Search

Background: Coronary intraplaque microluminal structures (MS) are associated with plaque vulnerability, and the inward progression of vascular inflammation from the adventitia towards the media and intima has also been demonstrated. Therefore, in the present study we investigated the relationships among MS, local inflammation in adjacent epicardial adipose tissue (EAT), and coronary plaque characteristics., Methods and results: Optical coherence tomography (OCT) revealed MS in the left anterior descending coronary artery in 10 fresh cadaveric hearts. We sampled 30 lesions and subdivided them based on the presence of MS: MS (+) group (n=19) and MS (-) group (n=11). We measured inflammatory molecule levels in the adjacent EAT and percentage lipid volume assessed by integrated backscatter intravascular ultrasound in each lesion. The expression levels of vascular endothelial growth factor B and C-C motif chemokine ligand 2 were significantly higher in the MS (+) group than in the MS (-) group (0.9±0.7 vs. 0.2±0.2 arbitrary units (AU), P=0.04 and 1.5±0.5 vs. 0.6±0.7 AU, P=0.02, respectively). Percentage lipid volume was significantly higher in the MS (+) group than in the MS (-) group (38.7±16.5 vs. 23.7±10.9%, P=0.03)., Conclusions: Intraplaque MS observed on OCT were associated with lipid-rich plaques and local inflammation in the adjacent EAT. Collectively, these results suggest that local inflammation in the EAT is associated with coronary plaque vulnerability via MS.

Aortic valve calcification (AVC), which causes aortic stenosis (AS), is more common in elderly persons. Controlling for conventional risk variables did not, however, reduce the incidence of AS. Thus, residual risk factors of AS should be identified. We enrolled 513 patients who underwent coronary angiography with computed tomography because of suspicion of coronary artery disease (CAD) or ruling out of CAD before aortic valve replacement. Calcium volume was calculated with a commercially available application. Conventional and lipid-related risk factors including serum levels of Lp(a) were evaluated for all patients. Calcium volume and Lp(a) levels were significantly higher in patients who underwent aortic valve replacement than in those who did not. A single regression analysis showed that the calcium volume was positively associated with age and the Lp(a) levels and negatively associated with the estimated glomerular filtration rate. No statistical significance was observed for other risk factors, including oxidized low-density lipoprotein, omega-3 fatty acids levels. The multiple regression analysis revealed that age (P<0.001), female sex (P<0.05), Lp(a) (P<0.01), and hemoglobin A1c (P<0.01) were determinants of the calcium volume. The area under the curve in receiver operating characteristic analysis of Lp(a) for implementation of AVR was 0.65 at an Lp(a) cut-off level of 16 mg/dL. In conclusion, the serum Lp(a) level is a potent risk factor of AVC in patients with high risk of atherosclerosis. J. Med. Invest. 70 : 450-456, August, 2023.

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders. J. Med. Invest. 68 : 189-191, February, 2021.

Background: The coronary adventitia has recently attracted attention as a source of inflammation because it harbors nutrient blood vessels, termed the vasa vasorum (VV). This study assessed the link between local inflammation in adjacent epicardial adipose tissue (EAT) and coronary arterial atherosclerosis in fresh cadavers., Methods and results: Lesion characteristics in the left anterior descending coronary artery of 10 fresh cadaveric hearts were evaluated using integrated backscatter intravascular ultrasound (IB-IVUS), and the density of the VV and levels of inflammatory molecules from the adjacent EAT were measured for each of the assessed lesions. The lesions were divided into lipid-rich, lipid-moderate, and lipid-poor groups according to percentage lipid volume assessed by IB-IVUS. Higher expression of inflammatory molecules (i.e., vascular endothelial growth factor A [VEGFA] andVEGFB) was observed in adjacent EAT of lipid-rich (n=11) than in lipid-poor (n=11) lesions (7.99±3.37 vs. 0.45±0.85 arbitrary units [AU], respectively, forVEGFA; 0.27±0.15 vs. 0.11±0.07 AU, respectively, forVEGFB; P<0.05). The density of adventitial VV was greater in lipid-rich than lipid-poor lesions (1.50±0.58% vs. 0.88±0.23%; P<0.05)., Conclusions: Lipid-rich coronary plaques are associated with adventitial VV and local inflammation in adjacent EAT in fresh cadavers. This study suggests that local inflammation of EAT is associated with coronary plaque progression via the VV.

Background: Compared with global cardiac adiposity, the local accumulation of fat surrounding coronary arteries might have a more direct impact on coronary artery disease (CAD). Here, we compared the local epicardial adipose tissue (EAT) thickness and global cardiac adiposity volumes for predicting CAD.Methods and Results:A total of 197 consecutive subjects underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into CAD (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. EAT thickness was measured at the right coronary artery (EAT RCA ), the left anterior descending artery (EAT LAD ), and the left circumflex artery (EAT LCX ). Although EAT RCA and EAT LCX were similar between the 2 groups, EAT LAD was larger in the CAD group than in the non-CAD group (5.45±2.16 mm vs. 6.86±2.19 mm, P<0.001). EAT LAD , after correcting for confounding factors, was strongly associated with CAD (r=0.276, P<0.001) and Gensini score (r=0.239, P<0.001). On multiple regression analysis, Framingham risk score combined with EAT LAD was a strong predictor of CAD (adjusted R 2 =0.121; P<0.001)., Conclusions: The local fat thickness surrounding the LAD is a simple and useful surrogate marker for estimating the presence, severity, and extent of CAD, independent of classical cardiovascular risk factors.

Background: Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA., Methods: Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indications were prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of >90% and the presentation of chest pain with ischemic changes on electrocardiography., Results: Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients; non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2 ± 2.7 vs 6.1 ± 2.5 mm, P = .002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve = 0.81, P < .001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve = 0.81 vs 0.64, P for comparison = .020)., Conclusions: EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known., Methods and results: A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5 ± 1.3 to 15.0 ± 1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9 ± 0.8 to 25.6 ± 1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3 ± 2.1 to 2.6 ± 1.2 ng/ml, 120.4 ± 26.2 to 110.2 ± 26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group., Conclusions: The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines.

Objectives: The promotion of adipose tissue inflammation by lifestyle-related diseases such as obesity and diabetes accelerates atherogenesis; however, the underlying mechanisms remain incompletely understood. Nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome contributes to chronic inflammation in adipose tissue. Here, we investigated the link between NLRP3 expression in subcutaneous adipose tissue (SAT) and the severity of coronary atherosclerosis., Methods and Results: SAT was obtained from 72 patients who underwent heart device implantation and coronary angiography. Expression of NLRP3 inflammasome-related molecules (NLRP3, IL-1β and IL-18) in SAT were evaluated by quantitative RT-PCR. Laboratory markers related to lifestyle-related diseases were measured. Patients with obesity, dyslipidemia (P < 0.05, respectively), diabetes or hyperuricemia (P < 0.01, respectively) had significantly higher expression of NLRP3. Multivariate analysis demonstrated that body mass index and serum level of uric acid were predictors of NLRP3 expression in SAT. The expression of NLRP3 in SAT correlated negatively with serum adiponectin level (r = -0.23, P < 0.05). Patients with coronary artery disease showed higher NLRP3 expression than patients without significant stenosis (P < 0.01). Furthermore, the expression of NLRP3 in SAT correlated positively with the severity of coronary atherosclerosis as determined by Gensini score (r = 0.47, P < 0.0001) or SYNTAX score (r = 0.55, P < 0.0001). Multiple regression analysis revealed that the expression of NLRP3 in SAT remains as an independent predictors for the severity of coronary atherosclerosis., Conclusions: The expression of NLRP3 in SAT, which is affected by lifestyle-related diseases, is associated with the severity of coronary atherosclerosis. Our results suggest that NLRP3 inflammasome in SAT may have a role in atherogenesis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Several studies have shown that various chemokines are more highly expressed in atherosclerotic plaques than in normal vessel walls. In the present study, we investigated the relationship between coronary atherosclerosis and noteworthy chemokines, including interferon-inducible protein of 10 kD (IP-10); monocyte chemoattractant protein 1 (MCP-1); regulated on activation, normal T-cell expressed and secreted (RANTES); and high-sensitivity C-reactive protein (hsCRP), an established marker of atherosclerotic disease. We studied 28 patients who underwent coronary angiography because of suspected coronary artery disease (CAD). CAD was defined as stenosis of more than 50% of the vessel diameter on coronary angiograms. Blood samples were obtained both from the aorta and the coronary sinus (CS) just before coronary angiography. Relative to CAD (-) patients, those who were CAD (+) tended to have higher plasma concentrations of IP-10 in the aorta, as well as significantly higher transcoronary concentration gradients of circulating IP-10. There were no significant differences between the two groups in aortic plasma concentrations or transcoronary concentration gradients of MCP-1, RANTES, and hsCRP. Furthermore, both the aortic plasma concentrations and transcoronary concentration gradients of IP-10 correlated with the Gensini score (r = 0.58 and r = 0.63, respectively, P < 0.01), while the plasma MCP-1, RANTES, and serum hsCRP concentrations did not. This study suggests that IP-10 is a good surrogate marker of coronary atherosclerosis.

Aim: The consumption of n-3 polyunsaturated fatty acids (PUFA), including docosahexaenoic acid DHA), reduces the incidence of cardiovascular events, and reduced serum levels of n-3 PUFA may be associated with an increased risk of cardiovascular events. However, controversy remains regarding which components of PUFA are associated with the endothelial function in patients with coronary artery disease (CAD). We therefore examined the associations between the n-3 and n-6 PUFA levels and CAD., Methods: We retrospectively reviewed 160 consecutive Japanese patients with CAD whose endothelial function was measured according to the percent change in flow-mediated dilation (FMD) and the serum levels of n-3 PUFA, including eicosapentaenoic acid (EPA) and DHA, and n-6 PUFA, including arachidonic acid (AA) and dihomo-gamma-linolenic acid (DHLA)., Results: A single regression analysis showed no relationships between the FMD and the serum levels of PUFA, including EPA, DHA, AA and DHLA. In contrast, a multiple regression analysis showed that the DHA level was a positive (＜ 0.01) and age was a negative (P ＜ 0.001) contributor to an increased FMD; however, sex, body mass index, systolic and diastolic blood pressure, current/past smoking and the levels of HbA1c, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, EPA, AA and DHLA did not significantly affect the outcome., Conclusions: The serum level of DHA is associated with the endothelial function evaluated according to the FMD in patients with CAD, thus suggesting that a low serum level of DHA may be a predictive biomarker for endothelial dysfunction.

Background: Uremic toxin has emerged as an important determinant of cardiovascular risk. The aim of this study was to examine the relationship between serum uremic toxin and coronary plaque composition on integrated backscatter intravascular ultrasound (IB-IVUS)., Methods and Results: IB-IVUS was performed in 47 patients with planned treatment for angina pectoris. Non-culprit intermediate plaque analyzed in this study had to be >5 mm apart from the intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid volume (LV) and fibrous volume (FV). We also measured serum uremic toxins (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]). Glomerular filtration rate correlated with IS (r=-0.329, P=0.04), but did not correlate with ADMA or PC. Percent LV correlated with IS (r=0.365, P=0.02), but did not correlate with ADMA or PC. Percent FV also correlated with IS (r=-0.356, P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=-0.305, P=0.04) independently of potentially confounding coronary risk factors., Conclusions: Among the uremic toxins, serum IS might be a novel useful biomarker to detect and monitor lipid-rich coronary plaque on IB imaging.

Background: Although numerous studies have reported altered plasma levels of various microRNAs (miRNAs) in patients with cardiovascular disease, there are no data on the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma miRNAs might be a sensitive marker of coronary plaque vulnerability., Methods and Results: Integrated backscatter intravascular ultrasound (IB-IVUS) was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were measured in EDTA-plasma simultaneously obtained from the aorta and the coronary sinus (CS). Muscle-enriched (miR-133a, miR-208a, miR-499), vascular-enriched (miR-92a, miR-100, miR-126, miR-127, miR-145), and myeloid cell-enriched miRNAs (miR-155, miR-223) were measured. Plasma miR-100 was higher in the CS than in the aorta, but there were no significant differences in the levels of other miRNAs between the aorta and CS. Plasma miR-100 in the aorta was positively correlated with %LV (r=0.48, P<0.01) and negatively correlated with %FV (r=-0.41, P<0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with %LV (r=0.53, P<0.01) and %FV (r=-0.56, P<0.01)., Conclusions: miR-100 might be released into the coronary circulation from vulnerable coronary plaques. This study provides insights into the role of miRNAs in coronary atherosclerotic disease.

Background: Augmentation index (AI) has been used as a clinical index of arterial stiffness and has been reported to be an independent predictor of cardiovascular events, but some investigators have reported that AI is not a useful marker to identify coronary artery disease (CAD) in elderly patients. The majority of CAD patients are elderly people, therefore the aim of this study was to examine whether AI is a useful marker to identify the risk of CAD., Methods and Results: A total of 120 patients (69±10 years of age; 83 male) who underwent cardiac catheterization for suspected CAD were enrolled. Invasive central blood pressure (BP) was measured using a fluid-filled catheter. Non-invasive AI was calculated by the SphygmoCor (AtCor Medical) system at the end of catheterization. Subjects consisted of 99 patients with CAD and 21 patients without CAD. There was no significant difference in AI between the CAD and the non-CAD groups (24±10 vs. 24±14%). Non-invasive systolic central BP was lower than the invasive systolic central BP (115±18 vs. 130±23 mmHg, P<0.001) in all patients. Non-invasive diastolic central BP was greater than the invasive diastolic central BP (67±10 vs. 63±10 mmHg, P<0.001)., Conclusions: In elderly patients, AI may not be a useful marker to identify CAD.

Background: Telmisartan has unique pleiotropic effects in addition to renin-angiotensin system (RAS)-inhibition effects. The aim of this study was to evaluate the effects of telmisartan on the coronary plaque component and local inflammatory cytokines., Methods and Results: A total of 50 patients with hypertension were randomized to 2 groups: the telmisartan group (additional treatment with telmisartan 80mg/day, n=25) or the control group (additional treatment with other anti-hypertensive drugs except RAS blockers, n=25) for 6 months. Tissue characteristics of target coronary plaque were analyzed using integrated backscatter intravascular ultrasound (IB-IVUS) before and after treatment. Plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein were also measured. Significant increases in fibrous volume (51.2±10.4 to 58.3±7.7%, P=0.03) and reductions in lipid volume (38.4±12.4 to 32.8±9.7%, P=0.03) were observed on IB in the telmisartan group, while there were no significant changes in the plaque component in the control group. CS levels of inflammatory cytokines (matrix metalloproteinase [MMP]3, tumor necrosis factor-α, high-sensitivity C-reactive protein and MMP9) were lower after than before treatment in the only telmisartan group (7.7±6.1 to 5.5±4.9ng/ml, 3.1±1.9 to 2.3±2.0pg/ml, 5.6±6.0 to 2.2±2.4mg/L, 36.1±39.3 to 19.9±27.5ng/ml, P=0.02, P=0.03, P=0.04, P=0.07, respectively)., Conclusions: Decreased local inflammatory response and plaque stabilization on IB imaging were observed after 6 months of telmisartan treatment. These findings might be associated with local anti-inflammatory and anti-arteriosclerotic effects of telmisartan.

Background: Growing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis., Methods: The study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group., Results: EATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia., Conclusions: Increased EATV is strongly associated with coronary atherosclerosis in men.

Background: Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques., Methods and Results: We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r=-0.67, p<0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes., Conclusions: PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Authors of recent studies have reported that there is a relationship between level of adhesion molecules and atherosclerosis. In an animal study it was demonstrated that there is an interaction between adhesion molecules and leukocytes in atherosclerotic tissue., Objective: To study the relationships between coronary-artery atherosclerosis and both differential blood-leukocyte count and concentrations of soluble adhesion molecules in patients with and without coronary artery disease (CAD)., Methods: Our subjects were 168 patients who underwent diagnostic coronary angiography. Forty-eight patients had normal coronary angiograms (control group), and 120 patients had significant coronary-artery stenoses (diameter stenosis > 70%) in at least one major coronary-artery branch (CAD group). Total and differential blood-leukocyte counts, and concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were assayed prior to angiography., Results: Monocyte counts for patients in the CAD group were significantly greater than those for patients in the control group (366 +/- 99 versus 258 +/- 44/microl, P < 0.0001), as were the sICAM-1 concentrations (272 +/- 52 versus 203 +/- 24 ng/ml, P < 0.0001). The mean concentrations of sVCAM-1 in members of the two groups were the same (671 +/- 138 versus 668 +/- 97 ng/ml, P=0.4). There was a higher incidence of significant coronary-artery stenosis among patients with both a high monocyte count and a high concentration of sICAM-1 (> or = mean + SD) than there was among patients with a low monocyte count and a low concentration of sICAM-1 (> or = mean - SD; 100 versus 25%, P < 0.0001)., Conclusions: Higher levels both of monocyte counts and of serum concentrations of ICAM-1 may serve as markers for coronary atherosclerosis.

Background: Circulating leukocytes are recruited at atherosclerotic sites through a family of adhesion molecules. Circulating forms of adhesion molecules in peripheral blood can be quantified now., Objective: To evaluate the relationship between circulating adhesion molecules and severity of coronary atherosclerosis., Methods: Subjects included 81 patients undergoing diagnostic coronary angiography, 12 of whom had normal coronary arteries (control group). The remaining 69 patients with demonstrable coronary atherosclerosis were divided into two groups by use of Gensini scores, namely mild atherosclerosis (n = 36, Gensini score 1-20) and severe atherosclerosis (n = 33, Gensini score > 20). Serum levels of circulating intercellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin of groups measured before angiography were compared., Results: Circulating levels of ICAM-1 in members of mild and severe atherosclerosis groups were significantly higher than those in members of the control group, whereas there was no significant difference among circulating levels of VCAM-1 in members of the three groups. Circulating levels of E-selectin in members of the mild atherosclerosis group were significantly higher than those in members of the severe atherosclerosis and control groups., Conclusions: These findings suggest that E-selectin is related to the early stage, and ICAM-1 is related to the advanced stage, of coronary atherosclerosis. With progression of atherosclerosis, one-step adhesion by ICAM-1 could become more important than multistep adhesion involving E-selectin, ICAM-1, and VCAM-1. These molecules may serve as markers for severity of coronary atherosclerosis.