[show abstract][hide abstract] ABSTRACT: To investigate the independent associations of proteinuria and the estimated glomerular filtration rate (eGFR) with incident hypertension.
We investigated 29,181 Japanese males 18-59years old without hypertension in 2000 and examined whether proteinuria and the eGFR predicted incident hypertension independently over 10years. Incident hypertension was defined as a newly detected blood pressure of ≥140/90mmHg and/or the initiation of antihypertensive drugs. Proteinuria and the eGFR were categorized as dipstick negative (reference), trace or ≥1+ and ≥60 (reference), 50-59.9 or <50ml/min/1.73m(2), respectively. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of incident hypertension.
At baseline, 236 (0.8%) and 477 (1.6%) participants had trace and ≥1+ dipstick proteinuria, while 1,416 (4.9%) and 129 (0.4%) participants had an eGFR of 50-59.9 and <50ml/min/1.73m(2), respectively. The adjusted HRs were significant for proteinuria ≥1+ (HRs 1.20, 95% CI: 1.06-1.35) and an eGFR of <50ml/min/1.73m(2) (1.29, 1.03-1.61). When two non-referent categories were combined (dipstick≥trace vs. negative and eGFR <60 vs. ≥60ml/min/1.73m(2)), the association was more significant for proteinuria (1.15, 1.04-1.27) than for eGFR (0.99, 0.92-1.07).
Proteinuria and a reduced eGFR are independently associated with future hypertension in young to middle-aged Japanese males.
[show abstract][hide abstract] ABSTRACT: Recently, we reported that angiotensin II receptor blocker (ARB), valsartan, and calcium channel blocker (CCB), amlodipine, had similar effects on the prevention of cardiovascular disease (CVD) events in diabetic hypertensive patients. We assessed the difference of cardiovascular protective effects between ARB and CCB in patients with and without previous CVD, respectively. A total of 1,150 Japanese diabetic hypertensive patients were randomized to either valsartan or amlodipine treatment arms, which were additionally divided into 2 groups according to the presence of previous CVD at baseline (without CVD, n = 818; with CVD, n = 332). The primary composite outcomes were sudden cardiac death, acute myocardial infarction, stroke, coronary revascularization, or hospitalization for heart failure. The incidence of primary end point events in patients with previous CVD was 3.5-times greater than that in patients without previous CVD (64.1 vs 17.9/1,000 person-years). The ARB- and the CCB-based treatment arms showed similar incidence of composite CVD events in both patients without previous CVD (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.76 to 2.40) and those with previous CVD (HR 0.79, 95% CI 0.48 to 1.31). The ARB-treatment arm showed less incidence of stroke compared with the CCB-based treatment arm in patients with previous CVD (HR 0.24, 95% CI 0.05 to 1.11, p = 0.068), whereas the 2 treatment arms showed similar incidence of stroke in patients without previous CVD (HR 1.52, 95% CI 0.59 to 3.91). In conclusion, the ARB- and the CCB-based treatments exerted similar protective effects of CVD events regardless of the presence of previous CVD. For stroke events, the ARB may have more protective effects than the CCB in diabetic hypertensive patients with previous CVD.
The American journal of cardiology 09/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mitochondrial damage is associated with histologic myocardial fibrosis. Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) can be used to identify focal fibrosis. We examined whether myocardial fibrosis on CMR and collagen volume fraction (CVF) from biopsies correlated with left ventricular (LV) and mitochondrial function in patients with nonischemic dilated cardiomyopathy (DCM).
Fifty-nine DCM patients underwent CMR, cardiac catheterization, and endomyocardial biopsy. Minimum first derivative of LV pressure (LVdP/dtmin) was measured as an index of LV relaxation. Mitochondrial RNA expression was also analyzed. For quantitative analysis of myocardial fibrosis, percentage LGE (%LGE) and CVF were calculated. Patients were divided into 2 groups on the basis of the presence (LGE group; n = 27) or absence (non-LGE group; n = 32) of LGE. Mean CVF and absolute value of LVdP/dtmin were significantly higher and lower, respectively, in the LGE group than in the non-LGE group. Multivariate analysis revealed that %LGE was an independent determinant of LVdP/dtmin. The abundance of mitochondrial enzyme mRNA was significantly lower in the LGE group.
Noninvasive CMR imaging is more useful in predicting diastolic dysfunction than invasive histologic assessments. In addition, it might indicate mitochondrial dysfunction in DCM.
Journal of cardiac failure 08/2013; 19(8):557-64. · 3.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: The purpose of the present study was to compare the 5-year clinical outcomes after implantation of drug-eluting stent (DES) and bare-metal stent (BMS) in Japanese patients with acute myocardial infarction (AMI). Methods and Results: This study was a subgroup analysis of the Nagoya Acute Myocardial Infarction Study (NAMIS). It included 658 AMI patients, of which 280 were treated with a DES and 378 with a BMS. The major adverse cardiac event (MACE)-free rates during the 5-year follow-up period were similar between the 2 groups (95.7% vs. 96.8%, P=0.482). A significant difference was seen, however, in the target lesion revascularization (TLR) rates (7.9% vs. 17.7%, P<0.0001). Interestingly, there was no significant difference between the 2 groups from year 1 to 5 with regard to late TLR (2.5% vs. 2.1%, P=0.906), despite the markedly lower incidence of TLR within the first year in the DES group compared with the BMS group (5.4% vs. 15.6%, P<0.0001). Conclusions: In this long-term follow-up analysis of DES compared to BMS in Japanese patients with AMI, there was no significant difference in the incidence of MACE. Although a lower rate of TLR was observed in DES group within the first year, the superiority of DES in relation to the incidence of TLR disappeared after the first year following primary percutaneous coronary intervention.
[show abstract][hide abstract] ABSTRACT: Cardiac troponins provide diagnostic and prognostic information on ischemic heart disease, but their roles in hypertrophic cardiomyopathy (HCM) are unclear. We sought to investigate the associations between elevated serum cardiac troponins T (cTnT) and I (cTnI) levels and cardiac injury in patients with HCM. We measured serum cTnT and cTnI in a peripheral vein of 73 consecutive HCM patients in stable condition. In addition, to examine the transcardiac release of cTnT and that of cTnI, we measured them in the aortic root and coronary sinus. Mitochondrial- and Ca(2+)-handling-related gene expression assays were analyzed by endomyocardial biopsy specimens. Based on the median value of serum cTnT, we divided the patients into two groups [group A: cTnT < 0.008 ng/mL, (n = 35), group B: cTnT group ≥ 0.008 ng/mL, (n = 38)]. Left ventricular (LV) mass index was significantly higher, while LV ejection fraction was significantly lower, in group B than in group A. Meanwhile, there was a significantly positive correlation between the transcardiac gradient of serum cTnT or cTnI, and the mRNA level of troponin I3 (r = 0.473, r = 0.516, respectively). The mRNA level of troponin T2 significantly correlated with mRNA levels of sarco-endoplasmic reticulum Ca(2+)-ATPase 2, cytochrome c oxidase subunit 5B, and troponin I3 (r = 0.486, r = 0.957, r = 0.633, respectively). These findings indicate that both elevated serum cTnT and cTnI might be associated with cardiac dysfunction in patients with HCM, resulting from the impairment of mitochondrial function and Ca(2+)-handling protein.
International Heart Journal 01/2013; 54(4):202-6. · 1.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE:: To clarify whether the impact of normal and high-normal BP (BP) per se on cardiovascular disease (CVD) and all-cause death differs depending on smoking status. METHODS AND RESULTS:: A prospective observational cohort study (median follow-up period: 7.5 years) was performed among 25 077 healthy nondiabetic Japanese men aged 20-61 years (mean age 37.3 years), whose BP was less than 150/95 mmHg and who were not on medication. Hazard ratios (HRs), adjusted by known risk factors and a change in annual BP during the follow-up, were calculated by the Cox proportional model with less than 119/75 mmHg as a reference. Among smokers, CVD events increased significantly from a SBP of 120 mmHg, with HRs of 2.68 (120-129 mmHg), 4.28 (130-139 mmHg), and 11.7 (140-149 mmHg). The CVD events also increased from a DBP of 75 mmHg (P for trend less than 0.0001), with 75-79 mmHg and 90-94 mmHg considered statistically significant. Among noncurrent smokers, 110-149 mmHg (SBP) and 75-89 mmHg (DBP) were not associated with elevated HRs for CVD. The relation between BP and all-cause mortality was similar among both current and noncurrent smokers: 140-149 mmHg (SBP) and 90-94 mmHg (DBP) were significantly associated with elevated risk, and 130-139 mmHg (SBP) among noncurrent smokers associated with elevated risk. CONCLUSION:: Young and middle-aged healthy Japanese individuals with normal and high-normal BP (120-139/75-89 mmHg) were at risk for CVD among smokers, even after adjusting for an annual change in BP.
Journal of hypertension 11/2012; · 4.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background: Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM). Methods and Results: The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (±standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5±10.7% and 204±219pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9μg/ml) and high IS (≥0.9μg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e' was significantly greater in the high IS group than in the low IS group. Furthermore, E/e' was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP. Conclusions: Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.
[show abstract][hide abstract] ABSTRACT: Background: Body fat percentage (BF%) determined by bioelectrical impedance analysis is widely used at home and in medical check-ups. However, the clinical significance of measuring BF% has not been studied in detail. Methods and Results: A cross-sectional study was carried out on a cohort of 10,774 middle-aged Japanese men who had undergone an annual check-up in 2008. Cut-off points were evaluated for body mass index (BMI), waist circumference (WC), and BF% for detecting participants with cardiovascular disease (CVD) risk factors (diabetes mellitus, hypertension, dyslipidemia), and effectiveness compared for each marker's cut-off point. Additionally, the effects of smoking on cut-off points were evaluated. The cut-off points of BMI, WC, and BF% for detecting participants with 1 or more CVD risk factors were 22.7kg/m(2), 81.4cm, and 20.3%, respectively. The cut-off points of BF% for 1 or more CVD risk factors classified 3.43% more subjects into correct categories than those of BMI (P<0.001). The cut-off points of BMI, WC, and BF% for detecting individuals with 3 CVD risk factors in current smokers were 24.9kg/m(2), 87.8cm, and 23.7%, while those in non-smokers were 23.3kg/m(2), 83.9cm, and 22.3%, respectively. Conclusions: BF% could be more effective in detecting individuals with early stage CVD risk accumulation than BMI. The cut-off points for current smokers were lower than those for non-smokers in all markers. (Circ J 2012; 76: 2435-2442).
[show abstract][hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) is induced by myocardial ischemia and is thought to facilitate cardiovascular repair after acute myocardial infarction (AMI). However, the association between the plasma VEGF levels and clinical outcome in AMI patients is unclear.
We evaluated 879 AMI patients undergoing successful primary revascularization within 24h of symptom onset. The patients were classified into 3 groups according to tertiles of plasma VEGF levels at 7 days after the onset of AMI. Major adverse cardiovascular and cerebrovascular events (MACCE), defined as cardiac death, recurrent acute coronary syndrome, hospital readmission for heart failure, or stroke, were assessed during the 6-month follow-up period. The incidence of MACCE was the least frequent in the middle tertile. Compared to the middle tertile, patients in the low tertile were at a significantly higher risk for MACCE even after adjusting for baseline characteristics (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.18-6.06, P=0.019). An absence of statin treatment before onset and a younger age (HR 0.54, 0.87; 95%CI 0.33-0.90, 0.76-0.99; P=0.017, 0.037; respectively) were significantly associated with low VEGF.
Low plasma VEGF levels at 7 days after the onset of AMI were associated with a significantly increased risk for MACCE during 6 months of follow-up.
[show abstract][hide abstract] ABSTRACT: It has not been fully examined whether angiotensin II receptor blocker is superior to calcium channel blocker to reduce cardiovascular events in hypertensive patients with glucose intolerance. A prospective, open-labeled, randomized, controlled trial was conducted for Japanese hypertensive patients with type 2 diabetes mellitus or impaired glucose tolerance. A total of 1150 patients (women: 34%; mean age: 63 years; diabetes mellitus: 82%) were randomly assigned to receive either valsartan- or amlodipine-based antihypertensive treatment. Primary outcome was a composite of acute myocardial infarction, stroke, coronary revascularization, admission attributed to heart failure, or sudden cardiac death. Blood pressure was 145/82 and 144/81 mm Hg, and glycosylated hemoglobin was 7.0% and 6.9% at baseline in the valsartan group and the amlodipine group, respectively. Both of them were equally controlled between the 2 groups during the study. The median follow-up period was 3.2 years, and primary outcome had occurred in 54 patients in the valsartan group and 56 in the amlodipine group (hazard ratio: 0.97 [95% CI: 0.66-1.40]; P=0.85). Patients in the valsartan group had a significantly lower incidence of heart failure than in the amlodipine group (hazard ratio: 0.20 [95% CI: 0.06-0.69]; P=0.01). Other components and all-cause mortality were not significantly different between the 2 groups. Composite cardiovascular outcomes were comparable between the valsartan- and amlodipine-based treatments in Japanese hypertensive patients with glucose intolerance. Admission because of heart failure was significantly less in the valsartan group.
[show abstract][hide abstract] ABSTRACT: Although the circadian variation of catecholamine has been reported, that of the pulse wave velocity (PWV) has not. Brachial ankle (ba) PWV is associated with well-established indices of central stiffness. It is not known whether arterial stiffness is associated with catecholamine. The aim of the present study was to evaluate the changes in baPWV and those on the plasma epinephrine and norepinephrine levels in the morning and evening in hypertensive patients (HPs) and normotensive subjects (NSs). The baPWV and blood pressure (BP) were measured in 14 NSs (14 males, 39 ± 5 years) and 10 HPs (9 males and 1 female, 55 ± 13 years) at 06:00 h, noon, 18:00 h, and midnight, respectively. The plasma epinephrine and norepinephrine levels were measured in 14 NSs and 5 HPs at 06:00 h and 18:00 h, respectively. There was no significant difference in BPs at 06:00 h, noon, 18:00 h, and midnight in either NSs or HPs. The baPWV at 06:00 h was significantly lower than that at noon, 18:00 h, and midnight in NSs (P = 0.01, 0.04, and 0.0008, respectively). The plasma epinephrine and norepinephrine levels at 06:00 h were markedly lower than those at 18:00 h in NSs (P = 0.002 and 0.003, respectively). There were no significant changes in the baPWV of HPs at 06:00 h, noon, 18:00 h, or midnight. The plasma epinephrine and norepinephrine levels at 06:00 h were notably lower than those at 18:00 h in HPs (P = 0.004 and 0.01, respectively). Only NSs showed a significant reduction in the baPWV with a decrease in the plasma catecholamine levels in the morning, suggesting that the baPWV of NSs may be correlated with the variation of the plasma catecholamine levels.
Heart and Vessels 10/2011; 27(5):493-8. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: The association between subjects with metabolic syndrome (MS) who were considered not to require medication by their attending physicians and all-cause mortality, ischemic heart disease (IHD) and cardiovascular disease (CVD) remains unknown and should be clarified.
This is an observational longitudinal cohort study with a median follow-up of 7.5 years performed for 25,471 Japanese men aged 20-61 years who were not on medication. We used a modified definition of MS from the Japanese Society of Internal Medicine and the NCEP ATPIII, both of which employed body mass index instead of waist circumference. MS was associated with increased rates of all-cause death (adjusted hazard ratio (HR): 4.88 [95% confidence interval, 2.96-7.66]), IHD (3.17 [1.06-7.65]), and CVD (2.63 [1.32-4.72]). In contrast, overweight subjects with no component or one component had similar rates to subjects of normal weight. Any combination of the three MS components was associated with significantly greater rates of all-cause mortality (HR: 3.18-11.2) and IHD (HR: 3.17-8.24), whereas blood pressure elevation plus dyslipidaemia was associated with a significantly higher rate of CVD (HR: 3.27). In any endpoint, MS defined by Japanese criteria had higher HRs than defined by NCEP ATP III criteria.
Young and middle-aged Japanese men with MS who had been viewed as not needing medication already showed increased rates of all-cause mortality, IHD and CVD. Additionally, the event rate depended on the specific combination of metabolic syndrome components.
European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 02/2011; 18(4):574-80. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Smoking is still a major health problem among males in Japan. The effects of smoking and quitting on mortality and cardiovascular disease (CVD) need updating.
This was a prospective cohort study with a median follow-up of 7.5 years of a total of 25,464 healthy male Japanese workers aged 20-61 years who were not on any medication. The adjusted hazard ratios (HR; 95% confidence interval) for all-cause death were 1.51 (0.73, 2.94), 1.68 (1.07, 2.70), 1.30 (0.70, 2.34), and those for total CVD events 1.91 (0.72, 4.67), 2.94 (1.65, 5.63), and 3.25 (1.69, 6.54) for light smokers (1-10 cigarettes/day), moderate smokers (11-20/day), and heavy smokers (≥ 21/day) compared to never-smokers, respectively. Total CVD events increased dose-dependently as the number of cigarettes/day increased. Acute myocardial infarction was increased at any level of smoking. Stroke was increased at a moderate level of smoking. Quitting for ≥ 4 years, compared with continuing smokers, reduced the HR for all-cause death to 0.64 (0.38, 1.01), and total CVD events to 0.34 (0.17, 0.62).
In healthy young- and middle-aged Japanese males, a significant increase in HR for total CVD events was confirmed for a smoking level of 11-20 cigarettes/day. Quitting reduced the HR for total CVD events, with quitting for ≥ 4 years being statistically significant. A similar trend was observed for all-cause mortality.
[show abstract][hide abstract] ABSTRACT: Inhibitors of the renin angiotensin system are recommended as the first-line medications for diabetic hypertensive patients. However, there is less evidence supporting this recommendation especially among East Asians, a population with a unique distribution of cardiovascular disease compared to the Western population.
The NAGOYA HEART Study is a prospective randomized open-label blinded-endpoint study to compare an angiotensin II receptor blocker, valsartan, and a calcium channel blocker, amlodipine, regarding their efficacies on cardiovascular morbidity and mortality in Japanese hypertensive patients with glucose intolerance. Of 1168 eligible patients, we enrolled 1150 patients from October 2004 to January 2009. The participants will be followed for more than a median follow-up period of 3 years. The primary composite endpoint includes myocardial infarction, stroke, coronary revascularization, and admission due to congestive heart failure or sudden cardiac death. Any of these events are adjudicated by an independent committee under blinded information regarding the treatment arm. Secondary endpoints include all-cause mortality, changes in glucose tolerance status, kidney function, left ventricular structure measured by echocardiogram, and incident atrial fibrillation/flutter. The study was registered at ClinicalTrials.gov NCT00129233.
The NAGOYA HEART Study will provide us with a relevant insight for appropriate treatment of hypertension with glucose intolerance.
Journal of Cardiology 07/2010; 56(1):111-7. · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective
Circulating CD34+CD133+ cells are one of the main sources of circulating endothelial progenitor cells (EPCs). Age is inversely related to the number and function of CD34+CD133+ progenitor cells in stable coronary artery disease (CAD), but the relationship remains unclear in acute myocardial infarction (AMI). The authors aimed to clarify how ageing affects the number and function of mobilised CD34+CD133+ progenitor cells in AMI.Design and resultsCirculating CD34+CD133+ progenitor cells were measured by flow cytometry. Measurements were made at admission for CAD, or on day 7 after the onset of AMI. In stable CAD (n=131), circulating CD34+CD133+ cells decreased with age (r=−0.344, p
[show abstract][hide abstract] ABSTRACT: Endothelial progenitor cells (EPCs) have been assumed to maintain vascular endothelial integrity, so the present study investigated whether the functional capacity of EPCs correlates with endothelial function in healthy young subjects, as has been confirmed in aged subjects with atherosclerotic disease.
EPCs in 41 healthy, young male nonsmokers (age 33.1 +/-3.9 years, mean +/- SD) were characterized. The correlation between flow-mediated vasodilation (FMD) and the number of EPCs or the plasma concentrations of growth factors, such as vascular endothelial growth factor, did not reach statistical significance. However, FMD was significantly correlated with the EPC differentiation index, defined as the ratio of the number of EPCs to the total number of adherent cells (r=0.391, P=0.011) and the abundance of endothelial nitric oxide synthase mRNA (r=0.340, P=0.030).
In healthy young men, despite a lack of correlation of the number or colony counts of EPCs, the ability of circulating progenitor cells to differentiate into an endothelial lineage is closely correlated with endothelial function. This cell function assay may serve as a novel biomarker for vascular function in healthy subjects in the pre-atherosclerotic stage.