Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 25 , Issue 6
Showing 1-9 articles out of 9 articles from the selected issue
Review
  • Yasufumi Sato
    2018 Volume 25 Issue 6 Pages 461-466
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: February 03, 2018
    JOURNALS FREE ACCESS

    The structural and functional integrity of endothelium is essential for the maintenance of vascular health. Vasohibin-1 (VASH1), originally isolated as an endothelium-derived angiogenesis inhibitor, has another function to promote stress tolerance of endothelial cells (ECs), and these functions are critical for the maintenance of vascular homeostasis preventing both pathological angiogenesis and stress-induced vascular diseases. The expression of VASH1 is downregulated during replicative senescence of ECs by the alteration of microRNA expression, and this age-associated downregulation of VASH1 might be a risk of deterioration of vascular homeostasis and age-related vascular diseases. Contrary to this expectation, the lack of Vash1 gene in mice exhibited healthy longevity. Thus, VASH1 has double-face for the maintenance of vascular homeostasis and healthy longevity. This feature of VASH1 and its mechanism will be described in this mini review.

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Original Article
  • Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Ak ...
    2018 Volume 25 Issue 6 Pages 467-476
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: December 08, 2017
    JOURNALS FREE ACCESS

    Aim: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight and fat mass in type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in patients with T2DM.

    Methods: We prospectively recruited uncontrolled (hemoglobin A1c [HbA1c] >7%) Japanese T2DM patients who had a body mass index (BMI) <35 kg/m2. Patients were treated with dapagliflozin (5 mg/day) or non-SGLT2i medicines for six months to improve HbA1c. We investigated changes in body composition using bioelectrical impedance analysis and changes in psoas muscle mass using abdominal computed tomography (CT).

    Results: Subjects were 50 T2DM patients (72% male) with a mean age of 56.1 years, mean BMI of 27.1 kg/m2 and mean HbA1c of 7.9%. HbA1c, body weight, and BMI were significantly decreased in both treatment groups, and the HbA1c decrease was not significantly different between groups. Dapagliflozin treatment significantly decreased body weight and total fat mass without affecting skeletal muscle mass. The absolute change in soft lean mass and skeletal muscle mass was not significantly different between groups. Dapagliflozin treatment did not significantly decrease psoas muscle index, and the absolute change in this index was not significantly different between groups. Dapagliflozin therapy also produced a significant increase in CT radiation attenuation in the third lumbar paraspinal muscles compared with non-SGLT2i therapy.

    Conclusions: Treatment with dapagliflozin for six months significantly improved glycemic control and reduced body weight without reducing muscle mass in T2DM patients.

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  • Tai Pham, Akira Fujiyoshi, Hisatomi Arima, Sachiko Tanaka-Mizuno, Taka ...
    2018 Volume 25 Issue 6 Pages 477-489
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: December 05, 2017
    JOURNALS FREE ACCESS

    Aim: The clinical significance of coronary artery calcification (CAC) is not fully determined in general East Asian populations where background coronary heart disease (CHD) is less common than in USA/Western countries. We cross-sectionally assessed the association between CAC and estimated CHD risk as well as each major risk factor in general Japanese men.

    Methods: Participants were 996 randomly selected Japanese men aged 40–79 y, free of stroke, myocardial infarction, or revascularization. We examined an independent relationship between each risk factor used in prediction models and CAC score ≥100 by logistic regression. We then divided the participants into quintiles of estimated CHD risk per prediction model to calculate odds ratio of having CAC score ≥100. Receiver operating characteristic curve and c-index were used to examine discriminative ability of prevalent CAC for each prediction model.

    Results: Age, smoking status, and systolic blood pressure were significantly associated with CAC score ≥100 in the multivariable analysis. The odds of having CAC score ≥100 were higher for those in higher quintiles in all prediction models (p-values for trend across quintiles <0.0001 for all models). All prediction models showed fair and similar discriminative abilities to detect CAC score ≥100, with similar c-statistics (around 0.70).

    Conclusions: In a community-based sample of Japanese men free of CHD and stroke, CAC score ≥100 was significantly associated with higher estimated CHD risk by prediction models. This finding supports the potential utility of CAC as a biomarker for CHD in a general Japanese male population.

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  • Tomohisa Nezu, Naohisa Hosomi, Shiro Aoki, Noriyuki Suzuki, Tsukasa Te ...
    2018 Volume 25 Issue 6 Pages 490-504
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: December 09, 2017
    JOURNALS FREE ACCESS

    Aims: Although several antihypertensive agents reduced the carotid intima–media thickness (IMT), it remains unclear whether those agents affect the interadventitial diameter (IAD). We aimed to examine whether cilnidipine, an L/N-type calcium channel blocker, reduced the common carotid IMT or IAD in post-stroke hypertensive patients.

    Methods: The common carotid IMT and IAD were measured at the start of cilnidipine treatment and 12 months from that. The changes in the mean max-IMT or IAD between baseline and the 12-month follow-up were evaluated and compared between the thick group (max-IMT ≥1.1 mm) and the normal group (max-IMT <1.1 mm).

    Results: A total of 603 post-stroke hypertensive subjects (mean age=69.3 yr, 378 males) were included in the analysis. At baseline, IAD was increased stepwise according to the value of max-IMT (p for trend <0.001). Among them, 326 subjects were followed up for 12 months. The mean max-IMT from baseline to 12 months did not change in the normal group (-0.01 mm, 95% confidence interval [CI] -0.03 to 0.01, n=170), whereas a significant reduction was observed in the thick group (-0.09 mm, 95% CI -0.13 to -0.05, n=156). The mean IAD was significantly reduced during the study period in the normal group (-0.14 mm, 95% CI -0.22 to -0.05) as well as in the thick group (-0.12 mm, 95% CI -0.21 to -0.03).

    Conclusions: Cilnidipine promoted the regression of common carotid IMT in post-stroke hypertensive patients, especially in the thick group. Cilnidipine also reduced the IAD in both normal and thick groups.

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  • Tian Xu, Peng Zuo, Lin Cao, Zhiwei Gao, Kaifu Ke
    2018 Volume 25 Issue 6 Pages 505-511
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: December 09, 2017
    JOURNALS FREE ACCESS

    Aims: Omentin-1 was proved to be associated with ischemic stroke clinical functional outcome. It also predicted carotid atherosclerosis among metabolic syndrome subjects and type 2 diabetes patients. Our aim was to examine the association of omentin-1 levels with carotid plaque instability and stenosis degree among ischemic stroke patients.

    Methods: A total of 173 acute ischemic stroke patients were included in this study. Serum omentin-1 levels were assayed. Carotid ultrasound examinations were performed to evaluate the carotid plaque instability and stenosis degree. Multivariable logistic analyses were used to examine the association of serum omentin-1 levels with carotid plaque instability and stenosis degree.

    Results: Ischemic stroke patients with unstable carotid plaque had significantly lower levels of serum omentin-1 than patients with stable plaque (53 [40.2–64.1] vs 61.8 [52.4–77.2] ng/ml, P<0.01). Subjects in the highest tertile of serum omentin-1 levels had a 0.31-fold risk of having unstable plaque compared with those in the lowest tertile (P<0.05), and its trend test was significant (P for trend=0.03). The integrated discrimination improvement was significantly improved in predicting carotid plaque instability when omentin-1 data was added to the multivariable logistic regression model. No significant association was detected between omentin-1 and moderate–severe carotid stenosis or occlusion.

    Conclusions: Among ischemic stroke patients, higher omentin-1 levels were inversely associated with carotid plaque instability, but not associated with moderate–severe carotid stenosis or occlusion. Omentin-1 may represent a biomarker for predicting carotid plaque instability of acute ischemic stroke patients.

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  • Daisaku Masuda, Takuya Kobayashi, Masami Sairyou, Hiroyuki Hanada, Toh ...
    2018 Volume 25 Issue 6 Pages 512-520
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: December 02, 2017
    JOURNALS FREE ACCESS

    Aim: The morbidity of cardiovascular disease in patients with type 2 diabetes mellitus (DM) deteriorates in combination with dyslipidemia. The accumulation of remnant lipoproteins in patients with fasting and postprandial hypertriglyceridemia is highly atherogenic. The current study investigated whether the dipeptidyl peptidase-4 inhibitor sitagliptin ameliorates dyslipidemia and hyperglycemia.

    Methods: We enrolled 38 patients with type 2 DM (20 males and 18 females, 65.7±9.9 years old, HbA1c levels <8.4%), and all patients gave written informed consent. Sitagliptin (50 mg/day) was added to current antidiabetic treatments and increased to 100 mg/day to achieve low HbA1c levels (<7.4%). Glucose and lipoprotein metabolism profiles were analyzed at 0, 4, and 12 weeks after sitagliptin administration.

    Results: Sitagliptin significantly decreased fasting levels of triglyceride (TG) (161±90 vs. 130±66 mg/dl, p<0.01) and non-HDL-C (129±29 vs. 116±20 mg/dl, p<0.01) in combination with glucose (150±47 vs. 129±27 mg/dl, p<0.01) and HbA1c (7.1±0.6 vs. 6.6±0.7 mg/dl, p<0.001). Sitagliptin also significantly decreased the fasting levels of apolipoprotein (apo) B-48 (7.8±6.7 vs. 5.6±4.0 µg/ml, p<0.01), remnant lipoprotein cholesterol (15.3±9.5 vs. 12.0±7.9 mg/dl, p<0.05) and other apolipoproteins, such as apoB, apoC-II, apoC-III, and apoE. Analyses of the lipoprotein profiles of fasting sera revealed that sitagliptin significantly decreased cholesterol and TG levels of lipoprotein fractions in the size of very low density lipoprotein and low density lipoprotein.

    Conclusions: These findings indicated that sitagliptin administration ameliorated the lipid and lipoprotein profiles in patients with diabetes, which may be due to the decrease in atherogenic remnant lipoproteins (UMIN#000013218).

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  • Hidenori Arai, Shizuya Yamashita, Koutaro Yokote, Eiichi Araki, Hideki ...
    2018 Volume 25 Issue 6 Pages 521-538
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: April 07, 2018
    JOURNALS FREE ACCESS

    Aim: To verify the superiority of pemafibrate over placebo and the non-inferiority of pemafibrate to the maximum dose of fenofibrate for determining the percent change in fasting serum triglyceride (TG) levels and to investigate safety by assessing the incidence of adverse events (AEs) and adverse drug reactions (ADRs).

    Methods: This phase III, placebo/active drug-controlled, randomized, double-blind, parallel group comparison study enrolled patients with high TG and low high-density lipoprotein cholesterol levels. Patients were randomly assigned to receive placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, or 0.4 mg/day; or fenofibrate 100 mg/day or 200 mg/day for 12 weeks.

    Results: Among 526 randomized patients, 489 completed the study, with drop-out rates of 0%, 6.7%, 5.5%, 5.9%, 8.2%, and 10.7% in the placebo; pemafibrate 0.1 mg/day, 0.2 mg/day, and 0.4 mg/day; and fenofibrate 100 mg/day and 200 mg/day groups. The study showed the non-inferiority of pemafibrate 0.4 mg/day and 0.2 mg/day to fenofibrate 200 mg/day as well the non-inferiority and superiority of all pemafibrate doses to fenofibrate 100 mg/day for reducing TG levels. No dose-dependent increase in the incidence of AEs or ADRs was observed among the pemafibrate dose groups. The incidence of AEs and ADRs for all pemafibrate doses was similar to that for placebo and fenofibrate 100 mg/day and significantly lower than that for fenofibrate 200 mg/day (P<0.05).

    Conclusions: The favorable safety profile of pemafibrate, with fewer adverse effects on kidney/liver-related laboratory tests and fewer AEs/ADRs, including those leading to treatment discontinuation, over fenofibrate 200 mg/day may justify the use of this novel and potent treatment option for reducing TG levels in a broader range of patients.

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Correspondence
  • Mariko Harada-Shiba, Takao Ohta, Akira Ohtake, Masatsune Ogura, Kazush ...
    2018 Volume 25 Issue 6 Pages 539-553
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: February 06, 2018
    JOURNALS FREE ACCESS

    This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.

    FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.

    Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be <140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.

    For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.

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  • Shinji Yokoyama
    2018 Volume 25 Issue 6 Pages 554-556
    Published: June 01, 2018
    Released: June 01, 2018
    [Advance publication] Released: February 02, 2018
    JOURNALS FREE ACCESS
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