Association of postural instability with asymptomatic cerebrovascular damage and cognitive decline: the Japan Shimanami health promoting program study.

BACKGROUND AND PURPOSE: Asymptomatic cerebral small-vessel disease (cSVD) in elderly individuals are potent risk factors for stroke. In addition to common clinical risk factors, postural instability has been postulated to be associated with cSVD in older frail patients. Here, we conducted a cross-sectional study to understand the possible link between postural instability and asymptomatic cSVD further, namely periventricular hyperintensity, lacunar infarction, and microbleeds, as well as cognitive function, in a middle-aged to elderly general population (n=1387). METHODS: Postural instability was assessed based on one-leg standing time (OLST) and posturography findings. cSVD was evaluated by brain MRI. Mild cognitive impairment was assessed using a computer-based questionnaire, and carotid intima-media thickness as an index of atherosclerosis was measured via ultrasonography. RESULTS: Frequency of short OLST, in particular <20 s, increased linearly with severity of cSVD (lacunar infarction lesion: none, 9.7%; 1, 16.0%; >2, 34.5%; microbleeds lesion: none, 10.1%; 1, 15.3%; >2, 30.0%; periventricular hyperintensity grade: 0, 5.7%; 1, 11.5%; >2, 23.7%). The association of short OLST with lacunar infarction and microbleeds but not periventricular hyperintensity remained significant even after adjustment for possible covariates (lacunar infarction, P=0.009; microbleeds, P=0.003; periventricular hyperintensity, P=0.601). In contrast, no significant association was found between posturographic parameters and cSVD, whereas these parameters were linearly associated with OLST. Short OLST was also significantly associated with reduced cognitive function independent of covariates, including cSVD (P=0.002). CONCLUSIONS: Postural instability was found to be associated with early pathological changes in the brain and functional decline, even in apparently healthy subjects.

Mechanical stresses, arterial stiffness, and brain small vessel diseases: Shimanami Health Promoting Program Study.

BACKGROUND AND PURPOSE: Arterial stiffness, a risk factor of brain small vessel diseases (SVD), causes hemodynamic changes. Mechanical stresses, circumferential wall tension (WT), and shear stress (SS) may change with arterial stiffness and be related to SVD. We investigated the associations between mechanical stresses and arterial stiffness and SVD. METHODS: A total of 1296 subjects without apparent cardiovascular diseases were recruited. Brachial-to-ankle pulse wave velocity (baPWV) was measured as an arterial stiffness index. Silent lacunar infarction and deep subcortical white matter hyperintensity were evaluated as SVD indices. Circumferential WT and SS at peak systole and end diastole were measured at the common carotid artery. Second peak of systolic blood pressure was obtained from the radial waveform and used as a central systolic blood pressure substitute. RESULTS: baPWV was associated positively with WT (P<0.0001) and negatively with SS (P=0.0007) even after correction for confounding parameters including baPWV. SVD was associated with significantly higher WT (P<0.0001) and lower SS (P<0.0001). After adjustment for confounding parameters (including baPWV), second peak of systolic blood pressure WT (odds ratio, 1.30; P=0.0017) and end diastolic WT (odds ratio, 1.60; P=0.0038) were related to presence of silent lacunar infarction, whereas peak systolic (odds ratio, 0.95; P=0.014) and end diastolic SS (odds ratio, 0.94; P=0.014) were associated with presence of deep subcortical white matter hyperintensity grade >3. Regression lines between blood pressure and WT were significantly steeper in subjects with SVD than without SVD (ß=0.02; P<0.0001). CONCLUSIONS: These findings indicate that SVD is phenotype-specifically associated with alterations in WT and SS independently of arterial stiffness.

[A case of Fisher syndrome with multiple cranial neuropathy and abnormal EEG findings].

A 69-year-old woman was admitted because of unconsciousness and multiple cranial neuropathy. She had suffered diarrhea 2 weeks previously. On examination, she was noted to have total external and internal ophthalmoplegia, bilateral facial palsy, dysphagia, dysarthria, neck weakness, distal motor weakness of all limbs, and ataxia. She had also presented with hyporeflexia and hypoesthesia, but with a bilateral pyramidal tract sign. A study of her cerebrospinal fluid revealed albuminocytologic dissociation, and nerve conduction study revealed demyelination of her peripheral nerves. Moreover, electroencephalography findings were abnormal and anti-GQ1b antibody was positive. We diagnosed Fisher syndrome with Guillain-Barré syndrome and Bickerstaff brainstem encephalitis. We administered intravenous immunoglobulin treatment for 5 days and her symptoms gradually improved. However, her external ophthalmoplegia continued for several months.

Abdominal fat, adipose-derived hormones and mild cognitive impairment: the J-SHIPP study.

BACKGROUND/AIM: Lower body weight in later life has been shown to be associated with dementia. However, abdominal fat distribution under conditions of mild cognitive impairment (MCI) and the possible involvement of leptin and adiponectin in MCI have not been fully investigated. METHODS: We analyzed 517 middle-aged-to-elderly community-dwelling persons. Abdominal subcutaneous fat and visceral fat areas were determined using computed tomography, and plasma leptin and adiponectin concentrations were measured in fasting samples. MCI was assessed using the Japanese version of the MCI screening method. RESULTS: In men, the abdominal subcutaneous fat area was significantly lower in participants with MCI than in those with normal cognitive function [median (interquartile range): 107.4 (85.9, 133.1) cm² vs. 136.4 (93.1, 161.4) cm²; p = 0.002]. Logistic regression analyses with confounding factors including age and abdominal subcutaneous fat area showed that a 10 mg/l increase in plasma adiponectin had a protective effect against the development of MCI in men (odds ratio: 0.46; 95% CI: 0.20-0.97; p = 0.041). In contrast, MCI was not found to be associated with abdominal fat area or adipose-derived hormones in women. CONCLUSION: Reduced amounts of subcutaneous fat and low levels of plasma adiponectin were found to be associated with MCI in men.

Postural instability is associated with brain atrophy and cognitive impairment in the elderly: the J-SHIPP study.

BACKGROUND/AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Reduced postural stability was an independent marker of brain atrophy and pathological cognitive decline in the elderly.

[A case of myasthenia gravis with an invasive thymoma infiltrating the superior vena cava and right atrium and causing lung metastasis].

A 72-year-old woman was admitted to a local hospital with general fatigue, ptosis and dysarthria. Her anti-AchR antibody titer was high, so myasthenia gravis was diagnosed. She was given a cholinesterase inhibitor, but her symptoms did not improve. CT and MRI scans revealed a mass in the anterior mediastinum infiltrating the superior vena cava (SVC) and the right atrium (RA) . The diagnosis was an invasive thymoma extending into the SVC and the RA. Moreover, there was a mass in the right middle lobe of her lung, which was suspected to be the result of metastasis of the thymoma. She was transferred to our hospital for medication and surgery for the invasive thymoma. Urgent surgery was performed without preoperative therapy, because the tumor was nearly obstructing her tricuspid valve. An expanded thymomectomy and a right middle lobectomy were performed. As the tumor had infiltrated into the SVC, the SVC was replaced with an artificial graft. The clinicopathological diagnosis of thymoma (Masaoka Stage IVb) was given. The patient had a myasthenic crisis for several weeks after surgery, so her breathing was controlled by an artificial respirator. Her symptoms improved after treatment with steroids, tacrolimus and a cholinesterase inhibitor. Although major surgery was required to prevent tumor embolism, the patient survived. Careful observation is necessary to detect signs of relapse of invasive thymoma.

Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensin II type 1 receptor blockade.

Angiotensin converting enzyme 2 (ACE2), a newly recognized homolog of ACE that converts angiotensin II (Ang II) to angiotensin-1-7 (Ang-(1-7)), is found in vascular smooth muscle cells. Expression of ACE2 may be a local determinant of vascular Ang-(1-7) production and, when increased, may augment the increasingly recognized protective effects of this peptide within injured tissues. We previously showed that treatment with the angiotensin II type 1 (AT1) receptor blocker (ARB) olmesartan increased aortic ACE2 and Ang-(1-7) in conjunction with improved vascular remodeling in spontaneously hypertensive rats (SHR). In the present study, we investigated balloon injury-related ACE2 in the vasculature by determining the effect of sustained AT1 blockade on ACE2 protein expression in the carotid arteries of 12-week-old male SHR treated with either vehicle (n=5) or 10 mg/kg olmesartan (n=5) in drinking water for 14 days. Olmesartan treatment caused a 61% reduction in the cross-sectional area of the neointima, from 0.27+/-0.01 mm2 in vehicle-treated rats to 0.11+/-0.01 mm2 in olmesartan-treated rats. In contrast, olmesartan treatment had no effect on the medial area of injured or uninjured carotid arteries compared to that in vehicle-treated rats. Quantitative analysis of ACE2 immunostaining intensity in the carotid artery of SHR was significantly greater (p<0.05) in the neointima of olmesartan-treated SHR compared to that in vehicle-treated animals. In contrast, ACE2 immunostaining intensity was not quantitatively different in uninjured carotid arteries of olmesartan and vehicle-treated animals. These studies suggest that changes in ACE2 within the vascular system of SHR are regulated by a factor other than arterial pressure.

[Migraine improved by amlodipine medication in a case with hypertension].

A 64-year old woman visited our outpatient clinic with chronic headache on August 30(th), 2005. She had been suffering from migraine from her 30's. Although sumatriptan improved her symptoms, migraine attacks had occurred every other day recently. At presentation, her headache was moderate in intensity and lasted about four hours. Daily activity worsened her pulsating headache associated with nausea and vomiting. She diagnosed with migraine without aura, which met the diagnostic criterion for migraine by International Classification of Headache Disorders. Lomerizine was administered as a prophylactic agent, however it did not reduce the frequency of migraine attacks. Accordingly, lomerizine was withdrawn from November 2005. Her blood pressure gradually increased during the course, and amlodipine, 2.5 mg/day, was started for her hypertension May 2007. After starting amlodipine, she noticed a reduction in migraine attacks, only two times a month in August 2007. Assessment with the HIT-6 questionnaire showed great improvement in her QOL score for daily life. Although the underlying mechanisms have not been elucidated, amlodipine was effective in reducing migraine attacks in this patient. The findings in this case may suggest that amlodipine administration might be a useful strategy to control migraine attack.

Habitual hot water bathing protects cardiovascular function in middle-aged to elderly Japanese subjects.

Favorable effects of sauna bathing on cardiovascular disease have been demonstrated. Hot water bathing is an alternative, and could also have similar effects. Information pertaining to hot water bathing frequency and water temperature was obtained from 873 subjects. Carotid mean and max intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices of atherosclerosis. Central haemodynamics were evaluated using radial pulse waveform analyses. Plasma levels of B-type natriuretic peptide (BNP) were measured as an index for cardiac loading. The mean duration of a single hot bath was 12.4 ± 9.9 min. Subject bathing in hot water ≥5 times per week had significantly lower baPWV, central pulse pressure (PP), and BNP after correcting for possible confounding parameters. Stepwise regression analyses revealed that hot water temperature was negatively associated with baPWV, while bathing frequency was negatively related to central PP and BNP. A longitudinal follow-up in 164 subjects showed that hot water bathing ≥5 times per week was associated with significantly lower increase in BNP over time, while the temperature of the water tended to be related to lower increases in carotid max IMT and baPWV. Hot water bathing showed a favorable effect on atherosclerotic and central haemodynamic parameters.

Migraine is associated with enhanced arterial stiffness.

Migraine is a common subtype of headache. Epidemiological studies have revealed that migraine could be an independent risk factor for ischemic stroke even in elderly subjects. Arterial stiffness is one of the major pathophysiological bases of stroke. In the present study, we cross-sectionally investigated the possible relationship between migraine and arterial stiffness in community-dwelling subjects. The study subjects were independently recruited from two sources (Group A, n=134, 68+/-5 years; Group B, n=138, 68+/-7 years). Augmentation index (AI), the ratio of augmented pressure by the reflection pressure wave to the pulse pressure, was obtained from the radial arterial waveform as an index of arterial stiffness. Brachial blood pressure was also measured simultaneously. Migraine was diagnosed using a previously validated questionnaire. The prevalence of migraine was 5.2% (Group A) and 16.7% (Group B). Subjects with migraine had higher radial AI in both Group A (migraine, 101+/-15%; other headache, 88+/-12%; no headache, 86+/-12%, p=0.003) and Group B (95+/-11%, 90+/-11%, 91+/-14%, p=0.058). Multiple linear regression analysis revealed that migraine was an independent determinant of AI (beta=0.154, p=0.002) after adjustment for other confounding factors: age (beta=-0.024, p=0.654); sex (beta=0.141, p=0.069); body height (beta=-0.215, p=0.005); systolic blood pressure (beta=0.174, p=0.001); medication for hypertension, hyperlipidemia, and diabetes mellitus (beta=-0.014, p=0.787); and heart rate (beta=-0.539, p<0.001). In a separate analysis by sex, migraine was also a significant determinant for AI (male, beta=0.246, p=0.019; female, beta=0.159, p=0.008). Migraine in the elderly could be a clinical manifestation of enhanced arterial stiffness.

[Multiple metastases from renal carcinoma 15 years after nephrectomy].

A 72-year-old man was admitted to our hospital complaining of an axillary mass. He underwent left total nephrectomy for renal cell carcinoma (RCC) 15 years previously (in 1990). Since further evaluation yielded no evidence of extra renal metastases, he was followed up in the outpatient clinic. On admission, there was a hard tumor in the right axilla. Ultrasonography demonstrated a vascular tumor with a smooth surface, 26 by 24mm. Laboratory findings were generally close to normal, including tumor markers. Chest contrast-enhanced dynamic CT showed that the tumor was enhanced. Furthermore, abdominal contrast-enhanced dynamic CT revealed some enhancing lesions within the right side of the rectus muscle of abdomen and pancreas head as well. Open simple axillary mass biopsy was performed on August 2 and the tumor was histologically confirmed as a metastasis of the RCC to the axillary. His overall status was normal, and he underwent an operation for the pancreas tumor and the tumor in the rectus muscle of the abdomen. On histological examination, both excised specimens were found to be metastases of RCC. During 2 years follow-up period in the outpatient clinic, additional metastasis has not been observed in any organ. Since this case confirms the potential of RCC for late and multiple distant metastases, careful long-term follow-up after radical nephrectomy is needed.

Office-based simple frailty score and central blood pressure predict mild cognitive impairment in an apparently healthy Japanese population: J-SHIPP study.

Frailty is associated with cognitive impairment and can be used to identify people at high risk for dementia. We developed a simple frailty (SF) score using a combination of low hand grip strength (<32.5 kg in men, <19.5 kg in women), and short one-leg standing time (<20 seconds). These can be easily measured in the clinician's office when seeing patients. We investigated the possible association between SF score and mild cognitive impairment (MCI) in a cross-sectional study with 838 independent middle-aged to elderly participants (319 men, mean age 65.1years). In total, 118 participants were diagnosed with MCI. A SF score of 2 was significantly associated with the presence of MCI (odds ratio 4.6, 95% confidence interval: 1.9-6.9, p = 0.0001) even after adjustment for age and sex. Stepwise regression analyses showed that a SF score of 2 was associated with the presence of MCI, independently of central pulse pressure and silent cerebral infarcts. These findings indicate that the SF score is a useful frailty parameter to predict MCI in an apparently independent population.

Muscle mass decline, arterial stiffness, white matter hyperintensity, and cognitive impairment: Japan Shimanami Health Promoting Program study.

BACKGROUND: There is a close association between frailty and cognitive impairment. However, the underlying contribution of sarcopenia to the development of cognitive impairment is unclear. We investigated the possible association between muscle mass decline and cognitive impairment in a cross-sectional study of 1518 subjects aged 55 years or above. We also evaluated arterial stiffness and white matter hyperintensities (WMHs) as possible underlying mechanisms for this association. METHODS: Two sarcopenic indices were measured: thigh muscle cross-sectional area (CSA; calculated by computed tomography) and skeletal muscle mass (bioelectric impedance). Muscle mass decline was defined as either the bottom 10% or 20% of participants for each sex. Cognitive function was assessed using the Touch Panel-type Dementia Assessment Scale, and brachial-ankle pulse wave velocity was measured as an index of arterial stiffness. RESULTS: Both sarcopenic indices were modestly but significantly associated with brachial-ankle pulse wave velocity in male and female subjects. The presence of WMHs was significantly associated with low thigh muscle CSA in men and with low skeletal muscle mass in women. The Touch Panel-type Dementia Assessment Scale score was modestly but significantly and positively associated with thigh muscle CSA in men and skeletal muscle mass in women. Muscle mass decline in the bottom 10% of participants on both sarcopenic indices was significantly and independently related to cognitive impairment in women. CONCLUSIONS: Lower sarcopenic indices are significantly related to lower cognitive scores. Arterial stiffness and WMHs could account, at least in part, for this association.

Interaction between serotonin 2A receptor and endothelin-1 variants in association with hypertension in Japanese.

Serotonin has been implicated in the pathogenesis of hypertension because of its ability to induce vasoconstriction via stimulation of serotonin 2 (5-HT2) receptors. Recently, an association between the T102C functional polymorphism of the serotonin 2A (5-HT2A) receptor gene and hypertension in the UK has been reported. Another association study, however, failed to replicate this association in a Chinese population. We therefore investigated the possible association between the 5-HT2A T102C polymorphism and hypertension in two large Japanese populations (n = 2,968 total). We also investigated the possible interaction between the 5-HT2A T102C polymorphism and the G/T (Lys198Asn) polymorphism of the endothelin-1 (ET-1) gene, based on robust biological evidence for the existence of an interaction between the serotonin and endothelin systems. The results showed that there was no significant difference in the frequencies of the alleles and genotypes between the hypertensive and normotensive subjects. However, a significant interaction between the 5-HT2A T102C and ET-1 G/T polymorphisms in their association with hypertension (p = 0.0040) and with diastolic blood pressure (p = 0.0013) was revealed. A marginally significant interaction in the association with systolic blood pressure was also shown (p = 0.045). The associations of the 5-HT2A T102C polymorphism with hypertension and diastolic blood pressure in ET-1 T allele carriers were significant (p = 0.0056 and 0.021, respectively). The association of the 5-HT2A T102C polymorphism with systolic blood pressure in ET-1 T allele carriers was marginally significant (p = 0.054). Thus, the present study suggests that the 5-HT2A T102C and ET-1 G/T polymorphisms are interactively associated with hypertension.

[An elderly fludrocortison-responsive woman with hyponatoremia].

An 89-years-old woman had anorexia for at least 1 month, and had been given symptomatic treatment at a nearby hospital. She was admitted to our hospital on August 22, 2003, for thorough examination and appropriate treatment for lack of spontaneity and appetite loss. On admission, laboratory data revealed hyponatremia (125 mEq/L) and hypoaldosteronism (0.7 ng/mL). Since hyponatremia did not improve by intravenous drip with saline, we identified the major cause of her complaint as hypoaldosteronism. She was treated with fludrocortisone (0.05 mg/day) and her condition improved immediately. Although she was discharged at that time, her condition shortly deteriorated. She was referred to our hospital on February 10, 2004 for medical treatment. On admission, inadequate oral intake, lack of spontaneity and weakness in her lower legs were noted. The plasma Na concentration was 127 mEq/L. Nasogastric tube feeding was started to prevent aspiration pneumonia because of her dysphagia. Fludrocortisone was given (0.2 mg/day), and she was able to swallow food without nasal feeding tube during the second month of therapy. Laboratory data including plasma natrium concentration were normal. Also she could perform bed-to-wheelchair transfer independently. This is a rare case of a critically ill elderly patient with hyponatremia caused by hypoaldosteronism possibly due to mineral corticoid-responsive hyponatremia of the elderly.

[A case of Werner syndrome with chromosomal abnormality].

A 52-year-old woman with diabetes mellitus (DM) complained of weakness of the arms and legs. She was referred to our hospital in November 2002 because of anemia, thyroid tumor and meningioma including DM. She was short in stature, juvenile bilateral cataract, intractable skin ulcers, clavus on the sole of her foot, a bird-like face and high-pitched voice. Typical physical features led to the final diagnosis of Werner's syndrome. Although the myelogram revealed no abnormal findings except erythroid hypoplasia, cytogenetic analysis of bone marrow cells showed deletion of chromosome 20 in 10% of the analyzed cells, which suggested the possibility of that myelodysplastic syndrome (MDS) or acute myeloblastic leukemia (AML) could occur. She had a thyroidectomy because both lobes of the thyroid gland were enlarged and caused hoarseness, In addition, it is common knowledge that the goiter could become malignant. We need to follow her carefully because she might be vulnerable to malignant disease, including leukemia and malignant meningioma.

Association of office-based frailty score with hypertensive end organ damage in the J-SHIPP cross-sectional study.

BACKGROUND: Frailty, a geriatric syndrome reflecting a state of reduced physiological reserve and increased vulnerability, is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between frailty and hypertensive end-organ damage is not fully established. METHOD AND RESULTS: We performed a cross-sectional study to investigate the association between frailty and end-organ damage in 1125 apparently healthy middle-aged to elderly subjects. We performed a simple frailty (SF) score that was easily obtainable in the office, in combination with low hand grip power and short one-leg standing (OLS) time. The association between SF score and hypertensive end-organ damage and other frailty-related parameters was evaluated. Odds ratio of SF score 1 to score 0 for the presence of hypertension was 1.9 [1.4-2.5, p<.0001] and that of SF score 2 was 3.3 [2.1-5.3, p<.0001]. SF score was also significantly associated with brachial-ankle pulse wave velocity (baPWV) and central pulse pressure (PP2). SF score was significantly associated with higher frailty index calculated from 21 parameters, lower cognitive test score, % vital capacity, skeletal muscle mass, and thigh muscle cross-sectional area. SF score was positively associated with stage of brain white matter hyperintenisty, plasma levels of B-type natriuretic peptide, and urinary protein excretion, even after correction for confounding parameters including baPWV and PP2. CONCLUSIONS: These findings indicate that frailty is significantly associated with end-organ damage in elderly subjects. SF score may be a useful clinical tool to identify frail subjects and advanced end-organ damage in elderly subjects.

Usefulness of the second derivative of the finger photoplethysmogram for assessment of end-organ damage: the J-SHIPP study.

Early detection of pathological changes in the vasculature is required to identify individuals at risk of cardiovascular diseases. Noninvasive measurement of the second derivative of photoplethysmogram (SDPTG) might aid in evaluating vascular aging. Here we clarified the diagnostic significance of four SDPTG indices for end-organ damage. A total of 1613 community residents (65±10 years) were enrolled. Changes in blood flow volume at the forefinger were measured by photoplethysmography. SDPTG was computationally calculated from the plethysmogram, and the height of five peaks (a-e) on the SDPTG was measured. Carotid intima-media thickness (IMT), brachial-to-ankle pulse wave velocity (baPWV) and silent cerebral lesions were used as indices of end-organ damage. Multivariate analysis identified age, sex, systolic blood pressure and heart rate as strong determinants for the evaluated SDPTG indices, namely b/a, d/a and aging index ([b-d-c-e]/a). In addition, poor glycemic control and carotid IMT were also weakly associated with the SDPTG indices. Compared with other established risk factors, however, the association between the SDPTG indices and carotid IMT was weak or insignificant (b/a: ß=0.069, P=0.002; d/a: ß=-0.009, P=0.669; and aging index: ß=0.047, P=0.037). Further, no significant association was noted between the SDPTG indices and silent lacunar infarction (b/a: P=0.111; d/a: P=0.263; and aging index: P=0.167) and periventricular hyperintensity (b/a: P=0.587; d/a: P=0.254; and aging index: P=0.429). Although the SDPTG indices evaluated here might represent structural and functional changes in arteries, they exhibited limited diagnostic significance for pathophysiological changes in large arteries, as well as small vessel diseases of the brain.

[Genetic analysis of life-style related diseases].

In our country to which the aging society was invited, life-style related diseases, such as cancer, ischemic cardiac disease, apoplexy, and diabetes, are increasing. These life-style related diseases are multi-factor diseases. And genetic factors, environmental factors, and aging factors are concerned. This genetic factors are prescribed by gene polymorphism between individuals. The method of identifying these gene polymorphism has two kinds, microsatellite and single nucleotide polymorphism (SNP). If the relation of life-style related diseases and gene polymorphism will be solved from now on, realization of patient-tailored treatment according to the individual, extension of healthy life expectancy, improvement in quality of life, and decrease of medical expenses are expected.

Muscle mass, visceral fat, and plasma levels of B-type natriuretic peptide in healthy individuals (from the J-SHIPP Study).

A paradoxical negative association between obesity and the plasma B-type natriuretic peptide (BNP) level has been firmly established. An individual's fat mass increases and muscle mass decreases with aging. Because aging is a potent determinant of plasma BNP levels, BNP may be related not only to fat mass but also to muscle mass. However, no studies have evaluated the associations between body composition and plasma levels of BNP. We performed a cross-sectional study to investigate these associations in 1,431 apparently healthy middle-aged to elderly subjects. The abdominal visceral fat area and thigh muscle cross-sectional area (CSA) were quantified by computed tomography. Plasma adiponectin and leptin levels were measured as possible confounding parameters. The brachial-ankle pulse wave velocity was measured as an index of arterial stiffness, and the pulse pressure (PP) of the second peak of the radial systolic blood pressure waveform (PP2) was used as an estimate of the central PP. Plasma BNP levels were significantly and negatively associated with the visceral fat area (r = -0.13, p <0.0001) and thigh muscle CSA (r = -0.25, p <0.0001). Corrections with possible confounding parameters including age, gender, heart rate, mean blood pressure, body weight, body height, adiponectin, leptin, brachial-ankle pulse wave velocity, and PP2 eliminated the association of BNP with visceral fat area but not with thigh muscle CSA (ß = -0.27, p <0.0001). These findings indicate that along with adiposity, muscle mass is an independent determinant of plasma BNP.