[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: Background:
The visit-to-visit variability in blood pressure (BP) has been shown to be a strong predictor of cardiovascular events. It is not known whether anti-hypertensive therapy using a single-pill fixed-dose combination of angiotensin II receptor blocker (ARB)/calcium channel blocker (CCB) or ARB/diuretic (DI) in hypertensive patients affects the visit-to-visit variability and seasonal variation of BP.
We enrolled 47 hypertensive patients who had received a single-pill fixed-dose combination of either ARB/CCB (n = 30) or ARB/DI (n = 17) for 15 months. Beginning 3 months after the start of ARB/CCB or ARB/DI treatment, we determined the visit-to-visit variability in BP expressed as the standard deviation (SD) of average BP and the seasonal variation in BP expressed as the SD of average BP in each season (spring, summer, fall and winter were defined as lasting from March to May, June to August, September to November and December to February, respectively) for a year.
There were no significant differences in baseline patient characteristics except for the prevalence of coronary artery disease and the percentage of CCB excluding amlodipine in the ARB/CCB group between the ARB/CCB and ARB/DI groups. There were no significant differences in the 1-year time course of systolic and diastolic BP (SBP and DBP) between the groups, although there were significant differences in SBP in August and November and DBP in December. Interestingly, the visit-to-visit variability and seasonal variation of BP in the ARB/CCB group were similar to those in the ARB/DI group.
Single-pill fixed-dose combinations of ARB/CCB and ARB/DI had similar effects on visit-to-visit variability and seasonal variation in BP in hypertensive patients.
Preview · Article · Sep 2015 · Journal of Clinical Medicine Research
[Show abstract][Hide abstract] ABSTRACT: The measurement of high-density lipoprotein (HDL) functionality could be useful for identifying patients who have an increased risk of coronary restenosis after stent implantation. In the present study, we elucidates whether HDL functionality can predict restenosis. The participants included 48 consecutive patients who had stable angina and were successfully implanted with a drug-eluting stent (DES) or bare-metal stent. Follow-up coronary angiography was performed after 6-8 months of stenting. Cholesterol efflux and the anti-inflammatory capacity of HDL were measured before stenting (at baseline) and at follow-up. The mean age was 64 ± 11 years and the body mass index was 24 ± 3 kg/m(2). While HDL cholesterol (HDL-C) significantly increased from baseline to follow-up, there was no significant association between HDL-C level at baseline and in-stent late loss. Cholesterol efflux capacity was significantly increased from baseline to follow-up. The efflux capacity at baseline was negatively correlated with in-stent late loss, whereas the anti-oxidative activity of HDL at baseline was not associated with in-stent late loss. We analyzed the predictors of in-stent late loss using independent variables (efflux capacity and anti-oxidative capacity at baseline in addition to age, gender, HDL-C and low-density lipoprotein cholesterol at baseline, hypertension, diabetes mellitus, smoking, lesion length and DES implantation, history of myocardial infarction and prior percutaneous coronary intervention) by a multiple regression analysis. The efflux capacity at baseline was only independently associated with in-stent late loss. In conclusion, cholesterol efflux capacity at baseline could predict coronary restenosis in patients with successful stent implantation.
No preview · Article · Sep 2015 · Heart and Vessels
[Show abstract][Hide abstract] ABSTRACT: Visit-to-visit variability (VVV) in blood pressure (BP) in addition to high BP has been shown to be a strong predictor of coronary events and stroke. Therefore, we investigated the associations between VVV in BP or BP levels and cardiovascular events after successful percutaneous coronary intervention (PCI).
We enrolled 176 hypertensive patients who had undergone successful PCI and who had four clinic visits to measure BP until follow-up coronary angiography (CAG) at 6 - 9 months after PCI. The patients were divided into those with acute coronary syndrome (ACS group; n = 50) and those with stable angina pectoris (SAP group; n = 126). We determined VVV in BP expressed as the standard deviation (SD) of average BP, average, and the maximum and minimum BP during the follow-up period. Major adverse cardiovascular events (MACEs) (myocardial infarction (MI), target lesion revascularization (TLR) and all-cause death) were also analyzed.
There were no significant differences in VVV in BP, average BP or maximum or minimum BP between the patients with and without MACE in all patients, the ACS and SAP groups. Interestingly, in the ACS group, VVV in SBP and maximum SBP in patients with MI were significantly higher than those in patients without MI. The cut-off levels for VVV in BP and maximum SBP that gave the greatest sensitivity and specificity for MI in the ACS group were 15.1 and 138 mm Hg, respectively.
Higher VVV in SBP and maximum SBP in patients with ACS after successful PCI were associated with the onset of MI.
Full-text · Article · Jul 2015 · Journal of Clinical Medicine Research
[Show abstract][Hide abstract] ABSTRACT: It is not known the relationships between a difference in systolic blood pressure (SBP) or diastolic BP (DBP) between arms by synchronal measurement and the presence of coronary artery disease (CAD), and between a difference in BP between arms and the severity of coronary atherosclerosis. We enrolled 425 consecutive patients (M/F = 286/139, 67 ± 13 year) who were admitted to our University Hospital and in whom we could measure the absolute (|rt. BP - lt. BP|) and relative (rt. BP - lt. BP) differences in SBP and DBP using a nico PS-501(®) (Parama-Tech). We divided all patients into those who did and did not have CAD. The relative differences in SBP between arms in patients with CAD were significantly lower than those in patients without CAD. However, the relative difference in SBP between arms was not a predictor of the presence of CAD. We also divided 267 patients who underwent coronary angiography into tertiles according to the Gensini score (low, middle, and high score groups). Interestingly, the middle + high score groups showed significantly lower relative differences in SBP between arms than the low score group. The mean Korotkoff sound graph in the middle + high Gensini score group was significantly higher than that in the low Gensini score group. Among conventional cardiovascular risk factors and nico parameters, the relative difference in SBP between arms in addition to the risk factors (age, gender, body mass index, hypertension, dyslipidemia, and diabetes mellitus) was associated with the score by a logistic regression analysis. In conclusion, the relative difference in SBP between arms as well as conventional risk factors may be associated with the severity of coronary arteriosclerosis.
No preview · Article · Apr 2015 · Heart and Vessels
[Show abstract][Hide abstract] ABSTRACT: Background:
It is well known that percutaneous coronary intervention (PCI) in hemodialysis (HD) patients is associated with higher rates of in-stent restenosis and major adverse cardiovascular events (MACE) compared to that in non-HD patients, even if the target value in cholesterol management is achieved.
To evaluate the factors that are associated with MACE in HD patients, we selected 142 HD patients (164 lesions) without acute coronary syndrome (ACS) from 2148 patients (2568 lesions) who underwent PCI in our database of the FU-Registry [UMIN000005679, Fukuoka University Hospital EC/IRB:10-1-08(09-105)], and compared 52 patients (53 lesions) with MACE [MACE(+)] to 90 patients (111 lesions) without MACE [MACE(-)].
Total cholesterol (TC: 150±30mg/dL vs 166±39mg/dL, p<0.05) and high-density lipoprotein cholesterol (HDL-C: 40.1±14.7mg/dL vs 47.8±13.5mg/dL, p<0.01) levels were significantly lower in the MACE(+) group at follow-up. No significant differences were observed in other parameters, including triglyceride, low-density lipoprotein cholesterol (LDL-C; LDL-C/HDL-C ratio, and % changes in HDL-C, non-HDL-C, LDL-C), and hemoglobin A1c (US National Glycohemoglobin Standardization Program) between before and after PCI. TC, LDL-C, and non-HDL-C at the time of PCI and TC, and HDL-C at the 9-month follow-up were negatively correlated with MACE, while body mass index (BMI) [odds ratio (OR): 0.81; 95% confidence interval (CI): 0.68-0.95)], prior coronary artery bypass graft (CABG) (OR: 3.89; 95%CI: 1.29-12.6), and insulin use (OR: 3.17; 95%CI: 1.23-8.55) were strongly correlated with MACE in a multivariate analysis.
BMI, CABG, and insulin use, but not LDL-C, are independent predictors of MACE in HD patients, suggesting that the application of lipid management for non-HD patients to HD patients at the time of PCI may not necessarily be beneficial for medium-term clinical outcomes.
No preview · Article · Jul 2014 · Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: Objective:
We compared the efficacies of irbesartan and olmesartan after successful stent implantation in patients with stable angina.
Twenty-six patients were randomly divided into irbesartan and olmesartan groups and treated for approximately eight months (at follow-up coronary angiography).
There were no differences in blood pressure (BP) reduction or late loss between the groups. The BP levels in both groups at follow-up were significantly reduced. The equality of variance of systolic (S)BP (i.e., the intragroup standard deviation of SBP) in the irbesartan group was significantly smaller than that observed in the olmesartan group at follow-up. In addition, log[pentraxin-3] was significantly decreased in all of the patients at follow-up, with no differences between the groups. Interestingly, the levels of log[high-sensitive C-reactive protein (hs-CRP)] measured at 0 weeks were positively associated with in-stent late loss, and among independent biochemical variables in addition to age, gender, body mass index and the kind of angiotensin receptor blockers at 0 weeks, only these levels were related to in-stent late loss, as assessed by a multivariate analysis.
The ability of irbesartan to reduce BP is comparable to that of olmesartan, and irbesartan exhibits a lower variance of systolic BP after treatment. The level of log[hs-CRP] before stent implantation is a predictor of in-stent late loss.
No preview · Article · Apr 2013 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Although the use of drug-eluting stents (DES) has reduced the rate of restenosis, some problems remain regarding the usefulness of DES in small coronary arteries in addition to late thrombosis and a longer duration of dual-antiplatelet therapy. We considered 335 patients with 698 lesions who underwent DES or bare-metal stent (BMS) implantation, and randomly selected 172 DES and 124 BMS lesions that had undergone a complete data analysis and evaluation. Patients had a history of stable angina with at least 1 lesion with 50% diameter stenosis in a vessel and with a successfully minimum stent implantation (stent diameter=2.5mm). The baseline characteristics including the clinical presentation and cardiovascular risk factors were similar between the DES and BMS groups, except for the percentage of dyslipidemia (DL). Pre-procedure reference vessel diameter (RVD pre) in the DES group was significantly smaller than that in the BMS group (p<0.01), and stent length in the DES group was significantly longer (p<0.01). There was no significant difference in the cumulative incidence of major adverse cardiac events including the target lesion revascularization rate, whereas in-stent restenosis (ISR) in the DES group was significantly lower than that in the BMS group. In a multivariate analysis of ISR, diabetes mellitus, prior percutaneous coronary intervention, and DES use in clinical background were identified as independent predictors of ISR. In addition, RVD pre, stent length, and DES use in angiographical background were also identified. In conclusion, DES use is an independent predictor of ISR, although the DES group included more severely diseased small coronary arteries.
No preview · Article · Nov 2012 · Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: Dietary habits are associated with obesity, and both are important contributing factors to lifestyle-related diseases. The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals (UMIN Registration No: 000006582).
Two-hundred adult patients with hypertension and/or diabetes mellitus were randomly divided into 2 groups with/without dietary counseling and consumed an ordinary diet for 4 weeks. Each group was then subdivided into 2 groups with/without dietary counseling and received calorie-controlled lunch and dinner boxes for the next 4 weeks. The calories in the delivered meals were based on the subject's ideal body weight (BW) and physical activity level. BW, waist circumference, blood pressure, and laboratory data, including glycoalbumin, were measured at 0, 4, and 8 weeks. BW and the other parameters were significantly reduced during the study period in patients who received diet counseling in the ordinary diet period and/or delivered meal period but not in patients without dietary counseling, as assessed by linear mixed models for longitudinal data.
The combination of dietary counseling by dietitians and delivery of calorie-controlled meals was effective in reducing BW, as well as blood pressure and glycoalbumin, in patients with hypertension and/or diabetes mellitus.
No preview · Article · May 2012 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in patients with coronary artery disease. The purpose of this study was to investigate the association between the plasma levels of PTX3 and plaque vulnerability and the effect of the levels using statin in patients with coronary artery disease.
We determined the associations among the plasma levels of PTX3 and coronary plaque vulnerability in nonculprit coronary lesions with stenosis as assessed by integrated backscatter intravascular ultrasound (study 1). One hundred and eighteen consecutive patients with stable angina who underwent a percutaneous coronary intervention were enrolled. We also enrolled 53 patients with stable angina, and they were treated either with (n=36) or without (n=17) atorvastatin (10 mg/day) (study 2).
In study 1, although there was no association between the plasma levels of PTX3 and plaque vulnerability in all patients, the level of PTX3 was positively correlated with the percentage of lipid volume and negatively correlated with the percentage of fibrous volume in patients without statin treatment. There were no associations between high-sensitivity C-reactive protein levels and percentage of lipid volume and fibrous volume. Moreover, in study 2, statin therapy for 6-8 months significantly decreased the level of PTX3 in addition to high-sensitivity C-reactive protein.
The plasma level of PTX3 may be a useful biomarker for predicting the tissue characteristics of coronary plaque using integrated backscatter intravascular ultrasound. Statin therapy may have a beneficial effect with regard to the reduction of PTX3 levels.
No preview · Article · May 2012 · Coronary artery disease
[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