Association between high plasma levels of legumain and cardiovascular events in patients undergoing coronary angiography.

Degradation of vascular extracellular matrix is important in atherosclerosis. Cysteine protease legumain is upregulated in atherosclerotic plaques. We recently reported that plasma legumain levels are high in patients with complex coronary lesions. This study investigated the association between legumain levels and cardiovascular events in 372 patients undergoing coronary angiography. Patients with acute coronary syndrome were excluded. Of the 372 patients, 225 had coronary artery disease (CAD). During a mean follow-up of 7.0 ± 4.3 years, cardiovascular events occured in 62 patients. Compared with 310 patients without events, 62 with events tended to have higher prevalence of complex lesions (15% vs. 10%). Notably, patients with events had higher legumain levels (median 5.51 vs. 4.90 ng/mL, P < 0.01) than those without events. A Kaplan-Meier analysis showed lower event-free survival in patients with legumain > 5.0 ng/mL than in those with ≤ 5.0 ng/mL (P < 0.01). In multivariate Cox regression analysis, legumain level was an independent predictor of cardiovascular events. The hazard ratio for legumain > 5.0 ng/mL for cardiovascular events was 2.18 (95%CI = 1.27-3.77, P < 0.01). Only among 225 patients with CAD, patients with events had higher legumain levels (5.49 vs. 4.73 ng/mL) than without events (P < 0.02). Legumain level was also a predictor of cardiovascular events in patients with CAD. Thus, high plasma legumain levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography and those with stable CAD.

High plasma levels of endosialin and cardiovascular events in patients undergoing coronary angiography.

Endosialin, also known as tumor endothelial marker-1, is a transmembrane glycoprotein that plays a role in inflammation and tumor progression. Endosialin is upregulated in atherosclerotic lesions. To elucidate the association between blood endosialin levels and cardiovascular events, we measured plasma endosialin levels in 389 patients undergoing coronary angiography who were followed up for a mean follow-up of 6.4 ± 4.2 years for cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, heart failure, stroke, or need for coronary revascularization). Of the 389 patients, 223 had coronary artery disease (CAD). No significant difference was found in plasma endosialin levels between patients with and without CAD (median 0.92 vs. 0.92 ng/mL). During the follow-up, cardiovascular events occurred in 62 patients. Compared with patients without events, those with events had higher endosialin levels (1.12 vs. 0.89 ng/mL), and more often had endosialin level of > 1.1 ng/mL (53% vs. 31%) (P < 0.01). A Kaplan-Meier analysis showed lower event-free survival in patients with endosialin > 1.1 ng/mL than those with ≤ 1.1 ng/mL (P < 0.01). In a multivariate Cox regression analysis, endosialin > 1.1 ng/mL was an independent predictor of cardiovascular events (hazard ratio = 2.00; 95%CI = 1.21-3.32; P < 0.01). Thus, high plasma endosialin levels were associated with an increased risk of cardiovascular events in patients undergoing coronary angiography.

High plasma concentrations of vanin-1 in patients with coronary artery disease.

Vanin-1 is a pantetheinase that hydrolyzes pantetheine to pantothenic acid and cysteamine. Vanin-1 has become recognized to be associated with oxidative stress and inflammation. In animal models, vanin-1 was reported to accelerate atherosclerosis. However, no study has reported blood vanin-1 concentrations in patients with coronary artery disease (CAD). We investigated plasma vanin-1 concentrations in 388 patients undergoing elective coronary angiography for suspected CAD. Patients with acute coronary syndrome were excluded. Of the 388 study patients, CAD was found in 207 patients [1-vessel (1-VD), n = 88; 2-vessel (2-VD), n = 66; and 3-vessel disease (3-VD), n = 53]. Plasma vanin-1 concentrations were higher in patients with CAD than in those without CAD (median 0.59 vs. 0.46 ng/mL, P < 0.005). Vanin-1 concentrations in patients without CAD and those with 1-VD, 2-VD, and 3-VD were 0.46, 0.58, 0.57, and 0.61 ng/mL, respectively, and were highest in 3-VD (P < 0.05). A high vainin-1 concentration (> 0.48 ng/mL) was found in 46% of patients without CAD, 61% of 1-VD, 65% of 2-VD, and 66% of 3-VD (P < 0.01). Vanin-1 concentrations significantly correlated with the number of stenotic coronary segments (r = 0.14, P < 0.02). In the multivariate analysis, vanin-1 concentration was a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.63 (95%CI = 1.04-2.55) for the high vanin-1 concentration of > 0.48 ng/mL. Thus, plasma vanin-1 concentrations in patients with CAD were found to be high and to be associated with the presence and severity of CAD.

No Significant Association Between Plasma Endosialin Levels and the Presence or Severity of Coronary Artery Disease.

Background: 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). Methods: 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. Results: 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 of > 50% 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 of > 50% and > 25% stenotic segments or CRP levels. In multivariate analysis, endosialin levels were not a significant factor associated with CAD independent of atherosclerotic risk factors. Conclusions: 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.

Associations between Green Tea Consumption and Coffee Consumption and the Prevalence of Coronary Artery Disease.

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 drank >3 cups/d had a lower prevalence of CAD compared to those who drank <1 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.

High Plasma Levels of Legumain in Patients with Complex Coronary Lesions.

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.

Plasma Betatrophin Levels and Carotid Atherosclerosis.

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.

Associations Between Plasma Betatrophin Levels and Coronary and Peripheral Artery Disease.

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.

Serum resistin levels and cardiovascular events in patients undergoing percutaneous coronary intervention.

AIM: Resistin is an adipocytokine that may link inflammation and atherosclerosis.We studied the associations of resistin levels with cardiovascular events and restenosis. METHODS: 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 as > 50% stenosis at follow-up angiography. Patients were followed for 3 years for major adverse cardiovascular events (MACE). RESULTS: 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 (p< 0.05). Patients with MACE more often had resistin >4.0 ng/mL than without MACE (75% vs. 35%, p< 0.001). 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 resistin > 4.0 ng/mL than without it (p< 0.001). 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 resistin > 4.0 ng/mL. CONCLUSION: Serum resistin levels were found to be associated with further cardiovascular events in patients undergoing PCI.

Tocotrienol suppresses adipocyte differentiation and Akt phosphorylation in 3T3-L1 preadipocytes.

In vivo studies show that alpha-tocotrienol and gamma-tocotrienol accumulate in adipose tissue. Furthermore, a recent study reports that the oral administration of gamma-tocotrienol from a tocotrienol-rich fraction from palm oil (TRF) decreases body fat levels in rats. The objective of this study was to evaluate the effect of TRF and its components on adipocyte differentiation in 3T3-L1 preadipocytes, which differentiated into adipocytes in the presence of 1.8 micromol/L insulin. TRF suppressed the insulin-induced mRNA expression of adipocyte-specific genes such as PPARgamma, adipocyte fatty acid-binding protein (aP2), and CCAAT/enhancer-binding protein-alpha (C/EBPalpha) compared with the differentiation of 3T3-L1 preadipocytes into adipocytes only in the presence of insulin. To confirm the suppressive effect of TRF, the major components of TRF, such as alpha-tocotrienol, gamma-tocotrienol, and alpha-tocopherol, were investigated. Alpha-tocotrienol and gamma-tocotrienol decreased the insulin-induced PPARgamma mRNA expression by 55 and 90%, respectively, compared with insulin, whereas alpha-tocopherol increased the mRNA expression. In addition, gamma-tocotrienol suppressed the insulin-induced aP2 and C/EBPalpha mRNA expression, triglyceride accumulation, and PPARgamma protein levels compared with insulin. The current results also revealed that gamma-tocotrienol inhibited the insulin-stimulated phosphorylation of Akt but not extracellular signal-regulated kinase (ERK)1/2 in the insulin signaling pathway of 3T3-L1 preadipocytes. Thus, the antiadipogenic effect of TRF depends on alpha-tocotrienol and gamma-tocotrienol, and gamma-tocotrienol may be a more potent inhibitor of adipogenesis than alpha-tocotrienol. Therefore, the results of this study suggest that tocotrienol suppresses insulin-induced differentiation and Akt phosphorylation in 3T3-L1 preadipocytes. Furthermore, tocotrienol could act as an antiadipogenic vitamin in the nutrient-mediated regulation of body fat through its effects on differentiation.

Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment.

BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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, P<0.05). 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, P<0.05), 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, P<0.05). 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, P<0.05). CONCLUSION: 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.

Antioxidant activities of black and yellow soybeans against low density lipoprotein oxidation.

Several studies have demonstrated that the daily intakes of soy foods were associated with a reduced cardiovascular risk. The aim of our study was to investigate the inhibitory effect of black soybeans on low density lipoprotein (LDL) oxidation in comparison to yellow soybeans. The extract from black soybean had a longer LDL oxidation lag time than that from yellow soybean (205 +/- 16 and 65 +/- 3 min, respectively). When both soybeans were divided into the seed coat and the mixture of the germ and cotyledon, the diluted extract solution from the black soybean seed coat prolonged the lag time significantly more than the original extract of the yellow soybean seed coat. On the other hand, antioxidant effects of the extract from the mixture of germs and cotyledons were similar in both soybeans. Regarding total polyphenol contents, the seed coat of black soybean had a higher polyphenol content than that of yellow soybean (29.0 +/- 0.56 and 0.45 +/- 0.02 mg/g, respectively). Interestingly, the mixture of the germ and cotyledon hydrolyzed by beta-glucosidase in both soybeans showed a stronger inhibitory effect on LDL oxidation than that before being hydrolyzed by beta-glucosidase. These results suggest that black soybeans may be more effective in inhibiting LDL oxidation than yellow soybeans because of total polyphenols contents in its seed coat. In addition, aglycones, which are rich in soybeans fermented or hydrolyzed by beta-glucosidase, may play a crucial role in the prevention of oxidation-related diseases.

The polyphenol content and antioxidant activities of the main edible vegetables in northern Vietnam.

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.

In vivo magnetic resonance evaluation of associations between aortic atherosclerosis and both risk factors and coronary artery disease in patients referred for coronary angiography.

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.

Plasma vascular endothelial growth factor level is elevated in patients with multivessel coronary artery disease.

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 (> or = 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.

Plasma osteopontin levels are associated with the presence and extent of coronary artery disease.

Recently, osteopontin (OPN) mRNA was reported to be highly expressed in atherosclerotic plaques, most strikingly in calcified plaques. We examined if plasma OPN levels are associated with coronary stenosis and calcification in patients with coronary artery disease (CAD). We measured plasma OPN levels in 178 patients undergoing coronary angiography. Compared with 71 patients without CAD, 107 with CAD had higher OPN levels (616+/-308 ng/ml versus 443+/-237 ng/ml, P<0.001). A stepwise increase in OPN levels was found depending on the number of >50% stenotic coronary vessels: 540+/-293 ng/ml in 1-vessel, 615+/-230 ng/ml in 2-vessel, and 758+/-416 ng/ml in 3-vessel disease. OPN levels also correlated with the numbers of >50% and >25% stenotic segments (r=0.35 and 0.43, respectively, P<0.001). In multivariate analysis, OPN levels were significantly associated with CAD (odds ratio=1.21, 95% CI=1.05-1.39 for a 100 ng/ml increase) independent of traditional risk factors. Coronary calcification was found in 86 patients. OPN levels were higher in patients with calcification than in those without calcification (608+/-328 ng/ml versus 490+/-246 ng/ml, P<0.01) and correlated with the number of calcified segment (r=0.26, P<0.001). However, OPN levels were not independently associated with coronary calcification. Thus, plasma OPN levels were found to be associated with the presence and extent of CAD.