Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 24 , Issue 4
Showing 1-10 articles out of 10 articles from the selected issue
  • Yoshihide Yamanashi, Tappei Takada, Ryoya Kurauchi, Yusuke Tanaka, Tok ...
    2017 Volume 24 Issue 4 Pages 347-359
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: January 17, 2017

    Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

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  • Insights from Optical Coherence Tomography Imaging
    Yu Kataoka, Jordan Andrews, Rishi Puri, Peter Psaltis, Stephen J. Nich ...
    2017 Volume 24 Issue 4 Pages 360-372
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: February 24, 2017

    Due to the pandemics of obesity and diabetes mellitus, especially in the Western countries, atherosclerotic cardiovascular disease (ASCVD) has become a major health burden and is expected to increase in the future. Modifying lipid targets, especially low-density lipoprotein cholesterol (LDL-C) level, has become the first-line therapy for primary and secondary prevention of ASCVD. Intravascular imaging modalities have contributed to elucidating clinical efficacy of lipid lowering therapy on atherosclerotic plaques. Optical coherence tomography (OCT) is a high-resolution imaging tool enables visualization of plaque microstructures associated with its instability. This modality has demonstrated favorable changes in plaque microstructures under lowering LDL-C level. In addition, clinical studies using OCT have suggested potential association of other lipid targets, including triglyceride and high-density lipoprotein cholesterol with plaque microstructures. Given continuing cardiovascular risks despite statin therapy, OCT will be an important imaging modality to evaluate novel therapeutic approaches that potentially modulates plaque instability.

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  • Dylan R. Morris, Kengo Ayabe, Takashi Inoue, Nobuyuki Sakai, Richard B ...
    2017 Volume 24 Issue 4 Pages 373-387
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: March 04, 2017

    Carotid artery stenosis is responsible for between 10-20% of all ischaemic strokes. Interventions, such as carotid endarterectomy and carotid stenting, effectively reduce the risk of stroke in selected individuals. This review describes the history of carotid interventions, and summarises reliable evidence on the safety and efficacy of these interventions gained from large randomised clinical trials.

    Early trials comparing carotid endarterectomy to medical therapy alone in symptomatic patients, and asymptomatic patients, demonstrated that endarterectomy halved the risk of stroke and perioperative death in these two unique populations. The absolute risk reduction was smaller in the asymptomatic carotid trials, consistent with their lower absolute stroke risk. More recent trials in symptomatic patients, suggest that carotid stenting has similar long term durability to carotid endarterectomy, but possibly has higher procedural hazards dominated by non-disabling strokes. The Asymptomatic Carotid Surgery Trial-2, along with individual patient data meta-analysis of all asymptomatic trials, will provide reliable evidence for the choice of intervention in asymptomatic patients in whom a decision has been made for carotid revascularisation. Given improvements in effective cardiovascular medical therapy, in particular lipid-lowering medications, there is renewed uncertainty as to whether carotid interventions still provide meaningful net reductions in stroke risk in asymptomatic populations. Four large trials in Europe and the US are currently underway, and are expected to report long-term results in the next decade.

    It is essential that surgeons, interventionalists, and physicians continue to randomise large numbers of patients from around the world to clarify current uncertainty around the management of asymptomatic carotid stenosis.

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Original Article
  • A Pilot Study
    Chizuko Maruyama, Rena Nakano, Mitsuha Shima, Asumi Mae, Yuri Shijo, E ...
    2017 Volume 24 Issue 4 Pages 393-401
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: September 21, 2016

    Aim: We conducted a pilot study to clarify the effects of the Japan Diet nutritional education program on metabolic risk factors for atherosclerotic cardiovascular disease in middle-aged men who were brought up in the westernized dietary environment of modern Japan.

    Methods: Thirty-three men, 30–49 years of age, attended a nutrition education class to learn food items and recommended volumes comprising the Japan Diet (more fish, soybeans and soy products, vegetables, seaweed, mushrooms and unrefined cereals, and less animal fat, meat and poultry with fat, sweets, desserts and snacks, and alcoholic drinks), and were encouraged to consume the Japan Diet for 6 weeks. Anthropometric and biochemical parameters were measured and 3-day weighted dietary records were kept before and at completion of the intervention.

    Results: Ninety-one percent of participants showed improvements in more than one cardiovascular risk factor after 6 weeks. Body weight, serum low density lipoprotein (LDL) cholesterol, malondialdehyde modified (MDA)-LDL and triglyceride concentrations decreased significantly, while high density lipoprotein cholesterol was unchanged. Fish, soy, and sum of seaweed, mushrooms and konjak intakes doubled, and green and yellow vegetable intakes also increased as compared to baseline. Meanwhile, intakes of refined cereals, meat and poultry, sweets, desserts and snacks, and margarine and shortening decreased. Total energy, lipid, and saturated and monounsaturated fatty acid intakes decreased, while n-3 polyunsaturated fatty acid, dietary fiber, beta-carotene, vitamins D and K, potassium, and magnesium increased, with no change in sodium intake.

    Conclusions: The Japan Diet is suggested to improve atherosclerotic cardiovascular disease risk factors in middle-aged Japanese men.

    The clinical trial registration number: UMIN000020639.

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  • Mariko Harada-Shiba, Katsunori Ikewaki, Atsushi Nohara, Yoshihiko Otsu ...
    2017 Volume 24 Issue 4 Pages 402-411
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: February 02, 2017

    Aim: There is an unmet need in Japan for more optimal lipid-lowering therapy (LLT) for patients with homozygous familial hypercholesterolemia (HoFH) who respond inadequately to available drug therapies and/or apheresis, to achieve goals of low-density lipoprotein cholesterol (LDL-C) reduction by 50% or to <100 mg/dL.

    Methods: In this study, Japanese patients with HoFH on stable LLT and diet were treated with lomitapide, initiated at 5 mg/day and escalated to maximum tolerated dose (up to 60 mg/day) over 14 weeks. The primary efficacy endpoint was mean percentage change from baseline to Week 26 in LDL-C. Secondary endpoints included changes in other lipid parameters and safety throughout the 56-week study (including follow-up).

    Results: Nine patients entered the efficacy phase of the study and, of these, eight completed 56 weeks. Mean LDL-C was reduced by 42% (p<0.0001) at 26 weeks, from 199 mg/dL (95% CI: 149–250) at baseline to 118 mg/dL (95% CI: 70–166). A 50% reduction in LDL-C and LDL-C <100 mg/dL was achieved by five and six of nine patients, respectively, at 26 weeks. After 56 weeks, LDL-C was reduced by 38% (p=0.0032) from baseline. Significant reductions in non-HDL-C, VLDL-C, triglycerides, and apolipoprotein B were also reported at Week 26. There were no new safety signals and, similar to previous studies, gastrointestinal adverse events were the most common adverse events.

    Conclusion: Lomitapide, added to ongoing treatment with other LLTs, was effective in rapidly and significantly reducing the levels of LDL-C and other atherogenic apolipoprotein B-containing lipoproteins in adult Japanese patients with HoFH.

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  • Yujiro Okute, Tetsuo Shoji, Tomoshige Hayashi, Yukinobu Kuwamura, Mika ...
    2017 Volume 24 Issue 4 Pages 412-421
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: September 13, 2016

    Aim: The cardiothoracic ratio (CTR) on a chest X-ray is an indicator of cardiac enlargement, although its predictive power for cardiovascular disease (CVD) events in chronic kidney disease is unknown. We examined it in a cohort of hemodialysis patients, as compared with an N-terminal fragment of probrain natriuretic peptide (NT-proBNP).

    Method: This was an observational study with cross-sectional and longitudinal analyses including 517 maintenance hemodialysis patients and 122 healthy control subjects. The main predictors were CTR and serum NT-proBNP, and the main outcome was CVD events in 5 years.

    Results: At baseline, the hemodialysis patients had higher median (interquartile range) levels of CTR [0.487 (0.457–0.520)] than the control group [0.458 (0.432–0.497)]. In the hemodialysis group, CTR was positively correlated with NT-proBNP (Spearman's r=0.44, P<0.001). During follow-up, 190 CVD events occurred. CTR was significantly associated with the risk of CVD [HR 2.12 (95% CI, 1.38–3.25) for the fourth quartile as compared with the second quartile of CTR] in a multivariate Cox model. In the same model, NT-proBNP (fourth versus first quartile) showed a HR of 3.27 (2.02–5.31). When CTR and NT-proBNP were simultaneously included as predictors, only NT-proBNP remained a significant predictor of CVD events, all-cause mortality and composite of CVD plus all-cause mortality.

    Conclusions: We showed that CTR was a significant and independent predictor of CVD in hemodialysis patients. CTR can be used for CVD risk stratification in hemodialysis patients when NT-proBNP is not available.

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  • Daisuke Sanoyama, Mototsugu Nagao, Akira Asai, Yuko Nakamura, Kazumi S ...
    2017 Volume 24 Issue 4 Pages 422-429
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: September 07, 2016

    Aim: The clinical significance of energy expenditure (EE) in the treatment of type 2 diabetes has not been fully elucidated. Here we analyzed the relationships between EE and clinical measurements in patients with type 2 diabetes receiving diet therapy.

    Methods: A total of 100 patients (34 women and 66 men) with type 2 diabetes admitted to our hospital for glycemic control were enrolled. The participants received an energy-restricted diet during their hospitalization (median, 15 days). EE was measured in the fasted (FEE) and postprandial (PPEE) states using indirect calorimetry. The postprandial increment of EE (ΔEE) was calculated from the FEE and PPEE (ΔEE=PPEE–FEE).

    Results: FEE, PPEE, and ΔEE were 0.997±0.203, 1.104±0.213, and 0.107±0.134 kcal/min, respectively. Body weight decreased from 68.7±16.6 to 66.8±16.0 kg (p<0.0001) during hospitalization. FEE and PPEE showed positive correlations with height, body weight, body mass index, and abdominal circumference at admission, but ΔEE was not correlated with these anthropometric measurements. On the other hand, ΔEE was inversely correlated with the body weight change. The association between ΔEE and the body weight change was independent of age, sex, and HbA1c.

    Conclusions: Postprandial increase in energy expenditure may be a determinant of individual differences in weight reduction in patients with type 2 diabetes on diet therapy. As a simple surrogate for diet-induced thermogenesis, ΔEE may serve as a useful predictive marker for the efficacy of diet therapy.

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  • Jing Dong, Ying-Zhi Liang, Jie Zhang, Li-Juan Wu, Shuo Wang, Qi Hua, Y ...
    2017 Volume 24 Issue 4 Pages 430-441
    Published: April 01, 2017
    Released: April 03, 2017
    [Advance publication] Released: September 13, 2016

    Aim: To explore the relationship between lipometabolism-related microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and the presence of coronary artery disease (CAD).

    Methods: In the present study, 161 stable CAD patients and 149 health controls were enrolled. The expression levels of seven miRNAs (miR-21, miR-24, miR-29a, miR-33a, miR-34a, miR-103a, and miR-122) in PBMCs were qualified by quantitative real-time polymerase chain reaction (qRT-PCR). The miRNA markers that showed significant difference between the two groups were used for further analysis. The risk of miRNA contributing to the presence of CAD was estimated by univariate and multivariate logistic regression models. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.

    Results: The expression levels of miR-24, miR-33a, miR-103a, and miR-122 in PBMCs were significantly increased in CAD patients compared with controls and were significantly correlated with blood lipids in both CAD patients and controls. The increased levels of miR-24 (adjusted OR=1.32, 95% CI 1.07–1.62, P=0.009), miR-33a (adjusted OR=1.57, 95% CI 1.35–1.81, P<0.001), miR-103a (adjusted OR=1.01, 95% CI 1.01–1.02, P<0.001), and miR-122 (adjusted OR=1.03, 95% CI 1.01–1.04, P<0.001) were associated with risk of CAD. We identified a miRNA panel (miR-24, miR-33, miR-103a, and miR-122) that provided a high diagnostic accuracy of CAD (AUC=0.911, 95% CI 0.880–0.942).

    Conclusion: The increased expression levels of miR-24, miR-33a, miR-103a, and miR-122 in PBMCs are associated with risk of CAD. A panel of the four miRNAs has considerable clinical value in diagnosing stable CAD.

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