Publications (14)38.12 Total impact
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Article: Association of hematological parameters with insulin resistance, insulin sensitivity, and asymptomatic cerebrovascular damage: The J-SHIP Toon Health Study.
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ABSTRACT: Background: Elevated hematocrit levels have been suggested to be an independent determinant of insulin resistance and type 2 diabetes. To clarify the diagnostic significance of hematocrit level, we investigated the association with hemodynamic profiles, insulin resistance and insulin sensitivity, arterial properties, and asymptomatic cerebrovascular damage in a general Japanese population. Methods: This study included 1,978 participants from two independent cohorts. Insulin sensitivity was assessed by the oral 75 g glucose tolerance test. Carotid ultrasonography was performed to evaluate atherosclerosis and wall shear stress. Periventricular hyperintensity and lacunar infarction were assessed by brain magnetic resonance imaging. Results: Hematocrit quartile showed a stepwise association with insulin sensitivity (Q1: 2.2 ± 0.7, Q2: 2.0 ± 0.7, Q3: 1.9 ± 0.7, Q4: 1.8 ± 0.6, p < 0.001) and insulin resistance (1.0 ± 0.6, 1.2 ± 0.7, 1.3 ± 0.8, 1.5 ± 1.0, p < 0.001). Multiple linear regression analysis adjusted for possible covariates identified hematocrit as an independent determinant of insulin sensitivity (β = -0.074, p = 0.019) and insulin resistance (β = 0.115, p < 0.001). However, this association was lost after further adjustment for visceral fat area and plasma alanine aminotransferase level. Further, no significant association was observed between hematocrit and carotid intima-media thickness (p = 0.306) where as wall shear stress was inversely associated with the carotid atherosclerosis (r = -0.250, p < 0.001). In contrast, a low hematocrit level was independently associated with periventricular hyperintensity (odds ratio 0.87 (95% CI 0.80-0.95), p = 0.001). Conclusion: Hematocrit was positively associated with insulin resistance and insulin sensitivity. This association was epiphenomenon of visceral and hepatic adiposity. Conversely, low hematocrit was a significant risk factor for periventricular hyperintensity independent of insulin resistance.Clinical hemorheology and microcirculation 10/2012; · 3.40 Impact Factor -
Article: Low-dose rosuvastatin improves the functional and morphological markers of atherosclerosis in asymptomatic postmenopausal women with dyslipidemia.
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ABSTRACT: OBJECTIVE: Several large-scale studies have shed light on the primary preventive efficacy of statins against atherosclerotic diseases in the course of treatment of dyslipidemia. However, this efficacy in the management of dyslipidemia in relatively low-risk patients, particularly in women, has not been clarified. Here, we investigated the efficacy of dyslipidemia treatment with a statin on three indices that are widely used to assess atherosclerosis in postmenopausal women: carotid intima-media thickness (CIMT), arterial stiffness index β of the common carotid artery (carotid stiffness β), and brachial artery pulse wave velocity (baPWV). METHODS: The study enrolled 51 postmenopausal women aged 55 years or older with dyslipidemia. The participants were randomly divided into two treatment groups and received a single daily administration of 2.5 mg of rosuvastatin or no statin therapy as control. RESULTS: At baseline, the groups did not significantly differ with regard to the three indices. At the third and 12th months of treatment, both carotid stiffness β and baPWV values were significantly lower than those of the control group. As for CIMT, the value was significantly lower in the statin group than in the control group at 12 months of treatment. These changes were in conjunction with a significant decrease in low-density lipoprotein cholesterol. Interestingly, changes in CIMT during the 12-month period were significantly correlated with changes in high-sensitivity C-reactive protein during the 3-month period independently of lipid profile. CONCLUSIONS: The potent statin improves baPWV and carotid stiffness β, in addition to CIMT (surrogate markers of coronary artery disease), in postmenopausal women with low-risk dyslipidemia. Further studies to clarify the common mechanisms underlying the link between cholesterol-lowering therapy and atherosclerosis in postmenopausal women are required.Menopause (New York, N.Y.) 07/2012; · 3.08 Impact Factor -
Article: Postprandial hypertension, an overlooked risk marker for arteriosclerosis.
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ABSTRACT: Increased blood pressure (BP) variability is suggested to be a risk factor for cardiovascular disease. Although a postprandial decline in BP is a frequently observed phenomenon in the elderly, little attention has been paid to the clinical and diagnostic significance of postprandial BP change. Here, we aimed to clarify the possible association between postprandial BP dysregulation and arteriosclerosis. The study subjects were 1339 apparently healthy middle-aged to elderly persons (66 ± 9 years old). Postprandial changes in BP were calculated by two readings on the same day, one just before lunch with a standardized Japanese meal and the second 30 min after lunch. Arteriosclerosis was assessed by carotid intima-media thickness and brachial-to-ankle pulse wave velocity. Mean preprandial and postprandial systolic BP was 127 ± 18 and 123 ± 18 mmHg respectively. One hundred and twelve subjects (8.4%) showed a greater than 20-mmHg postprandial decline in systolic BP, while 129 (9.6%) showed a greater than 10-mmHg increase. Arteriosclerosis was significantly higher in both postprandial hypotensive and hypertensive subjects. The postprandial changes in systolic BP were strongly associated with preprandial systolic BP (r = 0.335, p < 0.001). The association between postprandial hypotension and increased arteriosclerosis was therefore lost after adjustment for basal systoic BP. Multiple linear regression analysis adjusted for possible covariates, including basal BP, identified a postprandial increase in BP as an independent determinant of insulin resistance as assessed by HOMA-IR (β = 0.093, p < 0.001), carotid thickness (β = 0.086, p = 0.001) and pulse wave velocity (β = 0.170, p < 0.001). Postprandial increase in BP is a novel risk marker for arteriosclerosis.Atherosclerosis 07/2012; 224(2):500-5. · 3.79 Impact Factor -
Article: Liver enzyme and adipocytokine profiles are synergistically associated with insulin resistance: the J-SHIPP study.
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ABSTRACT: Alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) are associated with insulin resistance and arteriosclerotic disease. Since adiposity raises liver enzyme levels and causes insulin resistance, adipocytokines are thought to underlie the relationship between liver enzymes and insulin resistance. To clarify this hypothesis, we conducted a cross-sectional epidemiological study in a Japanese general population. The study subjects were 903 middle-aged to elderly persons. Plasma levels of adiponectin and leptin were measured, while other clinical parameters were obtained from personal health records of medical check-ups. Insulin resistance was assessed by a homeostasis model assessment index (HOMA-IR). Plasma levels of ALT (r=0.379, p<0.001), GGT (r=0.225, p<0.001), adiponectin (r= -0.346, p<0.001) and leptin (r=0.369, p<0.001) were significantly correlated with insulin resistance even on subgroup analysis by sex. Further, any combination of liver enzymes and adipocytokines was synergistically associated with insulin resistance (p<0.001) after adjustment for possible covariates (ALT*adiponectin: β=-0.098, p<0.001, ALT*leptin: β=0.129, p<0.001, GGT*adiponectin: β=-0.054, p=0.054, GGT*leptin: β=0.126, p<0.001); however, in simple obese subjects with normal adipocytokine levels, liver enzymes were not associated with insulin resistance (mean HOMA-IR: worsened adipocytokine +/visceral obesity +, 2.01±1.14; +/-, 1.39±0.84; -/+, 1.23± 0.55; -/-, 1.03±0.57; p<0.001). Plasma levels of ALT and GGT were independent determinants of insulin resistance only in subjects with a worsened adipocytokine profile. Use of liver enzyme levels as a marker of insulin resistance requires stratification by adipocytokine profile.Journal of atherosclerosis and thrombosis 05/2012; 19(6):577-84. · 2.69 Impact Factor -
Article: Response to "carotid flow augmentation as a risk for small vessel disease of the brain".
American journal of hypertension 09/2010; 23(9):933. · 3.10 Impact Factor -
Article: Arterial stiffness is associated with low thigh muscle mass in middle-aged to elderly men.
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ABSTRACT: Sarcopenia of legs is an important cause of physical dysfunctions, frailty and dependence. Many predisposing and underlying mechanisms of sarcopenia, including age, sedentary life style, oxidative stress, insulin resistance, and low testosterone levels, are also known to be related to atherosclerosis, which is another leading cause of morbidity and mortality in elderly subjects. In this study, we investigated our hypothesis that sarcopenia and atherosclerosis are associated with each other to facilitate mutual abnormalities. Study was performed in apparently healthy 496 middle-aged to elderly persons recruited consecutively among the visitors to the medical check-up program, Anti-Aging Doc, in a University hospital, from March 2006 to December 2007. Mid-thigh muscle cross-sectional area (CSA) was measured by computed tomography and corrected by body weight (CSA/BW). Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured. Thigh muscle CSA/BW was significantly and negatively associated with carotid IMT and baPWV in men but not in women. After correction for other confounding parameters, baPWV was an independent risk for the presence of sarcopenia in men (odds ratio of 1 m/s increase of baPWV=1.14, 95% CI=1.01-1.30, p<0.05) in addition to age, body height, low physical activity, free testosterone level. Conversely, thigh muscle CSA/BW was an independent determinant of baPWV (beta=-0.15, p<0.01) in addition to age, blood pressure, triglyceride, and antihypertensive drug use in men. Arterial stiffness is related to thigh muscle volume in men. Sarcopenia and atherosclerosis may share a common pathway and interact with each other to facilitate mutual abnormalities.Atherosclerosis 09/2010; 212(1):327-32. · 3.79 Impact Factor -
Article: Associations between short one-leg standing time and speed of sound of calcaneal bone in a general population: the Shimanami Health Promoting Program (J-SHIPP) study.
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ABSTRACT: Loss of bone mass is a major cause of fracture in the elderly. One-leg standing (OLS) time has been postulated to be predictive of reduced bone mass. Here, we conducted a cross-sectional study to clarify whether OLS time measurements are associated with the speed of sound (SOS) of calcaneal bone independent of muscle mass in the lower extremity, a major confounding factor for the association, in a community-dwelling population of middle-aged to elderly subjects. The study subjects consisted of 770 apparently healthy middle-aged to elderly community-residents. Quantitative assessment of calcaneal bone was done using a quantitative ultrasound technique. OLS time with eyes open was measured with a maximum time of 60 s. Femoral muscle cross-sectional area (CSA) was measured from a computed tomography image. Subjects who could not stand 60 s on one leg (n = 192) showed significantly lower SOS (1487 +/- 20, 1501 +/- 24 m/s, P < 0.001). In addition, femoral muscle CSA was positively associated with SOS (male, r = 0.148, P < 0.01; female, r = 0.204, P < 0.001). However, multiple regression analysis adjusted for age, sex and muscle CSA identified short OLS time less than 60 s as an independent determinant of SOS in both male (P < 0.001) and female (P < 0.05) subjects. OLS time was significantly associated with posturograph-measured mobility of the center of gravity. However, multiple regression analysis showed no significant correlation between balance impairment and SOS (P > 0.1). OLS time less than 60 s was significantly associated with reduced SOS independent of age, sex and muscle mass in the lower extremity.Geriatrics & Gerontology International 04/2010; 10(2):138-44. -
Article: Association of central systolic blood pressure with intracerebral small vessel disease in Japanese.
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ABSTRACT: Recent studies have reported the association between advanced arterial stiffness and brain small vessel diseases (SVDs). Two possible hemodynamic mechanisms, increases in central blood pressure (BP) and pulsatile flow load to the brain, have been speculated to link arterial stiffness and SVD. The carotid flow augmentation index (AI) has been proposed as an index of pulsatile flow to the brain. We compared its association with brain SVD with that of central BP in a general population. Subjects were 500 individuals free from symptomatic cardiovascular diseases with a mean age of 66.9 +/- 8.4 years. Brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Carotid flow AI was obtained by Doppler ultrasonography. The presence of silent cerebral lacunar infarcts (SCI) was determined as a manifestation of SVD by 3-tesla magnetic resonance imaging (MRI). Second peak radial systolic BP (SBP2) and pulse pressure (PP2) were used as estimates of central BP. baPWV was significantly associated with radial BP2 (r = 0.55, P < 0.0001) but not with carotid flow AI (r = 0.03, P = 0.51). Radial BPs and baPWV, but not flow AI, were significantly higher in subjects with SCI. Radial SBP2 had higher odds ratio for the presence of SCI than brachial SBP, PP, and radial PP2. Logistic regression analysis showed that radial SBP2, but not flow AI, was independently related to the presence of SCI. These findings indicate that the SBP2, an estimate of central SBP, is significantly associated with the presence of SVD in an apparently healthy general population.American Journal of Hypertension 03/2010; 23(8):889-94. · 3.18 Impact Factor -
Article: Quadriceps sarcopenia and visceral obesity are risk factors for postural instability in the middle-aged to elderly population.
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ABSTRACT: Aging shifts body composition to comprising more fat and less muscle. Sarcopenia, particularly in the knee extensors, and obesity, particularly visceral obesity, either alone or in combination, may exacerbate age-related physical disability. We investigated the association between age-related quadriceps (Qc) sarcopenia and visceral obesity, as measured by cross-sectional area (CSA), on postural instability. Mid-thigh muscle CSA and abdominal visceral and subcutaneous fat area at the level of the umbilicus were assessed from computed tomography (CT) images in 410 apparently healthy independent middle-aged to elderly subjects attending the medical check-up program in Ehime University Hospital. Static postural instability using a posturograph and one-leg standing time with eyes open were assessed. Both abdominal visceral fat area and Qc muscle CSA corrected by body weight (BW) were associated with static postural instability, in addition to age and sex, while BW-corrected Qc muscle CSA predicted a short one-leg standing time. The combination of Qc sarcopenia, defined as greater than 1 standard deviation below the mean of a young group (age <60 years), and visceral obesity, defined as a visceral fat area of more than 100 cm(2), were associated with static postural instability, while Qc sarcopenia was related to a higher prevalence of one-leg standing time of less than 30 s, irrespective of visceral obesity. Thigh Qc sarcopenia and visceral obesity are associated with postural instability in middle-aged to elderly subjects. These findings suggest that age-related, site-specific fat and muscle mass alterations are associated with functional impairment.Geriatrics & Gerontology International 02/2010; 10(3):233-43. -
Article: Postural instability is associated with brain atrophy and cognitive impairment in the elderly: the J-SHIPP study.
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ABSTRACT: Mobility impairment in older adults has been suggested to be a marker of subclinical structural and functional brain abnormalities. We investigated a possible association between static postural instability and brain abnormalities and cognitive decline. The study subjects were 390 community residents without definitive dementia (67 +/- 7 years old) and 21 patients with Alzheimer's disease (AD). Brain atrophy was measured by MRI. The mobility of the posturography-measured center of gravity (COG) was positively associated with the temporal horn area (THA; r = 0.260; p < 0.001). Subjects who could not stand on one leg for >40 s (n = 102) showed a significantly larger THA (22 +/- 18 vs. 14 +/- 11 x 10(-2) cm(2); p < 0.001). Multiple regression analysis identified COG path length (beta = 0.118; p = 0.032) and one-leg standing time (beta = 0.176; p = 0.001) as independent determinants of THA. Mild cognitive impairment (MCI) subjects (n = 61) had a significantly enlarged THA compared to that of normal cognitive subjects (22 +/- 16 vs. 16 +/- 13 x 10(-2) cm(2); p = 0.002). AD patients showed a more enlarged THA (78 +/- 55 x 10(-2) cm(2)). Subjects with cognitive decline showed a significantly shorter one-leg standing time (normal: 50 +/- 17 s; MCI: 42 +/- 21 s; AD: 18 +/- 20s; p < 0.001). Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly.Dementia and Geriatric Cognitive Disorders 01/2010; 29(5):379-87. · 2.14 Impact Factor -
Article: Abnormal nocturnal blood pressure profile is associated with mild cognitive impairment in the elderly: the J-SHIPP study.
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ABSTRACT: Mild cognitive impairment (MCI), a syndrome characteristic of the transition phase between normal cognitive function and dementia, has been shown to carry the risk of progression to dementia. Dysregulation of blood pressure (BP) is thought to be an indicator of cerebrovascular damage, including cognitive impairment. Here, we investigated the possible association of circadian BP variation with MCI in community-dwelling persons exhibiting no definitive dementia. Our study enrolled 144 persons (68+/-7 years). Nocturnal BP profile was defined as dipper, with a 10-19% drop in nocturnal systolic BP; extreme dipper, >or=20% drop; non-dipper, 0-10% drop; and riser, any increase in nocturnal BP. MCI was assessed using the MCI screen, a cross-validated, staff-administered battery of tests. Subjects with MCI (n=38) were significantly older (74+/-6, 67+/-6 years, P<0.001) and had higher frequency of apolipoprotein E varepsilon4 allele (36.8, 18.9%, P=0.018). Although the ambulatory measured BP and the percent changes in nocturnal systolic BP (-10+/-12% and -12+/-8%, respectively; P=0.291) did not differ between MCI subjects and normal controls, frequency of MCI was significantly higher in the extreme dippers (32.0%), non-dippers (30.0%) and risers (50.0%) than in dippers (13.2%, P=0.018). Multiple logistic regression analysis identified a blunted nocturnal BP decline, non-dipping or increase in nocturnal BP and extreme drop in BP as potent determinants of MCI (odds ratio 3.062, P=0.039), after adjustment for possible confounding factors, including apolipoprotein E varepsilon4 genotype. Abnormal nocturnal BP profile was found to be a strong indicator of MCI in otherwise apparently healthy community-dwelling elderly persons.Hypertension Research 10/2009; 33(1):32-6. · 2.58 Impact Factor -
Article: Silent cerebral microbleeds associated with arterial stiffness in an apparently healthy subject.
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ABSTRACT: Silent cerebral microbleeds (MBs) are a common finding in stroke patients, especially those with intracerebral hemorrhage, and are thought to be a marker of future cerebral hemorrhage. Clinically, two distinct forms of MBs have been documented, those observed with either or both stroke or small vessel disease (SVD) and those associated with cerebral amyloid angiopathy. We investigated a possible association between MBs and arterial stiffness in a general population. Subjects were 443 apparently healthy individuals with a mean age of 67.1+/-8.1 years. The presence of MBs, lacunar infarcts and periventricular hyperintensity (PVH) was determined by 3-tesla magnetic resonance imaging. Carotid intima-media thickness (IMT) was measured by ultrasonography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV), and the Framingham stroke risk score (FSRS) was obtained as an integrated cerebrovascular risk factor. The prevalence of MBs was 5.0%. Both baPWV and FSRS were significantly higher in subjects with MBs (1820+/-308 vs. 1645+/-325 cm/s, P=0.014 and 12.1+/-8.6 vs. 8.9+/-7.5%, P=0.047, respectively). Odds ratio of a high baPWV, defined as >or=1500 cm/s, for the presence of MBs was 6.05 even after correction for confounding parameters, including age and hypertension. This association with high baPWV remained irrespective of MBs location, whether strictly located in the lobes or in the basal ganglia and infratentorial regions. These findings indicate an association between arterial stiffness and the presence of MBs. Assessment of arterial stiffness may be useful in identifying subjects at high risk for the presence of MBs.Hypertension Research 04/2009; 32(4):255-60. · 2.58 Impact Factor -
Article: Asymptomatic cerebral microbleeds seen in healthy subjects have a strong association with asymptomatic lacunar infarction.
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ABSTRACT: Cerebral microbleed (CMB), which is conspicuous on gradient-echo T2-weighted magnetic resonance imaging, is a risk factor of intracerebral hemorrhage (ICH). CMBs have been detected even in neurologically healthy persons, who also seem prone to be affected by stroke, not only ICH but also cerebral infarction. The presence of CMB was investigated in brain dock participants, making reference to silent lacunar infarction (SLI). Participants comprised 377 neurologically healthy persons and 21 (5.6%) had CMB detected, which was associated with a high incidence of hypertension, other conventional risk factors having no significant correlation with CMB. In a simple correlation analysis, CMB showed a positive association with age and systolic blood pressure (SBP). Logistic regression analysis revealed that SLI was the factor most strongly associated with CMB. Moreover, individuals who had both CMB and SLI had higher SBP than other groups. The etiology of CMB is similar to that of SLI.Circulation Journal 02/2009; 73(3):530-3. · 3.77 Impact Factor -
Article: Composition of lower extremity in relation to a high ankle-brachial index.
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ABSTRACT: Clinical implications of a high ankle-brachial index (ABI) remain controversial. The involvement of atherosclerotic vascular changes as well as a close positive association with body weight has been postulated. We evaluated possible associations between a high ABI and atherosclerotic and anthropometric parameters. Study participants were 407 community residents (68 +/- 8 years). Atherosclerosis was evaluated by arterial pulse wave velocity, carotid hypertrophy, and related plasma markers. Composition of the body trunk and lower extremity was evaluated by computed tomography. The frequency of high ABI individuals (> or =1.3) was 6.6%, and that was higher in men (70.4 vs. 37.4%, P < 0.001). Characteristics included a significantly larger waist circumference (high ABI, 86 +/- 5; normal ABI, 82 +/- 9 cm, P = 0.033), lower high-density lipoprotein-cholesterol (60 +/- 16, 68 +/- 20 mg/dl, P = 0.042), and higher glucose (112 +/- 30, 104 +/- 20 mg/dl, P = 0.044), but not carotid hypertrophy (P = 0.315) and pulse wave velocity (P = 0.828). The high ABI individuals also had a significantly higher values for stature (162 +/- 8, 157 +/- 8 cm, P = 0.002), body weight (64 +/- 9, 56 +/- 10 kg, P < 0.001), and visceral fat area (132 +/- 60, 100 +/- 64 cm, P = 0.012). Femoral muscle area (133 +/- 23, 109 +/- 23 cm, P < 0.001) but not fat area (P = 0.301) was also larger in this group. Multiple regression analysis indicated that female sex (beta = -0.138, P = 0.019) and body weight (beta = 0.288, P < 0.001) were independent determinant for ABI. However, after adding femoral muscle cross sectional area to the model, the latter became the only determinant of ABI (beta = 0.341, P < 0.001). Lower extremity composition is a strong determinant of ABI. A high ABI value might not be an adverse maker of atherosclerosis in the general population.Journal of Hypertension 02/2009; 27(1):167-73. · 4.02 Impact Factor
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2009–2012
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Ehime University
- Department of Geriatric Medicine
Matsuyama-shi, Ehime, Japan
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