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Objective: The number of older patients with heart failure (HF) is increasing in Japan and has become a social problem. There is an urgent need to develop a comprehensive assessment methodology based on the common language of healthcare; the International Classification of Functioning, Disability and Health (ICF). The purpose of this study was to develop and confirm the appropriateness of a scoring methodology for 43 ICF categories in older people with HF., Design: Cross-sectional survey. We applied the RAND/University of California at Los Angeles (UCLA) Appropriateness Method with a modified Delphi method., Setting and Participants: We included a panel of 26 multidisciplinary experts on HF care consisting of home physicians, cardiovascular physicians, care managers, nurses, physical therapists, a pharmacist, occupational therapist, nutritionist and a social worker., Measures: We conducted a literature review of ICF linking rules and developed a questionnaire on scoring methods linked to ICF categories in older people with HF. In the Delphi rounds, we sent the expert panel a questionnaire consisting of three questions for each of the 43 ICF categories. The expert panel responded to the questionnaire items on a 1 (very inappropriate) - 9 (very appropriate) Likert scale and repeated rounds until a consensus of 'Appropriate' and 'Agreement' was reached on all items., Results: A total of 21 panel members responded to all the Delphi rounds. In the first Delphi round, six question items in four ICF categories did not reach a consensus of 'Agreement', but the result of our modifications based on panel members' suggestions reached to a consensus of 'Appropriate' and 'Agreement' on all questions in the second Delphi round., Conclusion: The ICF-based scoring method for older people with HF developed in this study was found to be appropriate. Future work is needed to clarify whether comprehensive assessment and information sharing based on ICF contributes to preventing readmissions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The effects of disease management using telemonitoring for patients with heart failure (HF) remain controversial. Hence, we embedded care coordination and enhanced collaborative self-management through interactive communication via a telemonitoring system (collaborative management; CM). This study evaluated whether CM improved psychosocial status and prevented rehospitalization in patients with HF in comparison with self-management education (SM), and usual care (UC).We randomly allocated 59 patients into 3 groups; UC (n = 19), SM (n = 20), and CM (n = 20). The UC group received one patient education session, and the SM and CM groups participated in disease management programs for 12 months. The CM group received telemonitoring concurrently. All groups were followed up for another 12 months. Data were collected at baseline and at 6, 12, 18, and 24 months.The primary endpoint was quality of life (QOL). Secondary endpoints included self-efficacy, self-care, and incidence of rehospitalization. The QOL score improved in CM compared to UC at 18 and 24 months (P < 0.05). There were no significant differences among the 3 groups in self-efficacy and self-care. However, compared within each group, only the CM had significant changes in self-efficacy and in self-care (P < 0.01). Rehospitalization rates were high in the UC (11/19; 57.9%) compared with the SM (5/20; 27.8%) and CM groups (4/20; 20.0%). The readmission-free survival rate differed significantly between the CM and UC groups (P = 0.020).We conclude that CM has the potential to improve psychosocial status in patients with HF and prevent rehospitalization due to HF.

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO 2 ) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO 2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO 2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO 2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO 2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

Although fractional flow reserve (FFR) and myocardial perfusion imaging (MPI) findings fundamentally differ, several cohort studies have revealed that these findings correlate. Here, we investigated whether flow-limiting FFR could be predicted from adenosine stress thallium-201 MPI with single-photon emission computed tomography (SPECT) findings derived from 84 consecutive, prospectively identified patients with stable coronary artery disease and 212 diseased vessels. Among them, FFR was measured in 136 diseased vessels (64%). The findings were compared with regional perfusion abnormalities including stress total perfusion defect (TPD) - rest TPD determined using quantitative perfusion single-photon emission computed tomography software. The FFR inversely correlated the most accurately with stress TPD - rest TPD (r = -0.552, p <0.001). Predictors of major vessels of interest comprising FFR <0.80, included stress TPD - rest TPD, the transient ischemic dilation ratio, left ventricular ejection fraction at rest and beta blockers for left anterior descending artery (LAD) regions, and stress TPD - rest TPD, left ventricular mass, left ventricular ejection fraction at rest, right coronary artery lesions, the transient ischemic dilation ratio, and age for non-LAD regions. The diagnostic accuracy of formulas to predict major vessels of interest with FFR <0.80 was high (sensitivity, specificity and accuracy for LAD and non-LAD: 84%, 87% and 86%, and 75%, 93% and 87%, respectively). In conclusion, although somewhat limited by a sample size and a single-center design, flow-limiting FFR could be predicted from MPI findings with a defined probability. A cohort study might validate our results and provide a novel adjunctive tool with which to diagnose functionally significant coronary artery disease from MPI findings., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Although several studies have shown the diagnostic and prognostic value of CT-based attenuation correction (AC) of single photon emission computed tomography (SPECT) images for diagnosing coronary artery disease (CAD), this issue remains a matter of debate. To clarify the characteristics of CT-AC SPECT images that might potentially improve diagnostic performance, we analyzed images acquired using adenosine-stress thallium-201 myocardial perfusion SPECT/CT equipped with IQ[Symbol: see text]SPECT (SPECT/CT-IQ[Symbol: see text]SPECT) from patients with angiographically proven normal coronary arteries after changing the CT attenuation correction (CT-AC) in a stepwise manner., Methods: We enrolled 72 patients (Male 36, Female 36) with normal coronary arteries according to findings of invasive coronary angiography or CT-angiography within three months after a SPECT/CT study. Projection images were reconstructed at CT-AC values of (-), 40, 60, 80 and 100 % using a CT number conversion program according to our definition and analyzed using polar maps according to sex., Results: CT attenuation corrected segments were located from the mid- and apical-inferior spread through the mid- and apical-septal regions and finally to the basal-anterior and basal- and mid-lateral regions in males, and from the mid-inferior region through the mid-septal and mid-anterior, and mid-lateral regions in females as the CT-AC values increased. Segments with maximal mean counts shifted from the apical-anterior to mid-anterolateral region under both stress and rest conditions in males, whereas such segments shifted from the apical-septal to the mid-anteroseptal region under both stress and rest conditions in females., Conclusions: We clarified which part of the myocardium and to which degree CT-AC affects it in adenosine-stress thallium-201 myocardial perfusion SPECT/CT-IQ[Symbol: see text]SPECT images by changing the CT-AC value stepwise. We also identified sex-specific shifts of segments with maximal mean counts that changed as CT-AC values increased.

Objectives: Primary pulmonary hypertension (PPH) is a pulmonary vasculopathy resulting in exercise intolerance, usually due to dyspnea. We hypothesized that ventilation is increased during exercise in PPH relative to normal because the ventilated lung is underperfused, cardiac output increase is restricted, and arterial hypoxemia may develop. Our aim was to determine the size of the reduction in end-tidal Pco(2) (Petco(2)) as a reflection of the abnormality in ventilatory efficiency and ventilatory drive in PPH patients., Methods: We performed cardiopulmonary exercise testing (CPET) in 52 PPH patients. All had hemodynamic measurements to confirm the diagnosis of PPH. A subgroup of 29 patients who underwent right-heart catheterization within 50 days of CPET were studied to compare their CPET responses to resting hemodynamics. Nine healthy volunteers matched for age and gender served as CPET control subjects., Results: In PPH patients, the percentage of predicted peak oxygen uptake (Vo(2)) correlated significantly with mean pulmonary artery pressure (mPAP) [r = - 0.59, p = 0.0007, n = 29]. Petco(2) values at rest, anaerobic threshold (AT), and peak Vo(2) were proportionately reduced as percentage of predicted peak Vo(2) decreased (r = 0.66 to 0.72, p < 0.0001, n = 52). Petco(2) values at rest, AT, and peak Vo(2) were also reduced as mPAP increased (r = - 0.51 to - 0.53, p < 0.005, n = 29). In contrast to normal subjects in whom Petco(2) increased from rest to AT, Petco(2) decreased in PPH patients, except for two patients with mild PPH in whom there was no change. Also, Petco(2) increased rather than decreased further at the start of recovery, in contrast to normal. Although usually normal at rest, oxyhemoglobin saturation decreased during exercise in most PPH patients., Conclusions: In patients with PPH, Petco(2) at rest and exercise is significantly reduced in proportion to physiologic disease severity. The range of values is unusually low. Furthermore, the directional changes of Petco(2) during exercise and early recovery are in the opposite direction of normal.

Background and Objectives: As part of a recent study, cardiopulmonary exercise tests (CPETs) were used to evaluate and follow up patients with pulmonary arterial hypertension (PAH). These patients were more impaired than those in other published series evaluating CPET reproducibility. We used these patient tests to assess patient performance variability and evaluate reading variability. To achieve this end, six independent evaluators graded key CPET measurements in patients with PAH who underwent duplicate CPETs within 3 days of each other., Setting and Patients: Over a 15-month period at two tertiary-care teaching hospitals, 42 patients with PAH underwent repeated, paired CPETs using cycle ergometry., Interventions and Measurements: Each patient underwent one to six pairs of cycle ergometry tests to maximal tolerance. Each pair of tests was separated by 3 months, with each test in the pair separated by 1 to 3 days. Specific guidelines were given to the independent evaluators for the key measurements assessed from each CPET study: peak O(2) uptake (Vo(2)), peak heart rate, peak O(2) pulse, anaerobic threshold (AT), and end-tidal Po(2), end-tidal Pco(2), and the ventilatory equivalent for CO(2) at the AT (Ve/Vco(2)@AT)., Results: There were no fatalities or complications occurring among the 242 tests performed on 42 patients. The mean peak Vo(2) was 722 mL/min or 41% of predicted; 34 patients were Weber class C or D. Using the specific guidelines to measure the variability of measurements made by the six independent evaluators, the coefficients of variation were < 2.2% for peak Vo(2), peak heart rate, peak O(2) pulse, end-tidal values at the AT, and Ve/Vco(2)@AT, while for the AT, it was 8.5%. There were no significant differences in these measurements between the first and second tests of any pair or between the earlier and later sets of pairs., Conclusions: Using specific guidelines, key CPET measurements can be safely, reliably, and reproducibly assessed even in patients with severe exercise intolerance.

Clinical studies and animal experiments have demonstrated that oxidized low-density lipoprotein (oxLDL) and oxysterols play important roles in atherogenesis. OxLDL is immunogenic, and autoantibodies (Ab) against oxLDL are detectable in serum. We investigated the relevance of oxysterols and Ab against-oxLDL to coronary artery disease (CAD) in 183 patients undergoing coronary angiography. Patient groups included angiographically normal subjects (< 75% stenosis), others with spasm (> 75% narrowing in response to acetylcholine), and some others with fixed stenosis (> 75%). The group with stenosis was subdivided into patients with stable and unstable angina. Serum concentrations of autoantibodies and 25-, 27-, and 7-beta-hydroxycholesterols were significantly higher in the stenotic group than in the normal group (P < 0.01, P < 0.05, P < 0.05, and P < 0.05, respectively). Antibodies, but not oxysterol concentrations, were significantly greater in subjects with unstable than with stable angina (P < 0.01). We conclude that anti-oxLDL antibody and oxysterol concentrations are associated with coronary artery stenosis, and that oxidative stress may be greatly increased in unstable angina.

Hot water extract of Chlorella vulgaris (CVE) is a biological response modifier (BRM) which enhances resistance to Listeria monocytogenes through augmentation of helper T cell type 1 (Thl) responses producing gamma-interferon (gammaIFN). We show here that oral administration of CVE in mice suppressed the production of immunoglobulin (Ig)E against casein antigen accompanied by increased gammaIFN and IL-12 mRNA expression. Oral administration of CVE enhanced Thl response to casein in the spleen of casein immunized mice. CVE may be useful for prevention of allergic diseases with a predominant Th2 response.

The effect of bezafibrate on plasma lipoproteins was investigated in Japanese familial combined hyperlipidemic patients with or without an impaired glucose tolerance accompanied by a low-density lipoprotein subclass, with the major gradient gel peak at a particle diameter of less than 25.5 nm. Bezafibrate treatment at a dose of 400 mg/d for 12 weeks produced an antiatherogenic effect on lipoprotein profiles, as reflected by a decrease in plasma triglyceride levels, an increase in plasma high-density lipoprotein-cholesterol levels, induction of the large-size subclass of low-density lipoprotein, and disappearance of intermediate-density lipoproteins. The plasma total and low-density lipoprotein-cholesterol-lowering effect of bezafibrate was significant in patients without impaired glucose tolerance but was not significant in patients with impaired glucose tolerance. Bezafibrate increased lipoprotein lipase activity and decreased the activity of cholesteryl ester transfer protein, both in patients with or without impaired glucose tolerance. There was no difference in the distribution of signal peptide insertion/deletion or Xbal polymorphisms of the apolipoprotein B gene in patients with or without impaired glucose tolerance. Mechanisms other than lipoprotein lipase, cholesteryl ester transfer protein activities, and an apolipoprotein B gene polymorphism may be responsible for the resistance to lowering of plasma total and low-density lipoprotein cholesterol levels with bezafibrate treatment in familial combined hyperlipidemic patients with impaired glucose tolerance.

The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0 and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations, were increased in a dose-dependent manner (0.01-1.0 microM) by exposure of Hep G2 cells to cerivastatin. The results suggest that cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors, but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin, therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

To assess the effect of recombinant human erythropoietin (EPO) on the factors regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide (ANP), and serum and intracellular concentrations of cations before and after 3 months of EPO treatment (40 units/kg/week of EPO intravenously after each hemodialysis session) in 11 patients undergoing maintenance hemodialysis. Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with flame photometry. EPO treatment was associated with significant increases in Hgb (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9 mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By multiple regression analysis, delta[Na+]q and deltaBV independently contributed to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These data suggest that intracellular sodium accumulation as well as increased blood viscosity may be independently involved in the blood pressure elevation after EPO treatment in patients under maintenance hemodialysis. We found no evidence supporting a role of circulating hormonal factors, such as the renin-angiotensin system, adrenaline, or ANP, in the change in blood pressure.

The antioxidative effect of monatepil maleate (CAS 103379-03-9, AJ-2615), a new antihypertensive agent, was investigated by measuring its ability to inhibit copper-induced lipid hydroperoxidation of low density lipoprotein (LDL) and was compared with those of diltiazem (Ca(2+)-channel antagonist), prazosin (alpha 1-adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to inhibit copper-induced lipid hydroperoxidation of LDL by 50% (IC50) was 28 mumol/l. The IC50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, > 1 mmol/l, and 17 mumol/l, respectively. These results indicate that AJ-2615 has the same potent antioxidative effect as probucol and suggest that a previously reported ability of AJ-2615 to inhibit the progression of atherosclerosis may be due to this antioxidative property. In addition, the dihydrodibenzothiepine ring of AJ-2615 may have an antioxidative functions.

We developed a simple, sensitive and accurate method for assaying cellular free and total cholesterol by monitoring 4-cholesten-3-one, a conversion product of the cholesterol oxidase-catalyzed oxidation of the free cholesterol that has a strong chromophoric alpha, beta-unsaturated ketone at 240 nm, using a high-pressure liquid chromatographic system. This method measured picomole quantities of free and total cholesterol and precisely determined their concentrations in cells (10(4) range) in culture using 7 beta-hydroxycholesterol as an internal standard.

The effects of dietary oleic acid on cholesterol metabolism were investigated and compared with those of palmitic acid in hamsters. Addition of 5% oleic acid to a 0.1% cholesterol-supplemented diet decreased plasma total cholesterol, very low density lipoprotein (VLDL) cholesterol, and low density lipoprotein (LDL) cholesterol, increased hepatic LDL receptor activity, and decreased plasma cholesteryl ester transfer protein (CETP) activity in comparison with 0.1% cholesterol alone. In contrast, addition of 5% palmitic acid to a 0.1% cholesterol-supplemented diet increased total cholesterol and LDL-cholesterol, increased plasma CETP activity, and suppressed hepatic LDL receptor activity to a greater extent than 0.1% cholesterol alone. Neither oleic acid nor palmitic acid altered hepatic microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, but oleic acid increased hepatic microsomal cholesterol 7 alpha-hydroxylase activity. These results suggest that dietary oleic acid inhibits the increases in total, VLDL-, and LDL-cholesterol induced by dietary cholesterol by preventing both LDL receptor suppression and increased CETP activity, whereas dietary palmitic acid augments the cholesterol-induced increases in total and LDL-cholesterol by both further suppression of LDL receptor activity and further stimulation of CETP activity.

The effects of administration of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on hepatic cholesterol 7 alpha-hydroxylase and acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities and bile lipid secretion were investigated in Syrian golden hamsters. Continuous administration of pravastatin induced no significant changes in hepatic cholesterol content, ACAT and cholesterol 7 alpha-hydroxylase activities, or bile lipid and acid composition. Abrupt withdrawal of pravastatin induced increases in hepatic cholesterol content and ACAT activity and no change in hepatic cholesterol 7 alpha-hydroxylase activity, and increased cholesterol saturation in bile. Hepatic cholesterol 7 alpha-hydroxylase activity paralleled hepatic mRNA levels of this enzyme. These results suggest that a change in hepatic cholesterol metabolism induced by continuous administration of pravastatin maintains a constant net balance of hepatic cholesterol content. In addition, the drug has no deleterious influence on metabolism of bile lipids and acids and related enzymes, except for a transient increase in cholesterol saturation in bile induced by an inappropriate increase in hepatic cholesterol content and a lack of response of cholesterol 7 alpha-hydroxylase activity to changes in hepatic cholesterol content upon abrupt withdrawal of pravastatin.