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JAMA internal medicine. 02/2013; 173(4):325-6.
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ABSTRACT: OBJECTIVE
To examine the BMI-stratified associations between diabetes and the risks of all-cause death, cardiovascular disease (CVD) death, and cancer death.RESEARCH DESIGN AND METHODS
Using a prospective study with 12 rural Japanese general populations (n = 3,641, mean age, 53.7 years; 33.5% men), we examined the associations between diabetes and the risk of all-cause death, CVD death, and cancer death. We also examined the effects of BMI and age on such associations.RESULTSDuring an average duration of 10.2 years (37,278 person-years), 240 deaths occurred (54 deaths from CVD, 101 from cancer, and 85 from other causes). Cox regression analysis showed leanness (defined as the lowest quartile of entire BMI; mean, 19.5 kg/m(2)), but not obesity (BMI ≥25 kg/m(2)), and diabetes were independently associated with an increased risk of all-cause death (hazard ratio [HR] 1.70 and 1.65, respectively; both P < 0.01.). Stratification with cause-specific deaths showed that leanness and obesity were associated with CVD death (HR 3.77 and 2.94, respectively), whereas diabetes was associated with cancer death (HR 1.87; all P < 0.05). The increased risk of all-cause death in diabetes was substantially higher in lean subjects aged <65 years (HR 3.4) or those aged ≥65 years (HR 4.2), whereas the risk in obese diabetes patients was significant only in subjects aged <65 years (HR 2.32; all P < 0.05).CONCLUSIONS
Among the Japanese general population, diabetes confers an increased risk of all-cause death. Particular attention must be paid to the pronounced high mortality in diabetes accompanied with leanness, regardless of age.
Diabetes care 12/2012; · 8.09 Impact Factor
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JAMA The Journal of the American Medical Association 11/2012; 308(20):2079-80; author reply 2080-1. · 30.03 Impact Factor
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ABSTRACT: BACKGROUND: Ultrasound-determined carotid intima-media thickness (IMT) is widely used as an indicator of generalized atherosclerotic burden, but there are limited autopsy findings in support of the association, directly. METHODS: We performed an autopsy analysis (n = 111, mean 68.8 years; 65.0% men; 86% non-cardiovascular disease death) to examine the associations of microscopy-determined carotid IMT including plaque thickness with the severity of atherosclerosis in the generalized arteries. RESULTS: Microscopy-determined carotid IMT was associated with the extent of intima/media layer ratio of the vasculature, a marker of atherosclerosis, in each structure examined, i.e., coronary artery, cerebrovasculature, thoracic aorta, abdominal aorta, and iliac artery (R = 0.31-0.42; all P < 0.01). The prevalence of a necrotic core in the coronary artery, cerebrovasculature, thoracic aorta, abdominal aorta, and iliac artery increased in accordance with increasing microscopy-determined carotid IMT (all P < 0.05). CONCLUSION: Our autopsy analysis confirms the validity of carotid IMT including plaque thickness as an indicator of generalized atherosclerosis.
Atherosclerosis 10/2012; · 3.79 Impact Factor
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Journal of Orthopaedic Science 08/2012; · 0.84 Impact Factor
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Kidney International 08/2012; 82(4):489. · 6.61 Impact Factor
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Yuji Sato, Yuichiro Yano,
Shouichi Fujimoto,
Tsuneo Konta,
Kunitoshi Iseki,
Toshiki Moriyama,
Kunihiro Yamagata,
Kazuhiko Tsuruya,
Hideaki Yoshida,
Koichi Asahi,
Issei Kurahashi,
Yasuo Ohashi,
Tsuyoshi Watanabe
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ABSTRACT: Background
There is little data on the assessment of prediabetes with proteinuria.Methods
This is a cross-sectional cohort study assessing prediabetes with proteinuria in a large Japanese population. Using a nationwide health checkup database of 228 778 Japanese aged ≥20 years (median 66 years; 39.3% were men; none had pre-existing cardiovascular disease), we examined the association between prediabetes and proteinuria (≥1+ on dipstick) separately in prediabetes subjects diagnosed with the new hemoglobin A1c (HbA1c) criterion only (PD-A1c), the impaired fasting plasma glucose only (PD-IFG) and fulfilling both criteria (PD-Both).ResultsAccording to the American Diabetes Association's (ADA's) criterion of 5.7-6.4% HbA1c and/or 100-125 mg/dL fasting plasma glucose, 43.8% of the subjects were judged as having prediabetes. Prediabetes subjects were divided into subclasses of PD-A1c (53.7%), PD-IFG (21.7%) and PD-Both (24.5%), respectively. Therefore, 21.7% of prediabetes subjects were missed using the new HbA1c criterion only. Compared with subjects with normal glucose tolerance (as a reference), the odds ratio (OR) [95% confidence interval (95% CI)] for the increased risk of proteinuria (≥1+) in diabetes itself was 2.191 (2.081-2.307) and in whole prediabetes was 1.093 (1.046-1.142); when prediabetes was subdivided, the OR for proteinuria in PD-IFG was 1.217 (1.140-1.300) and that in PD-Both was 1.249 (1.174-1.329), but that in PD-A1c was not significant, even after adjustment for significant covariates, such as age, sex, body mass index, systolic blood pressure, antihypertensive medication, eGFR, lifestyle and lipid profile.Conclusions
Prediabetes is a significant risk factor for proteinuria compared with completely normal glucose level, and subjects with prediabetes defined using IFG are at significantly higher risk for proteinuria than those defined by HbA1c only.
Nephrology Dialysis Transplantation 08/2012; · 3.40 Impact Factor
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The Lancet 07/2012; 380(9838):213-4; author reply 214-6. · 38.28 Impact Factor
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ABSTRACT: Our aim was to examine the pathophysiology of sleep onset of acute coronary syndrome (ACS); in particular, we focused on the association of sleep onset of ACS, sleep-apnea syndrome (SAS), and diurnal variation of hemostasis and adipokine levels. Seventy-four patients (mean 60.0 years; 84% men) with ACS were cross-sectionally examined. They were examined by circulatory levels of hemostasis [plasminogen activator inhibitor-1 (PAI-1), D-dimer, soluble fibrin] and adipokines (adiponectin, visfatin) before and after sleep, and cardiorespiratory function. The severity of SAS was defined as mild to no SAS [apnea-hypopnea index (AHI) <15/h, n = 30], moderate SAS (AHI 15-30/h, n = 26), and severe SAS (AHI >30/h, n = 18). Nineteen patients (26%) were diagnosed with sleep onset of ACS, and these patients had a greater extent of morning increase from the night-time levels of PAI-1 (median PAI-1 increase: +37.1 vs. +27.3 ng/ml; P = 0.01) and visfatin (median visfatin increase: +0.40 vs. +0.00 ng/ml; P = 0.08) than those who had daytime onset of ACS. Among patients who had sleep onset of ACS, 89% were diagnosed with moderate to severe SAS. According to the severity of SAS, the morning increase from the night-time levels of PAI-1 and visfatin became greater (median PAI-1 increase: +23.7 vs. +29.2 vs. +39.3 ng/ml; median visfatin increase: 0.00 vs. 0.00 vs. +0.45 ng/ml; both P < 0.05), and these differences remained unchanged even after adjustment for significant covariates (both P < 0.05). Patients who have sleep onset of ACS are likely to have high prevalence of SAS and abnormal diurnal variations of PAI-1 and visfatin levels.
Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 07/2012; 23(7):590-6. · 1.25 Impact Factor
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ABSTRACT: Cerebrovascular disease is a common cause of death and major cause of disability worldwide. Even in silent cases (e.g., silent cerebral infarction, white matter lesion), cerebrovascular disease can lead to physical and cognitive impairment, thereby substantially reducing the activities of daily living. Accordingly, the earliest possible action to prevent not only symptomatic but also silent cerebrovascular disease has become a major public health challenge. Hypertension is a potent risk factor for both symptomatic and silent cerebrovascular disease. Twenty-four-hour blood pressure (BP) rather than office BP is closely associated with cerebrovascular disease and/or poor physical and cognitive function. In particular, nocturnal BP and morning BP surge have attracted much attention as risk factors for cerebrovascular diseases independently of 24-h BP level. This review is an attempt to summarize some of the evidence on nocturnal BP level or nocturnal BP dipping status, and morning BP surge as potent risk factors for cerebrovascular disease.
Current Hypertension Reports 04/2012; 14(3):219-27. · 2.50 Impact Factor
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ABSTRACT: It is unknown whether home blood pressure (BP) variability reduction is associated with target organ damage (TOD) protection independently of home mean BP reduction. We enrolled 310 hypertensive patients whose systolic BP (SBP) at home was over 135 mm Hg. The subjects measured their BP in the morning and evening for 7 days. In addition, we measured urinary albumin excretion (UAE) as a marker of TOD before and after 6 months of candesartan treatment (+thiazidediuretics). At baseline, UAE was associated with average home SBP (r=0.24, P<0.001), the s.d. of home SBP (r=0.15, P=0.011), and the maximum home SBP (r=0.27, P<0.001). During the intervention, significant reductions were found in average home SBP (146±13 vs. 132±12 mm Hg, P<0.001), s.d. of home SBP (12.9±4.8 vs. 11.8±4.4 mm Hg, P<0.001), and maximum home SBP (172.5±18.0 vs. 155.9±17.5 mm Hg, P<0.001). UAE levels were significantly reduced after 6 months of therapy compared with baseline (18.9 vs. 12.1 mg g(-1) Cre, P<0.001). In multiple regression analysis, the treatment-induced reduction in UAE was significantly associated with that of average home BP (P=0.003) but was not associated with that of s.d. of home SBP or that of maximum home SBP. Home BP variability is not itself an interventional target beyond lowering mean home BP during anti-hypertensive treatment.
Hypertension Research 04/2012; 35(8):862-6. · 2.58 Impact Factor
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Yuichiro Yano,
Yuji Sato,
Shouichi Fujimoto,
Tsuneo Konta,
Kunitoshi Iseki,
Toshiki Moriyama,
Kunihiro Yamagata,
Kazuhiko Tsuruya,
Hideaki Yoshida,
Koichi Asahi,
Issei Kurahashi,
Yasuo Ohashi,
Tsuyoshi Watanabe
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ABSTRACT: To examine whether there is a difference in the association between high pulse pressure and proteinuria, independent of other blood pressure (BP) indices, such as systolic or diastolic BP, among subjects with diabetes, prediabetes, or normal glucose tolerance.
Using a nationwide health checkup database of 228,778 Japanese aged ≥ 20 years (mean 63.2 years; 39.3% men; none had pre-existing cardiovascular disease), we examined the association between high pulse pressure, defined as the highest quintile of pulse pressure (≥ 63 mmHg, n = 40,511), and proteinuria (≥ 1+ on dipstick, n = 12,090) separately in subjects with diabetes (n = 27,913), prediabetes (n = 100,214), and normal glucose tolerance (n = 100,651).
The prevalence of proteinuria was different among subjects with diabetes, prediabetes, and normal glucose tolerance (11.3 vs. 5.0 vs. 3.9%, respectively; P < 0.001). In subjects with diabetes, but not those with prediabetes or normal glucose tolerance, high pulse pressure was associated with proteinuria independently of significant covariates, including systolic BP (odds ratio 1.15 [95% CI 1.04-1.28]) or diastolic or mean BP (all P < 0.01). In patients with diabetes, a +1 SD increase of pulse pressure (+13 mmHg) was associated with proteinuria, even after adjustment for systolic BP (1.07 [1.00-1.13]) or diastolic or mean BP (all P < 0.05).
Among the Japanese general population, there was a significant difference in the association between high pulse pressure and proteinuria among subjects with diabetes, prediabetes, and normal glucose tolerance. Only in diabetes was high pulse pressure associated with proteinuria independent of systolic, diastolic, or mean BP levels.
Diabetes care 04/2012; 35(6):1310-5. · 8.09 Impact Factor
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Anadolu kardiyoloji dergisi: AKD = the Anatolian journal of cardiology 03/2012; 12(4):305-6. · 0.44 Impact Factor
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ABSTRACT: Asleep blood pressure (BP) has been shown to better reflect cardiovascular risk than awake BP in hypertensive patients. This study investigated the correlation of brain natriuretic peptide (BNP) to asleep BP during antihypertensive treatment.
In the Japan Morning Surge-Target Organ Protection (J-TOP) study, which was an open-label multicenter trial to compare bedtime or awakening dosing of candesartan (+ diuretics as needed) among individuals with home SBP higher than 135 mmHg, we evaluated 254 hypertensive patients who underwent ambulatory BP monitoring, and measured their BNP at baseline and after 6th month of treatment.
At follow-up, the decrease in log-transformed BNP was significantly related to the decrease in asleep SBP (r = 0.27, P < 0.001); the relationship remained significant (β = 0.20, P = 0.002) even after adjusting for the decrease in the awake SBP (β = 0.001, P = 0.991). When we divided participants by their time of candesartan administration, the relationship between the decrease in log-transformed BNP and asleep SBP was still significant in both the awakening-dosing group (β = 0.21, P = 0.028) and the bedtime-dosing group (β = 0.21, P = 0.029). Furthermore, this relationship was strong in the participants who were receiving diuretics.
The decrease in BNP is associated with asleep BP reduction by candesartan (+ diuretics as needed) over and above the awake BP reduction, regardless of the time of administration.
Journal of hypertension 03/2012; 30(5):1015-21. · 4.02 Impact Factor
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ABSTRACT: The accurate measurement, prediction and treatment of high blood pressure (BP) are essential issues in the management of hypertension. Ambulatory blood pressure monitoring (ABPM) has been shown to be superior to clinic BP measurements as ABPM can provide the following important information: (i) the mean BP levels, (ii) the diurnal variation in BP and (iii) the short-term BP variability. Among these parameters, there is increasing evidence that the mean nocturnal BP level is the most sensitive predictor of cardiovascular morbidity and mortality. Furthermore, several studies have shown that less nocturnal BP dipping, defined as less nocturnal BP decline relative to daytime BP, or a high night-day BP ratio was associated with poor prognosis irrespective of the 24-hour BP levels. These findings can be interpreted in at least two ways: namely, high nocturnal BP or less nocturnal BP dipping might be not only a potent risk factor for cardiovascular disease (CVD), but also a marker of pre-existing or concurrent diseases that can lead to nocturnal BP elevation. In this review, we consider the clinical utility of ABPM and in particular focus on the nocturnal BP levels or nocturnal BP dipping as a potent risk factor for CVD. In addition, the clinical management of high nocturnal BP and blunted nocturnal BP dipping with antihypertensive medications is discussed.
Hypertension Research 03/2012; 35(7):695-701. · 2.58 Impact Factor
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ABSTRACT: To examine whether or not the extent of morning blood pressure surge (MBPS), defined as a morning SBP increase from sleep SBP, is associated with that of platelet aggregation, coagulation/fibrinolytic activity, and silent cerebral infarction (SCI) in older hypertensive patients.
Sixty hypertensive patients aged at least 60 years (mean age 70.6 years; 40% men) underwent measurement of morning spontaneous small-sized platelet aggregation (SPA) detected by a light scattering intensity method, measurement of circulatory levels of von-Willebrand factor (vWF), noradrenalin, and plasma renin activity (PRA), and brain MRI.
The extent of MBPS, but not 24-h SBP, was associated with circulatory levels of noradrenalin, PRA, vWF, and spontaneous SPA (all P < 0.05); the association between MBPS and spontaneous SPA remained significant even after adjustment for significant covariates (P < 0.001). The patients with multiple (more than three per person) SCIs had a significantly greater extent of MBPS (43.3 vs. 31.8 mmHg), morning spontaneous SPA (20 471.9 vs. 4850.9 × 10(5) × 2 mV counts 10 min), and higher circulatory vWF (196.6 vs. 150.1%) compared with those without it (all P < 0.01). On multiple regression analysis, the odds ratio for multiple SCIs with a +1 SD increase of MBPS was 2.0, that of morning spontaneous SPA was 3.0, and that of circulatory morning vWF level was 3.3 (all P < 0.05). When MBPS increase and either platelet aggregation or vWF increases were entered into the same model, the latter parameters, but not the MBPS, were associated with multiple SCIs (both P < 0.05).
The extent of MBPS was associated with increased activity of morning platelet aggregation in older hypertensive patients.
Journal of hypertension 12/2011; 29(12):2433-9. · 4.02 Impact Factor
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Tsukasa Ohmori, Yuichiro Yano,
Asuka Sakata,
Tomokazu Ikemoto,
Masahisa Shimpo,
Seiji Madoiwa,
Takaaki Katsuki,
Jun Mimuro,
Kazuyuki Shimada,
Kazuomi Kario,
Yoichi Sakata
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ABSTRACT: High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis.
Thrombosis Research 11/2011; 129(4):e36-40. · 2.44 Impact Factor
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Yuichiro Yano,
Shouichi Fujimoto,
Yuji Sato,
Tsuneo Konta,
Kunitoshi Iseki,
Toshiki Moriyama,
Kunihiro Yamagata,
Kazuhiko Tsuruya,
Hideaki Yoshida,
Koichi Asahi,
Issei Kurahashi,
Yasuo Ohashi,
Tsuyoshi Watanabe
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ABSTRACT: The increased prevalence of chronic kidney disease (CKD) is a consequence of the accumulation of risk factors, one of which is hypertension. Here we assessed the prevalence of CKD according to blood pressure among 232,025 patients in a Japanese nationwide database with a focus on the prevalence and risk factors of CKD in prehypertension. Patients were stratified by blood pressure and included 75,474 with optimal blood pressure (less than 120/80 mm Hg); 59,194 with prehypertension and a normal blood pressure (120-129/80-84 mm Hg) or 46,547 patients with high-normal blood pressure (130-139/85-89 mm Hg); and 50,810 with hypertension (over 140/90 mm Hg without anti-hypertensive drugs). CKD was defined as an estimated glomerular filtration rate of stage 3 or lower or having proteinuria greater than 1+ by a dipstick method. The prevalence of CKD among patients with optimal blood pressure, prehypertension having normal or high-normal blood pressure, and hypertension was 13.9, 15.6, 18.1, and 20.7% in men, and 10.9, 11.6, 12.9, and 15.0% in women, with a significant difference between genders at each strata of blood pressure. In men, but not in women, whose blood pressure was high-normal, the CKD risk was significantly greater (odds ratio 1.11) than those with optimal blood pressure. Obesity (body mass index over 25) was significantly associated with an increased risk of CKD in both men and women (odds ratio 1.43 and 1.26, respectively), and there was an additive effect of obesity and pre-hypertension on CKD risk in men compared with men with optimal blood pressure. Thus, the prevalence of CKD increased with the severity of blood pressure. Prehypertension with high-normal blood pressure, particularly in conjunction with obesity, was found to be an independent risk factor of CKD in men.
Kidney International 09/2011; 81(3):293-9. · 6.61 Impact Factor
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ABSTRACT: Our aim was to examine the association between heart rate (HR) and visceral obesity and abnormal fat distribution in patients undergoing treatment for hypertension. We also ascertained whether such associations differ depending on the time of day when HR is measured and the venue at which the measurement is carried out (office or home).
The study enrolled a total of 390 patients (mean age 63.9 years; 45% men) receiving treatment with antihypertensive drugs other than β blockers or nondihydropyridine Ca-channel blockers. Office blood pressure (BP) and HR as well as home BP and HR, both morning and evening, were measured in all these patients for 14 days. The amount of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were determined using abdominal computed tomography (CT).
Evening HR was positively associated with VAT (r = 0.26) and negatively associated with SAT (r = -0.16); as a consequence, evening HR was closely associated with the VAT/SAT ratio (r = 0.30; all P < 0.01). In contrast, neither office nor morning HR was associated with VAT. The significant association between evening HR and VAT remained unchanged even after adjustment for significant covariates including SAT (P = 0.001). A multiple logistic regression analysis revealed that a 1-s.d. increase (10 beats per minute) in evening HR was significantly associated with visceral obesity (defined as VAT ≥100 cm)(2) (odds ratio (95% confidence interval: 1.7 (1.3-2.3)), P < 0.001), and that this association was independent of body mass index (BMI) and abdominal obesity (waist circumference ≥85 cm for men and ≥90 cm for women).
In these patients receiving treatment for hypertension, high evening HR was associated with visceral obesity, independent of the presence of subcutaneous fat and BMI. This novel finding could explain why cardiovascular risk is higher in individuals with high HR.
American Journal of Hypertension 03/2011; 24(7):783-8. · 3.18 Impact Factor
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ABSTRACT: We assessed the additional effects of eplerenone to angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on 24-h blood pressure (BP) level, fibrinolytic activity, and cardiovascular protection in elderly (>60 years) hypertensive patients.
In total, 20 patients (mean age 74 years, 25% men), whose BP was uncontrolled despite the use of anti-hypertensive drugs including ACEIs or ARBs (average 2.4 drugs), received eplerenone once daily (mean 37.5 mg) for 24 weeks.
Eplerenone treatment significantly reduced mean 24-h systolic/diastolic BP levels (143/80 mmHg to 132/74 mmHg, both p < 0.002). The reduction of 24-h systolic BP levels, especially night-time BP, was significantly associated with the reduction of atrial natriuretic peptide and brain natriuretic peptide levels (all p < 0.05). Furthermore, after eplerenone treatment, the mean plasminogen activator inhibitor-1 antigen level was significantly reduced (35 ng/ml to 25 ng/ml, p < 0.05), and the median level of plasma procollagen type III aminoterminal peptide and the urinary albumin excretion rate were also significantly reduced (0.8 U/ml to 0.6 U/ml, p < 0.003 and 53 mg/g·Cr to 23 mg/g·Cr, p < 0.05, respectively). During the intervention, eplerenone treatment was well tolerated with no reports of hyperkalaemia or hypotension.
Addition of eplerenone to ACEIs or ARBs in elderly hypertensive patients offers significant benefits in terms of 24-h BP levels, fibrinolysis, and cardiovascular protection.
Journal of Renin-Angiotensin-Aldosterone System 03/2011; 12(3):340-7. · 2.44 Impact Factor
