty-related measures, as well as age and inflammatory markers, had a relatively high variable importance compared with comorbidities and limb severity.

    Conclusion: The correlations between measures of frailty severity were not always strong but rather widely varied in CLTI patients who required assistance for their daily lives and were candidates for revascularization. Measures of frailty severity, as well as age and inflammatory markers, had a relatively large predictive impact on one-year mortality risk compared with comorbidities and limb severity in the population.

    Download PDF (559K)
  • Shinji Yokoyama
    Type: Editorial
    Article ID: ED159
    Published: 2021
    [Advance publication] Released: January 30, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (146K)
  • Tamaki Kobayashi, Makoto Kurano, Mai Nanya, Tomo Shimizu, Ryunosuke Oh ...
    Type: Original Article
    Article ID: 55699
    Published: 2020
    [Advance publication] Released: October 01, 2020
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Recently, it has been established that most of the pleiotropic effects of high-density lipoprotein (HDL) are attributed to sphingosine 1-phosphate (S1P), which rides on HDL via apolipoprotein M (ApoM). In subjects with diabetes mellitus, both the pleiotropic effects of HDL and its role in reverse cholesterol transport are reported to be impaired. To elucidate the mechanisms underlying the impaired pleiotropic effects of HDL in subjects with diabetes, from the aspects of S1P and ApoM.

    Methods: The incubation of HDL in a high-glucose condition resulted in the dimerization of ApoM. Moreover, the treatment of HDL with methylglyoxal resulted in the modulation of the ApoM structure, as suggested by the results of western blot analysis, isoelectric focusing electrophoresis, and two-dimensional gel electrophoresis, which was reversed by treatment with anti-glycation reagents.

    Results: The glycation of HDL resulted in impaired binding of the glycated HDL to S1P, and the S1P on glycated HDL degraded faster. In the case of human subjects, on the other hand, although both the serum ApoM levels and the ApoM content in HDL were lower in subjects with diabetes, we did not observe the polymerization of ApoM.

    Conclusions: Modulation of the quantity and quality of ApoM might explain, at least in part, the impaired functions of HDL in subjects with diabetes mellitus. ApoM might be a useful target for laboratory testing and/or the treatment of diabetes mellitus.

    Download PDF (1349K)
  • Kenichi Tanaka, Yosuke Okada, Maiko Hajime, Yoshiya Tanaka
    Type: Original Article
    Article ID: 59113
    Published: 2021
    [Advance publication] Released: January 29, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: This study aimed to determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels and vascular endothelial function in patients with type 2 diabetes (T2D).

    Methods: This retrospective study included 113 patients with poorly controlled T2D who were admitted for in-hospital diabetes educational program and underwent measurements of serum 25(OH)D levels and reactive hyperemia index (RHI).

    Results: Serum 25(OH)D levels significantly correlated with RHI in T2D patients. Receiver operating characteristic (ROC) curve analysis showed that serum 25(OH)D level of 16.5 ng/mL is the optimal cutoff level for predicting vascular endothelial dysfunction (RHI<1.67), with a sensitivity of 68.5%, specificity of 67.9%, and area under the ROC curve of 0.668 (95% confidence interval [CI]: 0.566–0.770, p=0.002). The mean RHI was significantly lower (1.70±0.54) in patients with low 25(OH)D levels (n=56, 25(OH)D levels <16.5 ng/mL) than that (1.99±0.58; p<0.001) in patients with high 25(OH)D levels (n=57, 25(OH)D level ≥ 16.5 ng/mL). The proportion of patients with RHI<1.67 was higher in the low 25(OH)D group than in the high 25(OH)D group (38% vs. 18%; p<0.001). Multivariate logistic regression analysis identified that serum 25(OH)D level <16.5 ng/mL was associated with increased odds of RHI <1.67 (odds ratio 4.598, 95% CI 1.961–10.783, p<0.001).

    Conclusion: The results demonstrated the association of serum 25(OH)D levels with endothelial function in poorly controlled T2D patients and identified serum 25(OH)D level of <16.5 ng/mL as a predictor of RHI <1.67. Serum 25(OH)D level is a potentially useful marker of vascular endothelial dysfunction in poorly controlled T2D patients.

    Download PDF (304K)
  • Shunsuke Katsuki, Jun-ichiro Koga, Tetsuya Matoba, Ryuta Umezu, Soichi ...
    Type: Original Article
    Article ID: 54379
    Published: 2021
    [Advance publication] Released: January 15, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Abdominal aortic aneurysm (AAA) is a lethal and multifactorial disease. To prevent a rupture and dissection of enlarged AAA, prophylactic surgery and stenting are currently available. There are, however, no medical therapies preventing these complications of AAA. Statin is one of the candidates, but its efficacy on AAA formation/progression remains controversial. We have previously demonstrated that nanoparticles (NPs) incorporating pitavastatin (Pitava-NPs)—clinical trials using these nanoparticles have been already conducted—suppressed progression of atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. Therefore, we have tested a hypothesis that monocytes/macrophages-targeting delivery of pitavastatin prevents the progression of AAA.

    Methods: Angiotensin II was intraperitoneally injected by osmotic mini-pumps to induce AAA formation in Apoe-/- mice. NPs consisting of poly(lactic-co-glycolic acid) were used for in vivo delivery of pitavastatin to monocytes/macrophages.

    Results: Intravenously administered Pitava-NPs (containing 0.012 mg/kg/week pitavastatin) inhibited AAA formation accompanied with reduction of macrophage accumulation and monocyte chemoattractant protein-1 (MCP-1) expression. Ex vivo molecular imaging revealed that Pitava-NPs not only reduced macrophage accumulation but also attenuated matrix metalloproteinase activity in the abdominal aorta, which was underpinned by attenuated elastin degradation.

    Conclusion: These results suggest that Pitava-NPs inhibit AAA formation associated with reduced macrophage accumulation and MCP-1 expression. This clinically feasible nanomedicine could be an innovative therapeutic strategy that prevents devastating complications of AAA.

    Download PDF (2237K)
  • Shinji Katsuragi
    Type: Editorial
    Article ID: ED158
    Published: 2021
    [Advance publication] Released: January 23, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (307K)
  • Ebtehal Salman, Aya Kadota, Takashi Hisamatsu, Hiroyoshi Segawa, Sayuk ...
    Type: Original Article
    Article ID: 58537
    Published: 2021
    [Advance publication] Released: January 22, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The relationship of blood pressure (BP) indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP], mean arterial pressure [MAP]) to subclinical cerebrovascular diseases (SCVDs) remains unclear. This study aimed to elucidate the relationship of four BP indexes measured at two visits on SCVDs assessed by magnetic resonance imaging (MRI) in general Japanese men.

    Methods: In general Japanese men aged 40–79 years (N=616), office BP indexes were measured at two visits (Visits 1 [2006–2008] and 2 [2010–2014]). MRI images obtained on the third visit (2012–2015) were examined for prevalent SCVDs: lacunar infarction, periventricular hyperintensity (PVH), deep subcortical white matter hyperintensity (DSWMH), microbleeds, and intracranial artery stenosis (ICAS). Using a multivariable logistic regression analysis, we computed and estimated the odds ratio of each prevalent SCVD for one standard deviation higher BP indexes. The same analyses were performed using home BP.

    Results: All four office BP indexes at both visits associated with lacunar infarction. Visit 1 and 2 DBP and Visit 1 MAP associated with PVH and DSWMH, and Visit 1 SBP associated with DSWMH. All Visit 2 BP indexes appear to show stronger association with microbleeds than Visit 1 indexes, and Visit 1 and 2 SBP, PP, and MAP showed similar associations with ICAS. Additional analyses using home BP indexes revealed similar relationships; however, the significance of some relationships decreased.

    Conclusion: In general Japanese men, BP indexes were associated with most of SCVDs, and BP indexes measured at different periods associated with different SCVDs assessed by MRI.

    Download PDF (320K)
  • Takashi Omatsu, Yohei Sotomi, Tomoaki Kobayashi, Yuma Hamanaka, Akio H ...
    Type: Original Article
    Article ID: 60566
    Published: 2021
    [Advance publication] Released: January 22, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: We aimed to validate the subjective and qualitative angioscopic findings by the objective and quantitative near-infrared spectroscopic (NIRS) assessment to compensate each other's drawbacks.

    Methods: This is a single-center prospective observational study. Patients undergoing a planned follow-up coronary angiography after percutaneous coronary intervention were prospectively enrolled from January 2018 to April 2019. The major three vessels were examined by NIRS-intravascular ultrasound, followed by coronary angioscopic evaluation. Yellow color grade on angioscopy was classified into four grades (0, white; 1, slight yellow; 2, yellow; and 3, intensive yellow) at a location of maximal lipid core burden index over 4 mm [LCBI (4)] on NIRS in each vessel.

    Results: A total of 95 lesions in 44 patients (72.6±6.7 years, 75% male) were analyzed. LCBI (4) was significantly different among different yellow color grades by coronary angioscopy (ANOVA, p<0.001). Positive correlation was found between angioscopic yellow color grade and LCBI (4) (beta coefficient 164.8, 95% confidence interval 122.9–206.7; p<0.001). The best cutoff value of LCBI (4) to predict the presence of yellow plaque (yellow color grade ≥ 2) was 448 (sensitivity 79.3%, specificity 69.7%, C-statistic 0.800, 95% confidence interval 0.713–0.887, p<0.001).

    Conclusion: The qualitative angioscopic assessment was objectively validated by the quantitative NIRS evaluation, which would be helpful for the reinterpretation of the existing evidences of both imaging modalities.

    Download PDF (1921K)
  • Yusuke Tomoi, Mitsuyoshi Takahara, Yoshimitsu Soga, Masahiko Fujihara, ...
    Type: Original Article
    Article ID: 60772
    Published: 2021
    [Advance publication] Released: January 22, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Originally developed for predicting the risk of stroke in patients with atrial fibrillation (AF), the CHA2DS2-VASc score also has the potential to predict the risk of other cardiovascular disease. This study aimed to investigate the prognostic value of the CHA2DS2-VASc score in patients with peripheral artery disease (PAD) requiring Femoral popliteal (FP) endovascular therapy (EVT).

    Methods: This multicenter, retrospective study analyzed the clinical database of 2190 patients who underwent FP EVT for symptomatic PAD (Rutherford categories 2–4) between January 2010 and December 2018. We calculated the CHA2DS2-VASc score and then investigated the association between the score, as well as AF, and their prognosis. Outcome measures were major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs).

    Results: During a median follow-up of 3.0 years (interquartile range, 1.5–5.0 years), 532 MACEs and 562 MALEs occurred. The CHA2DS2-VASc score and AF were independently associated with an increased risk of MACEs; their adjusted hazard ratios [95% confidence intervals] were 1.28 [1.20–1.36] (P<0.001) per 1-point increase and 1.49 [1.06–2.09] (P=0.022), respectively. The CHA2DS2-VASc score was almost linearly associated with MACEs, without any clear threshold point. On the other hand, these variables were not associated with MALEs risk (P=0.32 and 0.48).

    Conclusion: The CHA2DS2-VASc score and AF were independently associated with the increased risk of MACEs but not of MALEs in patients with symptomatic PAD who underwent FP EVT. The score might be useful in stratifying the MACEs risk in this type of patients.

    Download PDF (243K)
  • Takanori Honda, Sanmei Chen, Jun Hata, Daigo Yoshida, Yoichiro Hirakaw ...
    Type: Original Article
    Article ID: 61960
    Published: 2021
    [Advance publication] Released: January 22, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults.

    Methods: A total of 2,454 participants aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell's C statistics, a calibration plot with the Greenwood-Nam-D'Agostino test, and a bootstrap validation procedure.

    Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell's C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D'Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score).

    Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.

    Download PDF (448K)
  • Chikao Miyazaki, Kazuhiro Shimizu, Yoshinobu Nagasawa, Tatsuo Chiba, K ...
    Type: Original Article
    Article ID: 59451
    Published: 2021
    [Advance publication] Released: January 20, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Stroke is well known to lead to hypertension; nevertheless, the role of vascular function in hypertension remains unclear. In this study, we aimed to clarify the mechanism underlying increased arterial stiffness following stroke.

    Methods: The cardio-ankle vascular index (CAVI) was measured in five New Zealand White rabbits. Under general anesthesia, intracranial pressure (ICP) was increased by injecting saline (15 mL) into the cisterna magna. ICP was monitored using a catheter inserted into the subarachnoid space via right frontal bone craniotomy. Blood pressure (BP), CAVI, and common carotid flow (CCF) were evaluated, and the responses of these parameters to increased ICP were analyzed.

    Results: Saline injection into the cisterna magna increased the ICP by over 20 mmHg. Both BP and CAVI increased from 63.2±4.84 to 128.8±14.68 mmHg and from 4.02±0.28 to 4.9±0.53, respectively. Similarly, BP and CCF increased. When hexamethonium was administered before the increase in ICP, the increase in BP (132.2±9.41 mmHg with 10 mg/kg hexamethonium vs. 105.6±11.01 mmHg with 100 mg/kg hexamethonium) and CAVI (5.02±0.64 with 10 mg/kg hexamethonium vs. 4.82±0.42 with 100 mg/kg hexamethonium) were suppressed in a dose-dependent manner.

    Conclusion: Increased ICP causes an increase in BP and CAVI, suggesting that enhanced stiffness of the muscular arteries contributes to high BP. Blocking the autonomic nervous system with hexamethonium suppresses the increase in BP and CAVI, indicating that these increases are mediated by activation of the autonomic nervous system.

    Download PDF (804K)
  • Takanori Honda, Yuki Ishida, Masaaki Oda, Kenichi Noguchi, Sanmei Chen ...
    Type: Original Article
    Article ID: 59394
    Published: 2021
    [Advance publication] Released: January 17, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time.

    Methods: A total of 2,140 community-dwellers aged 40–74 years participated in both 2002 and 2007 health examinations. Obesity was defined as body mass index ≥ 25 kg/m2. Weight trajectories were classified as: “stable obese” (obese at both examinations), “obese to nonobese” (obese in 2002 but nonobese in 2007), “nonobese to obese” (nonobese in 2002 but obese in 2007), or “stable nonobese” (nonobese at both examinations). We compared changes in the model-predicted risk for CVD and individual CVD risk factors across weight-change categories.

    Results: The predicted risk for CVD increased during 5 years in all groups; the increment in the predicted risk for CVD was smallest in the obese to nonobese participants and steepest in the nonobese to obese subjects. Compared with the stable obese participants, the obese to nonobese participants had greater favorable changes in waist circumferences, blood pressure, fasting plasma glucose, serum high-density lipoprotein cholesterol, serum triglycerides, and liver enzymes. For all these parameters, opposite trends were observed when comparing the nonobese to obese participants with the stable nonobese group.

    Conclusions: We demonstrated the favorable association of losing weight in obese people and avoiding excessive weight gain in nonobese people with global risk of future CVD and individual CVD risk factors in a real-world setting. The findings could improve behavioral lifestyle interventions that provide information on the health consequences of weight change at health checkups.

    Download PDF (354K)
  • Chizuko Maruyama, Yuri Shijo, Noriko Kameyama, Ariko Umezawa, Aisa Sat ...
    Type: Original Article
    Article ID: 60376
    Published: 2021
    [Advance publication] Released: January 17, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The Japan Diet (JD) recommended by the Japan Atherosclerosis Society based on the traditional Japanese diet is presumably favorable for preventing atherosclerotic cardiovascular diseases, but few high-quality controlled clinical trials have examined its benefits as compared with other diets. We studied effects of nutrition education for JD intake as compared with partial JD (PJD) intake on serum lipids and inflammatory parameters in subjects with dyslipidemia.

    Methods: A randomized parallel controlled clinical trial was conducted on outpatients with dyslipidemia. Participants were randomly divided into the JD or the PJD group. Face-to-face nutrition education based on each diet at baseline and at 3 months, as well as monthly counseling by mail during the intervening 3-month period, were provided and participants practiced up to 6 months. Both groups were advised to reduce consumptions of animal fat/ fatty meat/poultry, confections, and alcoholic drinks. Additionally, the JD group participants were recommended to consume more fish, soybean products especially natto, vegetables, and seaweed/mushrooms/konjak, and to switch from refined to unrefined cereals or barley.

    Results: Mean LDL-cholesterol was 125 +/- 29 mg/dL at baseline, and the JD group (n=49) showed a greater mean LDL-cholesterol decrease than the PJD group (n=49) [- 8 mg/dL in JD vs 1 mg/dL in PJD, difference, -9 mg/dL (95%CI, -17 to 0) p=0.043)], and triglyceride (p=0.023) and insulin (p=0.033) reductions were larger in the JD group than in the PJD group at 6 months.

    Conclusion: Nutrition education for JD intake was suggested to improve serum lipid and metabolic parameters in patients with dyslipidemia.

    Download PDF (384K)
  • Yung-An Chua, Aimi Zafira Razman, Anis Safura Ramli, Noor Alicezah Moh ...
    Type: Original Article
    Article ID: 57026
    Published: 2021
    [Advance publication] Released: January 15, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: Familial hypercholesterolaemia (FH) is the most common autosomal dominant lipid disorder, leading to severe hypercholesterolaemia. Early detection and treatment with lipid-lowering medications may reduce the risk of premature coronary artery disease in FH patients. However, there is scarcity of data on FH prevalence, detection rate, treatment and control with lipid-lowering therapy in the Malaysian community.

    Methods: Community participants (n=5130) were recruited from all states in Malaysia. Blood samples were collected for lipid profiles and glucose analyses. Personal and family medical histories were collected by means of assisted questionnaire. Physical examination for tendon xanthomata and premature corneal arcus were conducted on-site. FH were clinically screened using Dutch Lipid Clinic Network Criteria.

    Results: Out of 5130 recruited community participants, 55 patients were clinically categorised as potential (Definite and Probable) FH, making the prevalence FH among the community as 1:100. Based on current total population of Malaysia (32 million), the estimated number of FH patients in Malaysia is 320,000, while the detection rates are estimated as 0.5%. Lipid-lowering medications were prescribed to 54.5% and 30.5% of potential and possible FH patients, respectively, but none of them achieved the therapeutic LDL-c target.

    Conclusion: Clinically diagnosed FH prevalence in Malaysian population is much higher than most of the populations in the world. At community level, FH patients are clinically under-detected, with majority of them not achieving target LDL-c level for high-risk patients. Therefore, public health measures are warranted for early detection and treatment, to enhance opportunities for premature CAD prevention.

    Download PDF (460K)
  • Chao Fang, Jia Lu, Shaotao Zhang, Jifei Wang, Yidan Wang, Lulu Li, Yin ...
    Type: Original Article
    Article ID: 60301
    Published: 2021
    [Advance publication] Released: January 15, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aims: Recent studies suggested plaque erosion with noncritical stenosis could be treated distinctly from that with critical stenosis, but their morphological features remained largely unknown. The present study aimed to investigate morphological features of eroded plaques with different lumen stenosis using optical coherence tomography (OCT).

    Methods: A total of 348 ST-segment elevated myocardial infarction patients with culprit OCT-defined plaque erosion (OCT-erosion) were analyzed. Based on the severity of lumen area stenosis, all patients with OCT-erosions were divided into the following three groups: Group A (area stenosis <50%, n=50); Group B (50% ≤area stenosis <75%, n=146); Group C (area stenosis ≥ 75%, n=152).

    Results: Compared with patients in Groups A and B, patients in Group C were older (p=0.008) and had higher prevalence of hypertension (p=0.029). Angiographic analysis showed that 72.0% of the eroded plaques in Group A were located in the left anterior descending artery, followed by 67.8% in Group B, and 53.9% in Group C (p=0.039). OCT analysis showed that Group A had the highest prevalence of fibrous plaques (p<0.001) and nearby bifurcation (p=0.036), but the lowest prevalence of lipid-rich plaques (p<0.001), macrophage accumulation (p<0.001), microvessels (p=0.009), cholesterol crystals (p<0.001), and calcification (p=0.023). Multivariable regression analysis showed fibrous plaque (odds ratio [OR]: 3.014, 95% confidence interval [CI]: 1.932–4.702, p<0.001) and nearby bifurcation (OR: 1.750, 95% CI: 1.109–2.761, p=0.016) were independently associated with OCT-erosion with an area stenosis of <75%.

    Conclusions: More than half of OCT-erosions presented with <75% area stenosis, having distinct morphological features from those of OCT-erosions with critical stenosis. Fibrous plaque and nearby bifurcation were independently associated with noncritically stenotic OCT-erosion, suggesting that eroded plaques might need individualized treatment.

    Download PDF (1758K)
  • Genshi Egusa
    Type: Editorial
    Article ID: ED156
    Published: 2021
    [Advance publication] Released: January 15, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION
    Download PDF (150K)
  • Kazunori Omote, Isao Yokota, Toshiyuki Nagai, Ichiro Sakuma, Yoshihisa ...
    Type: Original Article
    Article ID: 59881
    Published: 2021
    [Advance publication] Released: January 09, 2021
    JOURNALS OPEN ACCESS ADVANCE PUBLICATION

    Aim: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients.

    Methods: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) <120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months–at baseline) and (absolute difference/baseline)×100, respectively.

    Results: During a median follow-up period of 4.0 (IQR 3.2–4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91–1.08, HR 1.03, 95% CI 0.94–1.12, HR 1.05, 95% CI 0.98–1.12, and HR 1.08, 95% CI 0.94–1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months.

    Conclusions: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.

    Download PDF (1361K)
feedback
Top