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1.
Mod Rheumatol ; 34(2): 313-321, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-36726243

ABSTRACT

OBJECTIVES: To identify factors associated with plasma D-dimer levels in outpatients with rheumatoid arthritis (RA). METHODS: We consecutively recruited 460 RA patients who visited our hospital for routine follow-ups between June and October 2021. Plasma D-dimer, RA-related characteristics, comorbidities, and cardiovascular and venous thromboembolism (VTE) risk factors were examined at enrolment. Patients with elevated D-dimer levels underwent whole-leg venous ultrasonography to diagnose deep vein thrombosis (DVT). RESULTS: Participants had no DVT signs or symptoms. Among them, 252 (54.8%) were positive for plasma D-dimer (≥0.5 µg/ml) and 40 (8.7%) had high D-dimer levels (≥3 µg/ml). The mean was 1.07 µg/ml. After adjustments, age [odds ratio (OR) 1.88 per additional 10 years, P = .003], high and moderate clinical disease activity index (OR 8.79, P < .001), and the presence of comorbidities or cardiovascular/VTE risk factors (OR 2.94, P = .017) were identified as the factors independently associated with high D-dimer levels. Among patients with D-dimer levels ≥3 µg/ml, 10 (25%) had DVT in their lower limbs, and D-dimer levels were significantly higher in patients with DVT compared with those without it (mean 6.0 vs. 4.1 µg/ml, P < .001). CONCLUSIONS: Clinical disease activity is a major contributor to plasma D-dimer elevation in RA outpatients.


Subject(s)
Arthritis, Rheumatoid , Fibrin Fibrinogen Degradation Products , Venous Thromboembolism , Venous Thrombosis , Humans , Child , Venous Thromboembolism/diagnostic imaging , Venous Thromboembolism/etiology , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Outpatients , Cross-Sectional Studies , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis
2.
J Atheroscler Thromb ; 29(2): 229-241, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-33408315

ABSTRACT

AIM: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. METHODS: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. RESULTS: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. CONCLUSIONS: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 9/blood , Myocardial Infarction/blood , Myocardial Infarction/therapy , Rosuvastatin Calcium/administration & dosage , Aged , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Japan , Male , Middle Aged , Percutaneous Coronary Intervention , Time Factors
3.
J Cardiol ; 72(4): 350-355, 2018 10.
Article in English | MEDLINE | ID: mdl-29735336

ABSTRACT

BACKGROUND: Acute myocardial infarction (AMI) is mainly characterized by the rupture of lipid-rich vulnerable atherosclerotic plaque. The matrix metalloproteinases (MMPs) have been shown to play a critical role in inflammatory processes underlying plaque rupture. Some reports suggested statins inhibit the increased MMP levels after AMI. However, there are a few comparison studies between the different dosages of the same statin and circulating levels of MMPs. PURPOSE: This study will preliminarily investigate the potential effects of appropriate or low dose of rosuvastatin on circulating MMPs levels in AMI patients. Moreover, we will also obtain plasma from patients while undergoing diagnostic angiography to determine differences in various cardiac sites and peripheral vessels. METHODS: This study is a multicenter, open-label, randomized, parallel-group study to be conducted to compare the appropriate or low dose of rosuvastatin in the effect on serum levels of inflammatory markers in AMI patients. The eligible patients undergoing percutaneous coronary intervention (PCI) will be randomly assigned to receive either appropriate or low-dose rosuvastatin daily using a web-based randomization software within 24h after PCI. The low-dose group will be treated with rosuvastatin 2.5mg once daily with a follow-up. The appropriate-dose group will begin treatment with rosuvastatin 5mg once daily, and the dose of rosuvastatin will be titrated to 10mg within 4 weeks. During administration of the study treatment, subjects will undergo laboratory testing including MMPs and be monitored for the occurrence of adverse events up to 24 weeks. The primary endpoint will be the change rate of MMPs at 24 weeks after administration. CONCLUSIONS: INVITATION will compare the appropriate or low dose of rosuvastatin in the effects on serum levels of inflammatory markers including MMPs in AMI patients. This study will provide significant information on rosuvastatin as an anti-inflammatory agent for AMI.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Matrix Metalloproteinases/blood , Matrix Metalloproteinases/drug effects , Myocardial Infarction/drug therapy , Rosuvastatin Calcium/administration & dosage , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Japan , Male , Middle Aged , Myocardial Infarction/blood , Percutaneous Coronary Intervention , Randomized Controlled Trials as Topic , Treatment Outcome
4.
Atherosclerosis ; 237(1): 251-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25262434

ABSTRACT

OBJECTIVE: Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI). METHODS: Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-ß-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)]. RESULTS: Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01). CONCLUSION: Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with increasing CoQ10/LDL-C. CLINICAL TRIAL REGISTRATION: URL http://www.umin.ac.jp/ctr/index.htm Unique Identifier: UMIN000003893.


Subject(s)
Fluorobenzenes/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/drug therapy , Pyrimidines/therapeutic use , Sulfonamides/therapeutic use , Aged , Atorvastatin , Cholesterol, LDL/metabolism , Echocardiography , Fatty Acids/chemistry , Female , Heart/drug effects , Heptanoic Acids/therapeutic use , Humans , Hydrophobic and Hydrophilic Interactions , Iodobenzenes/chemistry , Male , Middle Aged , Myocardium/metabolism , Myocardium/pathology , Natriuretic Peptide, Brain/blood , Pilot Projects , Prospective Studies , Pyrroles/therapeutic use , Radionuclide Imaging , Rosuvastatin Calcium , Thallium/chemistry , Tomography, Emission-Computed, Single-Photon , Ubiquinone/analogs & derivatives , Ubiquinone/blood
5.
Free Radic Res ; 43(12): 1159-66, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19905978

ABSTRACT

Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2'-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n=70), a non-CAD group (n=61) and a control group (n=33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.


Subject(s)
Coronary Artery Disease/complications , Coronary Artery Disease/urine , Heart Failure/etiology , Heart Failure/urine , Oxidative Stress , 8-Hydroxy-2'-Deoxyguanosine , Aged , Bilirubin/urine , Biomarkers/urine , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/urine , Female , Humans , Male , Middle Aged
6.
Eur J Heart Fail ; 10(10): 1001-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18725184

ABSTRACT

BACKGROUND AND AIMS: Juvenile haemochromatosis (JH) is an autosomal recessive iron disorder characterized by the early onset of secondary cardiomyopathy. The candidate modifier genes are hemojuvelin (HJV) and hepcidin antimicrobial peptide (HAMP). In the Japanese population, the prevalence of JH is quite low. The influence of HJV mutation on the JH phenotype is still unclear. METHODS AND RESULTS: We searched for possible mutations in a Japanese family with 2 members who were JH patients with severe heart failure. To search for possible variants in the HJV and HAMP genes, we performed direct sequencing in the family members. A homozygous nonsense mutation in exon 4 of HJV (Q312X) was identified in the JH patients and their mother. Three individuals in the family were heterozygous for this mutation. Subsequently, we evaluated the frequency of Q312X mutation in a large population (n=361) without heart failure, using allele-specific real-time PCR assay. No Q312X mutation was detected in this population. In the patients with the homozygous HJV mutation, iron loading revealed high serum ferritin concentration with accompanying elevated transferrin iron saturation. In contrast, ferritin levels were within the normal range in individuals with the heterozygous mutation. CONCLUSIONS: We found a nonsense mutation in the HJV gene. This mutation elevates ferritin levels and leads to JH associated with severe cardiomyopathy.


Subject(s)
Antimicrobial Cationic Peptides/genetics , Cardiomyopathies/genetics , Hemochromatosis/complications , Membrane Proteins/genetics , Mutation , Adolescent , Adult , Aged , Aged, 80 and over , Cardiomyopathies/epidemiology , Cardiomyopathies/etiology , Cardiomyopathies/physiopathology , Child , Codon, Nonsense , Female , GPI-Linked Proteins , Hemochromatosis/epidemiology , Hemochromatosis/genetics , Hemochromatosis Protein , Hepcidins , Humans , Japan/epidemiology , Male , Middle Aged , Pedigree , Phenotype , Risk Factors , Young Adult
7.
Menopause ; 15(2): 352-6, 2008.
Article in English | MEDLINE | ID: mdl-18090872

ABSTRACT

OBJECTIVES: Coronary heart disease is relatively uncommon in premenopausal women but shows a sharp increase after menopause. The decline of endogenous ovarian hormones is commonly assumed to be a major component of this phenomenon. The effects of estrogens on the vasculature have been investigated extensively in previous studies. However, the effects of estrogens on myocardial function have not been evaluated in humans. We sought to examine the effects of hormone therapy (HT) on myocardial function and cardiac natriuretic peptides in postmenopausal women with chest pain and a normal coronary angiogram. DESIGN: Transdermal HT (estradiol: 0.72 mg/2 d) was administered to 15 postmenopausal women with chest pain and a normal coronary angiogram (mean age, 53 y) for 12 weeks, and oral HT (conjugated equine estrogens: 0.625 mg/d) was administered to another 15 postmenopausal women (mean age, 54 y) for 12 weeks. Echocardiography or cardiac catheterization showed no cardiac dysfunction in any woman at baseline. Cardiac function was evaluated by echocardiography, and plasma B-type natriuretic peptide was measured every 4 weeks. RESULTS: B-type natriuretic peptide levels increased after transdermal HT (baseline: 13.1 +/- 3.1, 4 wk: 22.1 +/- 2.9, 8 wk: 33.2 +/- 3.1, 12 wk: 38.4 +/- 3.3 pg/mL; P < 0.01 vs baseline). The levels were also augmented after oral HT (baseline: 14.1 +/- 3.8, 4 wk: 23.2 +/- 3.3, 8 wk: 35.6 +/- 3.9, 12 wk: 39.6 +/- 3.5 pg/mL; P < 0.01 vs baseline). Serial echocardiography showed no changes in ventricular function in either treatment group. At baseline the serum estradiol levels in the transdermal group were comparable with those in the oral group. CONCLUSIONS: The estradiol levels after HT increased in both groups, but there was no significant difference between the two groups. B-type natriuretic peptide levels increased without cardiac dysfunction, and the chest symptoms were relieved in some participants after HT. Thus, estrogen supplementation augments natriuretic peptide levels without harmful effects on ventricular function.


Subject(s)
Chest Pain/drug therapy , Estrogen Replacement Therapy , Natriuretic Peptide, Brain/drug effects , Postmenopause/drug effects , Ventricular Function/drug effects , Administration, Cutaneous , Administration, Oral , Chest Pain/blood , Coronary Angiography , Echocardiography , Estradiol/administration & dosage , Estradiol/pharmacology , Estrogens/administration & dosage , Estrogens/pharmacology , Female , Humans , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/pharmacology , Middle Aged
8.
Atherosclerosis ; 195(2): 361-6, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17125773

ABSTRACT

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.


Subject(s)
Brachial Artery/physiology , Chest Pain/physiopathology , Coronary Vessels/pathology , Endothelium, Vascular/physiology , Vasodilation/physiology , Aged , Arterial Occlusive Diseases , Coronary Vessels/diagnostic imaging , Female , Humans , Male , Middle Aged , Nitric Oxide/blood , Nitric Oxide/metabolism , Nitroglycerin , Statistics as Topic , Syndrome , Tunica Intima/diagnostic imaging , Tunica Intima/pathology , Tunica Media/diagnostic imaging , Tunica Media/pathology , Ultrasonography, Interventional , Vasodilator Agents
9.
Circ J ; 70(7): 832-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16799234

ABSTRACT

BACKGROUND: The effect of edaravone, a free radical scavenger, on long-term prognosis and its efficacy with regards to scavenging injurious free radicals in patients with acute myocardial infarction (AMI) was examined. METHODS AND RESULTS: One hundred and one initial AMI patients were randomly assigned to receive 30 mg edaravone (n = 50) or a placebo (n = 51) intravenously just before reperfusion. The infarct size, using serum biomarkers and Q-wave formations, and the incidence of reperfusion arrhythmia between the groups were compared. Cardiovascular event-free curves were estimated by using the Kaplan - Meier method. In addition, the serum thioredoxin levels, an oxidative stress marker, to assess the antioxidant effect of edaravone was determined. In all cases, successful reperfusion was obtained within 6 h after the onset of symptoms. Infarct size and reperfusion arrhythmia were significantly attenuated in the edaravone group compared with the placebo group (p = 0.035 and p = 0.031). The cumulative event-free rate was significantly higher in the edaravone group than in the placebo group (p = 0.045). Serum thioredoxin levels were significantly lower in the edaravone group than in the placebo group throughout the acute phase. CONCLUSIONS: The present study suggests that the edaravone administration just prior to reperfusion might reduce oxidative stress and improve the long-term clinical outcomes of AMI patients.


Subject(s)
Antipyrine/analogs & derivatives , Free Radical Scavengers/administration & dosage , Myocardial Infarction/drug therapy , Acute Disease , Antipyrine/administration & dosage , Arrhythmias, Cardiac/blood , Arrhythmias, Cardiac/prevention & control , Edaravone , Humans , Myocardial Infarction/blood , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/prevention & control , Oxidative Stress/drug effects , Retrospective Studies , Thioredoxins/blood , Time Factors
10.
Intern Med ; 44(11): 1127-32, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16357448

ABSTRACT

OBJECTIVE: The aim of the present study was to determine the effects of glucose intolerance on oxidative stress in patients with coronary artery disease (CAD). METHODS: The patients were divided into 3 groups, diabetes mellitus (DM), IGT or normal glucose tolerance (NGT) according to the criteria of the American Diabetes Association. PATIENTS: The present study consisted of 178 consecutive patients who underwent diagnostic coronary arteriography and a 75-g glucose tolerance test. RESULTS: The level of plasma thioredoxin, a marker of oxidative stress was measured in every patient during the fasting state. The levels of plasma thioredoxin were significantly higher in the DM and IGT groups than the NGT group. Furthermore, we found that there was a positive association between thioredoxin levels and glycosylated hemoglobin (sigma=0.225, p=0.018). In multivariate logistic regression analysis, glucose intolerance (DM or IGT) was only independently associated with the high levels of thioredoxin. The levels of plasma thioredoxin were significantly higher in the CAD group compared to the non-CAD group. In multivariate logistic regression analysis, high levels of thioredoxin, male, age and hypertension were independently associated with the presence of CAD. CONCLUSION: Glucose intolerance was associated with the high levels of thioredoxin. High levels of thioredoxin were related to the presence of CAD. The measurement of thioredoxin as the marker of oxidative stress may be useful for monitoring the development of the cardiovascular diseases.


Subject(s)
Glucose Intolerance/blood , Thioredoxins/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Glucose/metabolism , Coronary Angiography , Coronary Disease/blood , Coronary Disease/diagnostic imaging , Coronary Disease/etiology , Enzyme-Linked Immunosorbent Assay , Female , Glucose Intolerance/complications , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Oxidative Stress/physiology , Prognosis , Risk Factors
11.
Am J Cardiol ; 96(1): 71-3, 2005 Jul 01.
Article in English | MEDLINE | ID: mdl-15979437

ABSTRACT

We investigated whether the assessment of small platelet aggregates before percutaneous coronary intervention (PCI) could predict restenosis after PCI. This was a prospective cohort study that enrolled 189 consecutive patients who had coronary artery disease. In multiple logistic regression analysis, higher levels of preprocedural small platelet aggregates were independently associated with restenosis after PCI. Measurement of small platelet aggregates may serve as a useful clinical variable for stratifying patients who present for PCI.


Subject(s)
Angioplasty, Balloon, Coronary , Coronary Restenosis , Platelet Aggregation , Aged , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Regression Analysis
12.
Thromb Res ; 115(6): 483-90, 2005.
Article in English | MEDLINE | ID: mdl-15792679

ABSTRACT

INTRODUCTION: Inflammation is a key process in atherosclerotic formation. Structural changes in the carotid arterial wall including detection of focal plaques are measured as the intima-media thickness (IMT) providing an index of atheroma. Coronary arterial plaques may be considered as vascular structural changes. Distensibility of the arteries can be assessed by functional changes in pulse wave velocity (PWV) providing an index of sclerosis. Adiponectin has potential antiatherosclerotic properties. We hypothesized that adiponectin was associated with atherosclerotic vascular changes involved in inflammation. MATERIALS AND METHODS: We enrolled 142 patients with coronary artery disease (CAD) and 108 control patients, matched for age, sex, and body mass index (BMI) with CAD patients. We investigated the relationship between adiponectin, C-reactive protein (CRP), and atherosclerotic vascular changes. RESULTS: CRP (p=0.0009), high-density lipoprotein cholesterol (HDL-C; p=0.02), and IMTmax (p=0.02) were determinants of adiponectin independent of glucose intolerance (p=0.0001), BMI (p=0.002), and CAD (p=0.03), all of which have been significantly associated with adiponectin (r=0.38). Adiponectin was not correlated with PWV. CRP, glucose intolerance, and HDL-C that correlated with adiponectin were inversely correlated with IMTmax and CAD. CRP was negatively correlated with HDL-C (r=-0.24, p=0.0002) and positively correlated with glucose intolerance (r=0.15, p=0.01). CONCLUSIONS: Adiponectin has a close relationship with CRP, IMTmax, CAD, HDL-C, and other established risk factors. CRP, glucose intolerance, and HDL-C are common mediators between adiponectin and atheromatous vascular changes, which are contrary to each other. The exacerbation of atherogenesis may be involved in a decrease of adiponectin through abnormal glyco- and lipid-metabolism by promoting inflammation.


Subject(s)
Arteriosclerosis/blood , Intercellular Signaling Peptides and Proteins/blood , Adiponectin , Adult , Aged , Aged, 80 and over , Arteriosclerosis/diagnostic imaging , Body Mass Index , C-Reactive Protein/metabolism , Coronary Vessels/metabolism , Endarterectomy, Carotid/methods , Female , Humans , Male , Middle Aged , Regression Analysis , Risk Factors , Ultrasonography/methods
13.
Int J Cardiol ; 99(2): 225-31, 2005 Mar 18.
Article in English | MEDLINE | ID: mdl-15749180

ABSTRACT

Plasma levels of human thioredoxin are indicative of the responses against oxidative stress. We measured the plasma thioredoxin levels in patients with unstable angina in order to examine the relationships between subsequent clinical course and plasma thioredoxin levels before and after treatment for unstable angina. Blood was sampled both on admission and after treatment in 44 patients with unstable angina. In addition, blood samples were obtained from 41 patients with stable exertional angina and 41 patients with chest pain syndrome after admission. The plasma levels of thioredoxin were the highest in the unstable angina group among three groups (p<0.001). Treatment of unstable angina decreased the plasma thioredoxin levels (p<0.01). We divided the patients with unstable angina into two groups according to the plasma thioredoxin levels on admission and after treatment. There was a significant difference in Braunwald's classification between the high thioredoxin and the low thioredoxin group on admission, as analyzed by the chi2 test with Yates's correction (p<0.05). Moreover, there was a significant difference in incidence of recurrent anginal attacks at rest between the high thioredoxin and the low thioredoxin group after treatment, as analyzed by the chi2 test with Yates's correction (p<0.001). The present study demonstrated that plasma thioredoxin levels are significantly increased in patients with unstable angina compared to those with stable exertional angina and chest pain syndrome. Thioredoxin levels were associated with recurrent myocardial ischemia in patients with unstable angina.


Subject(s)
Angina, Unstable/blood , Thioredoxins/blood , Aged , Angina, Unstable/diagnostic imaging , Angina, Unstable/surgery , Biomarkers/blood , Coronary Angiography , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myocardial Revascularization , Oxidative Stress/physiology , Recurrence , Severity of Illness Index
14.
Intern Med ; 44(2): 136-40, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15750274

ABSTRACT

A 79-year-old woman was admitted due to chest pain with T wave inversion and anasarca. Echocardiography demonstrated a mass compressing the heart and computed tomography revealed a giant hiatal hernia within the intrathoracic stomach located just behind the heart. After drainage of the gastric contents, the T wave inversion disappeared, but subsequent ST elevation in leads V1-V6 was noted. After surgical correction of the hiatal hernia, the ST segment elevation returned to a nearly normal level. The changes in the compressed heart induced by hiatal hernia may cause pericarditis resulting in electrocardiographic changes.


Subject(s)
Electrocardiography , Heart Diseases/etiology , Heart/physiopathology , Hernia, Hiatal/complications , Aged , Diagnosis, Differential , Echocardiography , Female , Follow-Up Studies , Heart Diseases/diagnosis , Heart Diseases/physiopathology , Hernia, Hiatal/diagnostic imaging , Hernia, Hiatal/surgery , Humans , Tomography, X-Ray Computed
15.
Am J Cardiol ; 95(4): 514-7, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15695143

ABSTRACT

We assessed serial changes in oxidative stress in patients with acute myocardial infarction by measuring urinary 8-hydroxy-2'-deoxyguanosine excretion. The urinary 8-hydroxy-2'-deoxyguanosine creatinine levels peaked at 4 hours after reperfusion therapy and the levels were higher in the cardiac event group than in the noncardiac event group before and after reperfusion.


Subject(s)
Deoxyguanosine/analogs & derivatives , Deoxyguanosine/urine , Myocardial Infarction/therapy , Myocardial Infarction/urine , Myocardial Reperfusion , 8-Hydroxy-2'-Deoxyguanosine , Biomarkers/urine , Case-Control Studies , Creatinine/urine , Female , Humans , Male , Middle Aged
17.
Thromb Res ; 113(6): 345-51, 2004.
Article in English | MEDLINE | ID: mdl-15226088

ABSTRACT

INTRODUCTION: The fibrinolytic system has a major role as a defense mechanism against thrombus formation. Net fibrinolytic activity in plasma reflects the balance between tissue-type plasminogen activator and plasminogen activator inhibitor (PAI). PAI is the main factor determining overall fibrinolytic activity. MATERIALS AND METHODS: We examined the effects of oral administration of vitamin E, an antioxidant, on fibrinolytic activity and oxidative stress in patients with coronary spastic angina. Forty patients with coronary spastic angina were randomly assigned into two treatment groups, either vitamin E group (alpha-tocopherol acetate, 400 mg/day) or placebo group by means of computerized system. PAI activity and thioredoxin, a marker of oxidative stress, levels were measured before and at the end of 1 month treatment. RESULTS: Before treatment, the levels of PAI activity and thioredoxin were increased in patients with coronary spastic angina as compared with control subjects (n=17) (PAI activity levels: 13.6+/-1.4 vs. 7.6+/-2.2 IU/ml, p<0.05, thioredoxin levels: 22.8+/-1.7 vs. 16.0+/-1.4 ng/ml, p<0.05). In patients with coronary spastic angina, administration of vitamin E decreased both PAI activity and thioredoxin levels (PAI activity levels: 14.7+/-1.7 to 7.5+/-1.6 IU/ml, p<0.01, thioredoxin levels: 23.3+/-2.4 to 15.1+/-2.5 ng/ml, p<0.01), whereas placebo had no effect on these variables. CONCLUSIONS: Oral administration of vitamin E improved fibrinolytic activity and the improvement was associated with a decrease in oxidative stress. Administration of vitamin E is possible to be an effective adjunct therapy of coronary spasm in the absence of coronary atherosclerosis.


Subject(s)
Angina, Unstable/blood , Angina, Unstable/drug therapy , Coronary Vasospasm/blood , Coronary Vasospasm/drug therapy , Fibrinolysis/drug effects , Plasminogen Inactivators/blood , Vitamin E/administration & dosage , Administration, Oral , Angina, Unstable/diagnosis , Angina, Unstable/etiology , Biomarkers/blood , Coronary Thrombosis/blood , Coronary Thrombosis/diagnosis , Coronary Thrombosis/etiology , Coronary Thrombosis/prevention & control , Coronary Vasospasm/complications , Coronary Vasospasm/diagnosis , Double-Blind Method , Female , Fibrinolytic Agents/administration & dosage , Humans , Male , Middle Aged , Thioredoxins/blood , Tissue Plasminogen Activator , Treatment Outcome
18.
J Am Coll Cardiol ; 43(10): 1880-5, 2004 May 19.
Article in English | MEDLINE | ID: mdl-15145115

ABSTRACT

OBJECTIVES: We investigated the relationship between the urinary levels of biopyrrins and the severity of heart failure (HF). BACKGROUND: Oxidative stress is evident in heart disease and contributes to the development of ventricular dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin, have been discovered as potential markers of oxidative stress. METHODS: We measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects (30 men; mean age 65 years). Urine and blood samples were taken after admission in all subjects. Further urine samples were obtained from 40 patients after treatment of HF. RESULTS: The urinary biopyrrins/creatinine levels (micromol/g creatinine) were the highest in patients in New York Heart Association (NYHA) class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range 2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant differences in urinary biopyrrins/creatinine levels among each group. The treatment of HF significantly decreased both urinary biopyrrins/creatinine levels (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class (from 2.5 +/- 0.1 to 1.7 +/- 0.1). Log biopyrrins/creatinine levels were positively correlated with log BNP levels (r = 0.650, p < 0.001). CONCLUSIONS: These results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity.


Subject(s)
Heart Failure/physiopathology , Heart Failure/urine , Aged , Bilirubin/metabolism , Biomarkers/blood , Biomarkers/urine , Female , Heart Failure/blood , Heart Failure/complications , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Natriuretic Peptide, Brain/urine , Oxidative Stress , Severity of Illness Index , Ventricular Dysfunction/blood , Ventricular Dysfunction/etiology , Ventricular Dysfunction/physiopathology , Ventricular Dysfunction/urine
19.
Thromb Haemost ; 91(5): 1026-30, 2004 May.
Article in English | MEDLINE | ID: mdl-15116265

ABSTRACT

Adipose tissue is a secretory organ producing a variety of bioactive substances, such as adiponectin. Adiponectin has antiatherogenic properties while plasminogen activator inhibitor type 1 (PAI-1) is closely involved in the development of atherosclerosis. The relationship between adiponectin and PAI-1 in patients with coronary artery disease (CAD) has not been clarified. This study examined plasma levels of adiponectin and PAI-1 in 64 patients with stable exertional angina (SEA) and 65 patients with the chest pain syndrome (CPS). Plasma log-adiponectin levels were significantly lower in patients with SEA (0.62+/-0.08 micro g/dL) compared to those with CPS (0.86+/-0.05 micro g/dL) (p<0.0001). The plasma levels of log-PAI-1 were significantly higher in patients with SEA (1.23+/-0.18 ng/mL) compared to those with CPS (1.15+/-0.22 ng/mL) (p<0.05). Plasma log-adiponectin levels correlated negatively with diabetes mellitus (DM), body mass index (BMI), log-PAI-1 (r=-0.284, p<0.001), triglyceride (TG), and remnant-like particles cholesterol (RLP-C), and positively with high-density lipoprotein cholesterol (HDL-C) levels. Plasma levels of log-PAI-1 correlated positively with DM, BMI,TG and RLP-C levels, and negatively with HDL-C levels. Multiple logistic regression analysis identified sex, angina pectoris, and PAI-1 as independent determinants of hyperadiponectinemia (p<0.05). Adiponectin is inversely related to PAI-1. DM, BMI,TG, HDL-C, and RLP-C are common mediators between adiponectin and PAI-1, and treatment for common mediators may prevent the development of CAD by reducing PAI-1 and increasing adiponectin levels.


Subject(s)
Angina Pectoris/blood , Intercellular Signaling Peptides and Proteins/analysis , Plasminogen Activator Inhibitor 1/blood , Adiponectin , Adult , Aged , Aged, 80 and over , Chest Pain/blood , Diabetes Mellitus/blood , Female , Humans , Logistic Models , Male , Middle Aged , Sex Factors
20.
Circ J ; 68(4): 367-70, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15056836

ABSTRACT

BACKGROUND: Connective tissue disease, which is an inflammatory condition represented by C-reactive protein (CRP), is a risk factor for ischemic heart disease. The aim of the present study was to examine if there is a relationship between connective tissue disease and coronary spastic angina, and whether the inflammatory condition was associated with ischemic heart disease, even in patients with connective tissue disease. METHODS AND RESULTS: The study group comprised 73 consecutive patients with connective tissue disease who were admitted to the Department of Cardiovascular Medicine between April 2000 and March 2003. Of the 73 patients, 38 (19 men, 19 women) were diagnosed as having an ischemic heart disease (7 patients acute coronary syndrome, 19 patients coronary spastic angina, 12 patients stable exertional angina). In the present study, 19 (50.0%) of the 38 patients of ischemic heart disease were diagnosed as having coronary spastic angina. In the same study period, 151 (38.7%) of 390 patients with ischemic heart disease (without connective tissue disease) were diagnosed as having coronary spastic angina. The frequency of the patients with coronary spastic angina tended to be higher in patients with connective tissue disease than in patients without connective tissue disease. Among the study patients, serum CRP concentrations (mg/dl) were higher in patients with acute coronary syndrome (1.50 +/- 1.19, n=7) and those with coronary spastic angina (1.06 +/- 1.78, n=19) than in those with non-ischemia (0.35 +/- 0.40, n=35, p<0.05). CONCLUSIONS: Coronary spastic angina is a frequent complication in patients with connective tissue disease and the inflammatory condition is associated with coronary spastic angina and unstable angina in patients with connective tissue disease.


Subject(s)
Connective Tissue Diseases/complications , Coronary Vasospasm/etiology , Aged , Angina, Unstable/etiology , Biomarkers , C-Reactive Protein/analysis , Connective Tissue Diseases/blood , Connective Tissue Diseases/immunology , Coronary Vasospasm/blood , Coronary Vasospasm/immunology , Female , Humans , Inflammation/blood , Interferon-gamma/metabolism , Interleukin-4/metabolism , Male , Middle Aged , Myocardial Ischemia/blood , Myocardial Ischemia/complications , T-Lymphocyte Subsets/metabolism
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