Background:Waon therapy improves heart failure (HF) symptoms, but further evidence in patients with advanced HF remains uncertain.Methods and Results:In 19 institutes, we prospectively enrolled ...hospitalized patients with advanced HF, who had plasma levels of B-type natriuretic peptide (BNP) >500 pg/ml on admission and BNP >300 pg/ml regardless of more than 1 week of medical therapy. Enrolled patients were randomized into Waon therapy or control groups. Waon therapy was performed once daily for 10 days with a far infrared-ray dry sauna maintained at 60℃ for 15 min, followed by bed rest for 30 min covered with a blanket. The primary endpoint was the ratio of BNP before and after treatment. In total, 76 Waon therapy and 73 control patients (mean age 66 years, men 61%, mean plasma BNP 777 pg/ml) were studied. The groups differed only in body mass index and the frequency of diabetes. The plasma BNP, NYHA classification, 6-min walk distance (6MWD), and cardiothoracic ratio significantly improved only in the Waon therapy group. Improvements in NYHA classification, 6MWD, and cardiothoracic ratio were significant in the Waon therapy group, although the change in plasma BNP did not reach statistical significance. No serious adverse events were observed in either group.Conclusions:Waon therapy, a holistic soothing warmth therapy, showed clinical advantages in safety and efficacy among patients with advanced HF. (Circ J 2016; 80: 827–834)
The objective of this study is to determine whether pentraxin-3 (PTX-3) is clinically a biomarker of inflammation, a player in anti-inflammation, or both with regard to coronary atherosclerosis, we ...compared levels of PTX-3 with levels of adiponectin in addition to high-sensitivity C-reactive protein (hs-CRP). We enrolled 693 patients (51 % male; mean age 64 ± 12 years) at Fukuoka University Hospital. They were clinically suspected to have coronary artery disease (CAD) or had at least one cardiac risk factor and had undergone coronary computed tomography angiography (CTA). We evaluated the levels of PTX-3, hs-CRP, and adiponectin, the presence of CAD or metabolic factors, subcutaneous fat area, visceral fat area (VFA) and lipid profiles. The presence of CAD was independently associated with aging (
p
= 0.010) and the prevalence of hypertension (
p
< 0.0001), but not the levels of PTX-3, hs-CRP and adiponectin by a multivariate analysis. Although the number of significantly stenosed coronary vessels (VD) was not associated with PTX-3 or adiponectin, hs-CRP tended to increase as the number of VD increased. In addition, PTX-3 decreased as the number of metabolic factors increased, whereas hs-CRP increased as the number of metabolic factors increased. Interestingly, PTX-3 did not correlate with hs-CRP, but was positively correlated with adiponectin. In a multiple regression analysis, adiponectin (
p
= 0.003) and VFA (
p
= 0.008) were significant predictors of PTX-3 levels. In conclusion, PTX-3 and adiponectin showed similar associations with metabolic factors, whereas PTX-3 and hs-CRP showed opposite trends. Adiponectin and VFA were significant predictors of PTX-3 levels. PTX-3 might have an atheroprotective role as well as serving as a simple biomarker, like adiponectin.
Abstract Objective We investigated the associations between serum levels of glycated albumin (GA) or hemoglobin A1c (HbA1c) and the presence of coronary artery disease (CAD) in patients who underwent ...coronary computed tomography angiography (CTA). Methods and results The study consisted of 244 consecutive patients who underwent CTA and in whom we could measure the levels of both GA and HbA1c. Any narrowing of the normal contrast-enhanced lumen to >50% that could be identified in multiplanar reconstructions or cross-sectional images by CTA was defined as significant stenosis in CAD. We divided the patients into two groups: CAD group ( n = 72) and non-CAD group ( n = 172), as assessed by CTA. The CAD group showed significantly higher GA and HbA1c than the non-CAD group. GA and HbA1c showed a positive correlation ( r = 0.551, p < 0.0001). A multivariate logistic regression analysis was performed to examine the associations between the presence of CAD and age, gender, body mass index, and coronary risk factors (hypertension, dyslipidemia, and smoking), in addition to GA and HbA1c. Age odds ratio (OR): 1.04, p = 0.02, gender (OR: 2.84 p = 0.01), hypertension (OR: 3.20, p = 0.01), and GA (OR: 1.16, p = 0.03) were identified as significant independent variables that predicted the presence of CAD. In particular, GA (OR: 1.30, p = 0.02) was the only predictor of the presence of CAD in the diabetes mellitus group by a multivariate logistic regression analysis. We defined the cut-off value of GA for the prediction of CAD in patients with diabetes as 17.9% (sensitivity 0.639, specificity 0.639) by a receiver-operating characteristic curve analysis. Conclusion GA may be superior to HbA1c as a marker for evaluating the presence of CAD.
Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a ...pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.
A 39-year-old woman with a 9-week abdominal pregnancy noted pain in her lower abdomen and left leg. Since successive thrombi were observed extending from the left common iliac vein to the popliteal ...vein along with a thrombus in the left pulmonary artery, we diagnosed her with pulmonary thromboembolism with deep venous thrombosis (DVT). May-Thurner syndrome may have contributed to DVT in the left leg when the left iliac vein was compressed by the right iliac artery. She underwent anticoagulant therapy with heparin, followed by the subcutaneous injection of heparin at home after discharge. We herein report the case of a pregnant woman with May-Thurner syndrome who safely gave birth.
To delineate the molecular mechanism underlying the inverse agonist activity of olmesartan, a potent angiotensin II type 1 (AT1) receptor antagonist, we performed binding affinity studies and an ...inositol phosphate production assay. Binding affinity of olmesartan and its related compounds to wild-type and mutant AT1 receptors demonstrated that interactions between olmesartan and Tyr113, Lys199, His256, and Gln257 in the AT1 receptor were important. The inositol phosphate production assay of olmesartan and related compounds using mutant receptors indicated that the inverse agonist activity required two interactions, that between the hydroxyl group of olmesartan and Tyr113 in the receptor and that between the carboxyl group of olmesartan and Lys199 and His256 in the receptor. Gln257 was found to be important for the interaction with olmesartan but not for the inverse agonist activity. Based on these results, we constructed a model for the interaction between olmesartan and the AT1 receptor. Although the activation of G protein-coupled receptors is initiated by anti-clockwise rotation of transmembrane (TM) III and TM VI followed by changes in the conformation of the receptor, in this model, cooperative interactions between the hydroxyl group and Tyr113 in TM III and between the carboxyl group and His256 in TM VI were essential for the potent inverse agonist activity of olmesartan. We speculate that the specific interaction of olmesartan with these two TMs is essential for stabilizing the AT1 receptor in an inactive conformation. A better understanding of the molecular mechanisms of the inverse agonism could be useful for the development of new G protein-coupled receptor antagonists with inverse agonist activity.
Although angiotensin II (Ang II) binds to Ang II type 1 (AT1) and type 2 (AT2) receptors, AT1 and AT2 receptors have antagonistic actions with regard to cell signaling. The molecular mechanisms that ...underlie this antagonism are not well understood. We examined AT1 and AT2 receptor-induced signal cross-talk in the cytoplasm and the importance of the hetero-dimerization of AT1 receptor with AT2 receptor on the cell surface. AT1 and AT2 receptors showed antagonistic effects toward inositol phosphate production. AT1 receptors mainly formed homo-dimers, rather than hetero-dimers with AT2 receptor, on the cell surface as determined by immunoprecipitation, and subsequently induced cell signals. AT2 receptor mainly formed homo-dimers, rather than hetero-dimers with AT1 receptor, on the cell surface. The expression levels of homo-dimerized AT1 receptor or AT2 receptor on the cell surface did not change after treatment with Ang II, the AT1 receptor antagonist telmisartan or the AT2 receptor antagonist PD123319. Finally, AT1 and AT2 receptor-induced signals antagonized phospholipase C-β3 phosphorylation. In conclusion, Ang II-induced AT1 receptor signals may be mainly blocked by AT2 receptor signals through their negative cross-talk in the cytoplasm rather than by the hetero-dimerization of both receptors on the cell surface. The proper balance of the expression levels of AT1 and AT2 receptors might be critical for the antagonistic action between these receptors.
Plasma high-density lipoprotein (HDL) levels have an inverse correlation with incidence of ischemic heart disease as well as other atherosclerosis-related ischemic conditions. However, the molecular ...mechanism by which HDL prevents ischemic disease is not fully understood. Here, we investigated the effect of HDL on differentiation of endothelial progenitor cells and angiogenesis in murine ischemic hindlimb model.
Intravenous injection of reconstituted HDL (rHDL) significantly augmented blood flow recovery and increased capillary density in the ischemic leg. rHDL increased the number of bone marrow-derived cells incorporated into the newly formed capillaries in ischemic muscle. rHDL induced phosphorylation of Akt in human peripheral mononuclear cells. rHDL (50 to 100 microg apolipoprotein A-I/mL) promoted differentiation of peripheral mononuclear cells to endothelial progenitor cells in a dose-dependent manner. The effect of rHDL on endothelial progenitor cells differentiation was abrogated by coadministration of LY294002, an inhibitor of phosphatidylinositol 3-kinase. rHDL failed to promote angiogenesis in endothelial NO-deficient mice.
rHDL directly stimulates endothelial progenitor cell differentiation via phosphatidylinositol 3-kinase/Akt pathway and enhances ischemia-induced angiogenesis. rHDL may be useful in the treatment of patients with ischemic cardiovascular diseases.
There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is ...insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; − 7.9 mmHg vs. + 2.7 mmHg;
p
= 0.0002, diastolic BP; − 3.9 mmHg vs. + 0.6 mmHg;
p
= 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.
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