Ayako Kunimura

Impact of omega-3 polyunsaturated fatty acids on coronary plaque instability: An integrated backscatter intravascular ultrasound study

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.

The Association Between Plaque Characterization by CT Angiography and Post-Procedural Myocardial Infarction in Patients With Elective Stent Implantation

OBJECTIVES This study sought to evaluate the association between volumetric characterization of target lesions by multidetector computed tomography (MDCT) angiography and the risk of post-procedural myocardial injury after elective stent implantation. BACKGROUND Previous reports have shown that plaque characterization of the target lesion may provide useful information for stratifying the risk of coronary stenting. METHODS A total of 189 consecutive patients were enrolled; they underwent elective stent implantation after volumetric plaque analysis with 64-slice MDCT. Each plaque component and lumen (filled with dye) was defined as follows: 1) low-attenuation plaque (LAP) (<50 HU); 2) moderate-attenuation plaque (MAP) (50 to 150 HU); 3) lumen (151 to 500 HU); and 4) high-attenuation plaque (HAP) (>500 HU). The volume of each plaque component in the target lesion was calculated using Color Code Plaque. Post-procedural creatine kinase-MB isoform and troponin-T (TnT) at 18 h after percutaneous coronary intervention were also evaluated. RESULTS The volumes of LAP (87.9+/-94.8 mm3 vs. 47.4+/-43.7 mm3, p<0.01) and MAP (111.6+/-77.5 mm3 vs. 89.8+/-67.1 mm3, p<0.05) were larger in patients with post-procedural myocardial injury (defined as positive TnT) than in those with negative TnT. The volumes of LAP and MAP and fraction of LAP in total plaque (LAP volume/total plaque volume) correlated with biomarkers; the MAP fraction was inversely correlated with biomarkers. The volume of LAP was an independent predictor of positive TnT after adjusting for patient background, conventional IVUS parameters, and procedural factors. CONCLUSIONS Post-procedural myocardial injury was associated with the volume and fraction of LAP as detected by MDCT. The volume of LAP was an independent predictor of positive TnT. Plaque analysis by MDCT would be a useful method for predicting post-procedural myocardial injury after percutaneous coronary intervention.

Cardiac 64-Multislice Computed Tomography Reveals Increased Epicardial Fat Volume in Patients With Acute Coronary Syndrome

Inflammatory cytokines released from epicardial fat around coronary arteries may modulate the coronary arteries and promote coronary atherosclerosis. We assessed the hypothesis that epicardial fat volume (EFV) is increased in patients with acute coronary syndrome (ACS). EFV was measured in 80 Japanese patients hospitalized for ACS using 64-multislice computed tomography. The ACS group included 51 patients with ST-segment elevated myocardial infarction and 29 patients with non-ST-segment elevated myocardial infarction. All patients underwent emergency coronary angioplasty and 64-multislice computed tomographic scanning during hospitalization. The control group included 90 consecutive outpatients with suspected ACS whose coronary computed tomographic results were normal. EFV was larger in patients with ACS than in the control group (117 ± 47 vs 95 ± 33 ml, p <0.001). Multivariate regression analysis showed that EFV was associated with age, body mass index, and visceral fat area in the control group. However, these correlations did not appear in the ACS group. Multivariate logistic regression analysis showed that EFV >100 ml was independently associated with ACS (odds ratio 2.84, 95% confidence interval 1.17 to 6.87, p = 0.021). Receiver operator characteristic analysis determined a cut-off value of 100.3 ml with a sensitivity of 75% and a specificity of 60% for ACS (area under the curve 0.692, 95% confidence interval 0.596 to 0.777, p <0.001). Compared to subcutaneous adipose tissue, epicardial adipose tissue showed inflammatory cell infiltrates on a micrograph. In conclusion, the present study demonstrated significantly increased EFV in patients with ACS. A large amount of epicardial fat may be a risk factor for ACS.

Impact of Insulin Resistance on Post-Procedural Myocardial Injury and Clinical Outcomes in Patients Who Underwent Elective Coronary Interventions With Drug-Eluting Stents

OBJECTIVES This study sought to evaluate the associations between homeostatic indexes of insulin resistance (HOMA-IR) and post-procedural myocardial injury and clinical outcome after a percutaneous coronary intervention (PCI) with a drug-eluting stent. BACKGROUND Insulin resistance increases the risk of cardiovascular events. However, the association between insulin resistance and clinical outcome after coronary intervention is unclear. METHODS We evaluated 516 consecutive patients who underwent elective PCI with drug-eluting stents. Blood samples were collected from venous blood after overnight fasting, and fasting plasma glucose and insulin levels were measured. HOMA-IR was calculated according to the homeostasis model assessment. Post-procedural myocardial injury was evaluated by analysis of troponin T and creatine kinase-myocardial band isozyme levels hours after PCI. Cardiac event was defined as the composite endpoint of cardiovascular death, myocardial infarction, and any revascularization. RESULTS With increasing tertiles of HOMA-IR, post-procedural troponin T and creatine kinase-myocardial band levels increased. In the multiple regression analysis, HOMA-IR was independently associated with troponin T elevation. During a median follow-up of 623 days, patients with the highest tertiles of HOMA-IR had the highest risk of cardiovascular events. The Cox proportional hazard models identified HOMA-IR as independently associated with worse clinical outcome after adjustment for clinical and procedural factors. CONCLUSIONS These results indicated the impact of insulin resistance on post-procedural myocardial injury and clinical outcome after elective PCI with drug-eluting stent deployment. Evaluation of insulin resistance may provide useful information for predicting clinical outcomes after elective PCI.

Impact of chronic kidney disease on the incidence of peri-procedural myocardial injury in patients undergoing elective stent implantation

BACKGROUND It is well known that chronic kidney disease is a strong independent predictor of adverse outcomes after percutaneous coronary intervention in patients with ischemic heart disease. Recently, peri-procedural myocardial injury has been associated with adverse cardiac events. The aim of this study was to investigate the relationship between renal function and peri-procedural myocardial injury in patients undergoing elective stent implantation. METHODS This study comprised 273 consecutive patients who underwent elective stent implantation. They were divided into two groups: estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m(2) and eGFR ≥60 mL/min/1.73m(2). Peri-procedural TnT levels higher than three times the normal limit were defined as peri-procedural myocardial injury. RESULTS Patients with eGFR <60 mL/min/1.73m(2) showed a higher incidence of peri-procedural myocardial injury compared to patients with eGFR ≥60 mL/min/1.73m(2) (4.3 versus 20.9%, P < 0.0001). Even after a multivariate adjustment, the eGFR level predicted peri-procedural myocardial injury [odds ratio 0.92, 95% confidence interval (CI): 0.89-0.95, P < 0.0001]. Total stent length was also an independent predictor of peri-procedural myocardial injury (odds ratio 1.09, 95% CI: 1.02-1.16, P = 0.009). Using a receiver-operating curve analysis, eGFR level of 62.1 mL/min/1.73m(2) (sensitivity 93.3%, specificity 57.2%) was the best value (area under the curve = 0.803) to maximize the power of eGFR levels in predicting peri-procedural myocardial injury. CONCLUSIONS Patients with eGFR <60 mL/min/1.73m(2) were strongly associated with peri-procedural myocardial injury after elective stent implantation. Therefore, eGFR may be a simple and convenient predictor of peri-procedural myocardial injury.

Impact of abdominal and epicardial fat on the association between plasma adipocytokine levels and coronary atherosclerosis in non-obese patients

OBJECTIVE Ectopic fat accumulation is associated with coronary artery disease. Visceral adipose tissue has paracrine and systemic effects and is a source of adipocytokines. It has been implicated in the pathogenesis of coronary atherosclerosis; however, nothing is known about whether increases in epicardial fat have the same effect on coronary atherosclerosis as increases in abdominal visceral fat. METHODS We examined 216 consecutive patients suspected to have coronary artery disease. Individuals with acute coronary syndrome and inadequate computed tomography (CT) imaging were excluded. We enrolled 164 patients (65 ± 10 years old; 70% men; body mass index [BMI], 23.8 ± 3.6 kg/m(2)). The plasma concentrations of adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, and vascular endothelial growth factor were measured. The characteristics of coronary plaque, abdominal visceral fat area, and epicardial fat volume (EFV) were determined by 64-slice CT imaging. RESULTS EFV was greater in subjects with noncalcified plaque than in those with no plaque or with calcified plaque (126 ± 39 mL vs. 98 ± 34 mL and 97 ± 45 mL, respectively; P = 0.010). EFV was significantly correlated with BMI, triglycerides, and the triglyceride/high-density lipoprotein cholesterol ratio (r = 0.51, 0.19, and 0.20, respectively) but not with plasma levels of adipocytokines. The plasma adiponectin and IL-6 concentration was significantly correlated with abdominal visceral fat area in coronary plaque patients (r = -0.49 and 0.20). CONCLUSIONS In non-obese Japanese patients, epicardial fat may have unique mechanisms affecting the development of coronary atherosclerosis, which is different from abdominal visceral fat.

Prognostic impact of concurrence of metabolic syndrome and chronic kidney disease in patients undergoing coronary intervention: Involvement of coronary plaque composition

BACKGROUND AND PURPOSE Metabolic syndrome (MetS) and chronic kidney disease (CKD) have both been reported as risk factors for cardiovascular events. The aim of this study was to assess the synergistic effect of MetS and CKD on atherosclerotic plaque and cardiovascular outcomes. METHODS AND SUBJECTS A total of 545 consecutive patients who underwent percutaneous coronary intervention (PCI) were divided into 4 groups based on the presence or absence of MetS and CKD. MetS was defined using the criteria of the Adult Treatment Panel III of the US National Cholesterol Education Program. CKD was defined as an estimated glomerular filtration rate of <60ml/min/1.73m(2). We analyzed the incidence of major adverse cardiac events (MACE), including cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, and revascularization for new lesions. We also assessed coronary plaque characteristics of 204 patients using integrated backscatter intravascular ultrasound (IB-IVUS). RESULTS MACE occurred more frequently in patients with both MetS and CKD (51.4%) than in the other groups, during the follow-up period (log-rank p<0.001). In the IB-IVUS analyses, patients with both MetS and CKD exhibited greater plaque burden (p=0.003) with higher lipid content (p=0.048) compared to the other groups. In Cox analysis, both MetS and CKD proved to be independent predictors of MACE even after adjustment for confounding factors (p=0.018). CONCLUSIONS Comorbidity of MetS and CKD is an independent predictor of adverse cardiovascular outcomes in patients undergoing coronary intervention, an effect that may be attributed to coronary plaque instability.

Prognostic impact of lipid contents on the target lesion in patients with drug eluting stent implantation.

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.

Nutrition Status Predicts Severity of Vascular Calcification in Non-Dialyzed Chronic Kidney Disease

BACKGROUND Vascular calcification is a major complication in chronic kidney disease (CKD) that increases the risk of adverse clinical outcomes. Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that predicts poor prognosis in elderly subjects. The purpose of the present study was to evaluate the correlation between GNRI and severity of vascular calcification in non-dialyzed CKD patients.Methods and Results:We enrolled 323 asymptomatic CKD patients. To evaluate abdominal aortic calcification (AAC), we used aortic calcification index (ACI) determined on non-contrast computed tomography. The patients were divided into three groups according to GNRI tertile. Median ACI significantly decreased with increasing GNRI tertile (15.5%, 13.6%, and 7.9%, respectively; P=0.001). On multivariate regression analysis GNRI was significantly correlated with ACI (β=-0.15, P=0.009). We also investigated the combination of GNRI and C-reactive-protein (CRP) for predicting the severity of AAC. Low GNRI and high CRP were significantly associated with severe AAC, compared with high GNRI and low CRP (OR, 4.07; P=0.004). CONCLUSIONS GNRI was significantly associated with AAC in non-dialyzed CKD patients.

Differences in tissue characterization of restenotic neointima between sirolimus-eluting stent and bare-metal stent: integrated backscatter intravascular ultrasound analysis for in-stent restenosis

AIMS The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS). METHODS AND RESULTS A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004). CONCLUSION This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.