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Endosialin, also called tumor endothelial marker-1 or CD248, is a transmembrane glycoprotein that is suggested to play a role in inflammation as well as tumor progression. Endosialin expression was also reported to be upregulated in human atherosclerotic lesions. However, no study has reported blood endosialin levels in patients with coronary artery disease (CAD).We investigated the association between plasma endosialin levels and the presence or severity of CAD in 376 patients who underwent elective coronary angiography for suspected CAD. The severity of CAD was represented as the numbers of stenotic coronary vessels and segments.Of the 376 study patients, CAD was found in 210 patients (one-vessel disease (1-VD), n = 90; two-vessel disease (2-VD), n = 65; and three-vessel disease (3-VD), n = 55). Compared with 166 patients without CAD, 210 patients with CAD had higher C-reactive protein (CRP) levels (median 0.57 vs. 0.43 mg/L, P = 0.007). However, endosialin levels did not significantly differ between patients with and without CAD (0.91 vs. 0.92 ng/mL, P = 0.693). A stepwise increase in CRP levels was found depending on the number of50% stenotic vessels: 0.43 in CAD(-), 0.52 in 1-VD, 0.57 in 2-VD, and 0.58 mg/L in 3-VD (P = 0.019). No marked difference was found in endosialin levels among four groups of CAD(-), 1-VD, 2-VD, and 3-VD (0.92, 0.89, 0.98, and 0.87 ng/mL, respectively, P = 0.785). Moreover, no significant correlation was found between endosialin levels and the numbers of50% and25% stenotic segments or CRP levels. In multivariate analysis, endosialin levels were not a significant factor associated with CAD independent of atherosclerotic risk factors.Plasma endosialin levels in patients with CAD were found to be not higher than in those without CAD and to be not significantly associated with the presence or severity of CAD.

Green tea and coffee contain various bioactive compounds (e.g., polyphenols), and their consumption has been proposed to decrease the risk of cardiovascular diseases. Here, we investigated the associations between the consumption of green tea and that of coffee and the prevalence of coronary artery disease (CAD) in Japanese patients. The study group was 612 patients who underwent coronary angiography at Tokyo Medical Center between July 2008 and February 2017. CAD was confirmed in 388 of the patients: one-vessel disease (1-VD, n=166); two-vessel disease (2-VD, n=112); three-vessel disease (3-VD, n=110). Myocardial infarction (MI) was found in 138 patients. After adjustment for well-known atherosclerotic risk factors and other dietary habits, greater green tea consumption was significantly inversely associated with CAD prevalence (p for trend=0.044), and the patients who drank3 cups/d had a lower prevalence of CAD compared to those who drank1 cup/d (odds ratio [OR]: 0.54, 95% CI: 0.30-0.98). Greater green tea consumption (3 cups/d) was also associated with a decreased prevalence of 3-VD (OR: 0.49, 95% CI: 0.24-0.98, p-trend=0.047) and MI (OR: 0.51, 95% CI: 0.27-0.97, p-trend=0.037). In contrast, coffee consumption was not associated with CAD or MI. In subgroup analyses, the inverse association between green tea consumption and CAD or MI was found in the high intake groups of vegetables or fruits but not in the low intake groups of vegetables or fruits. These results suggest a beneficial effect of green tea consumption, especially with a diet rich in vegetables and fruits, against coronary atherosclerosis in Japanese.

Sestrin2 is a stress-inducible antioxidant protein that plays a protective role against oxidative stress. However, blood sestrin2 concentrations in subjects with carotid atherosclerosis have not been elucidated.We investigated plasma sestrin2 concentrations in 152 subjects undergoing carotid ultrasonography. Plaque severity was evaluated as plaque score.Of the 152 subjects, plaque was found in 63 (41%). Plasma sestrin2 concentrations were higher in 63 subjects with plaque than in 89 without plaque (median 14.1 vs. 12.8 ng/ml, P 0.02). A stepwise increase in sestrin2 concentrations was found depending on plaque score: 12.8 ng/ml in score = 0 (n = 89), 12.7 ng/ml in score = 1 (n = 31), and 15.9 ng/ml in score ≥2 (n = 32)(P 0.005). Especially, sestrin2 concentrations in subjects with score ≥ 2 were higher than in score = 0 and score = 1 (P 0.05). Sestrin2 concentrations correlated with plaque score (r = 0.24, P 0.005). In multivariate analysis, sestrin2 concentration was an independent factor associated with score ≥ 2. Odds ratio for score ≥ 2 was 5.70 (95%CI = 1.99-16.35) for high sestrin2 concentration (13.0 ng/ml).Plasma sestrin2 concentrations were found to be high in subjects with carotid plaque and to be associated with plaque severity. High plasma sestrin2 concentrations in subjects with carotid plaque may reflect a protective response against the progression of carotid atherosclerosis.

Heme oxygenase-1 (HO-1) degrades heme to CO, iron, and biliverdin/bilirubin. Although serum bilirubin levels were often reported in patients with coronary artery disease (CAD), HO-1 levels in patients with CAD and the association between HO-1 and bilirubin levels have not been clarified.We measured plasma HO-1 and serum total bilirubin levels in 262 patients undergoing coronary angiography.HO-1 levels were higher in patients with CAD than without CAD (median 0.46 vs. 0.35 ng/mL, P 0.01), but bilirubin were lower in patients with CAD than without CAD (0.69 vs. 0.75 mg/dL, P 0.02). Notably, HO-1 levels in CAD(-), 1-vessel, 2-vessel, and 3-vessel disease were 0.35, 0.51, 0.45, and 0.44 ng/mL, and were highest in 1-vessel disease (P 0.05). Bilirubin levels in CAD(-), 1-vessel, 2-vessel, and 3-vessel disease were 0.75, 0.70, 0.68, and 0.66 mg/dL (P = NS). No correlation was found between HO-1 and bilirubin levels. In multivariate analysis, HO-1 levels were a significant factor for CAD independent of atherosclerotic risk factors and bilirulin levels. Odds ratio for CAD was 2.32 (95%CI = 1.29-4.17) for high HO-1 (0.35 ng/mL).Patients with CAD were found to have high HO-1 and low bilirubin levels in blood, but no correlation was found between HO-1 and bilirubin levels.

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein known for its role in inflammation. However, plasma FSTL1 levels in patients with coronary artery disease (CAD) have not been fully elucidated. Thus, in this study, we investigated the plasma FSTL1 levels of 350 patients who underwent elective coronary angiography. The severity of CAD was represented as the numbers of50% stenotic vessels and segments and the severity score. CAD was detected in 196 patients, of whom 84 had 1-vessel disease (1-VD), 62 had 2-VD, and 50 had 3-VD. Plasma high-sensitivity C-reactive protein (hsCRP) levels were higher in patients with CAD than in those without CAD (median 0.56 versus 0.44 mg/L, P0.01). Notably, plasma FSTL1 levels were higher in patients with CAD than in those without CAD (median 4.05 versus 3.47 ng/mL, P0.02). A stepwise increase in FSTL1 levels was found depending on the number of50% stenotic vessels: 3.47 in CAD (-), 3.74 in 1-VD, 4.42 in 2-VD, and 4.65 ng/mL in 3-VD (P0.05). FSTL1 levels also correlated with the number of50% stenotic segments and the severity score (r = 0.14 and r = 0.15, respectively, P0.005) and hsCRP levels (r = 0.10, P0.05). In the multivariate analysis, FSTL1 levels were an independent factor associated with CAD. The odds ratio for CAD was 1.61 (95% CI = 1.01-2.58) for high FSTL1 level of3.6 ng/mL (P0.05). In conclusion, plasma FSTL1 levels in patients with CAD were found to be high and associated with the presence and severity of CAD, thus, suggesting that FSTL1 may play a role in the progression of coronary atherosclerosis.

Nesfatin-1 is a recently identified anorexigenic peptide mainly secreted from the brain and adipose tissue. Although nesfatin-1 may have pro-inflammatory and apoptotic properties, the association between plasma nesfatin-1 levels and coronary artery disease (CAD) has not been clarified yet. We investigated plasma nesfatin-1 levels in 302 patients undergoing elective coronary angiography. Of the 302 study patients, CAD was present in 172 (57%), of whom 67 had 1-vessel, 49 had 2-vessel, and 56 had 3-vessel disease. Compared with 130 patients without CAD, 172 with CAD had higher plasma nesfatin-1 levels (median 0.21 vs. 0.17 ng/mL, P 0.01). A stepwise increase in nesfatin-1 levels was found depending on the number of 50% stenotic coronary vessels: 0.17 in CAD(-), 0.20 in 1-vessel, 0.21 in 2-vessel, and 0.22 ng/mL in 3-vessel disease (P 0.05). A high nesfatin-1 level ( 0.19 ng/mL) was found in 43% of patients with CAD(-), 55% of those with 1-vessel, 55% of those with 2-vessel, and 68% of those with 3-vessel disease (P 0.05). Nesfatin-1 levels significantly correlated with the number of 50% stenotic coronary segments (r = 0.14, P 0.02). In multivariate analysis, plasma nesfatin-1 levels were a significant factor for CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.71 (95% CI 1.01-2.91) for high nesfatin-1 level of 0.19 ng/mL (P 0.05). Thus, plasma nesfatin-1 levels were found to be high in patients with CAD and were associated with CAD independent of atherosclerotic risk factors, suggesting that high nesfatin-1 levels in patients with CAD may play a role in the development of coronary atherosclerosis.

Aim: Betatrophin, a recently identified circulating adipokine, affects lipid and glucose metabolism. However, association between plasma betatrophin levels and atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), has not been elucidated. Methods: We investigated plasma betatrophin levels in 457 patients undergoing elective coronary angiography who also had ankle-brachial index (ABI) test for PAD screening. Results: Of the 457 study patients, CAD was present in 241 patients (53%) (1-vessel [1-VD], n = 99; 2-vessel [2-VD], n = 71; 3-vessel disease [3-VD], n = 71). Compared to 216 patients without CAD, 241 with CAD had higher betatrophin levels (median 1120 vs. 909 pg/mL, p < 0.001). A stepwise increase in betatrophin levels was found depending on the number of > 50% stenotic coronary vessels: 909 in CAD(-), 962 in 1-VD, 1097 in 2-VD, and 1393 pg/ml in 3-VD (p < 0.001). Betatrophin levels correlated with the number of > 25% stenotic segments (r = 0.24, p < 0.001). PAD (ABI < 0.9) was found in 41 patients (9%). Plasma betatrophin levels were also significantly higher in 41 patients with PAD than in 416 without PAD (1354 vs. 981 pg/mL, p < 0.001). In the multivariate analysis, betatrophin levels were not a factor for CAD, but they were a significant factor for 3-VD and PAD independent of atherosclerotic risk factors. The odds ratios for 3-VD and PAD were 1.06 (95%CI = 1.01–1.11) and 1.07 (95%CI = 1.01–1.13) for a 100-pg/mL increase in betatrophin levels, respectively (p < 0.05). Conclusion: Plasma betatrophin levels were associated with the presence and severity of CAD and PAD, suggesting betatrophin has a role in atherosclerosis.

Aim: Osteoglycin is one of proteoglycans that are biologically active components of vascular extracellular matrix. However, the role of osteoglycin in atherosclerosis remains unclear. Methods: We investigated plasma osteoglycin levels and the presence, severity, and lesion morphology of coronary artery disease (CAD) in 462 patients undergoing elective coronary angiography. Results: Of 462 patients, 245 had CAD. Osteoglycin levels were higher in patients with CAD than without CAD (median 29.7 vs. 25.0 ng/mL, P < 0.05). However, osteoglycin levels did not differ among patients with one-vessel, two-vessel, or three-vessel disease (30.8, 30.6, and 29.4 ng/mL, respectively) and did not correlate with the number of stenotic segments. Among 245 CAD patients, 41 had complex coronary lesions, and 70 had total occlusion, of whom 67 had good collateralization. Between 70 patients with occlusion and 175 without occlusion, osteoglycin levels did not differ (30.4 vs. 29.5 ng/mL). Notably, osteoglycin levels were lower in 41 patients with complex lesions than in 204 without such lesions (24.2 vs. 31.6 ng/mL, P < 0.02). In multivariate analysis, osteoglycin levels were an independent factor for complex lesion but not for CAD. Odds ratio for complex lesion was 0.80 (95%CI = 0.67–0.96) for each 10 ng/mL increase in osteoglycin levels (P < 0.02). Conclusion: Although plasma osteoglycin levels were high in patients with CAD, they did not correlate with the severity of CAD and were not an independent factor for CAD. Notably, osteoglycin levels were low in patients with complex lesions and were a factor for complex lesions, suggesting that osteoglycin plays a role in coronary plaque stabilization.

Aims. Atherosclerotic disease, such as coronary artery disease (CAD), is recognized to be associated with inflammation and oxidative stress. We investigated the association between CAD and plasma levels of sestrin2 which is one of the stress-inducible antioxidant proteins. Methods. We measured plasma sestrin2 levels in 304 patients undergoing elective coronary angiography. The severity of CAD was represented as the numbers of >50% stenotic coronary vessels and segments and the severity score. Results. CAD was found in 175 patients, of whom 73 had 1-vessel (1-VD), 59 had 2-vessel (2-VD), and 43 had 3-vessel disease (3-VD). Plasma sestrin2 levels were significantly higher in 175 patients with CAD than in 129 without CAD (median 16.4 vs. 14.2 ng/mL, P<0.05). A stepwise increase in sestrin2 levels was found depending on the number of >50% stenotic coronary vessels: 14.2 in CAD(-), 15.4 in 1-VD, 17.3 in 2-VD, and 17.7 ng/mL in3-VD (P<0.05). High sestrin2 level (>16.0 ng/mL) was present in 38% of patients with CAD(-), 47% of 1-VD, 66% of 2-VD, and 53% of 3-VD (P<0.005). Sestrin2 levels significantly, but weakly, correlated with the number of >50% stenotic segments and the severity score (rs=0.12 and rs=0.13, P<0.05). In the multivariate analysis, sestrin2 levels were a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.79 (95%CI=1.09‐2.95) for high sestrin2 level of >16.0 ng/mL (P<0.025). Conclusions. Plasma sestrin2 levels in patients with CAD were found to be high and to be associated with the severity of CAD. High sestrin2 levels in patients with CAD may reflect a protective response against the progression of CAD.

Aims. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme to generate CO, biliverdin, and iron. Since these products have antiatherogenic properties, HO-1 may play a protective role against the progression of atherosclerosis. However, plasma HO-1 levels in patients with atherosclerotic diseases, such as coronary artery disease (CAD) and peripheral artery disease (PAD), have not been clarified yet. Methods. We investigated plasma HO-1 levels by ELISA in 410 consecutive patients undergoing elective coronary angiography who also had an ankle-brachial index (ABI) test for PAD screening. Results. Of the 410 study patients, CAD was present in 225 patients (55%) (1-vessel (1-VD), n=91; 2-vessel (2-VD), n=66; 3-vessel disease (3-VD), n=68). PAD (ABI P<0.02). After excluding the 36 patients with PAD, HO-1 levels were significantly higher in 192 patients with CAD than in 182 without CAD (0.45 versus 0.35 ng/mL, P<0.05). HO-1 levels in 4 groups of CAD(−), 1-VD, 2-VD, and 3-VD were 0.35, 0.49, 0.44, and 0.44 ng/mL, respectively, and were highest in 1-VD (P<0.05). In the multivariate analysis, HO-1 levels were inversely associated with PAD, whereas they were also associated with CAD. The odds ratios for PAD and CAD were 2.12 (95% CI = 1.03–4.37) and 0.65 (95% CI = 0.42–0.99) for the HO-1 level of Conclusions. Plasma HO-1 levels were found to be low in patients with PAD, in contrast to high levels in patients with CAD.

text, 紀要論文 / Departmental Bulletin Paper

text, 紀要論文 / Departmental Bulletin Paper

Objective— Transforming growth factor-β inhibits migration and proliferation of endothelial and smooth muscle cells. Endoglin is a transmembrane receptor for transforming growth factor-β1 and transforming growth factor-β3. Endoglin is released into blood as a soluble form (soluble endoglin [sEng]), but plasma sEng levels in patients with coronary artery disease (CAD) have not been elucidated. Approach and Results— We measured plasma sEng levels in 244 patients undergoing coronary angiography. The severity of coronary atherosclerosis was evaluated as the numbers of >50% stenotic vessels and segments. CAD was found in 147 patients, of whom 55 had 1-vessel, 42 had 2-vessel, and 50 had 3-vessel disease. Compared with 97 patients without CAD, 147 with CAD had lower sEng levels (median 4.04 versus 4.37 ng/mL; P P r =−0.25; P P P Conclusions— Plasma sEng levels were low in patients with CAD, especially 3-vessel disease, and were inversely associated with the severity of coronary atherosclerosis.

Aim: The degradation of the vascular extracellular matrix is important for atherosclerosis. The cysteine protease legumain was shown to be upregulated in atherosclerotic plaques, especially unstable plaques. However, no study has reported blood legumain levels in patients with coronary artery disease (CAD). Methods: We investigated plasma legumain and C-reactive protein (CRP) levels in 372 patients undergoing elective coronary angiography. Results: CAD was found in 225 patients. Compared with patients without CAD, those with CAD had higher CRP levels (median 0.60 [0.32, 1.53] vs. 0.46 [0.22, 0.89] mg/L, P < 0.001), but no difference was found in legumain levels between patients with and without CAD (median 5.08 [3.87, 6.82] vs. 4.99 [3.84, 6.88] ng/mL). A stepwise increase in CRP was found depending on the number of > 50% stenotic vessels: 0.55 mg/L in 1-vessel, 0.71 mg/L in 2-vessel, and 0.86 mg/L in 3-vessel diseases (P < 0.001). However, legumain did not differ among 1-, 2-, and 3-vessel diseases (5.20, 4.93, and 5.01 ng/mL, respectively). Of 225 patients with CAD, 40 (18%) had complex lesions. No difference was found in CRP levels between patients with CAD with and without complex lesions (0.60 [0.34, 1.53] vs. 0.60 [0.32, 1.51] mg/L). Notably, legumain levels were higher in patients with CAD with complex lesions than without such lesions (6.05 [4.64, 8.64] vs. 4.93 [3.76, 6.52] ng/mL, P < 0.01). In multivariate analysis, legumain levels were not a factor for CAD, but were a factor for complex lesions. The odds ratio for complex lesions was 2.45 (95% CI = 1.26–4.79) for legumain > 5.5 ng/mL. Conclusion: Plasma legumain levels were associated with the presence of complex coronary lesions.

Aims. Betatrophin is a recently identified circulating adipokine that may affect lipid and glucose metabolism. However, the association between plasma betatrophin levels and carotid atherosclerosis has not been elucidated. Methods. We investigated plasma betatrophin levels in 153 subjects undergoing carotid ultrasonography. The severity of plaque was evaluated as plaque score. Results. Of the 153 subjects, plaque was found in 63 (41%). Plasma betatrophin levels were higher in 63 subjects with plaque than in 90 without plaque (median 906 vs. 729 pg/mL, P<0.025). A stepwise increase in betatrophin levels was found depending on the plaque score: 729 pg/mL in score=0 (n=90), 802 pg/mL in score=1 (n=31), and 978 pg/mL in score≥2 (n=32) (P<0.01). In particular, betatrophin levels in subjects with score≥2 were higher than in those with score=0 (P<0.05). Moreover, betatrophin levels correlated with plaque score (r=0.23, P<0.01), but no significant correlation was found between betatrophin levels and triglyceride or HbA1c levels. The percentage of subjects with betatrophin>800 pg/mL was higher in subjects with plaque than in those without plaque (65% vs. 44%) and was highest in score≥2 (78%) (P<0.005). In the multivariate analysis, betatrophin level was not a significant factor for the presence of plaque but was a significant factor for plaque score≥2, independent of atherosclerotic risk factors. The odds ratio for score≥2 was 4.9 (95% CI=1.9-12.8) for betatrophin>800 pg/mL. Conclusions. Plasma betatrophin levels were found to be high in subjects with carotid plaque and to be associated with the severity of plaque. Betatrophin may play a role in the progression of carotid atherosclerosis.

text, 紀要論文 / Departmental Bulletin Paper

text, 紀要論文 / Departmental Bulletin Paper

text, 紀要論文 / Departmental Bulletin Paper

text, 紀要論文 / Departmental Bulletin Paper

Resistin is an adipocytokine that may link inflammation and atherosclerosis.We studied the associations of resistin levels with cardiovascular events and restenosis.We measured pre-procedural serum resistin levels in 140 patients with coronary artery disease undergoing elective percutaneous coronary intervention (PCI), of whom 97 had a stent. Restenosis was defined as50% stenosis at follow-up angiography. Patients were followed for 3 years for major adverse cardiovascular events (MACE).At 8±6 months after PCI, reangiography was performed in 94 (67%) patients, of whom 42 had restenosis. Between 42 patients with restenosis and 52 without restenosis, resistin (4.5±2.6 vs. 4.5±2.5 ng/mL) and Creactive protein (CRP) (median 0.70 vs. 0.70 mg/L) levels did not differ. During 3-year follow-up, MACE occurred in 24 patients (1 death, 21 unstable angina, 2 stroke). Compared with 116 patients without MACE, 24 with MACE had higher resistin (5.4±2.4 vs. 4.3±2.5 ng/mL) and CRP (1.30 vs. 0.60 mg/L) levels (p0.05). Patients with MACE more often had resistin4.0 ng/mL than without MACE (75% vs. 35%, p0.001). Resistin correlated with CRP levels (r= 0.31). To clarify the association between MACE and resistin, patients were divided into 2 groups by resistin levels. Kaplan-Meier analysis showed a lower event-free survival rate in patients with resistin4.0 ng/mL than without it (p0.001). On multivariate analysis, resistin, but not CRP, was an independent predictor of MACE. The hazard ratio for MACE was 3.6 (95%CI=1.4-9.2) for resistin4.0 ng/mL.Serum resistin levels were found to be associated with further cardiovascular events in patients undergoing PCI.

text, 紀要論文 / Departmental Bulletin Paper

Using MRI, we reported plaque regression in thoracic aorta and retardation of plaque progression in abdominal aorta by 1-year atorvastatin. However, association between serial plaque changes and LDL-cholesterol levels was not fully elucidated.A prospective, randomized, open-label trial.We investigated the long-term effect of 20 versus 5-mg atorvastatin on thoracic and abdominal plaques and the association between plaque progression and on-treatment LDL-cholesterol levels in 36 hypercholesterolemic patients. MRI was performed at baseline and 1 and 2 years of treatment. Vessel wall area change was evaluated.The 20-mg dose markedly reduced LDL-cholesterol levels (-47%) versus 5-mg (-35%) dose. After 2 years of treatment, regression of thoracic plaques was found in the 20-mg group (-15% vessel wall area reduction), but not in the 5-mg group (+7%). Although the 20-mg dose induced plaque regression (-14%) from baseline to 1 year, no further regression was seen from 1 to 2 years of treatment (-1%). Regarding abdominal plaques, progression was found in the 5-mg group (+10%), but not in the 20-mg group (+2%). Plaque progression in the 5-mg group was found from baseline to 1 year (+8%), but not from 1 to 2 years (+2%). The degree of thoracic plaque regression correlated with LDL-cholesterol reduction (r = 0.61), whereas thoracic plaque change from 1 to 2 years correlated with on-treatment LDL-cholesterol levels (r = 0.64).Twenty milligrams of atorvastatin regressed thoracic plaques. However, maintaining low LDL-cholesterol levels was needed to prevent plaque progression. In abdominal aorta, only retardation of plaque progression was found after 2 years of 20-mg treatment.

Dietary therapy using phytosterols can reinforce statin treatment; however the value of a low-dose combination of those agents remains to be investigated. Plant sterols (PS), dissolved in diacylglycerol (DAG) oil, (PS/DAG) can be effective at a relatively low dose. The objective of the present study was to examine the effect of PS/DAG oil on blood cholesterol concentrations in hypercholesterolemic outpatients on low-dose pravastatin (10 mg/day).The patients (n=61) were randomly assigned to one of three groups, who consumed TAG (control), DAG or PS/DAG oil. The average intake of PS from the PS/DAG oil during the test period was significantly higher than that for TAG and DAG oils (502 vs. 49 and 38 mg/day, P0.05). Significant cholesterol-lowering effects from the baseline were observed in the case of the PS/DAG oil treatment alone. Changes in low-density lipoprotein (LDL) cholesterol were inversely correlated with baseline serum campesterol concentrations (r=-0.560, P0.05), but not baseline LDL cholesterol concentrations. In addition, serum apolipoprotein B concentrations were reduced to a greater extent in subjects with high versus low levels of baseline campesterol (-13.2 mg/dL vs. -3.1 mg/dL, P0.05). Furthermore, there was a mild, but significant reduction in serum lipoprotein (a) concentration from the baseline (-5.9 mg/dL), which was correlated with the reduction in serum apolipoprotein B concentration (r=0.596, P0.05).A low-dose combination of PS/DAG oil and pravastatin may be a useful strategy for further ameliorating blood cholesterol and lipoprotein (a) concentrations for hypercholesterolemic patients with a low response to pravastatin.

Fibrates reduce triglycerides (TG) and increase HDL-cholesterol levels, but there was no report showing plaque regression by fibrates. Using MRI, we investigated the effects of bezafibrate on aortic plaques in 22 dyslipidemic patients. All patients were asked to receive 400mg bezafibrate, but 8 who declined to have bezafibrate became the control group. Changes in vessel wall area (VWA) and lumen area (LA) from baseline to 1-year were evaluated. Bezafibrate reduced TG (-55%) and increased HDL-cholesterol levels (+29%). Bezafibrate reduced HDL size and increased LDL size. In thoracic plaques, bezafibrate reduced VWA (-6%, P

alpha-Tocopherol (alpha-Toc) is abundant in LDL and thought to prevent the oxidation of LDL together with various water-soluble antioxidants. Recently, it was reported that alpha-Toc and gamma-Toc metabolites, alpha-carboxyethyl-6-hydroxychromans (CEHC) and gamma-CEHC, are water-soluble antioxidants. In this study, we investigated the interaction between alpha-Toc and CEHC against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and LDL oxidation. We administered 600 mg of alpha-Toc to healthy male volunteers to obtain LDL including high levels of alpha-Toc before antioxidant administration. The alpha-Toc content of their LDL was increased after consumption at 24 h (18.3 microg/mL) above the level before consumption (6.6 microg/mL). The lag time of LDL at 24 h after alpha-Toc consumption (alpha-Toc rich LDL) with alpha-CEHC (98.5+/-8.2 min) or gamma-CEHC (101.3+/-9.0 min) was longer than that of only alpha-Toc-rich LDL (78.1+/-9.0 min). Furthermore, we examined the interaction of LDL with CEHC and alpha-Toc in vitro (5-20 microg/mL). The lag times of 5 and 10 microg/mL alpha-Toc were 65.5+/-18.9 min and 69.5+/-15.5 min, and that of 20 microg/mL alpha-Toc (83.5+/-20.2 min) was longer than the control value (55.7+/-14.1 min). The lag time of 20 microg/mL alpha-Toc with alpha-CEHC (98.7+/-25.7 min) or gamma-CEHC (100.6+/-25.3 min) was longer than that of only alpha-Toc (83.5+/-20.2 min). These results suggest that CEHC has the potential to delay the oxidation of LDL, while enhancing the antioxidative activity of alpha-Toc both in vitro and ex vivo.

Cholesteryl ester transfer protein (CETP) is understood to play a regulatory role in HDL cholesterol (HDLC) metabolism. In this study, the effect of CETP genotypes on plasma lipid and lipoprotein levels in 348 Vietnamese girls (aged 7-9) with different nutritional conditions was analyzed. The two mutations, intron 14 G(+1)-to-A (I14A) and Asp 442 to Gly within exon 15 (D442G), and the TaqIB polymorphism in the CETP gene were identified by an Invader assay. The D442G mutation was present with a frequency of 0.034, while the I14A mutation was absent. HDLC levels were significantly higher in carriers of the D442G mutation than in noncarriers, regardless of the nutritional status. Low-density lipoprotein (LDL) cholesterol and triglyceride levels were not significantly lower in carriers of D442G mutation. The frequency of the TaqIB2 allele was 0.34, which was lower than that observed in other Asian populations. TaqIB2B2 carriers also had significantly higher HDLC levels, but this association was weaker than that of the D442G mutation. Overall, genetic variations at the CETP gene locus may account for a significant proportion of HDLC variation in Vietnamese children.

Prospective studies showed plasma high sensitivity C-reactive protein (hsCRP) levels to be a powerful predictor of cardiac events. However, the association between hsCRP levels and the extent of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. We investigated the association between hsCRP levels and the extent of coronary stenosis in 273 patients undergoing elective coronary angiography. Plasma hsCRP levels were higher in patients with CAD than in those without CAD (0.70 mg/l versus 0.56 mg/l, P0.02), but hsCRP levels did not correlate with the number of50% stenotic vessels and were not a significant factor for CAD. However, after the exclusion of 76 patients taking statins, a step-wise increase in hsCRP levels was found depending on the number of50% stenotic vessels: 0.50 in CAD(-), 0.68 in 1-vessel, 0.77 in 2-vessel, and 0.88 mg/l in 3-vessel disease (P0.01). The hsCRP levels also correlated with the numbers of50% and25% stenotic segments (r = 0.30 and 0.32, P0.001). Multivariate analysis revealed the hsCRP levels to be a significant factor for CAD. Thus, after the exclusion of patients with statins, plasma hsCRP levels were found to be associated with the presence and extent of coronary stenosis in patients with stable CAD.

We investigated the frequency of apolipoprotein E (apoE) polymorphism and the effect of apoE polymorphism on plasma lipid and lipoprotein levels under different nutritional statuses in Vietnamese children living in urban and rural areas. Three hundred and forty-eight girls (aged 7 to 9 years) were randomly selected from urban and rural areas in southern Vietnam. Their apoE genotypes were analyzed by an Invader assay, and the plasma lipid and lipoprotein levels were determined by enzymatic methods using fasting blood samples. Dietary intake and anthropometry of children were also measured. The frequency of the allele epsilon 2 and epsilon 4 of the Vietnamese girls was 0.09 and 0.12, respectively. The levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) of the allele epsilon 2 carriers were significantly lower than those of the allele epsilon 3 carriers (P < .0001) in both the urban and rural groups. In contrast, the allele epsilon 4 carriers tended to show a higher LDL-C level than the allele epsilon 3 carriers, especially in subjects with a higher fat intake in urban area. The allele epsilon 2 carriers had the same high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) level as the allele epsilon 3 carriers, but the allele epsilon 4 carriers with a higher fat intake living in urban areas had lower HDL-C and higher TG level than allele epsilon 3 carriers. In conclusion, our findings showed that the LDL-C lowering effect of allele epsilon 2 was independent of the nutritional status, while allele epsilon 4 tended to lower HDL-C and increase the LDL-C level in a high-fat intake population. Therefore, the plasma lipid profiles of apoE epsilon 4 carriers may be a risk factor of atherogenesis in Vietnamese, who tend to have a westernized eating habit.

Background: A lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is the major receptor of oxidized LDL in endothelial cells. The expression of LOX-1 was shown to be upregulated in atherosclerotic lesions. Recently, LOX-1 gene polymorphism (G501C) was reported to be associated with myocardial infarction (MI). Hypothesis: Our study was undertaken to elucidate the association between this polymorphism and coronary artery disease (CAD). Methods: We evaluated LOX-1 gene polymorphism using Invader assay in 586 patients undergoing coronary angiography. Results: Study patients were categorized into three groups: normal/minimal stenosis (≤25%) (n = 128); mild stenosis (26-50%) (n = 39); and significant stenosis (> 50%) (n = 419). Of the 419 patients with significant stenosis, 163 had single-vessel, 165 had double-vessel, and 91 had triple-vessel disease. Myocardial infarction was present in 171 patients. The frequency of LOX-1 gene variants (C/C or C/G) was lower in patients with significant than in those with normal/minimal stenosis (36 vs. 49%, p < 0.01). The frequency of LOX-1 gene variants did not differ between patients with and without MI (34 vs. 37%). However, a stepwise decrease in the frequency of such variants was found depending on the severity of CAD: 49% in normal/minimal stenosis, 41% in mild stenosis, 39% in single-vessel, 35% in double-vessel, and 32% in triple-vessel disease. Multivariate analysis demonstrated LOX-1 gene variants to be inversely associated with the presence of significant stenosis (odds ratio = 0.61; 95% confidence interval = 0.41-0.92). Conclusions: The LOX-1 gene variants at 501 were found to be inversely associated with the severity of CAD. This polymorphism may be modifying the severity of CAD.

Mycoplasma pneumoniae (MP) seropositivity was reported to be associated with coronary events. MP organisms were detected with Chlamydia pneumoniae (CP) in coronary plaques. We investigated MP and CP seropositivity in 549 patients undergoing coronary angiography. Coronary artery disease (CAD) was found in 396 patients, of whom 154 had myocardial infarction (MI). MP seropositivity was more prevalent in patients with CAD than without CAD (14% versus 6%, P0.01). The highest prevalence was found in patients with MI. In contrast, the prevalence of CP seropositivity was similar in patients with and without CAD (62% versus 59%). To clarify interaction with CP infection, 549 patients were divided into two groups with and without CP seropositivity. Among patients with CP seropositivity, MP seropositivity was more prevalent in patients with CAD than without CAD (17% versus 5%, P0.01), whereas among patients without CP seropositivity, MP seropositivity did not differ between patients with and without CAD (9% versus 6%). In multivariate analysis, MP seropositivity was associated with CAD only in patients with CP seropositivity (odds ratio = 5.1, 95% CI = 1.8-14.9). Thus, MP seropositivity was associated with CAD. However, this association was confined to patients with CP seropositivity. Coinfection by MP and CP may be an important cofactor for CAD.

Background Magnetic resonance imaging was recently reported to detect atherosclerotic plaques in thoracic and abdominal aortas. Methods Using magnetic resonance imaging, we investigated associations of risk factors and plasma inflammatory markers with plaques in both thoracic and abdominal aortas in 102 patients undergoing coronary angiography. Associations between coronary artery disease (CAD) and aortic plaques were also evaluated. Results Plaques in thoracic and abdominal aortas were detected in 61% and 90% of patients, respectively. Age and systolic blood pressure correlated with plaque extents in both the aortas. Serum LDL cholesterol level correlated with plaque extent in the thoracic aorta ( r s = 0.42). The degree of smoking correlated with plaque extent in the abdominal aorta ( r s = 0.43). In multivariate analysis, age and systolic blood pressure were associated with plaques in both the aortas. The LDL cholesterol and smoking were characteristically associated with plaques in the thoracic and abdominal aortas, respectively. Regarding inflammatory markers, fibrinogen and C-reactive protein levels correlated with total plaque extent in the aortas ( r s = 0.50 and r s = 0.51). Compared with 24 patients without CAD, 78 with CAD more often had plaques in the thoracic (71% vs 29%) and abdominal (95% vs 75%) aortas. Although plaque extents in both the aortas correlated with the severity of CAD, only thoracic plaques were independently associated with CAD. Conclusions The thoracic and abdominal aortas may have different susceptibilities to risk factors. However, plasma inflammatory markers appear to reflect total extent of aortic atherosclerosis. Although aortic plaques are common in patients with CAD, only thoracic plaques are an independent factor for CAD.

Background: Vascular endothelial growth factor (VEGF) has been implicated in both angiogenesis and ischemia. However, the relationship between plasma VEGF level and coronary artery disease remains unknown. Hypothesis: Plasma VEGF level may be associated with severe coronary artery disease and other cardiovascular risk factors. Methods: We examined plasma VEGF concentration and coronary risk factors in 73 patients who underwent coronary angiography and 70 apparently healthy control subjects. According to the number of the three major coronary vessels with significant (≥ 75%) stenosis, we divided the patients into two groups: the mild stenosis group (0- and single-vessel disease, n = 36) and the severe stenosis group (double- and triple-vessel disease, n = 37). Results: The log VEGF value of the severe stenosis group was significantly higher than that of the mild stenosis (p < 0.05) and control groups (p < 0.05). Furthermore, there was a significant positive trend in the log VEGF value according to the number of vessels with significant stenosis (p = 0.016). However, there was no significant difference in log VEGF value between the mild stenosis and control groups. Soluble vascular cellular adhesion molecule, soluble intracellular adhesion molecule, and other coronary risk factors were found to be associated with the presence of vessel stenosis. Conclusion: Unlike established coronary risk factors, the plasma VEGF level may be associated with only severe coronary ischemia such as multiple coronary vessel disease.

Oxidized low-density lipoprotein (LDL) is considered a risk factor in atherosclerosis, and polyphenols are the potential agents to inhibit the oxidation of LDL. We determined the polyphenol contents and the antioxidant activities of commonly consumed vegetables in Vietnam and assessed the quantity of the polyphenol intake from vegetables in the current Vietnamese diet. The polyphenol contents in 30 kinds of vegetables was determined by the Folin-Ciocalteu method. The antioxidant activities of vegetables were evaluated by measuring the oxidation of LDL and the reduction of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. In this study, some herbs and edible wild vegetables possessed high contents of polyphenols and antioxidant activities. Among green vegetables, sweet potato leaves showed both a high polyphenol content and antioxidant activity. The mean polyphenol daily intake of the Vietnamese was a 595 mg catechin equivalent. Water spinach, a kind of green vegetable, contributed the highest amount (45%) of the total polyphenol intake, followed by other green vegetables. Neither herbs nor edible wild vegetables contributed significantly to the total polyphenol intake due to their low consumption. Green vegetables are therefore considered very important sources of polyphenol intake for the Vietnamese.

Interleukin (IL)-27, one of cytokines in the IL-12 family, is considered to have both pro- and anti-inflammatory properties. However, blood IL-27 levels in coronary artery disease (CAD) have not been fully elucidated yet. This cross-sectional study was done to elucidate the association between blood IL-27 levels and CAD. We investigated plasma IL-27 and high-sensitivity C-reactive protein (hsCRP) levels in 274 consecutive patients who underwent elective coronary angiography for suspected CAD. CAD was present in 177 patients [30 acute coronary syndrome (ACS) and 147 stable CAD]. Compared with 97 patients without CAD, 177 patients with CAD had higher IL-27 (median 0.26 vs 0.22 ng/mL, P 50% stenotic coronary vessels: 0.22 in CAD(-), 0.22 in 1-vessel disease, 0.31 in 2-vessel disease, and 0.27 ng/mL in 3-vessel disease (P

High levels of osteopontin (OPN) mRNA and proteins were reported in atherosclerotic plaques [1–3]. OPN-overexpressing transgenic mice developed marked atherosclerotic lesions [4]. These suggest that OPN plays an important role in atherosclerosis. Regarding blood OPN levels, we reported plasma OPN levels to be higher in patients with coronary artery disease (CAD) than without CAD [5]. However, some overlap in OPN levels was found between patients with and without CAD. Since atherosclerotic process is a generalized process that may involve the entire vasculature, we hypothesized that plasma OPN levels may reflect not only coronary atherosclerosis but also atherosclerosis in other vascular beds.