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Tetsuji Miura

Publications and source records attributed to Tetsuji Miura.

At least 19 recordsLinked to original sources
PubMed2007

Impact of abnormal glucose tolerance, hypertension and other risk factors on coronary artery disease.

BACKGROUND: The degree to which abnormal glucose tolerance contributes to the development of coronary artery disease (CAD) has not been clarified in Japanese. The relationship between abnormal glucose tolerance and severity of coronary artery stenosis, as well as the contributions of hypertension, diabetes and other risk factors for CAD to recurrence of the disease, were investigated in the present study. METHODS AND RESULTS: The subjects were 474 consecutive patients (mean age: 63.8+/-11.3 years) with suspected CAD who were admitted to Sapporo Medical University Hospital during April 1, 1997 to March 31, 2004. The coronary index and stenosis score were higher in subjects with diabetes mellitus (DM) and in subjects with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance (NGT). Ischemic episodes recurred during the observation period (mean 2.5 years) in 61 of 341 patients diagnosed as having CAD. In the follow-up subjects, systolic blood pressure (SBP) was significantly higher in the recurrence group than in the non-recurrence group, and SBP was a significant variable in logistic regression analysis after adjustment for age, gender, hemoglobin A1c, total cholesterol, body mass index, smoking history, family history and stenosis score. The relative risk of recurrence became 1.7-fold higher with a rise in SBP of 10 mmHg (95% confidence interval: 1.252-2.250). Analysis of the relationship between glucose tolerance and recurrence showed that the rate of recurrence was higher in patients with IFG+IGT+DM than in those with NGT. CONCLUSIONS: CAD progresses not only in patients with DM but also in those with IGT. The rate of recurrence of ischemic episodes increases in individuals with IGT or DM, and suggesting that hypertension is a risk factor for recurrence of ischemic episodes. Management of glucose tolerance and blood pressure is therefore important for prevention of CAD in Japanese.

Aged↗
PubMed2006

Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1.

Sir2 (silent information regulator 2) is an NAD(+)-dependent histone deacetylase that contributes to longevity in yeast. SIRT1, a mammalian Sir2 ortholog, deacetylates histones and various transcription factors, including p53, FOXO proteins, and peroxisome proliferator-activated receptor-gamma. We found that its subcellular localization varied in different tissues of the adult mouse. Some subsets of neurons predominantly expressed SIRT1 in the cytoplasm, but ependymal cells expressed it in both the nucleus and cytoplasm. On the other hand, spermatocytes expressed SIRT1 only in the nucleus. Cardiomyocytes in the day 12.5 mouse embryo expressed SIRT1 exclusively in the nucleus, but in the adult heart, they expressed it in both the cytoplasm and nucleus. C2C12 myoblast cells expressed SIRT1 in the nucleus, but it localized to the cytoplasm after differentiation. LY294002, an inhibitor of phosphoinositide 3-hydroxykinase, strongly inhibited the nuclear localization of SIRT1 in undifferentiated C2C12 cells. In a heterokaryon assay, SIRT1 shuttled between the nucleus and cytoplasm, and leptomycin B, an inhibitor of CRM1-mediated nuclear exportation, inhibited this shuttling. Two nuclear localization signals and two nuclear export signals were identified by deletion and site-directed mutation analyses. Overexpressed nuclear (but not cytoplasmic or dominant-negative) SIRT1 enhanced the deacetylation of histone H3 in C2C12 cells. Moreover, only the nuclear form suppressed the apoptosis of C2C12 cells induced by antimycin A, an oxidative stressor. These findings indicate that nucleocytoplasmic shuttling is a novel regulatory mechanism of SIRT1, which may participate in differentiation and in inhibition of cell death.

Active Transport, Cell Nucleus↗
PubMed2006

Impairment of cardioprotective PI3K-Akt signaling by post-infarct ventricular remodeling is compensated by an ERK-mediated pathway.

Recently we found that post-infarct remodeling disrupts PI3KAkt signaling triggered by erythropoietin (EPO) but an unknown compensatory mechanism preserves EPO-induced protection against infarction in those hearts. In this study, we examined the possibility that ERK-mediated signaling is the compensatory mechanism affording protection in post-infarct remodeled hearts. Four weeks after coronary ligation in situ (post-MI group, post-MI) or a sham operation (sham group, Sham), hearts were isolated, perfused and subjected to 25-min global ischemia/2-h reperfusion. Infarct size was expressed as a percentage of risk area size (%I/R), from which scarred infarct by coronary ligation was excluded. EPO infusion (5 U/ml) before ischemia reduced %I/R similarly in Sham and post-MI (from 62.0 +/- 5.1 to 39.4 +/- 4.8 in Sham and from 58.6 +/- 6.6 to 36.3 +/- 3.8 in post-MI). PD98059, a MEK1/2 inhibitor, abolished this EPO-induced protection in post-MI (%I/R = 60.7 +/- 4.9) but not in Sham (%I/R = 35.1 +/- 5.4). EPO induced PI3K-dependent phosphorylation of Akt in Sham but not in post-MI. EPO increased phosphorylation levels of ERK1/2 both in Sham and post-MI, but this phosphorylation was diminished by a PI3K inhibitor in Sham but not in post-MI. These results suggest that PI3K-independent activation of ERK compensates the lack of signal input from the PI3K-Akt pathway to achieve EPO-induced protection in the remodeled myocardium.

Animals↗
PubMed2006

Activation of ERK and suppression of calcineurin are interacting mechanisms of cardioprotection afforded by delta-opioid receptor activation.

The aim of this study was to examine possible interactions of ERK and calcineurin in cardioprotection afforded by delta-opioid receptor stimulation. Infarction was induced in rat hearts by 20-min coronary occlusion and reperfusion. Tissue ERK level and calcienurin activity were determined by immunoblotting and an assay using a phosphopeptide substrate, respectively. Administration of a delta-opioid receptor agonist, D-Ala2-D-Leu5-enkephalin (DADLE, 1 mg/kg), before ischemia increased the phospho-ERK levels during ischemia and reduced infarct size (as percentage of risk area, %IS/AR) from 47.7 +/- 2.3% to 23.2 +/- 2.5%. This protection was abolished by 10 mg/kg of natrindole hydrochloride (NTI), a delta-opioid receptor antagonist. PD98059, a MEK1/2 inhibitor, abolished both ERK1/2 activation and infarct size limitation by DADLE. Calcineurin inhibitors, cyclosporine-A (5 mg/kg) and FK506 (3.5 mg/kg), reduced %IS/AR (27.4 +/- 4.4% and 29.9 +/- 3.4%, respectively). The protective effects of these calcineurin inhibitors were inhibited by PD98059, and the combination of DADLE with cyclosporine-A or FK506 did not afford further cardioprotection. DADLE significantly suppressed myocardial calcineurin activity, and this effect was inhibited by NTI. Suppression of calcineurin activity by FK506 was associated with modest activation of ERK1/2. These results suggest that suppression of calcineurin and activation of ERK1/2 are interacting mechanisms involved in cardioprotection by delta-opioid receptor activation.

Animals↗
PubMed2006

Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3 beta.

The aim of this study was to determine whether erythropoietin (EPO) affords additional cardioprotection to the preconditioned myocardium by enhanced phosphorylation of Akt, STAT3, or glycogen synthase kinase-3beta (GSK-3 beta). Preconditioning (PC) with 5-min ischemia/5-min reperfusion and EPO (5,000 U/kg iv) reduced infarct size (as % of area at risk, %IS/AR) after 20-min ischemia in rat hearts in situ from 56.5 +/- 1.8% to 25.2 +/- 2.1% and to 36.2 +/- 2.8%, respectively. PC-induced protection was significantly inhibited by a protein kinase C inhibitor, chelerythrine (5 mg/kg), and slightly blunted by a phosphatidylinositol-3-kinase inhibitor, wortmannin (15 microg/kg). The opposite pattern of inhibition was observed for EPO-induced protection. The combination of PC and EPO further reduced %IS/AR to 8.9 +/- 1.9%, and this protection was inhibited by chelerythrine and wortmannin. The additive effects of PC and EPO on infarct size were mirrored by their effects on the level of phosphorylated GSK-3 beta at 5 min after reperfusion but not their effects on the level of phospho-Akt or phospho-STAT3. To mimic phosphorylation-induced inhibition of GSK-3 beta activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before ischemia or 5 min before reperfusion. Infarct size was significantly reduced by preischemic injection (%IS/AR = 40.4 +/- 2.2% by 0.6 mg/kg SB and 34.0 +/- 1.8% by 1.2 mg/kg SB) and also by prereperfusion injection (%IS/AR = 32.0 +/- 2.0% by 1.2 mg/kg SB). These results suggest that EPO and PC afford additive infarct size-limiting effects by additive phosphorylation of GSK-3beta at the time of reperfusion by Akt-dependent and -independent mechanisms.

Animals↗
PubMed2006

MitoKATP channel activation suppresses gap junction permeability in the ischemic myocardium by an ERK-dependent mechanism.

BACKGROUND: Ischemic preconditioning accelerates suppression of gap junction (GJ) permeability during myocardial ischemia, and GJ blockers reduce infarct size. We hypothesized that the mitochondrial ATP-sensitive K+ (mitoKATP) channel is one of the mechanisms regulating GJ permeability through the mitogen-activated protein kinase ERK, leading to cardioprotection. METHODS AND RESULTS: In isolated rabbit hearts, tissues were sampled before and after infusion of diazoxide, a selective mitoKATP channel opener, and their intercalated disc-rich fractions were obtained for immunoblotting of mitogen-activated protein kinases. GJ permeability in the myocardium was assessed by using Lucifer yellow as a tracer of GJ communication. Infarction was induced by 30-min global ischemia/2 h reperfusion, and infarct size was expressed as a percent of area-at-risk (%IS/AR). Diazoxide (100 microM) induced phosphorylation of ERK1/2 and 279Ser/282Ser of connexin-43, a GJ subunit protein, and phospho-ERK1/2 was co-immunoprecipitated with connexin-43 in the diazoxide-treated myocardium. This ERK1/2 phosphorylation by diazoxide was inhibited by N-2-mercaptopropionyl-glycine, a free radical scavenger. Diazoxide at 10 and 100 microM reduced intercellular transport of Lucifer yellow during ischemia by 44% and 69%, respectively, and this effect of diazoxide on GJ communication was abolished by PD98059, an ERK inhibitor. Pretreatment with 10 microM and 100 microM diazoxide reduced %IS/AR from 57.1+/-3.7% to 21.5+/-10.5% and 5.0+/-1.3%, respectively. PD98059 abolished cardioprotection by 10 microM diazoxide but not that by 100 microM diazoxide. CONCLUSIONS: Opening of the mitoKATP channel activates ERK1/2 via free radicals and induces ERK-mediated suppression of GJ permeability. This suppression of GJ permeability may partly contribute to cardioprotection afforded by mitoKATP channel activation.

Adenosine Triphosphate↗
PubMed2006

Macrophage colony-stimulating factor treatment after myocardial infarction attenuates left ventricular dysfunction by accelerating infarct repair.

OBJECTIVES: We aimed to determine the effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) treatment on both the repair process and ventricular function after myocardial infarction (MI). BACKGROUND: The M-CSF and G-CSF have multiple potential effects on cells involved in wound repair. METHODS: Myocardial infarction was induced by 45- or 90-min coronary occlusion and reperfusion in rats with or without subsequent injection of M-CSF (10(6) IU/kg/day) or G-CSF (50 microg/kg/day) for five days. We examined histology and messenger ribonucleic acid (mRNA), and assessed left ventricular function in situ using a conductance catheter. RESULTS: Five days after MI, M-CSF increased the number of ED-1-positive cells, mRNA levels of transforming growth factor-beta-1, collagen I and III, and collagen fibers within the infarct. Fourteen days after MI, induced by 45-min ischemia, left ventricular end-systolic elastance (Ees) was reduced (1,191 +/- 87 mm Hg/ml vs. 1,812 +/- 150 mm Hg/ml) and both isovolumic relaxation time constant (tau) (11.9 +/- 0.9 ms vs. 8.5 +/- 0.4 ms) and left ventricular end-diastolic volume (LVEDV) (0.225 +/- 0.014 ml vs. 0.172 +/- 0.011 ml) increased versus sham-operated rats. These alterations after MI were attenuated by M-CSF (Ees = 1,650 +/- 146, tau = 9.7 +/- 0.7, LVEDV = 0.199 +/- 0.012) but not by G-CSF. This beneficial effect of M-CSF on Ees was also detected in hearts with MI induced by 90-min ischemia. Furthermore, M-CSF increased collagen content within infarcts and reduced the proportion of thin collagen fibers 14 days after MI. The Ees significantly correlated with infarct collagen content. Nevertheless, neither M-CSF nor G-CSF modified infarct size. CONCLUSIONS: The M-CSF treatment attenuates deterioration of left ventricular function after MI by accelerating infarct repair.

Animals↗
PubMed2006

Assessment of left ventricular ejection fraction using long-axis systolic function is independent of image quality: a study of tissue Doppler imaging and m-mode echocardiography.

BACKGROUND: Quantitative assessment of left ventricular ejection fraction (LVEF) is technically difficult in patients with poor image quality (IQ). Mitral annulus velocity assessed by pulsed tissue Doppler imaging (TDI) and mitral annulus motion assessed by M-mode echocardiography has been shown to correlate with LVEF. Furthermore, mitral annulus sites are easy to identify even in patients with poor IQ. The purpose of this study was to determine whether these methods are useful for estimating LVEF in patients with poor IQ. METHODS: One hundred ten patients underwent TDI and M-mode echocardiography simultaneously. Mitral annulus velocity and mitral annulus motion were obtained from each of the four mitral annulus sites. Mean mitral annular peak systolic velocities (Sm) and mean mitral annular motions (MAM) were calculated by averaging at each site. IQ was defined according to a previous report. RESULTS: Both Sm and MAM were successfully measured in all patients. Mean Sm and mean MAM correlated with LVEF. These correlations were observed not only in patients with good IQ (p < 0.001, r = 0.61 for mean Sm; p < 0.001, r = 0.61 for mean MAM) or fair IQ (p < 0.001, r = 0.58 for mean Sm; p < 0.001, r = 0.68 for mean MAM) but also in patients with poor IQ (p < 0.05, r = 0.42 for mean Sm, p < 0.001, r = 0.61 for mean MAM). Using optimal cutoff values of mean Sm and mean MAM in each IQ group, sensitivity and specificity for identifying LVEF < 50% were comparable among three IQ groups. CONCLUSIONS: Assessment of long-axis systolic function by TDI and M-mode echocardiography enables estimation of LVEF even in patients with poor IQ.

Aged↗
PubMed2006

Long-term outcome of implanted cardioverter defibrillators in survivors of out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Little is known about the long-term outcome of implantable cardioverter defibrillator (ICD) therapy in survivors of out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS: The frequency of lethal ventricular arrhythmias and whether ICD implantation can prevent recurrence of cardiac arrest were examined. Long-term (24.4+/-11.9 months) outcome was examined in 23 patients with OHCA who were treated with an ICD (OHCA group) and 35 patients without OHCA (non-OHCA group) who were treated with an ICD. Patients in both groups had same clinical backgrounds; however, those in the OHCA group showed a significantly lower incidence of induced ventricular arrhythmias (71%) than the non-OHCA group (96%). In the follow-up period, patients in the OHCA group had almost the same incidence of ICD discharge (30%) as patients in the non-OHCA group (40%). The rate of recurrence of ventricular fibrillation in the OHCA patients was 13%, and it was difficult to estimate the rate by induced ventricular arrhythmia. CONCLUSION: The results suggest that ICD implantation for survivors of OHCA with favorable neurological recovery might be effective for preventing recurrence of cardiac arrest.

Adolescent↗
PubMed2006

Persistent insulin-sensitizing effects of sarpogrelate hydrochloride, a serotonin 2A receptor antagonist, in patients with peripheral arterial disease.

BACKGROUND: There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). METHODS AND RESULTS: Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76+/-9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0+/-10.3 vs 9.2+/-2.0 microU/ml, p=0.03) and HOMA-R (4.30+/-2.83 vs 2.40+/-0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11+/-4.13 vs 9.64+/-4.37 microg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). CONCLUSIONS: Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD.

Adiponectin↗
PubMed2006

[Treatment for hypertension with diabetes mellitus].

In the treatment for the hypertension patients with diabetes mellitus, the target blood pressure is below 130/80mmHg. As the first choice drugs, ARB, ACE inhibitor and Ca channel blocker are recommended. In the high normal blood pressure patient (130-139/80-89mmHg), the initial approach is life-style modification. In hypertension patients with diabetes (over 140/90mmHg), blood pressure should be controlled with the medication. The life-style modification should be performed even in the patients treated with anti-hypertensive drugs.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Alteration in erythropoietin-induced cardioprotective signaling by postinfarct ventricular remodeling.

Postinfarct remodeling impairs mechanisms of ischemic preconditioning. We examined whether myocardial response to activation of the erythropoietin (EPO) receptor is modified by postinfarct remodeling. Four weeks after induction of myocardial infarction (MI) by coronary ligation in post-MI group (post-MI) or a sham operation in sham group (sham), rat hearts were isolated and subjected to 25-min global ischemia/2-h reperfusion. Infarct size was expressed as a percentage of risk area (i.e., left ventricle) from which scarred infarct was excluded (%I/R). The heart weight was 15% larger in post-MI, but there was no intergroup difference in plasma EPO levels or myocardial EPO receptor levels. EPO infusion (5 U/ml) significantly reduced %I/R from 59.9 +/- 4.1 to 36.2 +/- 4.2 in sham and from 58.1 +/- 5.0 to 35.2 +/- 4.0 in post-MI. This EPO-induced protection was sensitive to a phosphatidylinositol 3-kinase (PI3K) inhibitor, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), in sham. However, neither LY294002 nor wortmannin inhibited the EPO-induced protection in post-MI. Phosphorylation of Janus kinase 2 by EPO was attenuated and phosphorylation of Akt was not detected in post-MI. A guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one, and a mitochondrial ATP-sensitive K(+) channel (mitoK(ATP) channel) blocker, 5-hydroxydecanoate, inhibited EPO-induced protection in both sham and post-MI. Suppressor of cytokine signaling (SOCS)-1 protein level was higher by 50% in post-MI than in sham, although SOCS-3 levels were similar. These findings suggest that postinfarct remodeling disrupts cellular signaling from the EPO receptor to PI3K, presumably by increased SOCS-1. However, in the remodeled myocardium, lack of PI3K/Akt activation by the EPO receptor seems to be compensated by a mechanism upstream of the guanylyl cyclase-mitoK(ATP) channel pathway to achieve EPO-induced protection.

Animals↗
PubMed2005

Strain rate imaging for noninvasive functional quantification of the left atrium: comparative studies in controls and patients with atrial fibrillation.

Strain rate (SR) imaging enables quantitative measurement of left ventricular (LV) function independent of cardiac translation. However, whether SR imaging is applicable for detection of left atrial (LA) dysfunction remains unknown. The purpose of this study was to assess the feasibility of measuring LA function by SR imaging, focusing on the effects of aging and LA dilatation during atrial fibrillation (AF). Echocardiographic evaluation including SR imaging was performed in 50 controls (29 males and 21 females; mean age, 41 +/- 14 years) and in 27 patients with AF (15 males and 12 females; mean age, 62 +/- 12 years; 8 with persistent AF and 19 with paroxysmal AF) from 3 apical views and analyzed off-line. Peak SR was measured at each LA segment (septum, lateral, posterior, anterior, and inferior), and mean peak systolic SR (SR-LAs), early diastolic SR (SR-LAe), and late diastolic SR (SR-LAa) were calculated by averaging the results for each segment. LA dimension, peak mitral and pulmonary velocities at late diastole, LA fractional shortening, and atrial filling fraction were calculated as parameters of LA function. Normal values for mean SR-LAs, SR-LAe, and SR-LAa were 3.4 +/- 1.0 s -1 , -3.9 +/- 1.7 s -1 , and -3.1 +/- 1.0 s -1 , respectively, and they were successfully measured in more than 95% of the LA segments. In controls, both mean SR-LAs and mean SR-LAe correlated with age, LA dimension, and early to late diastolic mitral flow velocity ratio. Conversely, mean SR-LAa did not show significant correlation with age or parameters of LA function. In AF patients, mean SR-LAs was correlated inversely with age. The mean SR-LAs was significantly lower in persistent AF patients than in age-matched controls (1.7 +/- 0.8 vs 2.9 +/- 0.9 s -1 ; P < .01). Based on our findings, we conclude that noninvasive quantification of LA function using SR imaging enables evaluation of LA dysfunction due to aging and LA dilatation.

Adult↗
PubMed2005

Early defibrillation and circulatory support can provide better long-term outcomes through favorable neurological recovery in patients with out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Early defibrillation and cardiopulmonary bypass have been postulated to be a promising intervention against out-of-hospital cardiac arrest (OHCA); however, little is known about the long-term prognosis. The effects of early recovery of circulation (ROC) on neurological recovery and the long-term outcome in patients with OHCA were examined. METHODS AND RESULTS: Functional recovery and long-term (22.0+/-15.3 months) outcome were examined in 100 patients with definite diagnosis of OHCA. Spontaneous circulation recovered in 79% of the patients (using on-site counter shock in 20% of the patients). Cardiopulmonary bypass was performed in 38 of the OHCA patients. The total survival and favorable neurological recovery rates were 40% and 25%, respectively. The patients with favorable recovery obtained early ROC (28.2+/-16.0 min). Receiver-operating characteristic analysis showed that a period of less than 35 min for ROC was the optimal period for achieving a favorable recovery, with sensitivity of 68% and specificity of 73%. The patients with a prior history of heart failure or reduced left ventricular ejection fraction exhibited more frequent, exacerbated heart failure and ventricular arrhythmias. CONCLUSIONS: Early ROC using on-site counter shock or cardiopulmonary bypass might result in better long-term outcome in patients with OHCA of cardiac origin.

Adult↗
PubMed2005

Development and progression of atherosclerotic disease in relation to insulin resistance and hyperinsulinemia.

It is unclear whether the role of insulin resistance in the development of atherosclerotic cardiovascular disease is similar in populations in which the incidence of atherosclerotic diseases significantly differs from that in Western countries. The aim of this study was to determine the relationship between insulin resistance and the development of cardiovascular disease in the Japanese population. We conducted 75 g-oral glucose tolerance tests (OGTTs) on 1,928 inhabitants of two towns in Hokkaido, Japan. Subjects using antihypertensive agents and known diabetic patients were excluded from the study. Data from the remaining 1,227 subjects (540 males and 687 females; mean age 56.0 +/- 10.8 years) were used for the analysis, and 1,051 subjects were seen in a follow-up care setting for a period of 8 years. The presence of insulin resistance was defined according to the guidelines reported our previous study: insulin levels of 64.0 mU/l or higher 2 h after the 75 g-OGTT. The insulin-resistant (IR) group had several risk factors such as hypertension, diabetes, treated or untreated hypercholesterolemia, hypertriglyceridemia, low high-density-lipoprotein (HDL) cholesterol levels, and obesity. During the follow-up period of 8 years, the incidence of coronary artery disease, which was adjusted for age, body mass index, sex, systolic blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and HDL cholesterol was significantly (3.2 times) higher in the IR group than in the insulin non-resistant group. The results suggested that insulin resistance is an independent risk factor for coronary artery disease in Japanese subjects, as has also been demonstrated in the case of individuals in Europe and USA.

Aged↗