[Show abstract][Hide abstract] ABSTRACT: Background:
To improve the clinical outcome of heart failure (HF), it is important to evaluate the etiology and comorbidities of HF. We previously reported the baseline clinical characteristics and medications in hospitalized patients with HF in years 2000 - 2002 (group 2000) and 2007 - 2009 (group 2008).
We conducted a retrospective study of 158 patients who were hospitalized due to HF between 2012 and 2014 (group 2013) in the Department of Cardiology, Fukuoka University Hospital. We analyzed the clinical characteristics and medications at admission and discharge, and compared the findings in group 2013 to those in group 2000 and group 2008.
The major causes of HF were ischemic heart disease, hypertensive cardiomyopathy, valvular heart disease, and dilated cardiomyopathy. The New York Heart Association classification in group 2013 was significantly higher than those in group 2000 and group 2008. There was no difference in the level of brain natriuretic peptide at admission between group 2008 and group 2013. Tolvaptan began to be administered in group 2013. The median dose of furosemide just before the use of tolvaptan was 40 mg/day. At discharge, group 2013 showed higher rates of β-blocker and aldosterone antagonist. There was no difference in the frequency of loop diuretics. The dose of carvedilol at discharge was only 6.2 ± 4.0 mg/day. Antiarrhythmic drugs and β-blocker were used more frequently in HF with reduced ejection fraction (EF) than in HF with preserved EF.
We may be able to improve the clinical outcome of HF by examining the differences in the clinical characteristics and medications at admission and discharge in hospitalized patients with HF.
Preview · Article · Jan 2016 · Journal of Clinical Medicine Research
[Show abstract][Hide abstract] ABSTRACT: Aims:
Angiotensin receptor-neprilysin inhibitors (ARNis) acts an ARB and neprilysin inhibitor. Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure (HF). Therefore, we evaluated the effects and mechanisms of ARNi in HF with reduced ejection fraction (HF-rEF) in streptozotocin-induced diabetic mice.
Methods and results:
Male C57BL/6J mice were injected with streptozotocin to produce diabetic mice. After myocardial reperfusion injury, diabetic mice were randomized to treatment for 4 weeks with LCZ696 (60 mg/kg), valsartan (30 mg/kg), or no treatment (n = 26-28 in each group). Cardiac function was assessed by a pressure-volume Millar catheter. The ratios of heart weight to body weight in the valsartan (P = 0.02) and LCZ696 (P = 0.005) groups were significantly less than that in the control group. Treatment with LCZ696 improved LVEF (43 ± 3.4%) with a significantly reduction of atrial natriuretic peptide mRNA in the left ventricle compared with that in the control group (29 ± 3.2%) (P = 0.006). The fibrotic area in the LCZ696 group was significantly suppressed compared with those in the control (P = 0.003) and valsartan (P = 0.04) groups. Moreover, the mRNA level of transforming growth factor-β (TGF-β) in the left ventricle was suppressed in the LCZ696 group compared with that in the control (P = 0.002) group.
The ARNi LCZ696 improved cardiac function with the reduction of fibrosis in an HF-rEF model in diabetic mice, by suppressing TGF-β. This effect may be due to the specific inhibition of neprilysin, beyond the ARB effect of LCZ696.
No preview · Article · Jan 2016 · European Journal of Heart Failure
[Show abstract][Hide abstract] ABSTRACT: While physiological levels of nitric oxide (NO) protect the endothelium and have vasodilatory effects, excessive NO has adverse effects on the cardiovascular system. Recently, new NO-releasing pharmacodynamic hybrids of angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) have been developed.We analyzed whether olmesartan with NO-donor side chains (Olm-NO) was superior to olmesartan (Olm) for the control of blood pressure (BP). Although there was no significant difference in binding affinity to AT1 wild-type (WT) receptor between Olm and Olm-NO in a cell-based binding assay, the suppressive effect of Olm-NO on Ang II-induced inositol phosphate (IP) production was significantly weaker than that of Olm in AT1 WT receptor-expressing cells. While Olm had a strong inverse agonistic effect on IP production, Olm-NO did not. Next, we divided 18 C57BL mice into 3 groups: Ang II (infusion using an osmotic mini-pump) as a control group, Ang II (n = 6) + Olm, and Ang II (n = 6) + Olm-NO groups (n = 6). Olm-NO did not block Ang II-induced high BP after 10 days, whereas Olm significantly decreased BP. In addition, Olm, but not Olm-NO, significantly reduced the ratio of heart weight to body weight (HW/BW) with downregulation of the mRNA levels of atrial natriuretic peptide.An ARB with a NO-donor may cancel BP-lowering effects probably due to excessive NO and a weak blocking effect by Olm-NO toward AT1 receptor activation.
Preview · Article · Nov 2015 · International Heart Journal
[Show abstract][Hide abstract] ABSTRACT: Long acting calcium channel blockers (CCBs) play major role in the treatment of hypertension, however, there is no direct comparison between CCBs about their chronotropic and renoprotective effects on top of renin-angiotensin system (RAS) blocker treatment. The present study compared chronotropic and renoprotective effects of four long acting CCBs (nifedipine CR, amlodipine, azelnidipine and cilnidipine) in uncontrolled hypertensive outpatients under treatment with one of RAS inhibitors. Based on clinical data survey, 81 hypertensive outpatients were recruited and were randomly treated for at least one year with one of four CCBs at free intention of outpatient physicians. Subsequent blood pressure, heart rate and renal parameters were monitored before and after 6 and 12 months CCB treatment for 79 patients with 2 dropouts. Equivalent blood pressure reduction was observed in each group without significant differences among four groups. Average blood pressure reduction at 1 year were - 22 in systolic and -10 mmHg in diastolic pressure, respectively. Azelnidipine significantly decreased heart rate, but other CCBs did not show any significant changes. Nifedipine CR or cilnidipine significantly decreased serum creatinine concentration. In addition, cilnidipine significantly decreased urinary microablbumin excretion rate, while other CCBs provided similar, but no-significant decrease. Multiple regression analysis revealed that the CCB type was a significant contributing factor for renoprotection. In conclusion, concomitant administration of CCB with RAS inhibitor was sufficiently antihypertensive, but each CCB provided differential chronotropic and renoprotective effects, suggesting the necessity to individualize each CCB use according to the underlying organopathy of each hypertensive patient.
[Show abstract][Hide abstract] ABSTRACT: Fifty-four patients were randomly divided into irbesartan and olmesartan groups. Blood pressure (BP) was significantly decreased in all patients at 12 weeks. In particular, BP in patients who initially received irbesartan showed significant reductions. The equality of variance of BP in the irbesartan group was significantly smaller than that in the olmesartan group at 12 weeks. Blood concentrations of adiponectin were significantly increased in the irbesartan group at 12 weeks. Log [pentraxin-3] in the irbesartan group were significantly decreased. In conclusion, the ability of irbesartan to reduce BP is comparable to that of olmesartan with equivalent safety.
No preview · Article · May 2012 · Clinical and Experimental Hypertension
[Show abstract][Hide abstract] ABSTRACT: Little is known about the efficacy and safety of intensive lowering of low-density lipoprotein cholesterol (LDL-C) with statin/ezetimibe therapy after coronary stent implantation in patients with stable angina. Fifty patients with stable angina were randomly divided into an atorvastatin (10 mg/day) (A) group and an atorvastatin (10 mg/day)/ezetimibe (10 mg/day) (A+E) group after stent implantation. Follow-up coronary angiography was performed at 6-9 months after stenting. The A and A+E groups showed significant reductions in LDL-C. The levels of LDL-C in the A+E group were significantly lower than those in the A group at follow-up, whereas there were no differences in major adverse cardiac events, in-stent restenosis, or in-stent % diameter stenosis (DS) between the groups. Only the A+E group showed a significant decrease in the levels of highly sensitive C-reactive protein. In a sub-analysis, %DS in the non-target vessel significantly decreased in both groups. Moreover, Δ%DS (Δ=the value at baseline minus that at follow-up) in the A+E group was more closely associated with LDL-C levels at follow-up than that in the A group. There were no significant differences in adverse effects between the A and A+E groups. In conclusion, although statin/ezetimibe therapy was effective and safe for intensive lipid-lowering in patients with stable angina after successful coronary stent implantation, improvement in clinical outcomes with the combination therapy remains unclear.
Preview · Article · Apr 2012 · Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: A 62-year-old woman complained of sudden chest pain and 64-multidetector row computed tomography (MDCT) was performed. The volume-rendered image showed severe stenosis of the left main coronary trunk artery (LMT). The mean density of the plaque was 32.4 hounsfield units (HU), which indicated soft plaque. Coronary angiography (CAG) showed significant focal stenosis of the LMT. Since the patient had experienced chest pain, and since focal stenosis of the LMT was demonstrated, lipid-lowering therapy using statin and coronary artery bypass graft (CABG, right internal mammary artery-left anterior descending branch, left internal mammary artery-obtuse marginal branch) were applied. Three years after treatment, 64-MDCT showed mild stenosis and a regression of plaque in the LMT. The mean density of the plaque was 73.1 HU (intermediate plaque). CAG showed a degradation of CABG flow, in addition to mild stenosis of the LMT. In conclusion, lipid-lowering therapy with statins may stabilize soft coronary plaque. In addition, non-invasive MDCT is a useful tool for diagnosing coronary artery disease, and for evaluating the size and properties of coronary plaque.
No preview · Article · Apr 2012 · Journal of Cardiology Cases
[Show abstract][Hide abstract] ABSTRACT: Many patients still have high blood pressure (BP) after treatment with high-dose angiotensin II type 1 receptor blockers (ARBs) or Preminent® (medium-dose of losartan (50 mg/day)/hydrochlorothiazide (HCTZ) (12.5 mg/day)). Therefore, we analyzed whether Micombi®BP (high-dose telmisartan (80 mg/day)/HCTZ (12.5 mg/day)) could provide better results with regard to efficacy and safety for patients with uncontrolled hypertension.
In total, 44 hypertensive patients (22 males, age 71±14 years) who showed uncontrolled BP despite the use of high-dose ARBs or Preminent® were enrolled in this study. We used a changeover design in which the patients were switched from high-dose ARBs or Preminent® to Micombi®BP. We analyzed BP, heart rate (HR), and biochemical parameters before and after treatment for 3 months.
Systolic BP and diastolic BP significantly decreased (125±15/69±11 mmHg) and 85% of the patients achieved their target BP at 3 months after changeover. Patients who switched from ARBs and those who switched from Preminent® showed similar BP-lowering effects. In addition, the reductions in BP after 3 months in patients with or without chronic kidney disease and in those with or without metabolic syndrome (MetS) were also similar. There were no significant changes in HR during the study period. Although blood levels of potassium, hemoglobin A1c and uric acid (UA) significantly increased after 3 months for all of the patients, none of the patients showed serious adverse effects.
High-dose telmisartan/HCTZ therapy was associated with a significant reduction in BP and helped patients achieve their target BP.
Full-text · Article · Mar 2012 · Journal of Renin-Angiotensin-Aldosterone System
[Show abstract][Hide abstract] ABSTRACT: Although plasma pigment epithelium-derived factor (PEDF) levels have been shown to be significantly correlated with the levels of creatinine (Cr) in type 2 diabetes, little is known about the association between PEDF levels and renal dysfunction in patients with coronary artery disease (CAD).
We enrolled 134 consecutive patients with diagnosed CAD and measured plasma levels of PEDF, serum Cr, uric acid (UA) and high-sensitive C-reactive protein (hsCRP).
Plasma PEDF levels were positively correlated with serum Cr (p 〈 0.0001) and UA (p 〈 0.0001) and negatively correlated with the estimated glomerular filtration rate (eGFR) (p 〈 0.0001), whereas there was no association between plasma PEDF and age or hsCRP. When the subjects were divided into five groups (0-4) according to the number of metabolic factors (obesity, diabetes, hypertension and dyslipidemia), PEDF levels in patients with four factors were significantly higher than those in patients without factors. Next, we divided the patients into quartiles according to their plasma PEDF levels (〈 9.9 μg/mL, 9.9-12.8, 12.9- -15.7, 〉 15.7). The eGFR in the first group was significantly higher than those in the third and fourth groups. Multivariate logistic analysis indicated that eGFR (p 〈 0.0001) and age (p = 0.030) were significant independent variables that correlated with the quartile classification according to PEDF levels.
This study revealed that PEDF may play a role in renal dysfunction in CAD patients.
[Show abstract][Hide abstract] ABSTRACT: Pigment epithelium-derived factor (PEDF) and pentosidine have received growing attention as sensitive biomarkers of the progression of atherosclerosis. The present study was performed to evaluate the utility of these biomarkers for assessing the effects of angiotensin II type 1 receptor blockers (ARBs). Sixty-three patients with coronary artery disease (CAD) following successful stent implantation were divided into an ARB group (n = 50), who initially received valsartan or olmesartan immediately following stent implantation, and a non-ARB group (n = 13) according to their blood pressure (BP) at baseline. Measurement of BP and blood sampling was performed prior to (at baseline) and 6-8 months following stent implantation (at follow-up). There were no significant differences in the baseline characteristics between the groups. Although there were no differences in the percentage of diameter re-stenosis between the groups, the BP level in the ARB group at follow-up showed a significant reduction and reached the target BP. The levels of plasma PEDF were significantly increased at follow-up in the ARB group, but not in the non-ARB group, while there were no differences in the levels of pentosidine between the groups. Changes in BP (ΔBP = BP at follow-up minus BP at baseline) were not associated with ΔPEDF. In conclusion, PEDF may be a useful biomarker for assessing the effects of ARBs independent of a reduction in BP.
Full-text · Article · Feb 2011 · Journal of Renin-Angiotensin-Aldosterone System
[Show abstract][Hide abstract] ABSTRACT: This study was performed to evaluate the safety and efficacy of additional antihypertensive therapy with angiotensin II type 1 receptor blocker (ARB; olmesartan or valsartan) after successful stent implantation in patients with coronary artery disease (CAD). Fifty patients with CAD after successful stent implantation were included in this study. They were divided into an ARB group, which initially received olmesartan (n=20, 14+/-8 mg day(-1)) or valsartan (n=20, 60+/-23 mg day(-1)) immediately after stent implantation, and a non-ARB group (n=10) according to their blood pressure (BP). Follow-up coronary angiography, measurement of BP and blood sampling were performed before (at baseline) and 6-8 months after stent implantation (at follow-up). There were no significant differences in the baseline characteristics between the groups, except for BP. Although there were no changes in % diameter restenosis between the groups, the BP level in the ARB group at follow-up showed a significant reduction (125+/-12/69+/-9 mm Hg) and reached the target BP. There were no critical adverse effects in the ARB group throughout the study period. In addition, serum high-sensitive C-reactive protein (hs-CRP) and pentraxin 3 were significantly decreased in the ARB group but not in the non-ARB group. Although olmesartan and valsartan induced similar BP-lowering effects, olmesartan but not valsartan induced a significant decrease in hs-CRP, but did not increase serum uric acid. In conclusion, antihypertensive therapy with add-on low-dose ARB after stent implantation was safe and achieved the target BP. In particular, olmesartan had an anti-inflammatory effect.
Full-text · Article · Jun 2009 · Hypertension Research
[Show abstract][Hide abstract] ABSTRACT: Although several clinical studies have evaluated plasma adiponectin levels in response to chronic heart failure, little is known about the relation between cardiac function and metabolic factors including adiponectin in patients with acute myocardial infarction (AMI).
We analyzed 50 consecutive patients with AMI who had undergone successful coronary stent implantation. Echocardiography and blood sampling were performed at 1 week and 6 months after AMI. Blood was analyzed with regard to brain natriuretic peptide (BNP) and metabolic factors including plasma levels of adiponectin, lipid profile, and hemoglobin A1c (HbA1c). Plasma adiponectin levels were significantly increased at 6 months (7.3 ± 4.9 μg/ml) compared to those at 1 week (6.1 ± 3.7). BNP (from 156 ± 151 to 96 ± 124 pg/ml) significantly decreased. In addition, BNP at 6 months was positively correlated with plasma adiponectin levels at 1 week (y = 0.019 x -23.1, r = 0.537, P = 0.002), while BNP at 6 months was not associated with maximal creatinine kinase after AMI. A multiple regression analysis was performed to analyze the relationship between BNP at 6 months and metabolic factors (plasma levels of adiponectin, lipid profile, HbA1c, blood pressure, age, sex, and body mass index) at 1 week after AMI. BNP at 6 months was most closely correlated with plasma levels of adiponectin at 1 week (P = 0.045).
Among the metabolic factors examined, a higher adiponectin level at 1 week is the predictor of a higher BNP as one marker of cardiac dysfunction at 6 months after AMI.
Full-text · Article · Mar 2009 · Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: We describe the case of a 43-year-old primiparous woman who had acute myocardial infarction. She underwent successful primary percutaneous coronary intervention. Elective cesarean section was performed uneventfully at 32 weeks gestation.
No preview · Article · Feb 2009 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: We describe the case of an 85-year-old woman in whom pericardiocentesis, prolonged bed rest and blood pressure control were performed without surgery to successfully treat an oozing-type myocardial rupture due to myocardial infarction.
No preview · Article · Feb 2008 · Internal Medicine