Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 21, Issue 12
Displaying 1-10 of 10 articles from this issue
Review
  • Cong He, Zhen Yang, Nong-Hua Lu
    2014 Volume 21 Issue 12 Pages 1229-1242
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: October 24, 2014
    JOURNAL OPEN ACCESS
    Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and low-grade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the long-term treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.
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Original Article
  • Saem Jung, Minjoo Kim, Jey Sook Chae, Sang-Hyun Lee, Jaehyun Joo, Jong ...
    2014 Volume 21 Issue 12 Pages 1243-1252
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 31, 2014
    JOURNAL OPEN ACCESS
    Aim: Identifying differences in plasma metabolic profiling between Lp-PLA2 279VV and 279FF in individuals without metabolic syndrome (MetS) can be used to elucidate the roles of novel Lp-PLA2 activities in normal physiological processes.
    Methods: Non-MetS individuals with 279FF (n=36) and age-, sex- and BMI-matched VV subjects (n=36) were included in this analysis.
    Results: The FF subjects exhibited no appreciable enzyme activity. No significant differences were observed between the VV and FF subjects in the serum lipid profiles or hs-CRP, plasma ox-LDL, MDA or urinary 8-epi-PGF2α levels. The FF subjects also showed lower activities of lyso-phosphatidylcholine (lysoPC) (16:0) (p=0.003) and oleamide (p<0.001) and a higher activity of L-tryptophan (p=0.016) than the VV subjects. In addition, the Lp-PLA2 activity positively correlated with the lysoPC (16:0) and lysoPC (18:0) activities and negatively correlated with the PC (16:0/22:6) and L-tryptophan activities in the VV subjects. Furthermore, in the VV subjects, the lysoPC (16:0) and lysoPC (18:0) activities negatively correlated with the presence of PCs containing 14:0/20:2, 14:0/22:4 and 16:0/22:6, while the oleamide activity exhibited a strong positive correlation with lysoPCs and a negative correlation with PCs, whereas the relationship between oleamide and lysoPCs and PCs was weaker in the FF subjects.
    Conclusions: The present results indicate that the natural absence of the plasma Lp-PLA2 activity due to carriage of the Lp-PLA2 279FF genotype may reduce the generation of lysoPC (16:0) and oleamide and thereby enhance the activity of plasma tryptophan in normal physiological processes.
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  • Daisuke Wajima, Ichiro Nakagawa, Yoshiaki Takamura, Shuta Aketa, Taiji ...
    2014 Volume 21 Issue 12 Pages 1253-1259
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 29, 2014
    JOURNAL OPEN ACCESS
    Aim: Population studies have shown obesity and diabetes to be risk factors for atherosclerosis. We assessed changes in the common carotid arteries in rat models of obesity and diabetes without hypertension.
    Methods: Twenty 30-week-old male spontaneously diabetic and obese model Otsuka Long-Evans Tokushima Fatty (OLETF) and 20 control Long-Evans Tokushima Otsuka (LETO) rats were used in the experiments. The animals were considered diabetic if the plasma glucose level peaked at >300 mg/dL and remained at >200 mg/dL for 120 minutes. Blood gas physiological parameters were continuously monitored under anesthesia, and the flow of the carotid artery was assessed with ultrasonography. All animals were sacrificed with an overdose of anesthesia at the end of the experiment. Sections of the middle portion of the internal carotid artery were cut and stained with hematoxylin and eosin to assess the overall morphology.
    Results: All OLETF rats were diabetic, and all LETO rats were non-diabetic. The physiological parameters did not differ significantly between the control and model rats, whereas the carotid artery wall thickness (19.3±3.2 vs. 6.1±4.5 μm) was significantly different between the two groups. The blood flow velocity in the common carotid artery determined using ultrasonography and color Doppler sonography was significantly increased during systole in the model rats compared with that observed in the control rats (203±20.3 vs. 55.3±21.4 cm/sec).
    Conclusions: The OLETF rats were obese, and diabetes worsened the degree of carotid artery stenosis. These results indicate the possibility of new therapies for carotid artery stenosis in obese and diabetic patients.
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  • Heiko Rühl, Jens Müller, Jana Wäschenbach, Johannes Oldenburg, Oliver ...
    2014 Volume 21 Issue 12 Pages 1260-1270
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 29, 2014
    JOURNAL OPEN ACCESS
    Aim: Venous stasis is a well-known risk factor for the development of venous thromboembolism. It is likely that stasis increases the risk of thrombosis by inducing hypercoagulability via the hypoxic procoagulant activation of endothelial and mononuclear cells and the accumulation of activated clotting factors. However, increased rates of thrombin formation have not been demonstrated in response to venous stasis in vivo.
    Methods: In this study, we used the venous occlusion (VO) test to determine, if stasis triggers thrombin formation in healthy individuals (n=25) and patients with additional thrombotic risk factors, such as inherited thrombophilia (n=19) and symptomatic atherosclerosis (n=15). Thrombin formation was monitored by measuring plasma levels of free thrombin using a highly sensitive oligonucleotide enzyme capture assay (OECA) in addition to the plasma levels of prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin-complexes (TAT). The plasma levels of activated protein C (APC) were additionally measured using an APC-OECA.
    Results: VO induced a significant (p<0.05) increase in the levels of tissue-type plasminogen activator and plasmin-α2-antiplasmin-complexes. In all three cohorts, the majority of samples obtained during VO showed no quantifiable thrombin or APC levels. Consistent with these findings F12 and TAT did not change.
    Conclusions: We conclude that short-term venous stasis induces a profibrinolytic response due to the activation of endothelial cells, but not a prothrombotic response, even in the presence of additional thrombophilic risk factors. Furthermore, our results support the hypothesis that the stasis-induced profibrinolytic activation of endothelial cells occurs independently from thrombin formation.
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  • Juan Chen, Man-Hua Chen, Sha Li, Yuan-Lin Guo, Cheng-Gang Zhu, Rui-Xia ...
    2014 Volume 21 Issue 12 Pages 1271-1282
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 29, 2014
    JOURNAL OPEN ACCESS
    Aim: The usefulness of the white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity of stable coronary artery disease (CAD) has not been sufficiently evaluated, particularly based on strict coronary assessments. The aim of the present study was to investigate the WBC count and NLR in predicting the severity of angiographically proven CAD.
    Methods: A total of 2,976 CAD patients and 571 non-CAD patients were consecutively enrolled, and the CAD patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS<18, n=989; intermediate GS 18-41, n=995 and high GS>41, n=992). The efficacy of the WBC count and NLR in predicting the risk and severity of CAD as well as the correlations between these markers and the GS were analyzed. A receiver operating characteristic (ROC) curve analysis was also performed.
    Results: The NLR was found to be an independent predictor of both the presence of CAD (OR=1.18, 95%CI: 1.09-1.27, p=0.009) and a high GS (OR=1.10, 95%CI: 1.01-1.16, p=0.032). In addition, there were mild positive correlations between the GS and the NLR, WBC and proportions of neutrophils and monocytes. In the ROC curves analysis, the NLR was found to have the largest area under the curve (AUC=0.63, 95%CI: 0.59-0.67, p=0.000), with an optimal cut-off value of 2.04 (sensitivity: 62.1%, specificity: 54.8%) for predicting a high GS.
    Conclusions: The NLR is a valuable independent predictor of the severity of CAD assessed according to the GS. In particular, an NLR of >2.04 indicates a higher risk of CAD and greater severity of CAD lesions.
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  • Renzhe Cui, Kazumasa Yamagishi, Hironori Imano, Tetsuya Ohira, Takeshi ...
    2014 Volume 21 Issue 12 Pages 1283-1289
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 31, 2014
    JOURNAL OPEN ACCESS
    Aim: Patients with peripheral artery disease (PAD) are at a high risk of cardiovascular disease (CVD) among Western populations. However, evidence for an elevated risk in Asian populations is limited.
    Methods: This prospective cohort study examined 939 Japanese men 60-74 years of age at the time of the baseline survey. A total of 115 cases of CVD were detected during a median 9.3 years of follow-up, and the ankle brachial blood pressure index (ABI) functioned as a surrogate measurement of PAD.
    Results: The age-adjusted risks of coronary heart disease, ischemic stroke and ischemic CVD (coronary heart disease and ischemic stroke) were higher among men in the lowest ABI tertile compared with that observed in the men in the highest tertile (<1.08 vs. >1.17). These associations did not change substantially after adjusting for cardiovascular risk factors. The respective multivariable hazard ratios (HRs, 95% CI) for the three conditions were as follows: 2.48 (1.08-5.71), p for trend=0.03; 1.95 (0.94-4.02), p for trend=0.04; and 2.16 (1.25-3.72), p for trend=0.004. These results did not vary based on a comparison of the three ABI categories: ≤0.90, 0.91-1.10 and >1.10. The multivariable HRs (95% CI) for an ABI ≤0.90 versus >1.10 were as follows: 2.04 (0.67-6.20), p for trend=0.14 for coronary heart disease; 3.39 (1.10-10.5), p for trend=0.006 for ischemic stroke; and 2.61 (1.19-5.76), p for trend=0.003 for ischemic CVD. There were no associations between the ABI and the risk of hemorrhagic stroke.
    Conclusions: A low ABI is associated with the risk of coronary heart disease, ischemic stroke and ischemic CVD in elderly Japanese men.
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  • Eduardo Campos Alberto, Takeshi Tanigawa, Koutatsu Maruyama, Yuri Kawa ...
    2014 Volume 21 Issue 12 Pages 1290-1297
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: July 24, 2014
    JOURNAL OPEN ACCESS
    Aim: Nocturnal intermittent hypoxia (NIH), a primary marker of obstructive sleep apnea, has increasingly been linked with cardiovascular morbidity and mortality. The purpose of this study was to investigate the association between NIH and arterial stiffness as measured according to the cardio-ankle vascular index (CAVI) based on cardiovascular risk factors in a Japanese community-dwelling population.
    Methods: We conducted a cross-sectional study in Toon city among 684 men and 1,241 women 30-79 years of age. The severity of NIH was defined as mild or moderate-to-severe according to five or 15 events/hour on the 3% oxygen desaturation index (ODI), respectively. Increased arterial stiffness was diagnosed according to a CAVI of ≥9.
    Results: The number of subjects with no, mild and moderate-to-severe NIH was 1,348 (70%), 451 (23%) and 126 (7%), respectively. Increased arterial stiffness was detected in 21.9% of the participants. The multivariable-adjusted odds ratio (95% CI) of severe NIH related to an increased CAVI in comparison with a 3% ODI of <5 was 1.36 (0.82-2.23). The stratified logistic regression analysis showed that the multivariable-adjusted OR of severe NIH for an increased CAVI was remarkably increased in the individuals with a BMI of ≥25 (OR=2.53, 1.08-5.96; p=0.03). An interaction test showed a trend for an overweight status to be a modifier of the association between OSA and increased arterial stiffness (p=0.05).
    Conclusions: NIH has a tendency to promote increased arterial stiffness as measured according to the CAVI, especially in overweight subjects.
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  • Kisaki Amemiya, Hiroyoshi Yokoi, Takenori Domei, Shinichi Shirai, Kenj ...
    2014 Volume 21 Issue 12 Pages 1298-1307
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: August 06, 2014
    JOURNAL OPEN ACCESS
    Aim: We used quantitative coronary angiography (QCA) to investigate whether coronary plaque progression can be inhibited by controlling lipids with rosuvastatin at Japanese standard doses following elective percutaneous coronary intervention (PCI).
    Methods: A total of 143 patients who underwent elective PCI were randomized to either the rosuvastatin (5 or 2.5mg/day) or non-statin group. Changes from baseline in the minimal lumen diameter (MLD) and average lumen diameter (ALD) measured using QCA were analyzed in both target and non-target lesions.
    Results: The changes in MLD and ALD from baseline to 24 months in the non-target lesions were significantly smaller in the rosuvastatin group than in the non-statin group (−0.079±0.014 mm vs.−0.135±0.019 mm, p=0.022; −0.062±0.012 mmvs. −0.109±0.016mm, p=0.025). The changes in MLD from six to 24 months in the target lesions were significantly lower in the rosuvastatin group than in the non-statin group among the patients treated with drug-eluting stents (−0.046± 0.108 mm vs. −0.133±0.108 mm, p=0.009) versus those treated with bare-metal stents (−0.011± 0.094 mm vs. −0.015±0.040 mm, p=0.255).
    Conclusions: The present study demonstrated that the administration of a standard dose of rosuvastatin slows coronary plaque progression and may prevent the late catch-up phenomenon associated with drug-eluting stents in patients who undergo elective PCI.
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  • Koji Suzuki, Soichiro Takahashi, Kazuhiro Watanabe, Daisuke Fujioka, T ...
    2014 Volume 21 Issue 12 Pages 1308-1325
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: August 15, 2014
    JOURNAL OPEN ACCESS
    Aim: Eicosanoids play various pathogenic roles in aortic valve calcification. Eicosanoids are derived from the arachidonic acid generated by phospholipase A2 (PLA2). We therefore sought to determine whether PLA2s are expressed in human aortic valves and, if so, whether the expression of PLA2s is related to the expression of osteogenic molecules in these tissues.
    Methods: Histological and gene expression analyses of 38 non-rheumatic aortic valves obtained at the time of cardiac valve replacement surgery were conducted. Moreover, gene expression analyses were performed using valve interstitial cells (VICs) obtained from human aortic valves.
    Results: Among the PLA2s examined, the degree of immunoreactivity for PLA2s-IIE and -V was found to significantly correlate with the grade of calcification in the aortic valves. The degree of immunoreactivity and gene expression levels of PLA2s-IIE and -V significantly correlated with those of bone morphogenetic protein (BMP)-2, osteopontin and alkaline phosphatase (ALP). In addition, immunoreactivity for cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase, downstream enzymes of PLA2 in the arachidonic acid cascade, was co-localized with that for PLA2s-IIE and -V in cells expressing α-smooth muscle actin and macrophages expressing CD68. Furthermore, in the in vitro experiments using cultured VICs, the mRNA expression levels of BMP-2, osteopontin and ALP were suppressed by the inhibition of the expression of PLA2s-IIE or -V with specific siRNAs.
    Conclusions: The expression of PLA2s-IIE and -V correlates with the development of calcification as well as the expression of pro-osteogenic molecules in human aortic valves, and inhibiting the expression of PLA2s-IIE and -V suppresses the induction of osteogenic molecules in cultured cells. Therefore, PLA2s-IIE and -V may play a role in the pathogenesis of valve calcification.
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Case Report
  • Hayato Tada, Atsushi Nohara, Masa-aki Kawashiri, Akihiro Inazu, Hirosh ...
    2014 Volume 21 Issue 12 Pages 1326-1329
    Published: December 17, 2014
    Released on J-STAGE: December 17, 2014
    Advance online publication: November 12, 2014
    JOURNAL OPEN ACCESS
    We herein report a case of marked transient hypercholesterolemia in a man receiving low-dose mitotane as adjuvant chemotherapy for adrenocortical carcinoma.
    A 58-year-old man without any clinical symptoms or history of hypercholesterolemia was admitted to our hospital to treat an adrenocortical carcinoma detected on general screening using computed tomography. He reported no chest symptom and did not exhibit any established risk factors for coronary artery disease, such as diabetes, obesity, hypertension or relevant family history, with the exception of current smoking, on admission. A stress electrocardiogram showed negative findings. The left adrenal tumor as well as left kidney, spleen and distal portion of the pancreas were subsequently resected using radical surgery. The histopathological findings confirmed the preoperative diagnosis of adrenocortical carcinoma. After the operation, treatment with low-dose mitotane (1g/day) was introduced as adjuvant chemotherapy. Interestingly, the patient developed marked hyper-LDL cholesterolemia at a level equivalent to that of familial hypercholesterolemia (LDL cholesterol level ~ 300 mg/dL) following the introduction of mitotane, without evidence of primary or secondary hypercholesterolemia due to other causes. A coronary angiogram performed to assess the new-onset angina revealed three-vessel disease, which was later revascularized via percutaneous coronary intervention eight months after the start of mitotane therapy. The cholesterol level normalized with the suspension of mitotane. This case suggests that mitotane can cause severe hypercholesterolemia, potentially resulting in coronary atherosclerosis.
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