Biomedical subjects

Tomohiro Sakamoto

Publications and source records attributed to Tomohiro Sakamoto.

At least 55 records · Page 3Linked to original sources

PubMed2004

Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type II diabetes mellitus.

OBJECTIVES: This study prospectively examined whether the levels of high remnant-like lipoprotein particles (RLP) cholesterol have a significant risk and influence prognosis in patients with coronary artery disease (CAD) and type II diabetes mellitus (DM). BACKGROUND: Several studies have shown that triglyceride-rich lipoproteins contribute to atherosclerotic complications in type II DM. However, it remains to be established which triglyceride-rich lipoproteins contribute to this risk. METHODS: Levels of RLP cholesterol in fasting serum were measured by an immunoseparation method in 240 type II DM patients with (n = 120) or without (n = 120) CAD. The patients with CAD were followed up for a period of < or =24 months until the occurrence of one of the following clinical coronary events: re-admission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, or cardiac death. RESULTS: Patients with CAD had higher RLP levels than patients without CAD. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>4.7 mg cholesterol/dl, representing the 75th percentile of the distribution of RLP cholesterol levels in control subjects) were a significant risk factor for the presence of CAD, independent of traditional risk factors. Kaplan-Meier analysis demonstrated that higher RLP cholesterol levels in patients with CAD resulted in a significantly higher probability for the development of coronary events. Multivariate Cox hazards analysis showed that high RLP cholesterol levels in patients with CAD were a significant predictor of future coronary events, independent of other risk factors. CONCLUSIONS: Increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in patients with CAD and type II DM.

Aged↗

PubMed2004

Comparison of frequency of interferon-gamma-positive CD4+ T cells before and after percutaneous coronary intervention and the effect of statin therapy in patients with stable angina pectoris.

We investigated the effect of statin therapy on T-cell activation in patients who underwent percutaneous coronary intervention by using flow cytometric analysis. The increased frequency of interferon-gamma-positive CD4(+) T cells after percutaneous coronary intervention was significant in the group treated without statins but not in the group treated with statins.

Aged↗

PubMed2004

Urinary biopyrrins levels are elevated in relation to severity of heart failure.

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.

Aged↗

PubMed2004

Echolucent carotid plaques predict future coronary events in patients with coronary artery disease.

OBJECTIVES: The purpose of this study was to examine whether echolucent carotid plaques predict future coronary events in patients with clinically stable coronary artery disease (CAD). BACKGROUND: Although rupture of coronary plaques is considered a major cause of acute coronary syndromes (ACS), the clinical estimation of coronary vulnerability still remains inconclusive. Ultrasound evaluation of carotid plaques with integrated backscatter (IBS) analysis can indicate the consistency/structure of the plaques. Lipid-rich lesions known as "unstable plaques" appear as echolucent plaques with low IBS values using this technique. METHODS: We investigated the echogenicity of carotid plaques using ultrasound with IBS in 286 consecutive CAD patients (71 with ACS and 215 with stable CAD). Coronary plaque complexity was also determined angiographically in stable CAD patients followed up for 30 months or until the occurrence of coronary events. RESULTS: The calibrated IBS values of carotid plaques in ACS patients were significantly lower than those in stable CAD patients (p < 0.01). Echolucent carotid plaques accurately predicted the existence of complex coronary plaques (predictive power of 83%). Kaplan-Meier analysis demonstrated a significantly higher probability of coronary events developing in patients with echolucent carotid plaques than in patients without this type of plaque (p < 0.001). The presence of echolucent carotid plaques in stable CAD patients predicted future coronary events independent of other risk factors (odds ratio 7.0, 95% confidence interval 2.3 to 21.4; p < 0.001). CONCLUSIONS: Echolucent carotid plaques with low IBS values predicted coronary plaque complexity and the development of future coronary complications in patients with stable CAD. Qualitative evaluation of carotid plaques using ultrasound with IBS is a clinically useful procedure for risk assessment of CAD patients.

Aged↗

PubMed2004

Vitamin E improves fibrinolytic activity in patients with coronary spastic angina.

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.

Administration, Oral↗

PubMed2004

The white blood cell count is an independent predictor of no-reflow and mortality following acute myocardial infarction in the coronary interventional era.

BACKGROUND: In the era before the use of coronary reperfusion therapy, an elevated white blood cell (WBC) count was associated with a higher risk of adverse events following acute myocardial infarction (AMI). However, the relationship between WBC count and prognosis after AMI has not been investigated since coronary intervention was introduced. AIM: To evaluate whether a high WBC count within 48 hours of the onset of AMI predicts future adverse events in patients undergoing percutaneous coronary intervention (PCI). METHOD: We evaluated 1,016 patients who underwent PCI in the acute phase of MI using the Japanese Acute Coronary Syndrome Study (JACSS) database. RESULTS. WBC count was significantly associated with smoking, sudden onset AMI, and the no-reflow phenomenon during PCI, as were age, peak creatine kinase level, and Killip class. An elevated WBC count was significantly associated with higher risk of in-hospital mortality. Patients in the highest quartile of WBC count were about three times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. CONCLUSIONS: The WBC count is of great significance for stratifying patient risk and can be used as a universal marker for predicting future adverse events following any treatment for AMI.

Age Factors↗

PubMed2004

Increased plasma levels of thioredoxin in patients with coronary spastic angina.

To determine whether plasma levels of thioredoxin are associated with coronary spasm, we measured the plasma levels of thioredoxin in 170 patients who had <25% organic stenosis in coronary arteriography. According to the results of cardiac catheterization, we divided the patients into two groups: a coronary spastic angina group (n=84) and a chest pain syndrome group (n=86). The plasma levels of thioredoxin were significantly higher in the coronary spastic angina group than in the chest pain syndrome group (40.7 +/- 4.1 versus 18.2 +/- 1.1 ng/ml, p<0.0001). Furthermore, the increased plasma levels of thioredoxin were associated with high disease activity indicated by the frequency of angina attacks (p=0.0004). In multiple logistic regression analysis, the higher levels of thioredoxin [relative risk 14.8, 95% confidence interval (5.13-42.9), p<0.0001] and current smoking [relative risk 3.39, 95% confidence interval (1.31-8.75), p=0.012] were significant and independent variables associated with coronary spasm. We demonstrated that the plasma levels of thioredoxin were increased in the coronary spastic angina group, and increased levels of thioredoxin were associated with high disease activity. The plasma levels of thioredoxin and current smoking were risk factors for coronary spastic angina, and they were independent from other traditional risk factors.

Adult↗

PubMed2004

Adiponectin is inversely related to plasminogen activator inhibitor type 1 in patients with stable exertional angina.

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.

Adiponectin↗

PubMed2004

Effects of nicorandil on endogenous fibrinolytic capacity in patients with coronary artery disease.

BACKGROUND: Nicorandil is a hybrid-type anti-anginal drug that combines a K(ATP) channel opener and a nitric oxide donor. Recently the IONA study reported that nicorandil improves the prognosis of patients with stable angina pectoris. METHODS AND RESULTS: To examine the effects of nicorandil on endogenous fibrinolysis, plasma concentrations of tissue-type plasminogen activator (t-PA) antigen, type-1 plasminogen activator inhibitor (PAI-1) antigen and PAI activity were measured in consecutive 11 patients (7 men and 4 women, mean age 63 years, ranges 41-84 years) with coronary artery disease. Nicorandil (15 mg/day) was administered orally to each patient for 2 weeks. Venous blood samples were obtained from each patient before and after the administration of the drug in the early morning before eating. There were no significant changes in the plasma concentrations of t-PA (12.4+/-1.9 to 9.8+/-1.5) or PAI-1 (26.3+/-3.9 to 21.5+/-4.9) antigens (ng/ml, mean +/- SEM) before and after nicorandil administration. On the other hand, the plasma activity of PAI (IU/ml, mean +/- SEM) decreased significantly after the treatment (12.9+/-3.2 to 5.6+/-1.9, p=0.039). CONCLUSIONS: It is well known that PAI activity determines the whole fibrinolytic capacity and oral administration of nicorandil decreased PAI activity in patients with coronary artery disease. This finding suggests that nicorandil improves the fibrinolytic capacity and may reduce the risk of coronary thrombus formation in such patients.

Aged↗

PubMed2004

Coronary spastic angina in patients with connective tissue disease.

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.

Aged↗

PubMed2004

Heart failure with silent coronary artery spasm exhibiting microscopic focal myocardial necrosis and amyloid-deposition.

We report a 67-year-old Japanese man who presented with worsening heart failure with asymptomatically transient ischemic ST-segment depression. Left ventriculography showed diffuse hypokinesis; asymptomatic coronary artery spasm was evoked by the acetylcholine provocation test. Endomyocardial biopsy exhibited hypertrophic cardiomyocytes and scattered microscopic focal myocardial necrosis with amyloid-deposition. Transient ST-segment depression improved after treatment with a calcium antagonist, but cardiac contraction was still impaired. We hypothesize that asymptomatic coronary spasm may cause irreversible cardiac damage and heart failure with amyloid-deposition; the presence or absence of coronary spasm in heart failure patients should be clarified in order to determine therapeutic strategy.

Acetylcholine↗

PubMed2003

Asymmetric synthesis of axially chiral biaryls: inversion of planar chirality vs axial isomerization and functionalization at the side chain of biaryl chromium complexes.

Axially chiral syn-biaryl chromium complexes having a coordinating heteroatom substituent at the benzylic position gave anti-biaryl chromium complexes 5 with inversion of the planar chirality by heating in a nonaromatic solvent, while syn-biaryl chromium complexes with an o-methyl or formyl substituent afforded axially isomerized anti-biaryl chromium complexes under heating in an aromatic solvent. syn-biaryl and both enantiomeric anti-biaryl chromium complexes with the o-formyl group were stereoselectively prepared from an identical planar chiral arene chromium complex as chiral source. The formyl group of the axially chiral chromium complexes was functionalized by radical cyclization and beta-lactam formation, and hetero-Diels-Alder reaction.

Journal Article↗

PubMed2003

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin.

OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment-elevated acute myocardial infarction (AMl). BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro. METHODS: After successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10). RESULTS: Adverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group). CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.

Aged↗

PubMed2003

Effects of preinfarction angina pectoris on infarct size and in-hospital mortality after coronary intervention for acute myocardial infarction.

We studied the effect of preinfarction angina on in-hospital outcomes after percutaneous coronary intervention for anterior and nonanterior acute myocardial infarction. Beneficial effects of preinfarction angina on infarct size and in-hospital outcome are evident in patients with anterior infarction, but not in those with nonanterior infarction.

Aged↗

PubMed2003

Attenuation of nitrate tolerance and oxidative stress by an angiotensin II receptor blocker in patients with coronary spastic angina.

BACKGROUND: Nitrates are widely used to treat coronary artery disease, but their therapeutic value is compromised by the rapid development of tolerance. Recently, the renin-angiotensin system has been suggested to play an important role in the development of nitrate tolerance. METHODS AND RESULTS: Sixty-four patients with coronary spastic angina were investigated to clarify the effect of angiotensin II type 1 receptor blocker (ARB) therapy on nitrate tolerance. Transdermal nitroglycerin (10 mg/d) and an ARB (candesartan, 8 mg/d) were administered to 21 patients (GTN+ARB group) for 3 days, whereas transdermal nitroglycerin and placebo were administered to 19 patients (GTN group). Another 18 patients were treated with placebo skin patches and placebo tablets for 3 days (control group). The brachial artery response to incremental doses of intravenous nitroglycerin (0.01, 0.1, and 1.0 micro;g/kg) was measured by ultrasound before and after transdermal nitroglycerin therapy. Before treatment, the arterial diameter was increased by nitroglycerin injection in each group. After treatment, the increase of arterial diameter was significantly suppressed in the GTN group but not in the control or GTN+ARB groups. The plasma level of thioredoxin (a marker of oxidative stress) was increased in the GTN group after treatment (P<0.01) but not in the control or GTN+ARB groups. CONCLUSIONS: An ARB suppressed the development of nitrate tolerance during transdermal nitroglycerin therapy. These results suggest that increased oxidative stress induced by activation of angiotensin II may play an important role in the development of nitrate tolerance.

Administration, Cutaneous↗

PubMed2003

Preference toward a T-helper type 1 response in patients with coronary spastic angina.

BACKGROUND: Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases such as unstable angina (UA) and acute myocardial infarction. Nitric oxide (NO) plays an important role in coronary artery spasm. We previously reported a deficiency in NO activity in the spasm arteries of patients with coronary spastic angina (CSA). Others have reported that NO influences the immune response. Therefore, we investigated the balance between T-helper type 1 (Th1) and 2 (Th2) responses in patients with CSA by evaluating the frequencies of interferon (IFN)-gamma-producing T cells and interleukin (IL)-4-producing T cells in the peripheral blood of such patients. METHODS AND RESULTS: Peripheral blood mononuclear cells were collected from 50 consecutive patients with CSA, 23 consecutive patients with UA, 36 patients with stable angina (SA), and 21 patients with chest pain syndrome (CPS). Cytokine-producing CD4+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA and CSA were associated with a significant increase in the frequency of CD4+ T cells that produced IFN-gamma, whereas these conditions caused no significant difference in the frequency of CD4+ T cells that produced IL-4. Culturing with an NO donor compound for 24 hours before stimulation inhibited the increase in the frequency of CD4+ T cells that produced IFN-gamma. CONCLUSIONS: We demonstrated that there was a preference toward the Th1-type response in patients with CSA and that T cells showed a reduced Th1-type response after being treated with NO.

Adult↗

PubMed2003

Increased plasma thioredoxin in patients with acute myocardial infarction.

BACKGROUND AND HYPOTHESIS: Thioredoxin is an important biomarker for oxidative stress. We investigated whether thioredoxin levels were elevated in patients with acute myocardial infarction (AMI) and were associated with the results of coronary reperfusion. METHODS: The present study determined plasma thioredoxin levels in 51 patients with AMI, 30 patients with stable exertional angina (SEA), and 30 patients with chest pain syndrome (CPS). Plasma sampling was performed on admission, at 12 h, 1 week, 2 weeks, and 4 weeks in patients with AMI, and after admission in patients with SEA and CPS. RESULTS: Plasma thioredoxin levels on admission were higher in patients with AMI than in those with SEA and CPS. Plasma thioredoxin levels in patients with AMI were decreased in 12 h without further change thereafter. However, thioredoxin levels in patients with AMI remained higher than in those with SEA. In multivariate analysis, higher levels of thioredoxin on admission were a risk factor for failure in emergent reperfusion therapy in patients with AMI independent of other factors. CONCLUSION: Plasma thioredoxin levels are elevated in patients with AMI, and higher thioredoxin levels may predict subsequent failed coronary reperfusion therapy in patients with AMI.

Adult↗

PubMed2003

Plasminogen activator inhibitor contributes to the coronary wall thickening in patients with angiographically normal coronary.

INTRODUCTION: Angiographically normal coronary arteries have concealed intimal thickening that importantly contribute to coronary arterial disease activity. Increased plasma levels of plasminogen activator inhibitor (PAI) are associated with myocardial infarction and atherosclerosis. However, it remains unclear whether the PAI contributes to vascular wall thickening detected by intravascular ultrasound (IVUS) in normal coronary angiogram. The aim of this study was to evaluate if the PAI activity contributes to the extent of atherosclerotic changes in angiographically normal coronary arteries using IVUS technique. MATERIALS AND METHODS: We studied 33 consecutive patients with normal coronary angiograms. These patients were divided into a high level of plasma PAI activity group (H-PAI; n=12) and a normal range of PAI activity group (N-PAI; n=21), according to the plasma PAI activity levels. RESULTS: The average of "percent intima+media area (%I+M area)" and "maximal intima+media (I+M) thickness" were significantly greater in the H-PAI group as compared with those in the N-PAI group (p<0.05). Minimal lumen diameter and lumen area were comparable between these groups. The plasma PAI activity level was the independent predictor of increase in maximal I+M thickness, in multiple regression analysis with the traditional risk factors as covariates. CONCLUSIONS: Thickened intima+media of angiographically normal coronary arteries were associated with high plasma level of PAI activity, independently of other traditional risk factors. PAI may contribute to the pathogenesis of coronary intimal thickening that might increase coronary arterial tone.

Cell Division↗