Background Changes in plasma volume, a marker of plasma volume expansion and contraction, are gai... more Background Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population. Methods and results We used a nationwide database of 134,291 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss–Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan–Meier analysis demonstrate...
The prevalence of hypertension (HT) is still increasing and is a well-known risk for cardiovascul... more The prevalence of hypertension (HT) is still increasing and is a well-known risk for cardiovascular disease and mortality. The mechanisms by which HT is involved in the development of cardiovascular disease includes several complex processes such as the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and oxidative stress. 5 Several guidelines, such as the Japanese Society of Hypertension (JSH) 2014, recommend lowering blood pressure (BP) to <140 and <90 mmHg for the primary A ortic artery disease (AAD), namely aortic artery dissection or aortic aneurysm rupture, is a major cause of sudden death. 1,2 In almost all cases of aortic aneurysm rupture, the patient dies before arriving at hospital; furthermore, the mortality rate ≤24 h after symptom onset reaches approximately 50-70% despite surgical treatment. 3 Similarly, the mortality rates in those with ascending aortic dissection between 24 h and 1 month after onset are 20% and 50%, respectively. 4 Therefore, it is critical to identify high-risk subjects and prevent the development of AAD in apparently healthy subjects using health checkups .
Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm... more Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm rupture remain fatal with extremely high mortality rates. Owing to the relatively low prevalence of AD, the risk of AD-related death has not yet been elucidated. The aim of the present study was to examine whether hyperuricemia is a risk factor for AD-related mortality in the general population. We used a nationwide database of 474,725 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” between 2008 and 2013. There were 115 deaths from aortic dissection and aortic aneurysm rupture during the follow-up period of 1,803,955 person-years. Kaplan–Meier analysis revealed that subjects with hyperuricemia had a higher rate of AD-related death than those without hyperuricemia. Multivariate Cox proportional hazard regression analysis demonstrated that hyperuricemia was an independent risk factor for AD-related death in the general population. Th...
In this paper, development and electrical characterization of sisal powder filled polyvinyl alcoh... more In this paper, development and electrical characterization of sisal powder filled polyvinyl alcohol (PVA) composites is reported. Dielectric measurements were conducted on these composites on a LCR meter in the temperature range from 30 to 150 °C and in the frequency range 1 kHz-10 kHz. The effects of temperature and frequency variation on dielectric constant (ε'), dielectric dissipation factor (tan δ) and on a. c. conductivity (σa.c.) were determined. On increasing the filler content, dielectric constant increased, it was mainly due to motion of the dipolar groups of the interfacial polarization occurring in the composites. The conductivity increased with rise in temperature.
Aims Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is incre... more Aims Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. Methods and results We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related...
Background: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a ... more Background: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a public health problem associated with high cardiovascular mortality. Iron deficiency (ID) is associated with poor clinical outcome in patients with heart disease, but whether ID is associated with the severity and clinical outcome of PAD remains unclear. Methods and Results: A total of 449 patients with PAD who received EVT and who had iron and red blood cell measurement were enrolled. ID was defined as transferrin saturation (TSAT) <20%, based on a previous report. TSAT and hemoglobin decreased with deteriorating Fontaine class. During a median follow-up period of 1,064 days, 71 major adverse cardiovascular and leg events (MACLE) and 47 major adverse cardiovascular events (MACE) were noted. All patients were divided into 2 groups based on the presence of ID. On Kaplan-Meier analysis, patients with ID had higher rates of MACE and MACLE than those without. On multivariate Cox proportional hazard regression analysis, TSAT and hemoglobin were independently associated with MACLE. Addition of TSAT to the known risk factors significantly improved the net reclassification index and integrated discrimination improvement. Conclusions: ID, as assessed by TSAT, was associated with the severity and clinical outcome of PAD, indicating that it could be a therapeutic target.
The purpose of this study was therefore to determine whether skeletal muscle mass and intramuscul... more The purpose of this study was therefore to determine whether skeletal muscle mass and intramuscular fat deposition evaluated on CT can predict major adverse cardiovascular and limb events (MACLE) in patients with PAD. Methods Subjects This prospective study involved 327 consecutive patients admitted to the present hospital with PAD. PAD was diagnosed using the ankle brachial index (ABI) and contrast-enhanced CT. Endovascular therapy (EVT) was performed by experienced cardiologists according to the TransAtlantic Inter-Society Consensus II (TASC II) guideline recommendations. Fontaine classes II, III, and IV were defined as intermittent claudication, rest pain, and critical limb ischemia (CLI), respectively. Exclusion criteria included acute coronary syndrome (ACS) ≤3 months prior,
Circulation journal : official journal of the Japanese Circulation Society, Jan 23, 2018
Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardio... more Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the ...
A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not re... more A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not reaching obvious hypertension, suggesting that target organ damages are latently induced by slight BP rising. The goal of this study was to determine whether presence of subclinical myocardial damage can predict the future development of hypertension in the normotensive general population. The cohort study was conducted with subjects who participated in a community-based annual health check. Normotensive subjects without prior cardiovascular diseases at baseline were eligible for analyses (n = 524, mean age 58 ± 9 years; 53% women). We measured heart-type fatty acid binding protein (H-FABP) at baseline as a biomarker of ongoing myocardial damage. Longitudinal changes in BP were examined during median follow-up period of 6.2 years, and we investigated the association between the baseline H-FABP level and longitudinal BP changes. During the follow-up, 177 subjects (34%) developed hypertensio...
BackgroundThe aim of this study was to establish a minimally invasive defibrillation testing (DT)... more BackgroundThe aim of this study was to establish a minimally invasive defibrillation testing (DT) protocol for patients with implantable cardioverter defibrillators (ICDs).MethodsTwo different energy DTs were performed, immediately after (15 J‐DT) and 7 days after (≤10 J‐DT) device implantation, in 20 consecutive ICD implantation patients. Cardiac‐troponin T (c‐TNT) and heart‐type fatty acid binding protein (H‐FABP) levels were measured before implantation, 2 h after implantation, and 1 day after each DT. For an additional 122 patients with ICD, we retrospectively analyzed 203 DTs immediately and 7 days after device implantation.ResultsSerum c‐TNT levels were significantly elevated 2 h after 15 J‐DT [0.008 (0.004–0.019) vs. 0.053 (0.037–0.068) ng/mL, p<0.001], but not ≤10 J‐DT [0.007 (0.004–0.018) ng/mL]. Similarly, serum H‐FABP levels were significantly elevated 2 h after 15 J‐DT (2.9±1.5 vs. 6.4±3.4 ng/mL, p<0.001), but not ≤10 J‐DT (2.7±1.5 ng/mL). The changes in c‐TNT and ...
Journal of atherosclerosis and thrombosis, Jan 5, 2016
Because the prevalence of hyperuricemia is lower in females than in males, the association betwee... more Because the prevalence of hyperuricemia is lower in females than in males, the association between hyperuricemia and cardiovascular disease has been frequently reported in females. Increased serum uric acid levels are associated with the presence of cardiovascular risk factors such as hypertension, renal dysfunction, insulin resistance, and metabolic syndrome. However, it is controversial whether hyperuricemia is an independent risk factor for coronary artery disease in both the genders. The purpose of this study was to investigate the relationship between serum uric acid levels and coronary plaque components assessed using integrated backscatter intravascular ultrasound (IB-IVUS) in males and females. In total, 385 patients (298 males and 87 females) who underwent percutaneous coronary intervention using IB-IVUS were divided into three groups in each gender according to their serum uric acid levels. We characterized tissue from coronary plaques in culprit lesions. Serum uric acid l...
In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to car... more In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to cardiac hypertrophy, which affects morbidity and mortality. In patients with renal insufficiency and heart failure, the expression of midkine, a heparin-binding growth factor, is increased. Therefore, we investigated the association between midkine and EGFR in the induction of cardiac hypertrophy and dysfunction in chronic kidney disease. We performed subtotal nephrectomies in midkine-knockout mice and wild-type mice. We found that subtotal nephrectomy-induced cardiac hypertrophy and phosphorylation of extracellular signal-regulated kinase 1/2 and AKT were attenuated in midkine-knockout mice compared with wild-type mice. An antiphosphotyrosine receptor antibody array was used to demonstrate that EGFR phosphorylation in the heart was also lower in midkine-knockout mice than in wild-type mice. Midkine induced EGFR, extracellular signal-regulated kinase 1/2, and AKT phosphorylation and led to ...
A 14-year-old patient was diagnosed with hypertrophic cardiomyopathy associated with Wolff-Parkin... more A 14-year-old patient was diagnosed with hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome. The two-dimensional speckle tracking strain method showed normal left ventricular local contraction, but the peak systolic longitudinal strain of the right ventricular (RV) anterior wall was earlier than that of the septal wall. As expected, the location of the accessory pathway was at the RV anterior wall. The patient's RV local contraction was normalized by successful radiofrequency application.
BackgroundImmediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter abl... more BackgroundImmediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter ablation is commonly observed within 3 d after the procedure. The mechanism and pharmacological management of immediate AF recurrence remain unclear.MethodsA total of 50 consecutive patients with paroxysmal AF were randomized to receive either low‐dose landiolol (landiolol group) or a placebo (placebo group). In the landiolol group, intravenous landiolol (0.5 μg kg−1 min−1) was administered for 3 d after AF ablation.ResultsNo serious adverse event associated with RF catheter ablation or landiolol administration was observed. The prevalence of immediate AF recurrence (≤3 d after RF catheter ablation) was significantly lower in the landiolol group than in the placebo group (16% vs. 48%, p=0.015). Although the postprocedural change in heart rate was significantly lower in the landiolol group compared to that in the placebo group, the changes in blood pressure and body temperature were not diff...
Objective The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudina... more Objective The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudinal Study (JALS) score, which is calculated from the traditional atherosclerotic coronary risk, is associated with the incidence of coronary vasospasms. Methods We performed vasospasm provocation tests with acetylcholine in 109 patients referred to our hospital due to suspected vasospastic angina and subsequently calculated the atherosclerotic risk score according to the JALS score. Consequently, coronary vasospasms were evoked in 51 patients. The patients were divided into three groups according to the tertile of the JALS score: 1st, <28, n=36; 2nd, 28-41, n=36, 3rd, >42, n=37. The third tertile exhibited the greatest risk for vasospasms. A multivariate logistic regression analysis revealed that the JALS score (odds ratio: 1.686, p<0.05) was independently associated with the incidence of vasospasms. Conclusion The JALS score can serve as a useful tool for evaluating patients with...
American journal of physiology. Heart and circulatory physiology, 2002
The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the re... more The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the relationship between electrical abnormalities and ventricular arrhythmia by using experimental heart failure models. Sixty unipolar electrograms were recorded from the entire cardiac surface in control dogs (n = 13) and pacing-induced heart failure dogs (n = 16). In failing hearts, activation time (AT) was delayed at the apex, and AT dispersion increased in failing hearts. Activation-recovery intervals (ARI) were prolonged mainly at the apex and ARI dispersion was significantly augmented. The slope of the ARI restitution curve, interaction of diastolic interval, and ARI in failing hearts was significantly steeper than in control hearts. Ventricular fibrillation (VF) was easily induced by programmed stimulation in failing hearts, whereas no arrhythmia occurred in control hearts. Computer simulation studies could reproduce the experimental results. Altering the ARI restitution to the steep s...
Chronic obstructive pulmonary disease is a known risk factor for cardiovascular death in Western ... more Chronic obstructive pulmonary disease is a known risk factor for cardiovascular death in Western countries. Because Japan has a low cardiovascular death rate, the association between a lower level of forced expiratory volume in 1 s (FEV 1) and mortality in Japan's general population is unknown. To clarify this, we conducted a community-based longitudinal study. This study included 3253 subjects, who received spirometry from 2004 to 2006 in Takahata, with a 7-year follow-up. The causes of death were assessed on the basis of the death certificate. In 338 subjects, airflow obstruction was observed by spirometry. A total of 127 subjects died. Cardiovascular death was the second highest cause of death in this population. The pulmonary functions of the deceased subjects were significantly lower than those of the subjects who were alive at the end of follow-up. The relative risk of death by all causes, respiratory failure, lung cancer, and cardiovascular disease was significantly increased with airflow obstruction. The Kaplan-Meier analysis showed that all-cause and cardiovascular mortality significantly increased with a worsening severity of airflow obstruction. After adjusting for possible factors that could influence prognosis, a Cox proportional hazard model analysis revealed that a lower level of FEV 1 was an independent risk factor for all-cause and cardiovascular mortality (per 10% increase; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.98; and HR, 0.72; 95% CI, 0.61-0.86, respectively). In conclusion, airflow obstruction is an independent risk factor for all-cause and cardiovascular death in the Japanese general population. Spirometry might be a useful test to evaluate the risk of cardiovascular death and detect the risk of respiratory death by lung cancer or respiratory failure in healthy Japanese individuals.
Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubu... more Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals 440 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (40.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3 ± 15.6 (n¼1886), A/T: 82.0 ± 15.5 (n¼652) and A/A: 87.4 ± 21.4 ml min À1 per 1.73m 2 (n¼66); mean ± s.d., P¼0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR o90 ml min À1 per 1.73m 2 ; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05-2.94, P¼0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.
The association between ongoing myocardial damage and outcomes in patients who have received an i... more The association between ongoing myocardial damage and outcomes in patients who have received an implantable cardioverter-defibrillator (ICD) is unclear. Consecutive patients with cardiomyopathy, who had received an ICD (n = 107, mean age 65 ± 11 years), were prospectively enrolled. Myocardial membrane injury (heart-type fatty acid binding protein [H-FABP] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.3 ng/mL) and myofibrillar injury (troponin T &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.01 ng/mL) were defined using receiver operating characteristic curves. Patients were followed for a median of 33.6 months, to an end point of appropriate ICD shock or cardiac death. Myocardial membrane injury (45%) and myofibrillar injury (41%) were equally prevalent among patients with cardiomyopathy who had received ICDs. Appropriate ICD shocks or cardiac death occurred in 31% and 15% of patients, respectively. Multivariate Cox regression analysis showed that serum H-FABP levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.3 ng/mL, but not troponin T levels, were a significant independent prognostic factor for cardiac events (hazard ratio 5.502, 95% confidence interval 1.705-17.75, P = .004). Subgroup analysis revealed that measuring H-FABP levels was valuable for anticipating event-free survival among patients with ICDs who were receiving amiodarone. High H-FABP levels also predicted subsequent outcomes in patients who had received ICDs for primary or secondary prevention. Evaluating myocardial damage using H-FABP may be a promising tool for predicting outcomes in patients with cardiomyopathy who have received ICDs.
Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenz... more Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Methods: Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with endpoints of cardiac death or re-hospitalization. Results: Serum concentration of pentosidine was significantly higher in NYHA class III/IV patients than in NYHA class I/II patients (P < 0.0001). Serum pentosidine was also higher in patients with cardiac events than in event free patients (P < 0.001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = 0.002). 2 JCF MS# 061472 R1 Patients were divided into 4 groups based on the serum pentosidine levels. The highest 4 th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Conclusions: Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure.
Background Changes in plasma volume, a marker of plasma volume expansion and contraction, are gai... more Background Changes in plasma volume, a marker of plasma volume expansion and contraction, are gaining attention in the field of cardiovascular disease because of its role in the prevention and management of heart failure. However, it remains unknown whether a 1-year change in plasma volume is a risk factor for all-cause, cardiovascular, and non-cardiovascular mortality in the general population. Methods and results We used a nationwide database of 134,291 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” check-up for 2 consecutive years between 2008 and 2011. A 1-year change in plasm volume was calculated using the Strauss–Davis-Rosenbaum formula. There were 220 cardiovascular deaths, 1,001 non-cardiovascular deaths including 718 cancer deaths, and 1,221 all-cause deaths during the follow-up period of 3.9 years. All subjects were divided into quintiles based on the 1-year change in plasma volume. Kaplan–Meier analysis demonstrate...
The prevalence of hypertension (HT) is still increasing and is a well-known risk for cardiovascul... more The prevalence of hypertension (HT) is still increasing and is a well-known risk for cardiovascular disease and mortality. The mechanisms by which HT is involved in the development of cardiovascular disease includes several complex processes such as the sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS), and oxidative stress. 5 Several guidelines, such as the Japanese Society of Hypertension (JSH) 2014, recommend lowering blood pressure (BP) to <140 and <90 mmHg for the primary A ortic artery disease (AAD), namely aortic artery dissection or aortic aneurysm rupture, is a major cause of sudden death. 1,2 In almost all cases of aortic aneurysm rupture, the patient dies before arriving at hospital; furthermore, the mortality rate ≤24 h after symptom onset reaches approximately 50-70% despite surgical treatment. 3 Similarly, the mortality rates in those with ascending aortic dissection between 24 h and 1 month after onset are 20% and 50%, respectively. 4 Therefore, it is critical to identify high-risk subjects and prevent the development of AAD in apparently healthy subjects using health checkups .
Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm... more Despite advances in medicine, aortic diseases (ADs) such as aortic dissection and aortic aneurysm rupture remain fatal with extremely high mortality rates. Owing to the relatively low prevalence of AD, the risk of AD-related death has not yet been elucidated. The aim of the present study was to examine whether hyperuricemia is a risk factor for AD-related mortality in the general population. We used a nationwide database of 474,725 subjects (age 40–75 years) who participated in the annual “Specific Health Check and Guidance in Japan” between 2008 and 2013. There were 115 deaths from aortic dissection and aortic aneurysm rupture during the follow-up period of 1,803,955 person-years. Kaplan–Meier analysis revealed that subjects with hyperuricemia had a higher rate of AD-related death than those without hyperuricemia. Multivariate Cox proportional hazard regression analysis demonstrated that hyperuricemia was an independent risk factor for AD-related death in the general population. Th...
In this paper, development and electrical characterization of sisal powder filled polyvinyl alcoh... more In this paper, development and electrical characterization of sisal powder filled polyvinyl alcohol (PVA) composites is reported. Dielectric measurements were conducted on these composites on a LCR meter in the temperature range from 30 to 150 °C and in the frequency range 1 kHz-10 kHz. The effects of temperature and frequency variation on dielectric constant (ε'), dielectric dissipation factor (tan δ) and on a. c. conductivity (σa.c.) were determined. On increasing the filler content, dielectric constant increased, it was mainly due to motion of the dipolar groups of the interfacial polarization occurring in the composites. The conductivity increased with rise in temperature.
Aims Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is incre... more Aims Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease and is increased with elderly population. However, effective drug therapy has not been established yet. This study aimed to investigate the role of microRNAs (miRs) in the development of CAVS. Methods and results We measured the expression of 10 miRs, which were reportedly involved in calcification by using human aortic valve tissue from patients who underwent aortic valve replacement with CAVS or aortic regurgitation (AR) and porcine aortic valve interstitial cells (AVICs) after treatment with osteogenic induction medium. We investigated whether a specific miR-inhibitor can suppress aortic valve calcification in wire injury CAVS mice model. Expression of miR-23a, miR-34a, miR-34c, miR-133a, miR-146a, and miR-155 was increased, and expression of miR-27a and miR-204 was decreased in valve tissues from CAVS compared with those from AR. Expression of Notch1 was decreased, and expression of Runt-related...
Background: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a ... more Background: Despite advances in endovascular therapy (EVT), peripheral artery disease (PAD) is a public health problem associated with high cardiovascular mortality. Iron deficiency (ID) is associated with poor clinical outcome in patients with heart disease, but whether ID is associated with the severity and clinical outcome of PAD remains unclear. Methods and Results: A total of 449 patients with PAD who received EVT and who had iron and red blood cell measurement were enrolled. ID was defined as transferrin saturation (TSAT) <20%, based on a previous report. TSAT and hemoglobin decreased with deteriorating Fontaine class. During a median follow-up period of 1,064 days, 71 major adverse cardiovascular and leg events (MACLE) and 47 major adverse cardiovascular events (MACE) were noted. All patients were divided into 2 groups based on the presence of ID. On Kaplan-Meier analysis, patients with ID had higher rates of MACE and MACLE than those without. On multivariate Cox proportional hazard regression analysis, TSAT and hemoglobin were independently associated with MACLE. Addition of TSAT to the known risk factors significantly improved the net reclassification index and integrated discrimination improvement. Conclusions: ID, as assessed by TSAT, was associated with the severity and clinical outcome of PAD, indicating that it could be a therapeutic target.
The purpose of this study was therefore to determine whether skeletal muscle mass and intramuscul... more The purpose of this study was therefore to determine whether skeletal muscle mass and intramuscular fat deposition evaluated on CT can predict major adverse cardiovascular and limb events (MACLE) in patients with PAD. Methods Subjects This prospective study involved 327 consecutive patients admitted to the present hospital with PAD. PAD was diagnosed using the ankle brachial index (ABI) and contrast-enhanced CT. Endovascular therapy (EVT) was performed by experienced cardiologists according to the TransAtlantic Inter-Society Consensus II (TASC II) guideline recommendations. Fontaine classes II, III, and IV were defined as intermittent claudication, rest pain, and critical limb ischemia (CLI), respectively. Exclusion criteria included acute coronary syndrome (ACS) ≤3 months prior,
Circulation journal : official journal of the Japanese Circulation Society, Jan 23, 2018
Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardio... more Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear.Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score- and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the ...
A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not re... more A modest rise in blood pressure (BP) reportedly increases cardiovascular mortality despite not reaching obvious hypertension, suggesting that target organ damages are latently induced by slight BP rising. The goal of this study was to determine whether presence of subclinical myocardial damage can predict the future development of hypertension in the normotensive general population. The cohort study was conducted with subjects who participated in a community-based annual health check. Normotensive subjects without prior cardiovascular diseases at baseline were eligible for analyses (n = 524, mean age 58 ± 9 years; 53% women). We measured heart-type fatty acid binding protein (H-FABP) at baseline as a biomarker of ongoing myocardial damage. Longitudinal changes in BP were examined during median follow-up period of 6.2 years, and we investigated the association between the baseline H-FABP level and longitudinal BP changes. During the follow-up, 177 subjects (34%) developed hypertensio...
BackgroundThe aim of this study was to establish a minimally invasive defibrillation testing (DT)... more BackgroundThe aim of this study was to establish a minimally invasive defibrillation testing (DT) protocol for patients with implantable cardioverter defibrillators (ICDs).MethodsTwo different energy DTs were performed, immediately after (15 J‐DT) and 7 days after (≤10 J‐DT) device implantation, in 20 consecutive ICD implantation patients. Cardiac‐troponin T (c‐TNT) and heart‐type fatty acid binding protein (H‐FABP) levels were measured before implantation, 2 h after implantation, and 1 day after each DT. For an additional 122 patients with ICD, we retrospectively analyzed 203 DTs immediately and 7 days after device implantation.ResultsSerum c‐TNT levels were significantly elevated 2 h after 15 J‐DT [0.008 (0.004–0.019) vs. 0.053 (0.037–0.068) ng/mL, p<0.001], but not ≤10 J‐DT [0.007 (0.004–0.018) ng/mL]. Similarly, serum H‐FABP levels were significantly elevated 2 h after 15 J‐DT (2.9±1.5 vs. 6.4±3.4 ng/mL, p<0.001), but not ≤10 J‐DT (2.7±1.5 ng/mL). The changes in c‐TNT and ...
Journal of atherosclerosis and thrombosis, Jan 5, 2016
Because the prevalence of hyperuricemia is lower in females than in males, the association betwee... more Because the prevalence of hyperuricemia is lower in females than in males, the association between hyperuricemia and cardiovascular disease has been frequently reported in females. Increased serum uric acid levels are associated with the presence of cardiovascular risk factors such as hypertension, renal dysfunction, insulin resistance, and metabolic syndrome. However, it is controversial whether hyperuricemia is an independent risk factor for coronary artery disease in both the genders. The purpose of this study was to investigate the relationship between serum uric acid levels and coronary plaque components assessed using integrated backscatter intravascular ultrasound (IB-IVUS) in males and females. In total, 385 patients (298 males and 87 females) who underwent percutaneous coronary intervention using IB-IVUS were divided into three groups in each gender according to their serum uric acid levels. We characterized tissue from coronary plaques in culprit lesions. Serum uric acid l...
In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to car... more In chronic kidney disease, activation of the epidermal growth factor receptor (EGFR) leads to cardiac hypertrophy, which affects morbidity and mortality. In patients with renal insufficiency and heart failure, the expression of midkine, a heparin-binding growth factor, is increased. Therefore, we investigated the association between midkine and EGFR in the induction of cardiac hypertrophy and dysfunction in chronic kidney disease. We performed subtotal nephrectomies in midkine-knockout mice and wild-type mice. We found that subtotal nephrectomy-induced cardiac hypertrophy and phosphorylation of extracellular signal-regulated kinase 1/2 and AKT were attenuated in midkine-knockout mice compared with wild-type mice. An antiphosphotyrosine receptor antibody array was used to demonstrate that EGFR phosphorylation in the heart was also lower in midkine-knockout mice than in wild-type mice. Midkine induced EGFR, extracellular signal-regulated kinase 1/2, and AKT phosphorylation and led to ...
A 14-year-old patient was diagnosed with hypertrophic cardiomyopathy associated with Wolff-Parkin... more A 14-year-old patient was diagnosed with hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome. The two-dimensional speckle tracking strain method showed normal left ventricular local contraction, but the peak systolic longitudinal strain of the right ventricular (RV) anterior wall was earlier than that of the septal wall. As expected, the location of the accessory pathway was at the RV anterior wall. The patient's RV local contraction was normalized by successful radiofrequency application.
BackgroundImmediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter abl... more BackgroundImmediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter ablation is commonly observed within 3 d after the procedure. The mechanism and pharmacological management of immediate AF recurrence remain unclear.MethodsA total of 50 consecutive patients with paroxysmal AF were randomized to receive either low‐dose landiolol (landiolol group) or a placebo (placebo group). In the landiolol group, intravenous landiolol (0.5 μg kg−1 min−1) was administered for 3 d after AF ablation.ResultsNo serious adverse event associated with RF catheter ablation or landiolol administration was observed. The prevalence of immediate AF recurrence (≤3 d after RF catheter ablation) was significantly lower in the landiolol group than in the placebo group (16% vs. 48%, p=0.015). Although the postprocedural change in heart rate was significantly lower in the landiolol group compared to that in the placebo group, the changes in blood pressure and body temperature were not diff...
Objective The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudina... more Objective The aim of this study was to investigate whether the Japan Arteriosclerosis Longitudinal Study (JALS) score, which is calculated from the traditional atherosclerotic coronary risk, is associated with the incidence of coronary vasospasms. Methods We performed vasospasm provocation tests with acetylcholine in 109 patients referred to our hospital due to suspected vasospastic angina and subsequently calculated the atherosclerotic risk score according to the JALS score. Consequently, coronary vasospasms were evoked in 51 patients. The patients were divided into three groups according to the tertile of the JALS score: 1st, <28, n=36; 2nd, 28-41, n=36, 3rd, >42, n=37. The third tertile exhibited the greatest risk for vasospasms. A multivariate logistic regression analysis revealed that the JALS score (odds ratio: 1.686, p<0.05) was independently associated with the incidence of vasospasms. Conclusion The JALS score can serve as a useful tool for evaluating patients with...
American journal of physiology. Heart and circulatory physiology, 2002
The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the re... more The mechanism of arrhythmogenicity in heart failure remains poorly understood. We examined the relationship between electrical abnormalities and ventricular arrhythmia by using experimental heart failure models. Sixty unipolar electrograms were recorded from the entire cardiac surface in control dogs (n = 13) and pacing-induced heart failure dogs (n = 16). In failing hearts, activation time (AT) was delayed at the apex, and AT dispersion increased in failing hearts. Activation-recovery intervals (ARI) were prolonged mainly at the apex and ARI dispersion was significantly augmented. The slope of the ARI restitution curve, interaction of diastolic interval, and ARI in failing hearts was significantly steeper than in control hearts. Ventricular fibrillation (VF) was easily induced by programmed stimulation in failing hearts, whereas no arrhythmia occurred in control hearts. Computer simulation studies could reproduce the experimental results. Altering the ARI restitution to the steep s...
Chronic obstructive pulmonary disease is a known risk factor for cardiovascular death in Western ... more Chronic obstructive pulmonary disease is a known risk factor for cardiovascular death in Western countries. Because Japan has a low cardiovascular death rate, the association between a lower level of forced expiratory volume in 1 s (FEV 1) and mortality in Japan's general population is unknown. To clarify this, we conducted a community-based longitudinal study. This study included 3253 subjects, who received spirometry from 2004 to 2006 in Takahata, with a 7-year follow-up. The causes of death were assessed on the basis of the death certificate. In 338 subjects, airflow obstruction was observed by spirometry. A total of 127 subjects died. Cardiovascular death was the second highest cause of death in this population. The pulmonary functions of the deceased subjects were significantly lower than those of the subjects who were alive at the end of follow-up. The relative risk of death by all causes, respiratory failure, lung cancer, and cardiovascular disease was significantly increased with airflow obstruction. The Kaplan-Meier analysis showed that all-cause and cardiovascular mortality significantly increased with a worsening severity of airflow obstruction. After adjusting for possible factors that could influence prognosis, a Cox proportional hazard model analysis revealed that a lower level of FEV 1 was an independent risk factor for all-cause and cardiovascular mortality (per 10% increase; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.98; and HR, 0.72; 95% CI, 0.61-0.86, respectively). In conclusion, airflow obstruction is an independent risk factor for all-cause and cardiovascular death in the Japanese general population. Spirometry might be a useful test to evaluate the risk of cardiovascular death and detect the risk of respiratory death by lung cancer or respiratory failure in healthy Japanese individuals.
Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubu... more Nephronophthisis (NPHP) 4 gene coding nephrocystin-4 is involved in the development of renal tubules and its congenital mutations cause juvenile end-stage renal disease, NPHP. To investigate the association between single-point single-nucleotide polymorphism (SNP) of NPHP4 gene and renal function, we conducted a cross-sectional study in Japanese population. The subjects of this study were non-diabetic general population consisting of 2604 individuals 440 years in Takahata town, Japan. We genotyped 11 SNPs within NPHP4 gene that displayed frequent minor allele frequencies (40.1) in Japanese general population. Among 11 SNPs in NPHP4 gene, only rs1287637 that induces amino acid substitution (A (Gln)/T (Leu)), located in the acceptor site of exon 21, showed a significant association with estimated glomerular filtration rate (eGFR; T/T: 81.3 ± 15.6 (n¼1886), A/T: 82.0 ± 15.5 (n¼652) and A/A: 87.4 ± 21.4 ml min À1 per 1.73m 2 (n¼66); mean ± s.d., P¼0.006). This SNP was not in linkage disequilibrium with the surrounding SNPs. The multivariate analysis adjusted with possible confounders showed that the A/T+T/T genotype of rs1287637 was independently associated with reduced renal function (eGFR o90 ml min À1 per 1.73m 2 ; odds ratio (OR) 1.75, 95% confidence interval (CI) 1.05-2.94, P¼0.033). These results indicate the novel and independent association between single-point SNP rs1287637 in NPHP4 gene and renal function in non-diabetic Japanese population.
The association between ongoing myocardial damage and outcomes in patients who have received an i... more The association between ongoing myocardial damage and outcomes in patients who have received an implantable cardioverter-defibrillator (ICD) is unclear. Consecutive patients with cardiomyopathy, who had received an ICD (n = 107, mean age 65 ± 11 years), were prospectively enrolled. Myocardial membrane injury (heart-type fatty acid binding protein [H-FABP] &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.3 ng/mL) and myofibrillar injury (troponin T &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.01 ng/mL) were defined using receiver operating characteristic curves. Patients were followed for a median of 33.6 months, to an end point of appropriate ICD shock or cardiac death. Myocardial membrane injury (45%) and myofibrillar injury (41%) were equally prevalent among patients with cardiomyopathy who had received ICDs. Appropriate ICD shocks or cardiac death occurred in 31% and 15% of patients, respectively. Multivariate Cox regression analysis showed that serum H-FABP levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;4.3 ng/mL, but not troponin T levels, were a significant independent prognostic factor for cardiac events (hazard ratio 5.502, 95% confidence interval 1.705-17.75, P = .004). Subgroup analysis revealed that measuring H-FABP levels was valuable for anticipating event-free survival among patients with ICDs who were receiving amiodarone. High H-FABP levels also predicted subsequent outcomes in patients who had received ICDs for primary or secondary prevention. Evaluating myocardial damage using H-FABP may be a promising tool for predicting outcomes in patients with cardiomyopathy who have received ICDs.
Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenz... more Background: Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure. Methods: Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with endpoints of cardiac death or re-hospitalization. Results: Serum concentration of pentosidine was significantly higher in NYHA class III/IV patients than in NYHA class I/II patients (P < 0.0001). Serum pentosidine was also higher in patients with cardiac events than in event free patients (P < 0.001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = 0.002). 2 JCF MS# 061472 R1 Patients were divided into 4 groups based on the serum pentosidine levels. The highest 4 th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold). Conclusions: Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure.
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Papers by Tetsu Watanabe