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Background: This study evaluated the effect of exercise training on body temperature and clarified the relationship between body temperature and body composition in the elderly. Methods: In this retrospective cohort study, a total of 91 elderly participants performed aerobic and anaerobic exercise training twice a week for 2 years. Non-contact infrared thermometer and bioelectrical impedance analysis were performed at baseline and at 2 years. Results: Mean age of study participants was 81.0 years. The participants were divided into two groups by baseline body temperature of 36.3 &deg, C, lower body temperature group (n = 67) and normal body temperature group (n = 24). Body temperature rose significantly after exercise training in the lower body temperature group (36.04 &plusmn, 0.11 &deg, C to 36.30 &plusmn, 0.13 &deg, C, p &lt, 0.0001), whereas there was no significant difference in the normal body temperature group (36.35 &plusmn, 0.07 &deg, C to 36.36 &plusmn, C, p = 0.39). A positive correlation was observed between the amount of change in body temperature and baseline body temperature (r = &minus, 0.68, p &lt, 0.0001). Increase in skeletal muscle mass was an independent variable related to the rise in body temperature by the multivariate logistic regression analysis (odds ratio: 4.77, 95% confidence interval: 1.29&ndash, 17.70, p = 0.02). Conclusions: Exercise training raised body temperature in the elderly, especially those with lower baseline body temperature.

Visit-to-visit blood pressure variability has been shown to be an independent risk factor for cardiovascular diseases. High visit-to-visit blood pressure variability and endothelial dysfunction are observed in patients with chronic kidney disease. It is therefore assumed that high variability in visit-to-visit blood pressure measurements may be associated with endothelial dysfunction in these patients. The present study investigated the associations between visit-to-visit blood pressure variability and renal and endothelial function in patients with chronic kidney disease. We analyzed 150 consecutive patients with predialysis chronic kidney disease who visited our outpatient clinic from January 2006 to December 2010. The study examined the relationships between variability in visit-to-visit systolic blood pressure levels or mean systolic blood pressure (M SBP) and estimated glomerular filtration rate (eGFR) and flow-mediated dilation, an index of endothelial function. Variability in visit-to-visit systolic blood pressure showed a significant negative association with eGFR, independent of age, hemoglobin A1c, low-density lipoprotein (LDL) cholesterol and uric acid, whereas M SBP did not. Similarly, variability in SBP showed a significant negative association with flow-mediated dilation, independent of age, eGFR, HbA1c, LDL cholesterol and M SBP. These data indicate that variability in visit-to-visit blood pressure measurements is associated with impaired renal and endothelial function in patients with chronic kidney disease. This finding suggests that reducing blood pressure fluctuations might have beneficial effects in patients with chronic kidney disease, although this point needs to be addressed by future studies.

Microfibrils are exracellular matrix components necessary for elastic fiber assembly and for suspending lenses. We previously reported that latent TGF-β binding protein 2 (LTBP-2), a microfibril-associated protein, is required for forming stable microfibril bundles in ciliary zonules. However, it was not understood why Ltbp2 null mice only showed an eye-specific phenotype, whereas LTBP-2 is abundantly expressed in other tissues containing microfibrils in wild type mice. Here, we show that LTBP-4, another microfibril-associated protein, compensates for the loss of LTBP-2 in microfibril formation. Ltbp2/4S double knockout (DKO) mice showed increased lethality due to emphysema, which was much more severe than that found in Ltbp4S null mice. Elastic fibers in the lungs of Ltbp2/4S DKO mice were severely disorganized and fragmented. Cultured mouse embryonic fibroblasts (MEFs) from Ltbp2/4S DKO embryos developed reduced microfibril meshwork in serum-free conditions, whereas the microfibril formation was restored by the addition of either recombinant LTBP-2 or -4. Finally, ectopic expression of LTBP-4 in the whole body restored ciliary zonule microfibril bundles in the eyes of Ltbp2 null mice. These data suggest that LTBP-2 and -4 have critical overlapping functions in forming the robust structure of microfibrils in vitro and in vivo.

Background:The safety of exercise-based cardiac rehabilitation (CR) has not been investigated in Japan, so a nationwide survey was conducted to investigate the incidence of adverse events (AEs) associated with CR and exercise testing.Methods and Results:In total, 136 hospitals reported operating recovery-phase CR programs, amounting to 383,096 patient-hours of exercise training. The incidence rates of all AEs and life-threatening AEs (LAE: death, cardiac arrest, acute myocardial infarction, cardiac rupture) during exercise sessions were 12 and 1 event/383,096 patient-hours (3.13 and 0.26 events/100,000patient-hours), respectively. When CR programs were categorized as “Formal” in which an exercise prescription based on exercise testing was issued to individual patients or “Non-formal” without exercise prescription, the incidence of AEs during and within the 24 h after an exercise session was significantly lower in the Formal than the Non-formal CR programs (P

OBJECTIVE Dyslipidemia is a risk factor for not only cardiovascular diseases (CVD), but also chronic kidney disease (CKD). Ezetimibe, a cholesterol absorption inhibitor, lowers cholesterol levels by inhibiting both extrinsic and intrinsic cholesterol absorption via the gastrointestinal duct. However, very few studies have examined its efficacy and safety for patients with dyslipidemia complicated with CKD. METHODS Thirty-seven dyslipidemic patients (low density lipoprotein cholesterol (LDL-C) levels ≥120 mg/dL) complicated with CKD were given ezetimibe (10 mg/day) for twenty-four weeks. The efficacy and safety of the therapy, including the anti-atherosclerotic and renal protective effects, were then examined. RESULTS Significant decreases were observed in the levels of LDL-C (158.9 ± 26.9 mg/dL→123.0 ± 31.8 mg/dL; p

Background Myocardial injury during elective percutaneous coronary intervention (PCI) is associated with higher subsequent cardiac events and mortality. β-Blockers have been used to reduce myocardial injury during ischemia and reperfusion. We investigated whether intracoronary followed by intravenous administration of the short-acting β-blocker landiolol prevents myocardial injury in the face of elective PCI. Methods and results Patients undergoing elective PCI (n=70) were randomly assigned to the landiolol (n=35) or control (n=35) group. Landiolol or saline was administered into target vessels through a balloon catheter for 1min before and after first balloon inflation followed by continuous intravenous administration for 6h after PCI. The incidence of myocardial injury defined by cardiac troponin-I (cTnI) ≧0.05ng/ml was 79% of the patients in the control group compared to 56% in the landiolol group (p=0.04). The cTnI level at 24h after PCI tended to be lower in the landiolol group (0.57±1.14 versus 1.27±2.48ng/ml; p=0.07), while the CK-MB level was not significantly different between the landiolol and control groups. The incidence of peri-procedural myocardial infarction defined by cTnI ≧0.12ng/ml was significantly (p=0.02) lower in the landiolol group (41%) compared to the control group (70%). There was no incidence of coronary spasm, hypotension, bradycardia or heart failure during and after PCI in the two groups. Conclusions Brief intracoronary followed by continuous intravenous administration of landiolol is safe and effective for myocardial protection in the face of elective PCI.

Summary Background Both obesity and left ventricular (LV) diastolic dysfunction are associated with an increased risk of cardiovascular morbidity and mortality. There is a paucity of data as to whether obesity is independently associated with LV diastolic dysfunction. Methods Adult patients with sinus rhythm referred for a transthoracic echocardiography between July, 2007, and December, 2007, were prospectively included. Exclusion criteria were patient who had a history of congenital or valvular heart disease, treatment with pacemaker implantation or implantable cardioverter defibrillator, myocardial infarction, or impaired LV systolic function. Diastolic function was classified by an algorithm incorporating data from mitral and pulmonary venous flow indices, and Doppler tissue imaging. Body mass index (BMI) was evaluated as a categorical variable (normal weight 2 ; overweight 25.0 to 2 ; and obese ≥30kg/m 2 ). Logistic models were used to assess the risk of abnormal LV diastolic function associated with BMI categories. Results Of a total number of 692 patients who met all study criteria (mean 59±15year-old; 50% women, 48% hypertension, 16% diabetes, 26% overweight, 8% obese), 538 (78%) had abnormal LV diastolic function. In multivariate analyses adjusting for age, sex, and cardiovascular risk factors, obesity was independently associated with LV diastolic dysfunction (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.12–7.88; P =0.03) compared to normal weight. LV mass did not weaken this association (OR: 2.88, 95% CI: 1.08–7.68; P =0.04). Overweight was not independently associated with LV diastolic dysfunction. Conclusion Obesity was associated with LV diastolic dysfunction independent of cardiovascular risk factors and LV mass.

Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 μg/dL to 12.2 ± 7.1 μg/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

Background: Patients with a normal stress image on technetium-99m (Tc-99m) single-photon emission computed tomography (SPECT) have a good prognosis for diagnosing coronary artery disease. However, current guidelines recommend stress and rest imaging to confirm that a stress image is normal. Methods and Results: We determined all-cause of cardiac events (acute coronary syndrome and sudden death) in 1,939 patients undergoing stress myocardial perfusion SPECT with Tc-99m radiotracers. Patients with an abnormal stress image were excluded, so we focused on 1,125 patients in whom the stress SPECT study was interpreted as normal. A stress-only protocol was used in 726 patients (adenosine=339; exercise=387), whereas 399 had both stress and rest imaging (adenosine=294; exercise=105). Mean follow-up was 1,252 days. At the end of follow-up, there were 39 cardiac events in the stress-only cohort and 19 in the stress-rest cohort. Kaplan-Meier analysis revealed that there were no differences for the entire cohort of cardiac events not only between the stress-only and stress-rest protocols but also for stressor modality, despite the fact that the stress-rest cohort showed higher coronary risk factors. Conclusions: Patients determined as having a normal SPECT on the basis of stress imaging alone have a similar cardiac event rate as those who have a normal SPECT on the basis of evaluation of both stress and rest images. This imaging strategy will significantly reduce radiation exposure in a substantial number of patients. (Circ J 2012; 76: 2386–2391)

Background Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. Methods and results We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. Conclusion Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

Uncoupling of nitric oxide synthase (NOS) has been implicated in left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). We hypothesized that inducible NOS (iNOS) plays a crucial role in LV remodeling after MI, depending on its coupling status. MI was created in wild-type, iNOS-knockout (iNOS−/−), endothelial NOS-knockout (eNOS−/−), and neuronal NOS-knockout (nNOS−/−) mice. iNOS and nNOS expressions were increased after MI associated with an increase in nitrotyrosine formation. The area of myocardial fibrosis and LV end-diastolic volume and ejection fraction were more deteriorated in eNOS−/− mice compared with other genotypes of mice 4 wk after MI. The expression of GTP cyclohydrolase was reduced, and tetrahydrobiopterin (BH4) was depleted in the heart after MI. Oral administration of sepiapterin after MI increased dihydrobiopterin (BH2), BH4, and BH4-to-BH2 ratio in the infarcted but not sham-operated heart. The increase in BH4-to-BH2 ratio was associated with inhibition of nitrotyrosine formation and an increase in nitrite plus nitrate. However, this inhibition of NOS uncoupling was blunted in iNOS−/− mice. Sepiapterin increased capillary density and prevented LV remodeling and dysfunction after MI in wild-type, eNOS−/−, and nNOS−/− but not iNOS−/− mice. Nω-nitro-l-arginine methyl ester abrogated sepiapterin-induced increase in nitrite plus nitrate and angiogenesis and blocked the beneficial effects of sepiapterin on LV remodeling and function. These results suggest that sepiapterin enhances angiogenesis and functional recovery after MI by activating the salvage pathway for BH4 synthesis and increasing bioavailable nitric oxide predominantly derived from iNOS.

A 42-year-old man was referred to our hospital for an electrophysiologic study because of recurrent episodes of palpitation. On coronary angiogram, an anomalous atresia of the coronary sinus (CS) ostium was discovered. The ablation catheter was inserted from the right femoral artery to the accessory pathway (AP) of posterior paraseptal area. The earliest retrograde atrial activation was recorded in the 5-6 o'clock region of the mitral annulus. Radiofrequency energy was delivered to this site, resulting in elimination of the AP. After this application, there was persistent ventriculoatrial dissociation and led to successful ablation of the AP.

BACKGROUND For patients with acute myocardial infarction (AMI), several studies have examined the relationship between the metabolic syndrome and prognostic outcome. However, few studies have revealed an association between the metabolic syndrome and clinical outcomes in patients with unstable angina (UA). This study compared the differences in the usefulness of recognizing metabolic disorders for the prediction of a 1-year prognosis in patients with UA and AMI. METHODS The study cohort consisted of 1173 patients with a mean age of 67 years. The focus was on general prognostic factors and five metabolic disorders (body mass index; hypertension; blood glucose/diabetes mellitus; and, serum concentrations of triglycerides and high-density lipoprotein cholesterol) at the time of admission. RESULTS According to multivariate logistic regression analysis, metabolic scores on admission positively related to 1-year mortality or major adverse cardiovascular events (MACE) for patients with UA, but not for those with AMI, with an increase in either all-causes mortality or MACE being associated with the degree of metabolic dysfunction. No other general prognostic factors were related to either 1-year mortality or MACE in patients with UA. By contrast, general prognostic factors such as age and the Killip classification had a positive effect on 1-year mortality or on MACE for the patients with AMI. CONCLUSION Accumulation of the effects of each metabolic disorder may affect mortality and MACE for patients with UA.

Oxidative stress may cause a loss of tetrahydrobiopterin (BH4), a co-factor of nitric oxide synthase (NOS), decrease the bioavailability of NO and aggravate ischemia/reperfusion (I/R) injury in diabetic heart. We hypothesized that ascorbic acid (AA) and N-acetyl cysteine (NAC) protect the diabetic heart from I/R injury by increasing BH4/dihydrobiopterin (BH2) ratio and inhibiting uncoupling of NOS. Diabetes mellitus was induced in rats by streptozotocin treatment, and the hearts were isolated and perfused. BH4 and BH4/BH2 ratio decreased in the diabetic heart associated with increased production of superoxide and nitrotyrosine (NT). Treatment with AA or NAC significantly increased BH4/BH2 ratio in the diabetic heart associated with decreased production of superoxide and NT and increased generation of nitrate plus nitrite (NOx). Pre-treatment with AA or NAC before 30 min ischemia followed by 120 min reperfusion improved left ventricular (LV) function and reduced infarct size in the diabetic but not non-diabetic hearts. The NOS inhibitor, L-NAME, inhibited the increase in the generation of superoxide, NT and NOx, but aggravated LV function and increased infarct size in the diabetic heart. L-NAME also abrogated the increase in NOx and improvement of LV function and the infarct size-limiting effect induced by AA or NAC in the diabetic heart. These results suggest that AA and NAC increase BH4/BH2 ratio and prevent NOS uncoupling in the diabetic heart. Resultant increase in the bioavailability of NO renders the diabetic heart toleratant to I/R injury.

1. Uncoupling of nitric oxide synthase (NOS) has been implicated in the pathogenesis of left ventricular (LV) dysfunction in diabetes mellitus. In the present study, we investigated the role of NOS uncoupling in oxidative/nitrosative stress and LV dysfunction in the diabetic mouse heart. 2. Diabetes was induced in wild-type (WT), endothelial (e) NOS knockout (eNOS(-/-)), inducible (i) NOS knockout (iNOS(-/-)) and neuronal (n) NOS knockout (nNOS(-/-)) mice by streptozotocin (STZ) treatment. 3. In the diabetic heart, iNOS, but not eNOS or nNOS, expression was increased. Levels of malondialdehyde (MDA), 4-hydroxy-noneal (HNE) and nitrotyrosine (NT), as markers of oxidative/nitrosative stress, were increased in the diabetic mouse heart, but the increase in oxidative/nitrosative stress was significantly repressed in the iNOS(-/-) diabetic mouse heart. Levels of nitrite and nitrate (NO(x)), as an index of nitric oxide, bioavailability were significantly decreased in the iNOS(-/-) diabetic mouse heart. 4. Oral administration of sepiapterin (10 mg/kg per day), a precursor of tetrahydrobiopterin (BH(4)), significantly increased BH(4) and the BH(4)/BH(2) ratio in diabetic mouse heart. Similarly, sepiapterin inhibited the formation of HNE, MDA and NT in diabetic hearts from all three genotypes, but the increase in NO(x) following sepiapterin treatment was significantly attenuated in the iNOS(-/-) diabetic mouse heart. Percentage fractional shortening (FS), evaluated by echocardiography, decreased significantly in all genotypes of diabetic mice. Sepiapterin significantly increased percentage FS in diabetic mice, except in iNOS(-/-) mice. 5. These results suggest that sepiapterin inhibits uncoupling of NOS and improves LV function presumably by increasing iNOS-derived nitric oxide in the diabetic heart.

Left atrial (LA) enlargement has been acknowledged as a significant predictor of cardiovascular morbidity and mortality.To evaluate the accuracy of two-dimensional and three-dimensional echocardiography for determining LA volume, LA volume measurements by echocardiography were compared with those measured by 64-slice multidetector computed tomography (MDCT) as a reference standard.Fifty-seven consecutive patients (mean age, 66 ± 11 years; 59% men) referred to echocardiography and MDCT on the same day were prospectively evaluated. LA volume by three-dimensional echocardiography was correlated closely with that by MDCT (r = 0.95, P.0001), with 8% underestimation. LA volume by two-dimensional echocardiography was correlated less well with that measured by MDCT (r = 0.86, P.0001) and consistently underestimated LA volume by 19%, particularly as the left atrium enlarged.LA volume assessment by three-dimensional echocardiography was correlated closely with that measured by MDCT, albeit with an 8% underestimation. Three-dimensional echocardiography is a feasible noninvasive method to evaluate LA volume.

Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality rates. Although a previous study reported that pretreatment with sodium bicarbonate is more effective than sodium chloride for prophylaxis of CIN, this has not been a universal finding. We performed a prospective randomized trial to investigate whether CIN can be avoided using sodium bicarbonate. In total 155 patients with a glomerular filtration rate (GFR)

Background Bone marrow-derived cells (BMCs) are critically involved in inflammation and regeneration after myocardial infarction (MI). However, the participation of BMCs in the reconstruction of infarcted myocardium remains unclear. In this study, we investigated phenotypic modulation of BMCs and their turnover in the heart following MI. Methods and results MI was produced in rats with intra-bone marrow-bone marrow transplantation from the syngenic rats expressing green fluorescence protein (GFP). The number of GFP-positive BMCs recruited to the infarcted myocardium peaked at 3 days after MI, and the majority of BMCs recruited to the heart after MI underwent turnover within 2 weeks. This turnover rate was unchanged for up to 16 weeks after MI, although the number of BMCs recruited to the infarcted myocardium rapidly decreased between 2 and 8 weeks after MI. A small number of BMCs recruited to the heart were positive for CD31 and α-smooth muscle actin, and the majority of these were positive for Vimentin at 3 days and 4 weeks after MI. None of BMCs expressed α-actinin or von Willebrand factor 4 weeks after MI. Conclusions These results suggest that BMCs recruited to the heart underwent phenotypic modulation to a fibroblastic cell type and turnover within 2 weeks after MI without differentiating into cardiomyocytes or endothelial cells, and that although the number of BMCs in the infarcted myocardium decreased over time, the rate of turnover remained relatively constant during the chronic phase of MI.

The diabetic heart is known to be susceptible to ischemia/reperfusion (I/R) injury by increased oxidative stress. Although oxidative stress upregulates inducible nitric oxide (iNOS), the role of iNOS in I/R injury in the diabetic heart has been poorly understood. Because iNOS-derived nitric oxide (NO) plays a crucial role in cardioprotection against I/R injury, we hypothesized that inhibition of iNOS uncoupling would restore tolerance to I/R injury in the diabetic heart. The present study demonstrated that iNOS-derived superoxide generation was reduced, and that the NO bioavailability was increased, by treatment with the NOS-cofactor, tetrahydrobiopterin (BH4), before I/R in the hearts isolated from diabetic rats. This was associated with a reduction of infarct size and improvement of left ventricular (LV) function after I/R. The cardioprotective effect of BH4 was abrogated by treatment with a thiol reducing agent dithiothreitol (DTT), but not a NO-sensitive guanylyl cyclase inhibitor ODQ, suggesting that iNOS-derived NO-mediated cardioprotection occurs through protein S-nitrosylation but not cGMP-dependent signaling in the diabetic heart. Indeed, protein S-nitrosylation was increased by treatment with BH4 in the diabetic heart and was inhibited by DTT. These results suggest that the inhibition of iNOS uncoupling unmasks tolerance to I/R injury through enhanced protein S-nitrosylation in the diabetic rat heart.

Background Although β-blockers are used to prevent myocardial ischemia/reperfusion injury, the risk of heart failure has limited β-blocker therapy in patients with acute myocardial infarction. This study evaluated efficacy of intracoronary administration of the short-acting β-blocker, landiolol, during reperfusion in pigs with acute myocardial ischemia. Methods and results In the non-ischemic model landiolol administered into the left anterior descending coronary artery (LAD) inhibited in a dose-dependent fashion segmental wall thickening (SWT) in the anterior LV wall without altering SWT in the posterior LV wall and without prolonged depression of global LV function except for the highest dose. In the ischemic model with 60min LAD occlusion followed by reperfusion the medium dose landiolol administered into the LAD 1min before and for 10min during reperfusion inhibited initial recovery of SWT in the anterior LV wall but improved SWT in this region and global LV function late after reperfusion. Ultrastructural studies showed inhibition of sub-sarcolemmal bleb formation by treatment with landiolol 10min after reperfusion associated with the inhibition of CK–MB release and the reduction of infarct size. There was no significant difference in CK–MB release and infarct size between landiolol treatment for 10min and 180min during reperfusion. Conclusions Selective and brief intracoronary administration of landiolol during reperfusion enhances myocardial salvage without causing deterioration of global LV function.

Objective3,5,3′-triiodothyronine-predominant Graves' disease (T3-P-GD) is characterized by a persistently high serum T3 level and normal or even lower serum thyroxine (T4) level during antithyroid drug therapy. The source of this high serum T3 level has not been clarified. Our objective was to evaluate the contribution of type 1 and type 2 iodothyronine deiodinase (D1 (or DIO1) and D2 (or DIO2) respectively) in the thyroid gland to the high serum T3 level in T3-P-GD.MethodsWe measured the activity and mRNA level of both D1 and D2 in the thyroid tissues of patients with T3-P-GD (n=13) and common-type GD (CT-GD) (n=18) who had been treated with methimazole up until thyroidectomy.ResultsThyroidal D1 activity in patients with T3-P-GD (492.7±201.3 pmol/mg prot per h) was significantly higher (P3-P-GD (823.9±596.4 fmol/mg prot per h) was markedly higher (P3-P-GD and CT-GD and the serum FT3-to-FT4 ratio (r=0.370, P3-to-FT4 ratio (r=0.676, PConclusionsOur results suggest that the increment of thyroidal deiodinase activity, namely D1 and especially D2 activities, may be responsible for the higher serum FT3-to-FT4 ratio in T3-P-GD.

A patient without any known congenital cardiac abnormalities who suffered from ventricular tachycardia was taken to the emergency room following successful resuscitation. Transthoracic echocardiography showed diffuse left ventricle dysfunction and mild aortic regurgitation. Coronary angiography demonstrated intact coronary and suspected morphological abnormalities of the aortic valve. In addition, transesophageal echocardiography revealed a rare quadricuspid aortic valve malformation. After controlling ventricular tachycardia and congestive heart failure with optimal medical therapy, the patient had an uneventful course and was subsequently discharged 3 weeks after admission. To our knowledge, this is the first report of quadricuspid aortic valve associated with idiopathic dilated cardiomyopathy.

Hemodialysis techniques have improved remarkably in recent decades and the number of long-term survivors among patients with end-stage renal disease has increased. The mortality rate of hemodialysis patients has been reported to be low in Japan. However, the long-term survival rate of dialysis patients is still low: 23.6% for 15 years and 17.4% for 20 years, even in Japan, and background information on patients undergoing hemodialysis therapy for more than 20 years is scarce in this country. In the present study, we investigated the characteristics of 20-year survivors undergoing maintenance hemodialysis at our medical center. We compared the characteristics of hemodialysis patients who had survived for more than 20 years after the initiation of hemodialysis with those of patients who started hemodialysis at the same time and had already died. No patient among those who were still alive had diabetes mellitus while 15% of patients who had died had diabetes mellitus at the time of initiation of hemodialysis. Age, cardiothoracic ratio, and serum levels of total cholesterol and triglyceride 6 months after the initiation of hemodialysis, as well as decreases in body weight per year were significantly lower in those who had survived than in those who had died. These results suggest that long-term hemodialysis survivors are characterized by (i) initiation of hemodialysis at a young age (ii) being free of diabetes mellitus (iii) a well-controlled cardiothoracic ratio (iv) small successive change in body weight, and (v) being free of hypercholesterolemia and hypertriglyceridemia.

Rigid control of blood pressure (BP) is essential to prevent cardiovascular disease. However, only about 40% of hypertensive patients undergoing pharmacological intervention with a single agent achieve their BP goals in contemporary clinical practice. Combined therapy using currently available agents is effective in maximizing treatment outcome, although it raises medical costs and decreases the drug compliance rate. To overcome such negative consequences, a combination tablet containing an angiotensin II receptor blocker (ARB) with a small dose of hydrochlorothiazide (HCTZ) is now available on the international market, including Japan. This article briefly describes the unique properties of telmisartan, a highly selective ARB for the angiotensin II type 1 receptor, including its long-acting characteristics and recent prospective multicenter randomized clinical trials, followed by a description of a newly-introduced combination tablet in Japan, which contains telmisartan and HCTZ. This article also reviews its safety and efficacy based on currently available evidence. Finally, evidence comparing telmisartan/HCTZ with other combination therapies is presented.

SummaryBackgroundContrast-induced nephropathy (CIN) is known to increase morbidity and mortality of cardiovascular disease. Recent studies have shown statins prevented CIN after contrast media exposure, but optimal statin type and dosage are still unknown.PurposeThe aims of the present study were to evaluate whether chronic pravastatin treatment before scheduled coronary angiography or percutaneous coronary intervention could reduce the incidence of CIN and to elucidate the factors related to CIN in patients with renal insufficiency.MethodsWe studied 431 consecutive patients with renal insufficiency. One hundred ninety-four patients were receiving pravastatin treatment as standard chronic treatment of hypercholesterolemia. Serum creatinine levels were measured at baseline (pre-procedure) and within 48h after contrast media exposure (peak post-procedure). CIN was defined as an increase in the serum creatinine values of ≥25% or ≥0.5mg/dl after contrast media exposure. Logistic regression analysis was performed to evaluate the important factors related to CIN using four variables: age, pravastatin, pre-procedure serum creatinine, and contrast volume.ResultsCIN was observed in 36 patients (8.4%). Patients without pravastatin (p

The effects of statins on platelet activation markers, chemokines and adiponectin, were investigated in 135 patients with hyperlipidemia. Of the 135 hyperlipidemic patients, 63 were allocated to the simvastatin group, treated with simvastatin at the dose of 10 mg daily, and the remaining 72 were allocated to the pitavastatin group, treated with pitavastatin at the dose of 2 mg daily. Plasma levels of platelet-derived microparticles (PDMP), cell adhesion molecules (sCD40L and sP-selectin), chemokines [monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normally T-cell expressed and secreted] and adiponectin were measured at the baseline and after 6 months of treatment in both the groups. In addition, we carried out a basic study to investigate the MCP-1-dependent induction of tissue factor expression on a histiocytic cell line (U937 cells). The plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 were higher, whereas those of adiponectin were lower, in the hyperlipidemic patients than in the normolipidemic controls. Plasma PDMP and sCD40L were positively correlated, whereas plasma adiponectin was negatively correlated, with the plasma levels of MCP-1. No significant differences in the plasma levels of PDMP, sCD40L, sP-selectin, regulated on activation normally T-cell expressed and secreted and MCP-1 measured before and after treatment were observed in either the simvastatin or pitavastatin group. A significant increase of the plasma adiponectin levels was observed after 6 months of treatment with pitavastatin but not after an equal duration of treatment with simvastatin. When pitavastatin-treated patients were divided into two groups according to the adiponectin response to pitavastatin treatment, significant decreases of the plasma MCP-1, PDMP and sCD40L levels were observed after pitavastatin treatment in the responder group. In the aforementioned basic study, MCP-1 by itself did not induce the expression of tissue factor on the U937 cells. However, the recombinant sCD40L-induced expression of tissue factor on U937 was enhanced by the addition of MCP-1. These findings suggest that PDMP, sCD40L and MCP-1 may participate in the development of atherothrombosis in patients with hyperlipidemia and that pitavastatin may exert an adiponectin-dependent antiatherothrombotic effect in hyperlipidemic patients.

We analyzed the association between platelet activation, adiponectin, insulin resistance and oxidative stress in aging. In addition, we included American football (AB) players to investigate whether this association is modulated by exercise. Eighty-six old age patients (or = 65 years old) hospitalized at the nursing institution and 62 AB players were recruited as study subjects. Reactive oxygen metabolites (ROM), soluble CD40 ligand (sCD40L) and adiponectin were estimated with these patients. In comparison to old age, plasma adiponectin levels in AB players were significantly low. In addition, the adiponectin values of elder group (80 years) in old age were significantly increased higher than those for younger group (or = 80 years). There were no differences of sCD40L in two groups. Levels of ROM in AB players were also significantly lower than that in old age. However, the ROM values of younger group in old age were significantly increased higher than those for elder group. The sCD40L also exhibited the same results. There were no significant differences in ROM and adiponectin levels between the high homeostasis model assessment-insulin resistance (HOMA-IR) (2.0) and the low HOMA-IR (or = 2.0). In contrast, in the old age, the sCD40L and ROM levels in the high HOMA-IR group were significantly higher than those in the low HOMA-IR group. In addition, the adiponectin level in the high HOMA-IR group was significantly lower than that in the low HOMA-IR group. Our results suggest that platelet activation, adiponectin and oxidative stress are the very important factors for aging, and the maintenance of exercise could prevent the occurrence of metabolic syndrome or insulin resistance.

The amount of myocardial salvage after percutaneous coronary intervention (PCI) is reported to be a major determinant of functional recovery in patients with ST-elevation acute myocardial infarction (MI). However, factors related to the amount of myocardial salvage remain unknown. The goal of this study was to investigate the factors related to the amount of myocardial salvage after emergent PCI in patients with ST-elevation acute MI by incorporating pre- and post-treatment indices and adjunctive treatments.Technetium-99m myocardial imaging was performed before, immediately after, and one month after emergent PCI in 161 patients with ST-elevation acute MI, and the defect score was serially evaluated. A good myocardial salvage was defined as/=4 change (before minus immediately after PCI) of the defect score.Good myocardial salvage was observed in 89 patients. Based on nine clinical variables, logistic regression analysis was performed to determine the important variables related to myocardial salvage. Multivariate analysis revealed that earlier time from onset to PCI (chi (2) = 6.55, P = 0.01, odds ratio = 2.78), larger defect score before PCI (chi (2) = 7.29, P = 0.01, odds ratio = 1.13) and administration of nicorandil before PCI (chi (2) = 9.88, P = 0.008, odds ratio = 4.42) were independently associated with good myocardial salvage. Thrombolysis In Myocardial Infarction (TIMI) flow grade2 before PCI (chi (2) = 4.91, P = 0.03, odds ratio = 0.36) and TIMI flow grade/=2 after PCI (chi (2) = 4.82, P = 0.03, odds ratio = 0.31) were independently associated with poor myocardial salvage. In contrast, the number of asynergic segments before PCI, infarct-related artery, adequate collaterals before PCI and stent implantation were not determinants of myocardial salvage.This study demonstrated that patients with a greater improvement of (99m)Tc tetrofosmin myocardial uptake immediately after PCI had better recovery of left ventricular function and smaller final infarct size. Reperfusion time and TIMI flow grade/=2 after PCI were important determinants of myocardial salvage, and nicorandil was a major determinant of myocardial salvage.

The prevalence of peripheral arterial occlusive disease is high in patients with terminal renal failure, and it is a major problem in those on dialysis. A low ankle–brachial index (ABI) suggests the presence of arterial stenotic lesions between the aorta and the ankle joint, while a low toe–brachial index (TBI) suggests stenotic lesions between the aorta and the toes. Therefore, a normal ABI (≥0.9) and a low TBI (

Sympathetic nerve overactivity and reduced exercise tolerance are characteristic features of patients with heart failure. However, to what extent sympathetic nerve overactivity contributes to limiting exercise tolerance has not been clearly defined. Myocardial iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy, muscle sympathetic nerve activity (MSNA), and cardiopulmonary exercise testing were performed within 3 days in 30 patients with left ventricular dysfunction (LVD). Cardiac sympathetic nerve activity was estimated using H/M ratio and washout rate (WR) of 123I-MIBG imaging. MSNA was recorded by microneurography. The patients with peak VO2

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 +/- 34.2 vs. 53.3 +/- 56.7 U/ml, P0.05: sP-selectin; 134 +/- 52 vs. 235 +/- 70 ng/dl, P0.01: sL-selectin; 569 +/- 183 vs. 805 +/- 146 ng/ml, P0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 +/- 1.23 vs. 5.87 +/- 1.92 microg/ml, P0.05; diabetes versus controls, 2.81 +/- 0.95 vs. 6.13 +/- 1.24 microg/ml, P0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.

症例は67歳，男性．既往歴として，閉塞性動脈硬化症に対して2003年6月に，Aorto-bifemoral bypassを受けた．また腹部大動脈人工血管に仮性動脈瘤を生じ，人工血管置換術，ステントグラフト挿入術を受けていた．その後腎機能低下のため2006年3月に，血液透析が開始となった．2006年11月20日右大腿部の疼痛および腫脹を認めたため当科に入院した．CTにて右大腿部の血腫，血管造影にて右大腿回旋動脈瘤破裂によると思われる出血点が2箇所にみられたため同部位に塞栓術を施行された．第37病日には，人工血管仮性動脈瘤破裂をきたしたが，破裂部の閉鎖術に成功した．透析患者は，動脈硬化性疾患の発症のリスクが高く，透析患者が下肢痛や腫脹を認めた場合には，本症例のような下肢動脈瘤破裂も鑑別疾患の1つとして考慮すべきであると考えられた．

Platelet-derived microparticles (PDMP) play an important role in the pathogenesis of diabetic vasculopathy, and statins or eicosapentaenoic acid (EPA) have been shown to have a beneficial effect on atherosclerosis in hyperlipidemic patients. However, the influence of EPA and statins on PDMP and adiponectin in atherosclerosis is poorly understood. We investigated the effect of pitavastatin and EPA on circulating levels of PDMP and adiponectin in hyperlipidemic patients with type II diabetes. A total of 191 hyperlipidemic patients with type II diabetes were divided into three groups: group A received pitavastatin 2 mg once daily (n = 64), group B received EPA 1800 mg daily (n = 55) and group C received both drugs (n = 72). PDMP and adiponectin were measured by ELISA at baseline and after 3 and 6 months of drug treatment. Thirty normolipidemic patients were recruited as healthy controls. PDMP levels prior to treatment in hyperlipidemic patients with diabetes were higher than levels in healthy controls (10.4 +/- 1.9 vs. 3.1 +/- 0.4 U/ml, p < 0.0001), and adiponectin levels were lower than controls (3.20 +/- 0.49 vs. 5.98 +/- 0.42 microg/ml, p < 0.0001). PDMP decreased significantly in group B (before vs. 6M, 10.6 +/- 2.0 vs. 8.0 +/- 1.7 U/ml, p < 0.01), but not in group A (before vs. 6M, 9.4 +/- 1.9 vs. 9.6 +/- 1.7 U/ml, not significant). In contrast, group A exhibited a significant increase in adiponectin levels after treatment (before vs. 6M, 3.29 +/- 0.51 vs. 4.16 +/- 0.60 microg/ml, p < 0.001). Furthermore, group C exhibited significant improvement in both PDMP and adiponectin levels after treatment (PDMP, before vs. 6M, 11.2 +/- 2.0 vs. 4.5 +/- 2.7 U/ml, p < 0.001; adiponectin, before vs. 6M, 3.24 +/- 0.41 vs. 4.02 +/- 0.70 microg/ml, p < 0.001). Reductions of PDMP in combined therapy were significantly greater than those observed with EPA alone (p < 0.05 by ANOVA). In addition, soluble CD40 ligand exhibited almost the same change as PDMP in all therapy groups. These results suggest that pitavastatin possesses an adiponectin-dependent antiatherosclerotic effect, and this drug is able to enhance the anti-platelet effect of EPA. The combination therapy of pitavastatin and EPA may be beneficial for the prevention of vascular complication in hyperlipidemic patients with type II diabetes.

Background - Although brachial-ankle pulse wave velocity is a widely used index of arterial stiffness, there are several limitations of this method. The actual length of an artery used for measuring pulse wave velocity is estimated based on an anatomical correction value, and brachial-ankle pulse wave velocity is directly affected by systemic blood pressure or vascular occlusion. Thus, the aim of this study was to determine whether aortic wall strain rate as measured by tissue Doppler imaging is a more useful modality for evaluating regional arterial stiffness than brachial-ankle pulse wave velocity. Methods - Seventy-two patients (18 to 78 years) with normal cardiac function and without large vessel complications were enrolled in this study. Results - A significant positive correlation was found between brachial-ankle pulse wave velocity and age, and brachial-ankle pulse wave velocity increased with age (r = 0.64, P < 0.0001).A significant negative correlation was found between strain rate and age, and strain rate decreased with age (r = -0.44, P< 0.05). A significant correlation was also found between brachial-ankle pulse wave velocity and systolic blood pressure (r = 0.45, P< 0.02), but not between strain rate and systolic blood pressure. There was no significant difference in brachial-ankle pulse wave velocity between hyperlipidaemic and normolipidaemic subjects. However, strain rate was lower in hyperlipidaemic than in normolipidaemic subjects (P < 0.05). Conclusion - Strain rate on the ascending aortic wall is a novel and more accurate index of regional arterial stiffness than brachial-ankle pulse wave velocity.

The aim of this study was to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Seventy-five hyperlipidemic patients with and without type 2 diabetes were enrolled to receive pitavastatin 2 mg daily. Cell adhesion molecules (sCD40L, sP-selectin, sE-selectin, and sL-selectin), chemokines (MCP-1 and RANTES) and adiponectin were measured at baseline and after 3 and 6 months of pitavastatin treatment. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the LDL-cholesterol (LDL-C) decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with type 2 diabetes exhibited a significant increase in adiponectin levels after pitavastatin treatment (before vs. 3 months, 6 months, 2.81+/-0.95 vs. 3.84+/-0.84 microg/ml (p

Backgrounds Nicorandil exerts beneficial effects as an adjunctive therapy for patients with ischemic heart disease. This study was designed to assess the effects of nicorandil on the myocardial protective benefits of elective percutaneous coronary intervention (PCI). Methods We randomly divided 49 patients scheduled to undergo elective PCI into two groups, nicorandil and control. Before PCI, the former received an intravenous bolus injection of nicorandil (4 mg), followed by continuous infusion at 6 mg/h for 24 h after intervention. Oral administration of nicorandil was continued until follow-up coronary angiography (CAG). Serial venous blood samples, for measurement of creatine kinase (CK), creatine kinase MB isoform (CK-MB), troponin I (TnI) and myoglobin, were obtained before PCI, and at 0 h, 4 h, 24 h and 48 h after PCI. Left ventricular function and left ventricular wall motion were evaluated by means of contrast ventriculography before PCI and follow-up CAG. Results At 24 h after PCI, elevations of cardiac enzymes were significantly suppressed in the nicorandil as compared to the control group; CK (78.1±34.9 versus 117.4±137.9 U/l, P =0.0141), CK-MB (1.57±1.90 versus 2.67±4.50 U/l, P =0.0485) and TnI (0.37±0.55 versus 0.86±1.65 ng/ml, P =0.0101). Regional left ventricular wall motion was significantly improved at follow-up in the nicorandil as compared to the control group. Conclusions Nicorandil suppressed elevations of cardiac enzymes after elective PCI and left ventricular wall motion was also significantly improved at follow-up, suggesting that nicorandil enhances the myocardial protective effect of PCI against angioplasty-related myocardial injury.

The combination of angiotensin I-converting enzyme inhibitors and angiotensin receptor blockers has been shown to be more effective than the individual drugs alone in the treatment of chronic kidney disease and chronic heart failure. In the present study, we evaluated the effect of treatment with the calcium channel blocker amlodipine or the angiotensin I-converting enzyme inhibitor perindopril on vascular endothelial function and arteriosclerosis in patients with essential hypertension who had already been receiving angiotensin receptor blocker monotherapy. Thirty-two patients with essential hypertension treated with angiotensin receptor blocker monotherapy were randomized to receive 5 mg of amlodipine (n=16) or 4 mg of perindopril (n=16) once daily in the morning for 24 weeks. The patients were evaluated before and after therapy to assess changes in blood pressure, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arteriosclerosis). Before treatment, there were no significant differences in the above parameters between groups. After treatment, there was a similar significant decrease in blood pressure in both groups. Flow-mediated vasodilation increased significantly in the perindopril group compared with the amlodipine group; however, the decrease in brachial-ankle pulse wave velocity was not significantly different between groups. In conclusion, these results suggest that the angiotensin I-converting enzyme inhibitor perindopril is superior to the calcium channel blocker amlodipine for reducing vascular endothelial dysfunction when co-administered with angiotensin receptor blockers in patients with essential hypertension.

Objectives Cilnidipine is a calcium channel blocker that blocks both L and N-type calcium channels. L/N-type calcium channel blockers exhibit sympatholytic action and a renal protective effect via dilation of afferent and efferent arterioles of the renal glomerulus, and afford more potent protection against hypertension-related organ damage than L-type calcium channel blockers. Few studies, however, have directly compared the organ protective effects of L-type calcium channel blocker monotherapy and L/N-type calcium channel blocker monotherapy. This study compares the effects on renal and vascular endothelial functions and arterial stiffness of monotherapy regimens of amlodipine, an L-type calcium antagonist, and cilnidipine, in patients with essential hypertension. Methods Fifty patients with untreated essential hypertension were randomized to receive 5 mg of amlodipine (n = 25) or 10 mg of cilnidipine (n = 25) once daily in the morning for 24 weeks. The patients were evaluated before and after the therapy to assess changes in renal function, flow-mediated vasodilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (a parameter of arterial stiffness). Results Before treatment, the above parameters showed no significant differences between groups. After treatment, urinary albumin excretion was decreased significantly in the cilnidipine group compared with the amlodipine group, and the decrease of brachial-ankle pulse wave velocity was significantly larger in the cilnidipine group than in the amlodipine group. Conclusions These results suggest that cilnidipine is more effective than amlodipine at improving renal function and arterial stiffness in patients with essential hypertension.

An autopsy case of pseudoxanthoma elasticum is reported. A Japanese female patient complained of yellow papules on the neck, precordium, and axilla, beginning at 54 years of age. When the patient was 58 years old, in response to her visual disturbance a funduscopic examination was performed, revealing angioid streaks, and skin biopsy identified a characteristic pseudoxanthoma elasticum (PXE) lesion. The patient developed congestive heart failure, and following mitral valve prolapse and regurgitation flow into the left atrium, mitral valve replacement with a prosthetic valve was performed when the patient was 65 years old. Soon afterward, the patient complained of gait disturbance, and she died of congestive heart failure at 68 years of age. Autopsy specimen revealed fragmented, granular, and calcified elastic fibers in the middle to deep dermis and in the thickened subendocardium, and small to medium-sized muscular arteries revealed fragmented, laminated, and calcified elastic lamina; vascular changes were seen in the heart, lung, kidney, gastrointestinal tract, and iliac artery. Disrupted elastic fibers were visualized using the Weigert resorcin fuchsin method and were stained positive by antielastin and antifibronectin antibodies. Calcification was confirmed by von Kossa staining. Affected areas were PAS-positive after diastase digestion, indicating the presence of glycoprotein. Affected areas were colloidal iron-positive, indicating the presence of proteoglycan matrix.

Aims To estimate the incidence of dementia after the first atrial fibrillation (AF), and its impact on survival in a community-based cohort. Methods and results Olmsted County, Minnesota adult residents diagnosed with first AF during 1986–2000 were identified, and followed until 2004. The primary outcome was new detection of dementia. Interim stroke was censored in the analyses. Of 2837 subjects (71 ± 15 years old) diagnosed with first AF and without any evidence of cognitive dysfunction or stroke at the time of AF onset, 299 were diagnosed with dementia during a median follow-up of 4.6 years [interquartile (IQR) range 1.5–7.9 years], and 1638 died. The Kaplan–Meier cumulative rate of dementia was 2.7% at 1 year and 10.5% at 5 years. After adjustment for age and sex, dementia was strongly related to advancing age [hazard ratio (HR)/10 years, 2.8; 95% confidence interval (CI), 2.5–3.2], but did not vary with sex ( P = 0.52). The occurrence of post-AF dementia was associated with significantly increased mortality risk (HR 2.9; 95% CI 2.5–3.3), even after adjustment for multiple comorbidities, and did not vary with age ( P = 0.75) or sex ( P = 0.33). Conclusion Dementia appeared common following the diagnosis of first AF, and was associated with premature death.

Our objective was to examine the influence of leg muscle weakness and body mass index (BMI) on ultrasonography (US) of the knee joint in middle-aged women. US and measurements of leg muscle strength and BMI were performed at the beginning of the study and after 6 months. Subjects with US abnormalities at the first examination were excluded from the study. Muscle strength and BMI were compared between subjects with normal US findings at the beginning of the study and after 6 months (N) and those in whom initially normal US findings became abnormal after 6 months (A). Analysis was performed for 20 knees with a mean age of 52.9 years old. In Group N, there were no significant changes in muscle strength and BMI between the initial results and those after 6 months. Significant changes in muscle strength occurred in Group A, but there was no significant change in BMI. There were significant differences between Groups N and A in the changes after 6 months; however, there was no significant difference in the change in BMI between the two groups. We conclude that abnormal knee-joint findings in US of the knee are associated with leg muscle weakness in middle-aged women.

Background Pulmonary artery pressure (PAP) is reduced dramatically after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it is unclear whether pulmonary artery compliance increases in conjunction with the reduction in PAP. Pulmonary artery compliance may affect right ventricular afterload and prognosis. Methods and Results In 33 patients with CTEPH (9 men, 22-76 years), changes in the tricuspid regurgitation pressure gradient (TRPG) and the acceleration time (ACT) of pulmonary artery flow (a surrogate parameter of pulmonary artery compliance) were examined before and after pulmonary thromboendarterectomy using echocardiography to clarify factors affecting the changes. At 6 months, both TRPG and ACT normalized (≤30 mmHg, ≥100 ms, respectively) in 25 patients (group A) but not in 8 (group B). In group B, there were 5 with normal TRPG and shortened ACT at 6 months that normalized at 17±3 months. Group A patients showed shorter disease period and shorter period without anticoagulation than group B patients (p=0.04, 0.02 respectively). All patients in group A had the proximal type, and 2 patients of group B had the distal type (p=0.05). Clinical improvement was more remarkable in group A. Conclusions The recovery of PAP and the ACT of pulmonary artery flow was not always concordant after pulmonary thromboendarterectomy, suggesting a presence of a time lag in the recovery between pressure and compliance in some patients. A long period of CTEPH, a long period without anticoagulation and the distal embolism type may be predictive factors of an unfavorable operative result with reduced pulmonary artery compliance, and hence poor recovery of clinical performance. (Circ J 2007; 71: 1771 - 1775)

Background: Low-density lipoprotein (LDL) apheresis is effective in the treatment of peripheral arterial occlusive disease (PAOD). In the present study, we attempted to determine whether LDL apheresis is effective even for PAOD patients undergoing hemodialysis, who tend to be refractory to any treatment, and if so, to determine the mechanism of its efficacy. Methods: Serum levels of lipids and vascular growth factors, leg symptom, and endothelium-dependent vasodilation were investigated before and after 10 sessions of LDL apheresis in 11 PAOD patients undergoing hemodialysis. Results: Serum levels of total cholesterol, LDL cholesterol, and triglyceride exhibited drastic reduction, which completely disappeared 4 weeks after the final apheresis. Resting leg pain was improved in 6 cases even 4 weeks after final apheresis. Endothelium-dependent vasodilation was significantly increased 4 weeks after final apheresis (1.6 ± 0.6 to 4.7 ± 1.0%, p < 0.05). Levels of vascular growth factors, hepatocyte growth factor and vascular endothelial growth factor were not changed during treatment. Conclusions: These findings suggested that LDL apheresis is effective even in PAOD patients undergoing hemodialysis. Our findings suggest that its mechanisms of efficacy include improvement of vascular endothelial dysfunction, in addition to drastic but acute reduction of lipid levels. Since PAOD patients undergoing hemodialysis tend to be resistant to any treatment and are at high risk for lower-extremity amputation, LDL apheresis could be a useful strategy for treatment of them.

Background The implementation of cardiac rehabilitation (CR) after acute myocardial infarction (AMI) has not been fully investigated in Japan, so a nationwide survey of hospitals was conducted. Methods and Results Questionnaires were sent in 2004 to a total of 1,875 hospitals in Japan, including all the 859 Japanese Circulation Society (JCS)-authorized cardiology-training hospitals (THs), 311 JCS-associated hospitals (AH), and 705 randomly sampled non-THs (NTHs). The response rate was 59% (1,106/1,875). The percentages of hospitals treating hospitalized AMI patients were 97% in 526 TH, 85% in 194 AH, and 20% in 339 NTH. Although the rates of implementation of emergency percutaneous coronary intervention were very high (92%, 56%, and 4%, respectively), the rates of implementation of recovery phase CR were low (20%, 8%, and 2%, respectively). In addition, patient education programs (23%, 13% and 2%) and formulated exercise prescriptions based on exercise testing (16%, 7% and 1%) were poorly implemented. More importantly, only 9%, 2% and 0% of these hospitals had outpatient CR programs. From these data, the nationwide participation rate in outpatient CR after AMI in Japan was estimated to be only 3.8-7.6%. Conclusion This first nationwide survey demonstrated that, in contrast to the broad dissemination of acute phase invasive treatment for AMI, the implementation of recovery phase CR, especially outpatient CR, is extremely poor in Japan. In addition, patient education programs and exercise prescription based on exercise testing are only poorly implemented. (Circ J 2007; 71: 173 - 179)

Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO.