Poor toe flexor strength, but not handgrip strength, is associated with the prevalence of diabetes mellitus in middle-aged males.

Previous studies suggested that reduced muscular strength was one of the potential predictor of prevalence of diabetes mellitus. The purpose of this study was to investigate the association between toe flexor strength (TFS) and handgrip strength (HGS) and the prevalence of diabetes mellitus. Cross-sectional analysis was conducted using data from 1,390 Japanese males (35-59 years). TFS and HGS were measured and medical examinations undertaken. The prevalence of diabetes mellitus was defined as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% (48 mmol/mol), and/or current use of anti-diabetes mellitus drugs. A total of 114 participants had diabetes mellitus. TFS in participants with diabetes mellitus was significantly lower than that in persons not suffering from diabetes mellitus but HGS was not. Odds ratio (OR) and 95% confidence interval (CI) per 1-standard deviation-increase in muscular strength measurements for the prevalence of diabetes mellitus were obtained using a multiple logistic regression model. Prevalence of diabetes mellitus was inversely related to TFS (OR 0.769, 95% CI 0.614-0.963), TFS/body mass (BM) (0.696, 0.545-0.889) and TFS/body mass index (BMI) (0.690, 0.539-0.882) after adjustment of covariates. Such associations were not observed in HGS (OR 0.976, 95% CI 0.773-1.232), HGS/BM (0.868, 0.666-1.133) or HGS/BMI (0.826, 0.642-1.062). These results suggested that poor TFS was associated with an increased prevalence of diabetes mellitus independent of visceral fat accumulation, but HGS was not, in middle-aged males. TFS may be a better marker for the prevalence of diabetes mellitus than HGS.

Shoshin beriberi in a young man with gambling addiction.

We report a case of a 24-year-old previously healthy Japanese man who presented to the emergency department due to cardiopulmonary arrest lasting for 4 min. He had complained of chest pain and worsening dyspnea but was well until 3 days before admission. He had no history of alcohol consumption. Marked lactic acidosis, high-output heart failure, and hypotension with widened pulse pressure led to a diagnosis of shoshin beriberi. The patient recovered successfully without any residual symptoms after appropriate thiamine therapy. Because of the complexity of the clinical presentation and the lack of rapid diagnostic tests, thiamine deficiency remains difficult to diagnose. In this patient, we suspected that shoshin beriberi was caused by long-term poor nutritional status secondary to a severe gambling addiction to Japanese pinball games, known as 'pachinko'. Alcoholism, long-term intravenous alimentation, and diuretic use are well-known causes. We should not miss the opportunity for early intervention, even in young non-alcoholic patients such as this case. If left untreated, patients may die from cardiopulmonary collapse within hours of symptom onset. Thiamine should be administered as soon as suspicion for thiamine deficiency arises, such as in conditions of widened pulse pressure in a young patient. Learning objective: Alcoholism, long-term intravenous alimentation, and diuretic use are well-known causes of thiamine deficiency. However the complexity of the clinical presentation and the lack of rapid diagnostic tests make its diagnosis difficult. Shoshin beriberi is a fulminant form of this disease. We should not miss opportunities for early intervention. Thiamine should be administered as soon as its deficiency is suspected, such as in conditions of widened pulse pressure especially in a young patient.

Increased Impact of Serum Uric Acid on Arterial Stiffness and Atherosclerosis in Females.

AIMS: Serum uric acid increases with metabolic disorders; however, whether the effects of uric acid on atherosclerosis are different in females and males has not been sufficiently evaluated. Therefore, this study compared the impact of uric acid on arterial stiffness and atherosclerosis between females and males. METHODS: We enrolled 10196 untreated middle-aged subjects (46±8 years, 3021 females and 7175 males) who underwent periodic health check-ups. Serum uric acid levels were measured and arterial stiffness and atherosclerosis were assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and plaque, using ultrasound imaging. RESULTS: Females with increased arterial stiffness (CAVI ≥ 8.0) or carotid plaques had higher uric acid than those without (P＜0.0001), but males did not. In multivariable regression analyses including overall participants, uric acid was significantly associated with the CAVI, where sex interacted with uric acid. In sex-specific analyses, uric acid was significantly associated with the CAVI, but not with carotid IMT, in both sexes. However, logistic regression analyses revealed that serum uric acid was independently associated with the presence of carotid plaques in females. The exclusion of subjects with abdominal obesity or metabolic syndrome from the analysis did not alter the results in females. CONCLUSIONS: Serum uric acid was significantly associated with the CAVI in both sexes, but the interaction of sex was confirmed and associated with a carotid plaque only in females. These findings support the increased impact of serum uric acid on arterial stiffness and atherosclerosis in females.

Examination of Large Artery Atherosclerosis could Reveal Small Artery Retinopathy in Untreated Middle-Aged Individuals.

AIMS: Small arteries can be visualized in the ocular fundus, and findings of retinopathy based on Scheie classification are often applied to evaluate the impact of hypertension and atherosclerosis. However, the relationship between damage in the large and small arteries has not been investigated sufficiently, especially in the early stages. The present study investigated possible associations between large artery atherosclerosis and small artery retinopathy in untreated middle-aged individuals. METHODS: Untreated middle-aged workers undergoing periodic health check-ups (n=7,730, 45±8 years) were enrolled in this study. The absence or presence and extent of retinopathy were characterized by ophthalmologists as hypertensive (H0-4) and atherosclerotic grades (S0-4) based on Scheie classification. Large artery atherosclerosis was examined based on functional assessment of the cardio-ankle vascular index (CAVI) and morphological assessment of the carotid intima-media thickness (IMT) by ultrasound. RESULTS: We found significant differences in CAVI and carotid IMT between individuals with and without hypertensive or atherosclerotic retinopathy. Multivariable regression analysis showed that the presence of hypertensive and atherosclerotic retinopathy was significantly associated with CAVI and carotid IMT. Logistic regression analysis with the endpoint of a hypertensive or atherosclerotic lesion revealed that CAVI and carotid IMT are independent determinants of retinopathy. CONCLUSIONS: CAVI and carotid IMT were significantly associated with the presence of retinopathy based on Scheie classification in untreated middle-aged subjects, implying that atherosclerotic examination in large arteries could reveal early-stage small artery retinopathy.

A body shape index could serve to identify individuals with metabolic syndrome and increased arterial stiffness in the middle-aged population.

BACKGROUND: A body shape index (ABSI) is a novel anthropometric measure calculated using waist circumference (WC), body mass index (BMI), and body height. This study investigated the usefulness of ABSI to identify individuals with metabolic syndrome (MetS) and increased arterial stiffness in the middle-aged population. METHODS: Middle-aged workers who underwent periodic health check-ups and who were without previous cardiovascular events were enrolled (n = 10,182). In addition to ABSI, visceral fat area (VFA) was evaluated using computed tomography. Obesity and MetS were diagnosed on the basis of WC, VFA, and ABSI. Arterial stiffness was examined by measuring the cardio-ankle vascular index (CAVI). RESULTS: ABSI was significantly associated with CAVI in multivariable regression analysis. Logistic regression analysis revealed that ABSI was independently associated with the presence of MetS diagnosed on the basis of WC or VFA after adjustment for potential confounders, including BMI. Subjects with MetS diagnosed on the basis of each obesity index showed higher CAVI values than those without. Among subjects with MetS diagnosed on the basis of WC or VFA, those with MetS who met the definition of ABSI obesity showed significantly higher CAVI than those who did not. The other logistic regression analysis demonstrated that CAVI was independently associated with MetS defined on the basis of ABSI. CONCLUSIONS: ABSI was significantly associated with CAVI and the presence of MetS in the middle-aged population and helped to discriminate individuals with MetS and increased CAVI. ABSI could serve to identify individuals with MetS and increased arterial stiffness.

Beneficial effects of growth hormone-releasing peptide on myocardial oxidative stress and left ventricular dysfunction in dilated cardiomyopathic hamsters.

BACKGROUND: Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, suggesting a potential new approach to the treatment of cardiomyopathic hearts. The present study tested the hypothesis that the beneficial cardiac effects of GHRP might include attenuation of myocardial oxidative stress. METHODS AND RESULTS: Dilated cardiomyopathic TO-2 hamsters were injected with GHRP-2 (1 mg/kg) or saline from 6 to 12 weeks of age. F1B hamsters served as controls. Untreated TO-2 hamsters progressively developed LV dilation, wall thinning, and systolic dysfunction between 6 and 12 weeks of age. Marked myocardial fibrosis was apparent in untreated hamsters at 12 weeks of age in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and the concentration of 4-hydroxynonenal (4-HNE) was increased in the hearts of untreated TO-2 hamsters. Treatment with GHRP-2 attenuated the progression of LV remodeling and dysfunction, as well as myocardial fibrosis, in TO-2 hamsters. GHRP-2 also inhibited both the decrease in the GSH/GSSG ratio and the increase in the concentration of 4-HNE in the hearts of TO-2 hamsters. CONCLUSIONS: GHRP-2 can suppress the increase in the level of myocardial oxidative stress, leading to attenuation of progressive LV remodeling and dysfunction in dilated cardiomyopathic hamsters. (Circ J 2010; 74: 163 - 170).

Relationships of Obesity-Related Indices and Metabolic Syndrome with Subclinical Atherosclerosis in Middle-Aged Untreated Japanese Workers.

AIM: Obesity is a social problem due to the prevalence of the Western lifestyle. In particular, visceral fat accumulation, which is a main component of metabolic syndrome, is closely associated with the progression of atherosclerosis. This study aimed to investigate the relationships of obesity-related indices and metabolic syndrome with subclinical atherosclerosis in middle-aged untreated workers. METHODS: Employees undergoing their periodic health check-up but without previous cardiovascular events or cardiovascular medications were enrolled in this study (n=7,750). Body mass index (BMI), percent body fat, waist circumference, and visceral fat area were evaluated as obesity-related indices. Assessment of visceral fat area was performed by computed tomography (CT). Subclinical atherosclerosis was assessed by measuring arterial stiffness using cardio-ankle vascular index (CAVI) and by ultrasound examination of carotid intima-media thickness (IMT). RESULTS: Obesity-related indices were significantly correlated with each other and were positively associated with carotid IMT but negatively associated with CAVI in multivariate regression analysis. In a logistic regression analysis including CAVI and carotid IMT simultaneously, CAVI was negatively associated, but carotid IMT was positively associated, with obesity defined by each obesity-related index. In contrast, both CAVI and carotid IMT were positively associated with the presence of metabolic syndrome based on visceral fat accumulation. CONCLUSIONS: Obesity-related indices were negatively associated with CAVI and positively associated with carotid IMT in middle-aged untreated workers, while both CAVI and carotid IMT were worsened in the presence of metabolic syndrome.

Impacts of lifestyle behavior and shift work on visceral fat accumulation and the presence of atherosclerosis in middle-aged male workers.

Work style, and particularly shift work, can affect an individual's circadian rhythms. Moreover, lifestyle habits, including dietary and exercise routines, might be altered by irregular shift hours. The present study investigated how lifestyle and shift work affect the accumulation of visceral fat and the presence of atherosclerosis in middle-aged male workers. This study enrolled employees undergoing their periodic health check-up (n = 10,073). Visceral fat area (VFA) was evaluated by computed tomography. Atherosclerosis was assessed by the cardio-ankle vascular index (CAVI), carotid intima-media thickness (IMT), and carotid plaque. Lifestyle was evaluated by the following items: (1) eating breakfast, (2) nighttime eating, (3) regular exercise, (4) habitual drinking, (5) habitual smoking, (6) sleeping hours, and (7) working hours. Shift workers were defined as employees who were not engaged in fixed daytime work. The VFA and CAVI were significantly greater in fixed daytime workers than in shift workers, while the carotid IMT was lower in fixed daytime workers than in shift workers. Reduced regular exercise and fixed daytime work were independently associated with visceral fat accumulation by both multivariate regression and logistic regression analyses. Habitual smoking was independently associated with an increased CAVI and carotid atherosclerosis in both multivariate regression and logistic regression analyses. Reduced regular exercise and fixed daytime work were significantly associated with visceral fat accumulation, while habitual smoking had a consistent association with the presence of atherosclerosis. These findings support the idea that unhealthy lifestyles should be modified before considering an intervention in work style.

Close Association between Subclinical Atherosclerosis and Pulmonary Function in Middle-Aged Male Smokers.

AIMS: Cigarette smoking provokes deleterious influences on cardiovascular and pulmonary systems, although the underlying relationship has not been sufficiently investigated especially in early-stage disease. The present study investigated possible associations between subclinical atherosclerosis and pulmonary function in middle-aged male smokers. METHODS: Male smokers undergoing their periodic health check-up were enrolled in this study (n=3,775, 45±8 years). Pulmonary function was evaluated using spirometry by calculating forced vital capacity (FVC) as a percentage of predicted value (FVC%-predicted), forced expiratory volume in one second (FEV1) as a percentage of predicted value (FEV1%-predicted), and the ratio of FEV1 to FVC (FEV1/FVC). Subclinical atherosclerosis was assessed based on ankle-brachial pressure index (ABI), cardio-ankle vascular index (CAVI), ultrasound examination of the carotid intima-media thickness (IMT), and presence of plaque. RESULTS: Multivariate regression analysis showed that ABI was positively associated with FVC%-predicted and FEV1%-predicted after adjustment for confounders including smoking intensity, while CAVI or carotid IMT was inversely associated with both. Participants with chronic obstructive pulmonary disease (COPD, n=256) showed reduced ABI and increased CAVI or carotid IMT compared with those without COPD, and participants with carotid plaque had lower pulmonary function than those without plaque. Reduced FEV1/FVC was an independent determinant of carotid plaque and decreased ABI was an independent determinant of COPD, as revealed by logistic regression analysis with the endpoint of carotid plaque presence or a diagnosis of COPD revealed. CONCLUSIONS: Middle-aged male smokers showed a close association between subclinical atherosclerosis and pulmonary function, implying that smoking induced-vascular and pulmonary damage are interacting in early-stage disease.

Relationship between severity of renal impairment and 2-year outcomes after sirolimus-eluting stent implantation.

BACKGROUND: The presence of chronic kidney disease (CKD) is associated with an increased risk of restenosis and major adverse cardiac events (MACEs) after coronary interventions, especially in patients on hemodialysis (HD). The aim of this study was to assess the impact of varying degrees of renal impairment on angiographic and 2-year clinical outcomes after treatment with sirolimus-eluting stents (SESs). METHODS: A total of 675 lesions of 593 patients treated with SES were analyzed. Patients were classified into 3 groups: 34 patients on HD; 337 patients with estimated glomerular filtration rate > or =60 mL min(-1) 1.73 m(-2) (non-CKD group); and 222 patients who had lower estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) without HD dependency (CKD group). RESULTS: At angiographic follow-up (201 +/- 73 days), in-segment late loss was markedly higher in the HD group versus the non-CKD and CKD groups (0.68 +/- 1.06 vs 0.11 +/- 0.45 and 0.15 +/- 0.50 mm, respectively, P < .001), resulting in a significantly higher in-segment restenosis rate (40.0% vs 10.4% and 11.5%, respectively, P < .001). At 2 years, HD vs non-CKD and CKD was associated with a significantly higher MACE rate (35.3% vs 10.4% and 12.6%, respectively, P < .001), mainly driven by significantly higher mortality (11.8% vs 0.6% and 2.3%, respectively, P < .001) and target-lesion revascularization (23.5% vs 9.2% and 8.1%, respectively, P = .016) rates. Multivariable analysis revealed that HD was the independent predictor of 2-year MACE (hazard ratio 4.70, 95% CI 2.40-9.20, P < .001). CONCLUSIONS: Although angiographic and clinical outcomes after SES implantation were similarly favorable in non-HD-dependent CKD patients, regardless of renal function, in patients with end-stage CKD requiring HD, frequencies of restenosis and 2-year MACE were markedly higher than in non-HD-dependent patients.

Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters.

BACKGROUND: Oxidative stress is implicated in cardiac remodeling and failure. We tested whether xanthine oxidase (XO) inhibition could decrease myocardial oxidative stress and attenuate left ventricular (LV) remodeling and dysfunction in the TO-2 hamster model of dilated cardiomyopathy. METHODS AND RESULTS: TO-2 hamsters were randomized to treatment with the XO inhibitor, allopurinol, or vehicle from 6 to 12 weeks of age. F1B hamsters served as controls. TO-2 hamsters treated with vehicle progressively developed severe LV systolic dysfunction and dilation between 6 and 12 weeks. Marked cardiac fibrosis was apparent in these hamsters at 12 weeks in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and malondialdehyde levels were increased in the hearts of vehicle-treated TO-2 hamsters. Treatment with allopurinol from 6 to 12 weeks attenuated LV dysfunction and dilation as well as myocardial fibrosis and the upregulation of a fetal-type cardiac gene. Allopurinol also inhibited both the decrease in GSH/GSSG ratio and the increase in malondialdehyde levels in the heart. CONCLUSIONS: These results indicate that chronic XO inhibition with allopurinol attenuates LV remodeling and dysfunction as well as myocardial oxidative stress in this model of heart failure. Allopurinol may prove beneficial for the treatment of heart failure.

Association of body flexibility and carotid atherosclerosis in Japanese middle-aged men: a cross-sectional study.

OBJECTIVE: This study examined the associations of body flexibility with carotid arterial remodelling, including intima-media thickness (IMT) and plaque formation in middle-aged men. METHODS: The subjects of this cross-sectional study included 1354 Japanese men aged 35-59 years without histories of stroke or cardiac diseases. The arm extensibility test, which can estimate flexibility of the upper extremity (composed of shoulder external rotation and forearm supination), and the sit-and-reach test were performed. Common carotid IMT and plaque formation (≥1.1 mm) were estimated by ultrasound. RESULTS: The proportion of subjects who fully completed the arm extensibility test was 55.0%, and who had plaques in the common carotid artery was 37.8%. IMT was associated with poor arm extensibility (ß=-0.073, 95% CI -0.02224 to -0.00041, P=0.004), while plaque formation was associated with poor sit-and-reach (OR 0.98579, 95% CI 0.97257 to 0.99919, P=0.038) after adjustment by all covariates. CONCLUSIONS: This study demonstrated that poor upper extremity and trunk flexibility were associated with characteristics of early onset of atherosclerosis. Furthermore, these associations were independent of covariates such as age, blood pressure, blood lipids glucose levels and abdominal fat accumulation, handgrip strength and lifestyle, including sleeping, drinking, exercise and smoking habits. Poor flexibility may reflect subclinical atherosclerosis in middle-aged men.

Differential cardiovascular effects of endotoxin derived from Escherichia coli or Pseudomonas aeruginosa.

Sepsis is characterized by various symptoms, signs and underlying pathophysiology. To investigate possible mechanisms underlying this diversity, we compared the cardiovascular effects of lipopolysaccharide (LPS) derived from Escherichia coli (E-LPS) with those of LPS from Pseudomonas aeruginosa (P-LPS) in rats. We also examined the possible roles of tumor necrosis factor-alpha (TNF-alpha) and oxidative stress in LPS-induced cardiovascular damage. E-LPS (10 mg/kg body weight) or P-LPS (2 mg/kg body weight) was administered intravenously to Wistar rats. Echocardiography was serially performed. E-LPS induced an increase in left ventricular fractional shortening that persisted for at least 6 h, whereas P-LPS elicited an initial increase and a subsequent decrease in this parameter. Histological analysis revealed that P-LPS induced interstitial edema, congestion, intramyocardial bleeding, myocardial necrosis, infiltration of inflammatory cells, and formation of fibrin thrombi in the heart, whereas no pathological changes were apparent in the hearts of rats treated with E-LPS. Furthermore, the plasma concentration of TNF-alpha in rats treated with P-LPS was greater than that in rats treated with E-LPS, but the glutathione redox ratio in the heart was not affected by either type of LPS. In conclusion, E-LPS and P-LPS induced distinct patterns of functional and structural responses in the cardiovascular systems of rats. These differential responses may be attributable in part to the difference in the associated increases in the plasma concentration of TNF-alpha. The cardiovascular effects of LPS thus depend on the causative organisms.

Age-related reduction and independent predictors of toe flexor strength in middle-aged men.

BACKGROUND: Toe flexor muscles play an important role in posture and locomotion, and poor toe flexor strength is a risk factor for falls. In this cross-sectional study, we estimated the age-related change in toe flexor strength and compared it with that of handgrip strength. Independent factors predicting toe flexor and handgrip strength were also determined. METHODS: A total of 1401 male (aged 35-59 years) study participants were divided into five groups according to their chronological age; 35-39, 40-44, 45-49, 50-54, and 55-59 years. Toe flexor and handgrip strength, anthropometry, and resting blood pressure were measured. Fasting blood samples were collected to measure blood glucose, triglycerides, high- and low-density lipoprotein-cholesterols, and albumin. A self-administered lifestyle questionnaire was conducted. RESULTS: Decline in absolute toe flexor and handgrip strength began in the age groups 50-55 and 55-59 years, respectively. In comparison to the mean values of the youngest group, relative toe flexor strength (87.0 ± 26.6%) was significantly lower than handgrip strength (94.4 ± 13.1%) for the oldest group. Multiple regression analyses showed that independent factors predicting both toe flexor and handgrip strength were lean body mass, age, serum albumin, drinking habit, and fat mass. Additionally, fasting blood glucose, diastolic blood pressure, sleeping time and exercise habit were predicting factors of toe flexor strength but not of handgrip strength. CONCLUSIONS: Age-related reduction in toe flexor strength was earlier and greater than handgrip strength, and toe flexor strength reflects body composition and metabolic status.

Discrimination of nonobstructive hypertrophic cardiomyopathy from hypertensive left ventricular hypertrophy on the basis of strain rate imaging by tissue Doppler ultrasonography.

BACKGROUND: The differentiation of hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) on the basis of morphological information obtained by conventional echocardiography is occasionally problematic. We investigated whether strain rate (SR) imaging derived from tissue Doppler imaging (TDI) is able to discriminate HCM from H-LVH. METHODS AND RESULTS: Conventional echocardiography and TDI were performed with 34 patients with LVH and 16 reference subjects. Mean values of systolic strain (epsilon(sys)), peak systolic SR, and early diastolic SR obtained from 8 left ventricular (LV) segments were calculated. LV pressures were recorded simultaneously in the patients. Patients were diagnosed with HCM (n=20) or H-LVH (n=14) on the basis of conventional echocardiography and endomyocardial biopsy findings. Multivariate analysis revealed that septum/posterior wall thickness ratio (P=0.00013) and epsilon(sys) (P<0.0001) were each able to discriminate HCM from H-LVH. A epsilon(sys) cutoff value of -10.6% discriminated between HCM and H-LVH with a sensitivity of 85.0%, specificity of 100.0%, and predictive accuracy of 91.2%. The combination of the septum/posterior wall thickness ratio and epsilon(sys) discriminated HCM from H-LVH with a predictive accuracy of 96.1%. The epsilon(sys) parameter was significantly correlated with pulmonary arterial wedge pressure, LV end-diastolic pressure, the peak positive first derivative of LV pressure, and the time constant of LV pressure decay. CONCLUSIONS: SR imaging is able to discriminate HCM from H-LVH, with epsilon(sys) reflecting myocardial contractile and lusitropic properties.