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Objectives: Cigarette smoking is associated with atherosclerosis and is an important risk factor for cardiovascular disease. We evaluated the impact of cigarette smoking on coronary plaque composition using integrated backscatter intravascular ultrasound (IB-IVUS)., Methods: A total of 143 consecutive patients undergoing percutaneous coronary intervention were enrolled. A history of illness, as well as smoking habits, was obtained by interview. Participants were asked to report whether they were current smokers, had quit smoking, or had never smoked. According to interview results, patients were divided into the following three groups: current, former, and never smokers. Conventional and IB-IVUS tissue characterization analyses were carried out. Three-dimensional analyses were carried out to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcified)., Results: IB-IVUS analysis indicated that the patients in the current smoker group had significantly increased percent lipid volume and significantly decreased percent fibrous volume (P=0.01 and 0.03). Logistic regression analysis showed that the current smoking state (odds ratio 3.51, 95% confidence interval 1.02-12.10, P=0.04) was independently associated with the presence of lipid-rich plaques, which was defined as the upper 75th percentile of the study population., Conclusion: Smoking is independently associated with lipid-rich plaques, contributing to the increasing risk for plaque vulnerability.

We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES), using integrated backscatter intravascular ultrasound (IB-IVUS). Conventional IVUS and IB-IVUS were performed in 260 consecutive patients who underwent PCI with DES. Three-dimensional analyses were performed to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcification). Patients were divided into two groups according to the median lipid volume (LV) in the target lesion. MACEs were defined as death, nonfatal myocardial infarction, and any repeat revascularization. The median follow-up interval was 1285 days. MACEs were observed in 64 patients (24.6 %). Patients having a larger LV compared with their counterparts had worse long-term clinical outcomes regarding mortality (3.8 vs. 0 %, P = 0.02) and MACEs (31.5 vs. 17.7 %, P = 0.008) by log-rank test. After adjustment for confounders, large LV (odds ratio 1.95, 95 % confidence interval 1.14-3.33, P = 0.02) was significantly and independently associated with MACEs. The assessment of coronary plaque characteristics in the target lesion may be useful to predict long-term outcome following successful coronary intervention.

Eicosapentaenoic acid (EPA), a member of the omega-3 polyunsaturated fatty acid family, prevents cardiovascular disease. C-reactive protein (CRP) is a marker of inflammation, which promotes atherosclerosis. The aim of this study was to investigate the relationship among EPA, CRP, and the prevalence of peripheral artery disease (PAD), which is a manifestation of systemic atherosclerosis. A cross-sectional study was performed on 238 patients with coronary artery disease (CAD). Blood EPA and CRP levels and ankle-brachial pressure indices were measured. Cut-off values for plasma EPA levels and serum CRP levels were determined using receiver operating characteristic (ROC) analysis. Patients with ABIs ≤0.9 were defined as having PAD. EPA levels were significantly lower and CRP levels were significantly higher in patients with PAD than in those without [48 (26-77) vs. 58 (41-83) μg/ml, p = 0.026 and 3.3 (0.64-14.0) vs. 0.70 (0.32, 2.4) mg/l, p = 0.004]. Multivariate analysis for PAD revealed that high CRP levels and low EPA levels were significant and independent predictors of PAD [odds ratio 3.1 (95 % CI 1.4-6.9), p = 0.006 and odds ratio 4.9 (95 % CI 1.5-9.7), p = 0.004]. Furthermore, to predict PAD, adding high CRP levels and low EPA levels to the established risk factors significantly improved the area under the ROC curves, from 0.66 to 0.78, of the PAD prediction model (p = 0.004). A significant relationship among EPA, CRP, and PAD was confirmed in patients with CAD.

Background: Indoxyl sulfate (IS), a uremic toxin, has cardiovascular as well as uremic toxicity. We evaluated the prognostic value of blood IS level for long-term outcome., Methods and Results: This study followed 311 patients with coronary artery disease. Plasma IS level and estimated glomerular filtration rate (eGFR) were determined. The endpoint was a major adverse cardiac event (MACE). Median follow-up was 759 days. IS was significantly higher in patients with MACE than in those without (P<0.001). Patients were divided according to quartiles (Q) of plasma IS level (Q1, Q2, Q3, and Q4). On Kaplan-Meier analysis a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P<0.001). In patients with eGFR ≥90, 89-60, 59-30, 29-15, and <15 ml·min(-1)·1.73 m(-2), the percentage of patients in Q4 was 0%, 13%, 29%, 100%, and 100%, respectively. In patients with eGFR 89-60 ml·min(-1)·1.73 m(-2), there was no significant difference in MACE-free rate between Q4 and the other quartiles; in patients with eGFR 59-30 ml·min(-1)·1.73 m(-2), a significantly lower MACE-free rate was obtained for Q4 compared with the other quartiles (P=0.832 and P=0.015, respectively)., Conclusions: Plasma IS level is a significant predictor of MACE, especially in patients with eGFR 59-30 ml·min(-1)·1.73 m(-2).

We evaluated the association between inflammatory markers and coronary artery plaque assessed by 64-slice multidetector computed tomography. Coronary computed tomography angiography was performed in patients with chest discomfort suggestive of coronary artery disease (CAD). Individuals with an acute coronary syndrome were excluded from the study. Coronary plaque morphology, the number of artery segments exhibiting plaque, and the number of vessels with >50% stenosis were evaluated. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. Among the 178 patients studied (age 65 ± 10 years; 70% men), 125 were diagnosed with CAD. Hs-CRP and IL-6 concentrations were significantly higher in patients with CAD than in patients without (2.73 ± 4.7 vs. 1.32 ± 2.6 mg/L, P = 0.018, and 3.06 ± 3.3 vs. 2.19 ± 2.4 pg/mL, P = 0.036). The IL-6 level was high in patients with predominantly calcified plaque, and was significantly higher in patients with 4-9 plaque segments than in those with no or 1-3 plaque segments (4.07 ± 5.3 vs. 2.19 ± 2.4 pg/mL and 2.43 ± 2.0 pg/mL, respectively, P = 0.025). The number of stenotic vessels was not significantly related to inflammatory markers. Multivariate logistic analysis revealed that plasma levels of hs-CRP but not IL-6 were associated with the presence of coronary plaque with calcification (OR 3.37, P = 0.026). This study supports the usefulness of inflammatory markers for the evaluation of coronary plaque in patients with stable CAD.

Coronary calcification is proportional to the extent and severity of atherosclerotic disease, and is a predictor of cardiac events. Furthermore, coronary calcification protruding into the lumen is considered as one type of vulnerable plaque. Optical coherence tomography (OCT) can provide in vivo imaging of the detailed vessel wall structure of the coronary artery with high resolution, as in the histological approach. We analyzed coronary calcification in that fashion using OCT in vivo. This study consisted of 70 superficial coronary calcifications of 39 consecutive patients who underwent percutaneous coronary intervention. After revascularization, OCT was performed in the treated vessel. We analyzed morphologic characteristics and the quantification of OCT-determined coronary calcification. Superficial coronary calcifications were classified into two groups depending on whether they did not intrude the lumen (type I) or did (type II). The distance from the lumen and the volume of each calcification were then measured. Superficial coronary calcifications were classified into two groups; type I, n = 39 (56%) and type II, n = 31 (44%). Type II calcifications were located significantly closer to the lumen [80 microm (60-130) vs.130 microm (90-260), p = 0.015], and tended to be smaller, but did not show a significant difference [0.65 (0.2631.3) mm3 vs. 1.2 (0.47-1.9) mm3, p = 0.153] compared to those of type I. In conclusion, OCT could visualize superficial coronary calcifications in detail and enable us to evaluate in vivo morphologic characterizations and quantify them.

Objective: Eicosapentaenoic acid (EPA) of the omega-3 polyunsaturated fatty acids (ω-3 PUFA) family plays important roles in the prevention of cardiovascular disease (CVD), while, arachidonic acid (AA) of the ω-6 PUFA family promotes inflammatory and prothrombotic influences. The complexity of coronary lesions represents the vulnerability of patients. The aim of this study was to investigate the association between the plasma EPA/AA ratio and the prevalence of complex coronary lesion morphology., Methods: This study consisted of 206 consecutive patients with stable angina pectoris (sAP). Each coronary lesion was determined either as complex or simple based on angiographic findings. To examine the plasma fatty acid level, blood samples were obtained. Patients were divided into three groups according to the obtained plasma EPA/AA ratio: the highest tertile, n=67, the 2nd tertile, n=70, or the lowest tertile, n=69., Results: A higher incidence of complex coronary lesion was obtained from patients with a lower plasma EPA/AA ratio [43 (62%) vs. 31 (44%) vs. 25 (37%), p=0.011]. High-sensitivity CRP levels and a low plasma EPA/AA ratio could independently predict the prevalence of complex coronary lesions on multivariate logistic regression analysis [odds ratio 1.83 (95%CI 1.03-3.25), p=0.038 and odds ratio 2.10 (95%CI 1.11-3.94), p=0.02)]., Conclusion: In patients with sAP, a low plasma EPA/AA ratio was significantly associated with a high prevalence of complex coronary lesions.

Objective: To assess the impact of omega-3 polyunsaturated fatty acids (ω3 PUFAs) on coronary plaque instability., Methods: Serum content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) was measured in 336 of 368 consecutive patients suspected of having coronary artery disease who underwent coronary angiography. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were analyzed in 116 patients with 128 coronary plaques, using a 43-MHz (motorized pullback 0.5mm/s) intravascular catheter (View It, Terumo Co., Japan). Lipid-rich plaques were classified into two categories according to their components., Results: Patients with acute coronary syndrome had significantly lower levels of ω3 PUFAs (especially of EPA and DPA) than those without it. IB-IVUS analyses showed that ω3 PUFAs correlated inversely with % lipid volume and positively with % fibrous volume. Patients with low EPA levels, low DPA levels, and low DHA levels had a significantly higher % lipid volume (p=0.048, p=0.008, and p=0.036, respectively) and a significantly lower % fibrous volume (p=0.035, p=0.008, and p=0.034, respectively) than those with high levels of these fatty acids. Even after adjustment for confounders, the presence of both low EPA and low DPA levels proved to be an independent predictor for lipid-rich plaques in any of the two categories., Conclusions: A lower serum content of ω3 PUFAs (especially of EPA and DPA) was significantly associated with lipid-rich plaques, suggesting the contribution to the incidence of acute coronary syndrome., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Metabolic syndrome (MetS) is associated with adverse cardiovascular events and mortality, where acute coronary syndrome significantly impacts on mortality and morbidity. In contrast, evidences have accumulated that the lipid-rich plaque might play a critical role in acute coronary syndrome., Methods and Results: The study population consisted of 94 patients with suspected angina pectoris who underwent multi-detector computed tomography (MDCT). Of those, we identified 41 with MetS. In MDCT analysis, low-density plaque volume (LDPV) (42 ± 28 vs 24 ± 18 mm(3), P=0.0003), moderate-density plaque volume (105 ± 41 vs 82 ± 33 mm(3), P=0.003), total plaque volume (164 ± 70 vs 118 ± 59 mm(3), P=0.0008) and %LDPV (24.2 ± 10.0 vs 18.3 ± 7.1%, P=0.01) were significantly increased in the MetS group compared to the non-MetS group. Multivariate linear regression analysis after adjusting for confounding variables revealed that MetS was significantly correlated with an increase in %LDPV (β=0.48, P=0.0001). Multivariate logistic regression analysis for lipid-rich plaque after adjusting for confounding variables indicated that MetS was significantly associated with lipid-rich plaque (odds ratio: 5.99, 95% confidence intervals: 1.94-18.6, P=0.002)., Conclusions: Patients with MetS were strongly related to having a lipid-rich composition in their coronary plaque, as detected by MDCT.

Objectives: This study sought to determine lipid and fibrous volume of coronary atherosclerotic plaques in subjects with abnormal glucose regulation (AGR) by integrated backscatter (IB) intravascular ultrasound (IVUS) during percutaneous coronary intervention., Background: Abnormal glucose regulation, including impaired glucose regulation (IGR) and diabetes mellitus (DM), has emerged as an important determinant of cardiovascular risk. We hypothesized that AGR would be associated with coronary plaque instability., Methods: Conventional intravascular ultrasound and IB-IVUS using a 40-MHz (motorized pullback 1 mm/s) intravascular catheter was performed in 172 consecutive patients. The percentage of fibrous area and the percentage of lipid area were automatically calculated by IB-IVUS. Three-dimensional analysis of IB-IVUS images was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Following the World Health Organization criteria, the subjects were classified into the DM group, the IGR group, and the normal glucose regulation group. The cutoff point for the lipid-rich plaque was defined as %LV >44% or %FV <52%, which was the 75th percentile of %LV or the 25th percentile of %FV in this study population. Insulin resistance (IR) was defined as the homeostasis model assessment of insulin resistance (HOMA-IR)., Results: There were no significant differences in the baseline characteristics except for glucometabolic parameters. The conventional IVUS analysis indicated that the DM group had a significantly increased plaque volume (and percent plaque volume). In the IB-IVUS analysis, as compared with the normal glucose regulation group, the DM and the IGR groups showed a significant increase in %LV (36 +/- 14% and 37 +/- 13% vs. 29 +/- 14%, p = 0.02) and a significant decrease in %FV (59 +/- 11% and 58 +/- 11% vs. 64 +/- 11%, p = 0.03). The lipid-rich plaque rate was significantly associated with an increasing HOMA-IR in the tertile (p = 0.008). On logistic regression analysis after adjusting for confounding and coronary risk factors, the DM group (odds ratio 3.52, 95% confidence interval 1.13 to 11.0, p = 0.03) and the IGR group (odds ratio 3.92, 95% confidence interval 1.13 to 13.6, p = 0.03) were significantly associated with the lipid-rich plaque., Conclusions: Coronary lesions in patients with AGR are associated with more lipid-rich plaque content, which may be related to the increased IR in these patients.

Background Although functional ischemia identification is important when determining revascularization, angiographic assessment alone is challenging in intermediate coronary stenosis. Previous studies have reported that lesion-specific characteristics affected the fractional flow reserve (FFR). However, the relationship between morphological lesion complexity and FFR has not yet been fully evaluated. This study aimed to evaluate the impact of morphological lesion complexity on FFR in intermediate coronary stenosis. Methods A total of 109 consecutive patients with 136 intermediate coronary stenoses (visually estimated diameter stenosis: 40–70%) were assessed via quantitative coronary angiography, lesion-specific characteristics, and FFR. Indexed lesions were assessed according to 6 morphological lesion characteristics: eccentricity, bend, irregularity, calcification, bifurcation, and diffuse. The lesions were then classified into 3 groups according to the morphological severity count represented by the number of present characteristics (mild-complex: 0–1, moderate-complex: 2–3, and severe-complex: 4–6), and their functional severities were evaluated. Lesions with an FFR <0.80 were considered functionally significant coronary stenoses. Results Of the 136 lesions, 51% were located in the left anterior descending artery (LAD) and 47% had an FFR <0.80. The FFR differed significantly among the 3 lesion complexity groups (0.84 ± 0.10 vs. 0.79 ± 0.10 vs. 0.73 ± 0.07, for mild-, moderate-, and severe-complex, respectively; p < 0.01). In a multivariate logistic analysis, LAD lesions, moderate- and severe-complex, and diameter stenosis were independently associated with an FFR <0.80 [odds ratio (OR): 5.65, 95% confidence interval (CI): 2.50–12.80, p < 0.01; OR: 2.96, 95% CI: 1.30–6.72, p < 0.01; OR: 7.11, 95% CI: 1.25–40.37, p = 0.03, and OR: 2.65, 95% CI: 1.04–6.72, p = 0.04, respectively]. Conclusions Both indexed vessels and the degree of diameter stenosis affected the FFR. In addition, the severity of morphological lesion complexity correlated with the degree of functional severity in intermediate coronary stenosis. [ABSTRACT FROM AUTHOR]

Background and purpose: Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is one of the standard treatments for patients with stable angina pectoris (AP). In spite of a notable effect in preventing restenosis after PCI, DES cannot improve the mortality of patients compared to a bare-metal stent (BMS). On the other hand, periprocedural myocardial injury (PMI) is related to poor prognosis in patients undergoing PCI. We compared DES to BMS in the incidence of PMI in patients with stable AP. Methods and subjects: We enrolled 265 consecutive patients with AP undergoing successful stent implantation. A blood sample was obtained from all patients immediately before and 24 h after PCI. PMI was defined as an increase in creatine kinase-myocardial band isozyme fraction (CK-MB) greater than the upper limit of reference range 24 h after PCI. During the study period, sirolimus- and paclitaxel-eluting stents were used as DES. The strategy of PCI including the type of stent to implant was left to the discretion of the operator. Results: Patients were divided into two groups (DES group, n = 136 and BMS group, n = 129). The incidence of PMI was significantly higher in the DES group than in the BMS group (24% vs. 12%, p = 0.015). Use of DES remained an independent predictor of PMI on multivariate logistic regression analysis after adjustment for confounding factors (odds ratio 2.20,95% CI, 1.07-4.51, p = 0.032). Conclusions: Implantation of the first-generation DES including sirolimus- and paclitaxel-eluting stents was associated with a higher incidence of PMI in patients with AP compared to BMS. [ABSTRACT FROM AUTHOR]