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Biomedical subjects

K Kugiyama

Publications and source records attributed to K Kugiyama.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of remnant-like lipoprotein particles in postmenopausal women with and without coronary artery disease and in men with coronary artery disease.

It is known that hypertriglyceridemia is a risk factor of coronary artery disease (CAD) in postmenopausal women. This study prospectively examined whether remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, may have a significant risk and prognostic values in postmenopausal women with angiographically verified CAD. Remnant-like lipoprotein particles cholesterol (RLP cholesterol) levels in fasting serum were measured in 134 consecutive postmenopausal women with (n = 56) or without (n = 78) CAD by an immunoseparation method. The women with CAD were followed for < or =24 months until occurrence of the following clinical coronary events: readmission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, and cardiac death. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>5.7 mg/dl cholesterol; 90th percentile of the distribution of RLP cholesterol levels in controls) were a significant risk factor for the presence of CAD independent of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and other traditional risk factors. Kaplan-Meier analysis demonstrated that women with CAD and higher RLP cholesterol levels had a significantly higher probability of developing coronary events (p <0.001). In multivariate Cox hazard analysis, high RLP cholesterol levels as well as diabetes and hypercholesterolemia were a significant predictor of future coronary events independent of other risk factors in women with CAD (odds ratio 9.7, 95% confidence intervals 1.3 to 20.3, p = 0.02). In conclusion, increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in postmenopausal women with CAD.

Aged↗
PubMed2001

Menstrual cyclic variation of myocardial ischemia in premenopausal women with variant angina.

BACKGROUND: An abundance of ovarian hormones is assumed to be a major contributor to the low incidence of ischemic heart disease in premenopausal women. However, the effects of ovarian hormones remain undetermined. OBJECTIVE: To examine whether the variation in ovarian hormone levels throughout a menstrual cycle affects myocardial ischemia in women with variant angina. DESIGN: Prospective, observational study. SETTING: University medical center in Japan. PARTICIPANTS: 10 premenopausal women with variant angina. MEASUREMENTS: Frequency of spontaneous ischemic episodes, flow-mediated dilation of brachial artery, and serum levels of estradiol and progesterone. RESULTS: Frequency of ischemic episodes was highest from the end of the luteal phase to the beginning of the menstrual phase and was lowest in the follicular phase. Flow-mediated vasodilation and estradiol levels were lowest from the end of the luteal phase to the beginning of the menstrual phase and were highest in the follicular phase. CONCLUSIONS: In premenopausal women with variant angina, we documented a cyclic variation in endothelial function and the frequency of myocardial ischemia that was associated with the variation in estrogen levels.

Adult↗
PubMed2001

Enhanced platelet aggregation in the coronary circulation after coronary spasm.

A recently developed platelet aggregometer using a laser light scattering method is capable of monitoring the increase in size of small-sized platelet aggregates (diameter 9-25 microm), which cannot be detected with the conventional methods. Whether coronary spasm can cause platelet aggregation in the coronary circulation is unknown. We investigated platelet aggregation, especially small-sized platelet aggregates, simultaneously in the coronary sinus and the aortic root in 18 patients with coronary spastic angina before and after a left coronary artery spasm induced by intracoronary injection of acetylcholine, and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid right atrial pacing. Platelet aggregation in 12 patients with chest pain syndrome was also examined before and after coronary spasms provoked by acetylcholine. The number of small-sized platelet aggregates increased significantly in the coronary sinus [2.0+/-0.6 x 104 to 4.1+/-1.0 x 104 (V), P<.01] and in the aortic root [1.7+/-0.6 x 104 to 3.2+/-0.6 x 104 (V), P<.05], and the coronary sinus-arterial difference in the number of small-sized platelet aggregates [2.3+/-1.9 x 103 to 1.1+/-0.4 x 104 (V), P<.01] increased significantly after attacks in the coronary spastic angina group, but remained the same in the stable exertional angina group after attacks and in the chest pain syndrome group after the administration of acetylcholine. Therefore, we can conclude that acute myocardial ischemia induced by coronary spasm causes platelet aggregation in the coronary circulation.

Acetylcholine↗
PubMed2001

Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina.

OBJECTIVES: We sought to examine whether estradiol (E2) supplementation suppresses anginal attacks in women with variant angina. BACKGROUND: Estrogen is known to improve endothelial function. Coronary spasm plays an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general, and endothelial dysfunction seems to be involved in the pathogenesis of coronary spasm. METHODS: Fifteen postmenopausal women with variant angina (mean age 54.2 years) were given a hyperventilation (HV) test, a provocation test for coronary spasm, in the early morning of day 1 (baseline), day 3 (after 2-day transdermal E2 supplementation, 4 mg) and day 5 (after 2-day placebo administration). We measured the flow-mediated (endothelium-dependent) dilation (FMD) of the brachial artery with the ultrasound technique before each HV test. RESULTS: The anginal attacks with ST segment elevation were induced by HV in all patients on days 1 and 5. However, no attacks were induced on day 3. Supplementation with E2 augmented FMD (3.5 +/- 0.6*, 8.9 +/- 0.7 and 4.0 +/- 0.5* on days 1, 3 and 5, respectively; *p < 0.01 vs. day 3). The serum E2 levels on days 1, 3 and 5 were 22.7 +/- 2.8*, 96.2 +/- 9.2 and 30.7 +/- 7.1* pg/ml, respectively (*p < 0.01 vs. day 3). CONCLUSIONS: The present results demonstrated for the first time, to our knowledge, that E2 supplementation suppresses the HV-induced attacks in women with variant angina, in part because of the improvement of endothelial function.

Angina Pectoris, Variant↗
PubMed2001

Increase in plasma levels of oxidized low-density lipoproteins in patients with coronary spastic angina.

Oxidized low-density lipoproteins (LDL) impair endothelium-dependent dilation and constrict arteries. This study examined possible relation of the circulating plasma levels of Ox-LDL to coronary spastic angina (CSA). The plasma levels of Ox-LDL were measured by ELISA in 37 consecutive patients with CSA and normal coronary angiograms and in 79 consecutive control patients. The Ox-LDL levels in patients with CSA were significantly higher than those in controls. In multivariate analysis, higher levels of Ox-LDL were a risk factor for CSA independently of other traditional risk factors. The Ox-LDL levels had a significant and positive correlation with constrictor response of coronary arteries to the intracoronary acetylcholine infusion. Thus, Ox-LDL may play a possible role in pathogenesis of coronary spasm.

Acetylcholine↗
PubMed2001

The prognostic value of small-sized platelet aggregates in unstable angina: detection by a novel laser-light scattering method.

Platelet activation plays a pivotal role in the pathogenesis of acute coronary syndromes. This study was designed to evaluate the platelet aggregability in patients with unstable angina using a new aggregometer with laser-light scattering. We also examined whether there was a relationship between these platelet aggregabilities and unfavorable outcome during in-hospital stay. We measured platelet aggregability, in particular small-sized platelet aggregates in 31 patients with unstable angina, 31 patients with stable exertional angina, and 30 patients with chest pain syndrome. The patients with unstable angina were divided into two groups by their cardiac events during in-hospital stay, cardiac events (+)(n=11) group and cardiac events (-)(n=20) group. On admission, the number of small-sized platelet aggregates (V) was higher in patients with unstable angina (3.0+/-0.5x10(4)) than in those with stable exertional angina (1.4+/-0.3x10(4), P=.017) and chest pain syndrome (0.7+/-0.2x10(4), P=.0003). The number of small-sized platelet aggregates was higher in the cardiac events (+) group than in the cardiac events (-) group (5.5+/-0.9x10(4) vs. 1.6+/-0.4x10(4), P=.0001). A previous study elucidated that small-sized platelet aggregates ultimately developed into medium-sized and large-sized aggregates as platelet aggregation proceeds. Therefore, the production of small-sized platelet aggregates is more sensitive for hyperaggregability. Furthermore, the production of small-sized platelet aggregates increased significantly in patients with unstable angina than in those with stable exertional angina and chest pain syndrome. These findings suggest that a tendency toward thrombus formation increases markedly in patients with unstable angina and increased number of small-sized platelet aggregates on admission predicts poor prognosis during in-hospital stay in patients with unstable angina.

Adult↗
PubMed2001

Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women.

The addition of medroxyprogesterone acetate (MPA) is widely accepted to remove the endometrial-cancerogenic effect of estrogen replacement therapy in postmenopausal women. To evaluate the effect of MPA on endothelial function, we measured flow-mediated vasodilation of brachial arteries after transient occlusion in a randomized, double-blind, placebo-controlled study; we concluded that the addition of MPA attenuates the favorable effects of estradiol on endothelium-dependent vasodilation.

Brachial Artery↗
PubMed2001

Aldosterone production is activated in failing ventricle in humans.

BACKGROUND: Recent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart. METHODS AND RESULTS: Plasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysfunction (LVDD), and 23 control subjects. Aldosterone levels were significantly higher in AIV and CS than Ao in LVSD (98+/-10 versus 72+/-9 pg/mL, P:<0.001, and 97+/-11 versus 72+/-9 pg/mL, P:<0.001, respectively) and LVDD (87+/-10 versus 71+/-9 pg/mL, P:<0.01, and 84+/-10 versus 71+/-9 pg/mL, P:<0.01, respectively) groups, but no differences were observed in levels for these sites in the control group. Levels of ACE activity and BNP also were higher in AIV than Ao in both LV dysfunction groups. The difference in aldosterone levels between AIV and Ao and those in BNP and angiotensin-converting enzyme had a significant positive correlation with LVEDP and a significant negative correlation with LV ejection fraction in the LVSD group. CONCLUSIONS: Production of aldosterone, angiotensin-converting enzyme, and BNP are activated in failing human ventricle in proportion to severity.

Adult↗
PubMed2001

Acute effects of melatonin administration on cardiovascular autonomic regulation in healthy men.

BACKGROUND: Previous studies have suggested that melatonin, a major pineal hormone, possibly modulates the autonomic nervous system in animals. The aim of this study was to examine the effects of melatonin administration on heart rate variability (HRV) in human beings. METHODS: In 26 healthy men, melatonin (2 mg) or placebo was randomly administered. Power spectral analysis of HRV and blood pressure monitoring were performed in the supine position before and 60 minutes after administration and in the standing position 60 minutes after administration. Plasma catecholamine levels were also assessed. RESULTS: No differences in any baseline parameters were found between the two groups. Compared with placebo, melatonin administration within 60 minutes increased R-R interval, the square root of the mean of the squared differences between adjacent normal R-R intervals, high-frequency power, and low-frequency power of HRV and decreased the low-frequency to high-frequency ratio and blood pressure in the supine position (all P <.01). Plasma norepinephrine and dopamine levels in the supine position 60 minutes after melatonin administration were lower compared with placebo (P <.05 and P <.01, respectively). Standing up resulted in the decrease of HRV and the increase of blood pressure and plasma catecholamine levels in both administration groups, and the differences between the groups found in the supine position disappeared. CONCLUSIONS: These findings indicate that melatonin administration increased cardiac vagal tone in the supine position in awake men. Melatonin administration also may exert suppressive effects on sympathetic tone.

Blood Pressure↗
PubMed2001

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina.

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.

Acetylcholine↗
PubMed2001

The relationship of left ventricular mass to endothelium-dependent vasodilation of the brachial artery in patients with hypertension.

Although echocardiographically determined left ventricular mass and geometry predict cardiovascular morbid events in patients with hypertension, the mechanisms underlying this relation are unclear. There is considerable evidence that endothelium-dependent vasodilation is impaired in patients with hypertension. Thus, endothelial dysfunction may contribute to the mechanism that causes cardiovascular morbid events. This study was designed to examine the relationship between left ventricular geometry and endothelial function in patients with hypertension. The percentage increase in brachial arterial diameter during reactive hyperemia was examined by a high-resolution ultrasound technique in 49 patients with hypertension and 64 normotensive subjects. Patients with hypertension had an impairment of the percentage increase in brachial arterial diameter during reactive hyperemia and an increase in thiobarbituric acid-reactive substances (TBARS) compared to normotensive subjects (percentage increase in diameter 5.6 +/- 3.0 vs. 8.0 +/- 2.5%, p < 0.001; TBARS levels 6.1 +/- 1.3 vs. 5.3 +/- 1.0 nmol/ml, p < 0.001). In patients with hypertension, there was a significant correlation between the left ventricular mass index and the percentage increase in brachial arterial diameter during reactive hyperemia (r = -0.583, p < 0.001), and the percentage increase in brachial arterial diameter during reactive hyperemia varied with the pattern of left ventricular geometry (normal ventricular geometry: 7.7 +/- 2.6%; concentric remodeling: 5.2 +/- 2.3%; eccentric hypertrophy: 4.2 +/- 1.8%; concentric hypertrophy: 2.9 +/- 2.6%). We conclude that (1) flow-mediated endothelium-dependent vasodilation in the brachial artery is impaired in patients with hypertension, (2) a relationship exists between the left ventricular mass index and flow-mediated endothelium-dependent vasodilation in the brachial artery in patients with hypertension and (3) increased oxidative stress may play a role in the endothelial dysfunction in patients with hypertension.

Adult↗
PubMed2001

Increased autoantibodies against oxidized low-density lipoprotein in coronary circulation in patients with coronary spastic angina.

Oxidized low-density lipoproteins are important in the progression of atherosclerosis. Autoantibodies against malondialdehyde-modified low-density lipoproteins have been reported to be predictive of the progression of atherosclerosis. This study sought to examine whether plasma levels of autoantibodies against oxidized low-density lipoprotein increase in the coronary circulation in patients with coronary spastic angina. The authors examined plasma antioxidized low-density lipoprotein antibody levels (activity unit values (AcU)/mL) simultaneously in the coronary sinus and the aortic root in 20 patients with coronary spastic angina, 23 patients with stable exertional angina, and 15 control subjects by measuring plasma levels of immunoglobulin G (IgG) autoantibodies against malondialdehyde-modified low-density lipoproteins by enzyme-linked immunosorbent assay. The plasma antioxidized low-density lipoprotein antibody levels (AcU/mL) in the coronary sinus increased in coronary spastic angina (38 +/- 16) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < or = 0.0001). The levels (AcU/mL) in the aortic root also increased in coronary spastic angina (33 +/- 12) compared with stable exertional angina (23 +/- 7) and control subjects (20 +/- 6) (p < 0.005). Furthermore, the coronary sinus-arterial differences of the levels (AcU/mL) were also higher in coronary spastic angina (5 +/- 9) than in stable exertional angina (0 +/- 6) and healthy subjects (-1 +/- 5) (p < 0.05). The generation of malondialdehyde-modified low-density lipoproteins is reported to be associated with atherothrombosis. These findings suggest that elevated levels of autoantibodies against malondialdehyde-modified oxidized low-density lipoproteins in coronary circulation are associated with the development of atherothrombosis from the progression of atherosclerosis rather than with the extent of coronary atherosclerosis in patients with coronary spastic angina.

Acetylcholine↗
PubMed2001

Nitric oxide-mediated vasodilatation is decreased in forearm resistance vessels in patients with coronary spastic angina.

It has been reported that coronary endothelial dysfunction is associated with the pathogenesis of coronary spasm, and that endothelial nitric oxide (NO) mediated vasodilatation was decreased in coronary epicardial arteries in patients with coronary spastic angina (CSA). However, there are few reports about the endothelial function in peripheral resistance vessels of patients with CSA, so the present study investigated the role of NO in forearm resistance vessels in such patients. The responses of forearm blood flow to acetylcholine (ACh; 8-24 microg/min) and sodium nitroprusside (SNP; 0.4-1.2 microg/ml) infusions was examined using plethysmography, and subsequently the responses to ACh after an infusion of N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min, for 5 min) in 17 patients with CSA and 17 age- and sex- matched controls. The vasodilator responses to ACh and SNP were comparable between the 2 groups (p=NS). L-NMMA significantly suppressed the vasodilator responses to ACh in controls (p<0.05), but there was no significant difference in the responses to ACh before and after infusion of L-NMMA in patients with CSA (p=NS). These results indicate that endothelial NO-mediated vasodilatation is decreased in the forearm resistance vessels of patients with CSA.

Acetylcholine↗
PubMed2001

Increased plasminogen activator inhibitor activity and diabetes predict subsequent coronary events in patients with angina pectoris.

BACKGROUND: Plasminogen activator inhibitor (PAI) is a marker of recurrence of myocardial infarction. Diabetes mellitus is also an important risk factor of coronary artery disease, including myocardial infarction and angina pectoris. AIM: We examined baseline plasma PAI activity levels, clinical variables, and angiographic findings and assessed them as prospective values for subsequent coronary events, such as sudden death, nonfatal myocardial infarction and coronary revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass surgery during the follow-up period. METHODS: We conducted a prospective study for 4 years of 249 consecutive patients admitted with angina pectoris. Blood samples for PAI were drawn at discharge. RESULTS: In the multivariate Cox proportional hazard model, PAI activity and diabetes mellitus were significant and independent risk factors (the risk increased by 10% in those with a higher PAI concentration and by 70% in diabetic patients). Event-free survival was reduced by higher PAI activity (> or = 8.4 IU/mL) and the presence of diabetes. The patients with higher PAI activity and diabetes had a 4.2-fold risk in comparison with the patients with lower PAI activity and no diabetes. However, patients with lower PAI activity were less likely to have coronary events even when they had diabetes. CONCLUSIONS: Higher PAI activity and diabetes predict subsequent coronary events in patients with angina pectoris. Diabetes has less prognostic value for subsequent coronary events in patients with lower PAI activity.

Angina Pectoris↗
PubMed2000

Plasma levels of A- and B-type natriuretic peptides in patients with hypertrophic cardiomyopathy or idiopathic dilated cardiomyopathy.

We investigated the relation between left ventricular structure and the secretion patterns of A- and B-type natriuretic peptides (ANP and BNP) by comparing their plasma levels in patients with hypertrophic cardiomyopathy (HC) and patients with idiopathic dilated cardiomyopathy (IDC). The secretion of ANP and BNP was much higher in patients with HC than in those with IDC; this shows that left ventricular cavity size is a key factor that regulates the secretion of ANP and BNP.

Aged↗
PubMed2000

Prognostic value of plasma levels of secretory type II phospholipase A2 in patients with unstable angina pectoris.

Plasma levels of secretory nonpancreatic type II phospholipase A2 (sPLA2) are increased in various chronic inflammatory diseases; this increase is correlated with disease severity. sPLA2 plays a possible role in atherogenesis and is highly expressed in atheromatous plaques. Thus, this study prospectively examined whether plasma levels of sPLA2 may have a prognostic value in patients with unstable angina, which is known to have inflammatory features. Plasma levels of sPLA2 were measured in 52 patients with unstable angina, in 107 patients with stable angina, and in 96 control subjects by radioimmunoassay. sPLA2 levels were significantly higher in patients with unstable angina than in those with stable angina and in control subjects. sPLA2 remained elevated after stabilization of disease. The levels were not increased in the blood in the coronary sinus. Kaplan-Meier analysis demonstrated that patients with unstable angina and with the higher sPLA2 levels had a significantly higher probability of developing clinical coronary events during a follow-up period of 2 years compared with those with the lower levels. In multivariate Cox hazard analysis, the higher levels of sPLA2 were a significant predictor of developing coronary events in patients with unstable angina, independent of other risk factors, including C-reactive protein levels, an established inflammatory predictor. In conclusion, the increase in circulating levels of sPLA2 predicts clinical coronary events independently of other risk factors in patients with unstable angina. sPLA2 levels were persistently elevated but the elevated levels may not be derived from coronary circulation.

Aged↗