Predictive value of serum dihomo-γ-linolenic acid level and estimated Δ-5 desaturase activity in patients with hepatic steatosis.

BACKGROUND: Hepatic steatosis is considered one of the features of metabolic syndrome (MetS). Polyunsaturated fatty acid (PUFA) metabolism is modulated in obesity. However, it has yet to be fully elucidated whether a serum PUFA profile is associated with hepatic steatosis. OBJECTIVE: We aimed to clarify the relationship between a serum PUFA profile and liver lipid content. METHODS: A cross-sectional study was conducted on 288 patients with dyslipidemia, diabetes, or coronary artery disease on statin therapy. Several PUFAs were measured, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) in serum lipids, and Δ-5 desaturase (D5D) activity was estimated by AA to DGLA ratio. Abdominal computed tomography (CT) measured visceral fat area (VFA) and the ratio of CT attenuation for liver to spleen (L/S). RESULTS: The L/S ratio showed significant correlations with serum DGLA level and D5D activity (p<0.0001 for both). Serum DGLA level and D5D activity were significantly correlated with body mass index (BMI) or VFA, and with Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) (p<0.0001 for all). Multivariate logistic analysis revealed that a high DGLA level or low D5D activity was a significant determinant for hepatic steatosis (p<0.0001 for both) independent of BMI and HOMA-IR. ROC analysis revealed that they significantly enhanced the value of MetS-related factors in predicting hepatic steatosis (p<0.05 for both). CONCLUSIONS: A high DGLA level and low D5D activity in serum lipids may be useful markers predicting hepatic steatosis incrementally to MetS-related conventional factors.

Primary cardiac rhabdomyosarcoma developed after receiving radiotherapy for left breast cancer 18 years prior.

The heart is an organ where primary malignant tumors rarely develop. In particular, the incidence of cardiac rhabdomyosarcoma (RMS) is extremely low. It has been reported that the risk of second malignant tumors in mediastinum is increased by radiotherapy in women with breast cancer. However, little is known about the association between irradiation to heart and cardiac RMS. Here, we report a case of a 68-year-old woman with primary cardiac RMS. She suddenly presented syncope at a workplace, and was taken to the emergency room at our hospital. Several imaging tests, including echocardiogram and cine magnetic resonance imaging, detected two tumors in the right ventricle (RV) and its outflow tract, which had almost obstructed the main trunk of the pulmonary artery (PA). To avoid sudden PA occlusion by the tumor, we emergently performed surgical excision of the tumors from the RV. Pathological analysis revealed that these tumors were embryonal type RMS. She had received radiotherapy after mastectomy for left breast cancer 18 years previously, and no recurrence of breast cancer had been detected. This cardiac RMS is considered as a second malignant tumor related to radiotherapy for breast cancer. .

Betacellulin and amphiregulin induce upregulation of cyclin D1 and DNA synthesis activity through differential signaling pathways in vascular smooth muscle cells.

Activation of EGF receptors is closely involved in vascular proliferative diseases. The signaling mechanisms of EGF ligands, including betacellulin (BTC) and amphiregulin (AR), are poorly understood. We examined how BTC and AR induced DNA synthesis activity in primary cultures of human thoracic aortic smooth muscle cells (HTASMCs). BTC induced phosphorylation of all four EGF receptors present on HTASMCs: ErbB1, ErbB2, ErbB3, and ErbB4. BTC rapidly induced the phosphorylation of Akt, GSK3alpha/beta, and two FoxO factors, FKHR and AFX, in a dose- and time-dependent manner. BTC increased nuclear beta-catenin accumulation. BTC increased cyclin D1 mRNA, cyclin D1 protein, and DNA synthesis activity. Pretreatment with the phosphatidylinositol 3'-kinase (PI 3'-kinase) inhibitor wortmannin suppressed BTC-induced cyclin D1 mRNA and protein and DNA synthesis activity. In contrast, AR, a specific ErbB1 ligand, induced sustained ERK1/2 and Elk1 phosphorylation, increased cyclin D1 mRNA and protein, and increased DNA synthesis activity. AR did not produce any changes in Akt phosphorylation. Pretreatment with PD98059 suppressed AR-induced cyclin D1 mRNA and protein. Thus, the PI 3'-kinase/Akt/GSK/FoxO/beta-catenin pathway could be the major signaling cascade for BTC-induced upregulation of cyclin D1 protein, whereas a sustained ERK/Elk1 activation could be the major signaling cascade for AR-induced upregulation of cyclin D1 protein in HTASMCs. Moreover, immunohistochemical staining revealed that that BTC, ErbB1, and ErbB4 are upregulated in the plaques of human atherosclerotic coronary arteries. Taken together, BTC and AR could be potent growth factors in proliferative vascular diseases.

Clinical outcome of percutaneous coronary intervention with antecedent mutant t-PA administration for acute myocardial infarction.

OBJECTIVE: We investigated the acute-phrase and chronic-phase outcomes of patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) with or without antecedent mutant tissue-type plasminogen (t-PA) administration. METHODS: Thirty-nine patients with a first AMI within 6 hours of onset were randomly assigned to the treatment group (1,600,000 IU IV monteplase, n = 19) or the nontreatment group (n = 20), followed by PCI. Clinical outcomes were then evaluated. RESULTS: Patient characteristics did not differ between the 2 groups. A significantly higher number of patients in the monteplase group achieved Thrombolysis In Myocardial Infarction trial (TIMI) grade 2 flow or more at the first angiography (84.2% vs 40.0%; P <.005), reduced number of devices (1.44 vs 1.80 devices, P <.05), and reduced procedure times (59.7 vs 86.7 minutes; P <.01), with no differences in peak creatine kinase and rates of major complications and no reflow or distal embolization. Observation over an average of 5.5 months revealed a tendency toward lower target lesion revascularization rates in the monteplase group (17.6% vs 31.6%) but no intergroup difference in rates of major complications. Pretreatment quantitative coronary angioplasty only showed a significant difference in minimal lumen diameter and percent diameter stenosis in the acute phase (1.13 mm in the monteplase group vs 0.66 mm in the nontreatment group, 57.0% vs 73.0%; P <.05). (99m)Tc-QGS (quantitative electrocardiographically gated single-photon emission computed tomographic scintigraphy) showed no intergroup differences in left ventricular end-diastolic volume index, end- systolic volume index, and ejection fraction in the acute and chronic phases. CONCLUSIONS: Our results suggest that PCI with antecedent mutant t-PA for AMI not only accelerates reperfusion, thereby facilitating PCI, but also attenuates restenosis in the chronic phase.

Comparison of eight- versus 16-slice multidetector-row computed tomography for visibility and image quality of coronary segments.

Ten patients who underwent conventional coronary angiography (CA) were examined with both 8- and 16-slice multidetector-row computed tomography (MDCT) angiography within 6 months, and visibility and image quality of 16-slice MDCT-CA were compared with those of 8-slice MDCT-CA directly. In 136 segments determined by conventional CA, 101 (74.3%) and 126 (92.6%) segments were judged assessable by 8- and 16-slice MDCT-CA, respectively. Segment visibility in the right coronary and left circumflex arteries, as well as distal segments and small segments with diameters of <3.0 mm, was higher using 16-slice MDCT-CA than that of 8-slice MDCT-CA. As causes for invisibility in segments considered to be invisible, adjacent structures, as well as small diameters, were reduced by 16-slice MDCT-CA, suggesting that high spatial resolution contributes to higher visibility; however, nonassessable segments due to extensive calcium by 8-slice MDCT-CA were also judged nonassessable by 16-slice MDCT-CA.

Comparison of visibility and diagnostic capability of noninvasive coronary angiography by eight-slice multidetector-row computed tomography versus conventional coronary angiography.

The usefulness of multidetector-row computed tomography (MDCT) for visualization of coronary arteries has been reported; however, little is known about the diagnostic capability of noninvasive coronary angiography (CA) using 8-detector row CT. We investigated the visualization and diagnostic values of 8-slice MDCT-CA. Twenty-five consecutive patients who underwent conventional CA were investigated. The entire heart was scanned for approximately 20 seconds. Images were created using different reconstruction methods (half-scan and multisectors) followed by image creation during different time windows of the cardiac cycle. The data set containing the fewest artifacts was selected, then reformatted images were created and evaluated. In 348 segments in 25 subjects as determined by conventional CA, 258 segments (74.1%) were judged visible by MDCT-CA. Lower visibility was observed in segments with smaller diameters. Visibility in segments with diameters of > or =2.0 mm was 85.8% (212 of 247 segments). Patients with higher mean heart rates and a larger range of heart rate alteration during the breath-holding scan time had lower visibility. The most frequent cause for invisibility was "adjacent structure" (47%), followed by "small diameter" (33%), and "motion artifact" (16%), suggesting that motion artifacts were reduced by multisector reconstruction and search for the best-optimized time window. MDCT-CA detected 27 of 37 significant stenotic lesions (73%) that had a diameter reduction of >50% and correctly judged 226 of 311 segments (72.7%) as normal. Sensitivity, specificity, and accuracy of the visualized segments by MDCT-CA was 90% (27 of 30 segments), 99.1% (226 of 228 segments), and 98.1% (253 of 258 segments), respectively. Low visibilities in the left circumflex artery and distal and small segments are limitations of 8-slice MDCT-CA because of limited spatial resolution.

Predictive value of adiponectin in patients with multivessel coronary atherosclerosis detected on computed tomography angiography.

AIM: Multislice computed tomography coronary angiography (CTCA) can be used to detect coronary plaques that predict the risk of cardiovascular events. This study aimed to identify the risk factors associated with the extent of coronary plaques detected using CTCA and to determine the value of adiponectin measurement for identifying high-risk patients with multivessel coronary atherosclerosis. METHODS: The study included 298 patients who underwent CTCA for coronary artery disease (CAD) screening between July 2008 and October 2011. We investigated the relationship between the extent of coronary atherosclerosis in terms of the number of diseased vessels and various risk factors, including the serum adiponectin level. RESULTS: The adiponectin level was found to be significantly associated with multivessel coronary atherosclerosis in a univariate analysis (p=0.001). A multivariate analysis revealed the adiponectin level to also be significantly associated with multivessel coronary atherosclerosis (p=0.01), independent of other significant risk factors, including an advanced age, male gender, diabetes mellitus (DM) and hypertension (HT). A receiver operating characteristic curve analysis revealed that a combination of these factors significantly predicted multivessel coronary atherosclerosis (area under the curve, 0.73;95% confidence interval, 0.67-0.78). As the number of these factors increased, the proportion of patients with multivessel coronary atherosclerosis increased, while the proportion of patients with normal coronary arteries decreased (p < 0.0001). CONCLUSIONS: A low adiponectin level combined with an advanced age, male gender, DM, and HT is independently and incrementally associated with multivessel coronary atherosclerosis. The number of factors may predict the extent of coronary atherosclerosis in patients without documented CAD.

A case of a young, healthy woman with spontaneous coronary artery dissection associated with oral contraceptive use: Long-term residual dissection of the coronary artery.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome, typically affecting young, healthy women, particularly during the peripartum period. Oral contraceptive use is also recognized as a risk factor for SCAD. In the present report, we describe a case of a young woman with an anterior wall myocardial infarction caused by SCAD of the left anterior descending artery (LAD). The event was probably associated with the patient's oral contraceptive use. The patient underwent percutaneous coronary intervention, and she did not experience any recurrent chest pain or other cardiac symptoms. Although the coronary angiography revealed good LAD flow and no symptoms after 6 months, cardiac computed tomography and intravascular ultrasound revealed that LAD dissection was still present. We continued to closely follow-up the patient without initiating any additional intervention, and the patient has had no cardiac event for up to 4 years of follow-up. .

Impact of dyslipidemic components of metabolic syndrome, adiponectin levels, and anti-diabetes medications on malondialdehyde-modified low-density lipoprotein levels in statin-treated diabetes patients with coronary artery disease.

BACKGROUND: A residual risk of cardiovascular disease tends to persist despite standard prevention therapy with statins. This may stem partly from increased oxidized low-density lipoprotein (LDL) levels. However, how oxidized LDL can be further reduced beyond statin therapy in high-risk diabetes patients remains unclear. We aimed to clarify the clinical factors associated with oxidized LDL levels in statin-treated high-risk diabetes patients. METHODS: This cross-sectional observational study included 210 diabetes patients with coronary artery diseases (CAD) who were treated with statins. We determined serum malondialdehyde-modified LDL (MDA-LDL), LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), remnant lipoprotein cholesterol, hemoglobin (Hb) A1c, adiponectin, and C-reactive protein (CRP) levels and investigated the factors influencing the MDA-LDL level. RESULTS: In univariate analysis, the MDA-LDL level was significantly correlated with LDL cholesterol (p < 0.0001), TG (p < 0.0001), HDL cholesterol (p = 0.017), and adiponectin (p = 0.001) levels but not with age, body mass index, waist circumference, blood pressure, or HbA1c levels. Even after adjusting for the LDL cholesterol level, the correlations between the MDA-LDL level and the TG, HDL cholesterol, and adiponectin levels were still significant. Among these significant factors, multivariate analysis revealed that the MDA-LDL level was independently associated with the LDL cholesterol, TG, and HDL cholesterol but not with adiponectin levels. The MDA-LDL level was also significantly associated with the CRP level (p = 0.014) and the remnant lipoprotein cholesterol level (p < 0.0001) independently of the LDL cholesterol level. The number of metabolic syndrome (MS) components was significantly associated with the MDA-LDL/LDL cholesterol ratio (p < 0.0001). Furthermore, the use of metformin and α-glucosidase inhibitors was inversely associated with high MDA-LDL levels (p = 0.033 and 0.018, respectively). CONCLUSION: In statin-treated diabetes patients with CAD, the MDA-LDL level was significantly correlated with TG and HDL cholesterol levels. Adiponectin level was also significantly associated with the MDA-LDL level, but not independent of the above-mentioned factors. The management of dyslipidemic MS components, including the use of metformin or α-glucosidase inhibitors, may be important for reducing the oxidized LDL levels beyond statin therapy in high-risk diabetes patients.

Cardiovascular risk management with liaison critical path in Japan: its effects on implementation of evidence-based prevention in practice.

BACKGROUND: Liaison critical paths (LCPs) for coronary artery disease (CAD) were developed to support collaborative care for CAD patients between cardiologists in emergency hospitals and referring physicians through sharing of medical information, including cardioprotective medications and cardiovascular risk factors. However, little is known about the effects of LCPs in practice. METHODS: We conducted an observational study of CAD patients undergoing percutaneous coronary intervention in our hospital between September 2007 and June 2010; these patients were managed with an LCP by referring physicians after discharge. We surveyed implementation of scheduled hospital visits, prescription of cardioprotective medicines, and risk factor measurements 6 and 12 months after discharge. RESULTS: Implementation rate of hospital visits was significantly elevated from 50.7% to 89.3% after establishing LCPs. At the 12-month visit, prescription rates for anti-platelet drugs, statins, ß-blockers, and angiotensin-converting enzyme inhibitors or angiotensin II type I receptor blockers were 99.7%, 95.0%, 77.1%, and 74.3%, respectively. Target achievement rates for low-density lipoprotein cholesterol (LDL-C; < 100 mg/dL) and high-density lipoprotein cholesterol (HDL-C; ≥ 40 mg/dL) significantly increased from 48.6% to 64.5% and 62.0% to 82.7%, respectively, while those for body mass index (BMI; < 25 kg/m(2)), blood pressure (< 130/80 mmHg), triglycerides (< 150 mg/dL), and HbA1c (< 7.0 %) were unchanged. BMI, triglycerides, HDL-C, LDL-C, and HbA1c levels significantly improved in patients who implemented all visits. Moreover, risk factor management did not differ significantly between cardiologists and non-cardiologists using LCPs. CONCLUSIONS: LCPs for CAD may facilitate implementation of optimal medical therapy and target achievement of risk factors in practice. KEYWORDS: Liaison critical path; Coronary artery disease; Cardiovascular prevention; Risk factors; Clinical practice.

Peripartum cardiomyopathy presenting with syncope due to Torsades de pointes: a case of long QT syndrome with a novel KCNH2 mutation.

Peripartum cardiomyopathy (PPCM) is a cardiomyopathy of unknown cause that occurs in the peripartum period. We report a case of PPCM presenting with syncope 1 month after an uncomplicated delivery. Electrocardiography showed Torsades de pointes (TdP) and QT interval prolongation. Echocardiography showed left ventricular systolic dysfunction and endomyocardial biopsy showed myocyte degeneration and fibrosis. Administration of magnesium sulfate and temporary pacing eliminated recurrent TdP. Genetic analyses revealed that recurrent TdP occurred via electrolyte disturbance and cardiac failure due to PPCM on the basis of a novel mutation in KCNH2, a gene responsible for inherited type 2 long QT syndrome.

Combination of serum adiponectin level and metabolic syndrome is closely associated with coronary artery disease in Japanese subjects with good glycemic control.

OBJECTIVE: Metabolic syndrome (MetS) and decreased adiponectin level have been reported to be clinically associated with type 2 diabetes mellitus and coronary artery disease (CAD). However, it has not been fully defined whether they are associated with the severity of CAD, independent of hyperglycemia. In the current study, we investigated the clinical relationship between serum adiponectin level and MetS, and its association with the severity of CAD in patients with good glycemic control. PATIENTS AND METHODS: In this study, we enrolled 97 subjects with an HbA1c concentration of < 7.0% (5.5+/-0.6%), who underwent coronary angiography. We measured serum adiponectin levels and various metabolic variables, and assessed the severity of CAD by angiography. RESULTS: Multivariate analysis revealed that the number of MetS components was not correlated with adiponectin level, despite their significant correlation in the univariate analysis. Low adiponectin levels (< 4.5 microg/mL) or > or = 3 of 5 MetS components showed significant association with the severity of CAD (adiponectin, p=0.002; MetS, p=0.049). The correlation of adiponectin levels (divided by tertiles or quartiles) with the severity of CAD was not significant after adjustment for age and gender. On the other hand, two models of combined scores from adiponectin levels and the number of MetS components showed a significant correlation with the severity of CAD even after adjustment for age and gender (model 1, p=0.023; model 2, p=0.018). CONCLUSION: Our findings suggest that the combination of adiponectin levels and the number of MetS components is linked to the severity of CAD in subjects with good glycemic control.