Analytical evaluation of serum non-transferrin-bound iron and its relationships with oxidative stress and cardiac load in the general population.

ABSTRACT: Excessive iron accumulation provokes toxic effects, especially in the cardiovascular system. Under iron overload, labile free non-transferrin-bound iron (NTBI) can induce cardiovascular damage with increased oxidative stress. However, the significance of NTBI in individuals without iron overload and overt cardiovascular disease has not been investigated. We aimed to examine the distribution of serum NTBI and its relationship with oxidative stress and cardiac load under physiological conditions in the general population.We enrolled individuals undergoing an annual health check-up and measured serum NTBI and derivatives of reactive oxygen metabolites (d-ROM), an oxidative stress marker. In addition, we evaluated serum levels of B-type natriuretic peptide (BNP) to examine cardiac load. We excluded patients with anemia, renal dysfunction, cancer, active inflammatory disease, or a history of cardiovascular disease.A total of 1244 individuals (57.8 ±â€Š11.8 years) were enrolled, all of whom had detectable serum NTBI. d-ROM and BNP showed significant trends across NTBI quartiles. Multivariable regression analysis revealed that serum iron and low-density lipoprotein cholesterol were positively associated with NTBI but that age, d-ROM, and BNP showed an inverse association with this measure. In logistic regression analysis, NTBI was independently associated with a combination of higher levels of both d-ROM and BNP than the upper quartiles after adjustment for possible confounding factors.Serum NTBI concentration is detectable in the general population and shows significant inverse associations with oxidative stress and cardiac load. These findings indicate that serum NTBI in physiological conditions does not necessarily reflect increased oxidative stress, in contrast to the implications of higher levels in states of iron overload or pathological conditions.

Effects of physical therapy on blood pressure in daily clinical practice-a pilot study.

[Purpose] Most exercise therapy procedures induce hemodynamic changes and could be a cardiovascular risk. This pilot study investigated factors that induce an exaggerated increase in blood pressure during exercise therapy. [Participants and Methods] We measured the blood pressure and pulse rate before and after exercise therapy for ambulation on days 1, 2, and 7 of the exercise therapy in patients (n=23; age, 69 ± 11 years) who were hospitalized for a stroke or an orthopedic surgery. [Results] Each participant's blood pressure and pulse rate were significantly increased after the exercise therapy. Regression analysis demonstrated that the increase in systolic blood pressure was independently predicted by body weight and pulse rate before the exercise therapy. In the logistic regression analysis, age and body weight were independent predictors of the exaggerated increase in systolic blood pressure (fourth quartile). [Conclusion] A significant increase in blood pressure was induced by exercise therapy. There was a correlation between systolic blood pressure increase and pulse rate before the exercise therapy. Old age or increased body weight predicts exaggerated increase in blood pressure during exercise therapy.

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.

Indices of left ventricular voltage on electrocardiogram are closely associated with serum cardiac troponin I levels in normotensive Japanese individuals.

The high-sensitivity cardiac troponin I (hs-cTnI) in serum can increase due to an increase in left ventricular (LV) overload in individuals with hypertension. Since LV voltage on an electrocardiogram (ECG) reflects LV load, it is possible that LV voltage is closely associated with hs-cTnI in individuals without hypertension. This study investigated the association between LV voltage indices and serum hs-cTnI levels in normotensive Japanese individuals.Subjects who visited the Enshu Hospital for a health check-up were screened for their eligibility. Subjects with renal dysfunction, cancer, active inflammatory disease, or a history of cardiovascular events were excluded, as were subjects with obvious ST segment or T wave abnormality, Wolff-Parkinson-White syndrome, pacemaker implantation, or frequent arrhythmia in the ECG. Exclusion of individuals with hypertension left 803 subjects (54.8 ±â€Š11.3 years) for final inclusion. The R wave voltage in lead V5 (RV5 voltage), the Sokolow-Lyon voltage (a sum of the QRS wave (a complex wave consists of Q, R, and S wave) of the S wave voltage in lead V1 and the R wave voltage in lead V5), and the Cornell product (a product of QRS duration and QRS voltage) were evaluated by ECG as LV voltage indices. Laboratory measurements included serum hs-cTnI levels. Possible associations between indices of LV voltage on ECG and serum hs-cTnI levels were cross-sectionally investigated in the normotensive subjects.The median values [interquartile range] of hs-cTnI and BNP were and 2.1 [1.4-3.0] and 13.8 [7.7-24.9] pg/mL, respectively. Multivariate regression analysis identified that the levels of hs-cTnI, but not BNP, were significantly associated with RV5 voltage (ß 0.090, P = .0087), Sokolow-Lyon voltage (ß 0.112, P = .0009), and Cornell product (ß 0.101, P = .039) after adjustment for possible confounding factors. Moreover, the RV5 voltage, Sokolow-Lyon voltage, and Cornell product were significantly associated with the hs-cTnI levels after adjustment for possible confounding factors including ECG findings (ß 0.109, P = .0075; ß 0.125, P = .0010; and ß 0.096, P = .0116, respectively).Indices of LV voltage in ECG had close associations with serum hs-cTnI levels in normotensive subjects. These findings support that the ECG findings of LV voltage have significant associations with slight myocardial micro-damage even in normotensive subjects.

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.

Factors associated with longitudinal changes in serum concentrations of Mac-2 binding protein: A prospective 3-year observational study.

BACKGROUND AND AIMS: Mac-2 binding protein (M2BP) plays an important role in cell adhesion. In a recent cross-sectional study we reported that serum M2BP concentrations may reflect silent atherosclerosis. The aim of the present prospective follow-up study was to investigate possible relationships between changes in concentrations of M2BP and other factors over a >3-year period. METHODS AND RESULTS: The present study enrolled subjects who visited Enshu hospital from 2014 to 2015 for a periodic physical check-up and then attended for another physical check-up after >3 years (n = 174). Factors affecting changes in M2BP concentrations were investigated at both baseline and follow-up. Subjects with liver dysfunction, a history of hepatic disease, malignant neoplasm, or cardiovascular events at baseline were excluded. Univariate and multivariate regression analyses showed that changes in serum M2BP concentrations during the follow-up period were significantly associated with changes in low-density lipoprotein cholesterol (LDL-C), triglyceride, and oxidative stress marker derivatives of reactive oxygen metabolites (d-ROM) concentrations. Moreover, the increase in LDL-C was significantly greater in subjects in whom M2BP concentrations increased during the follow-up period. Logistic regression analysis with an endpoint of increased M2BP revealed that increased LDL-C was an independent determinant of an increase in M2BP during the follow-up period. CONCLUSION: During the observation period of >3 years, serum M2BP concentrations were increased in subjects who also exhibited increases in levels of metabolic parameters, especially LDL-C, and the oxidative stress marker d-ROM. These results support that serum M2BP reflects one of the contributors to the progression of silent atherosclerosis.

Smoking Cessation without Educational Instruction could Promote the Development of Metabolic Syndrome.

AIM: Smoking cessation is particularly important for maintaining health; however, the subsequent risk of an increased body weight is of major concern. The present study investigated the influence of smoking cessation on the incidence of metabolic syndrome and its components in the Japanese general population. METHODS: This study enrolled individuals without metabolic syndrome or a history of smoking via our annual health checkup program (n=5,702, 55.2±11.5 years). Participants were divided into three groups mentioned below and followed up with the endpoint being the development of metabolic syndrome: (1) subjects who had never smoked and did not smoke during the observation period (non-smoker); (2) those who continued smoking during the observation period (continuous smoker); and (3) those who ceased smoking during the observation period (smoking cessation). RESULTS: During the observation period (median 1,089 days), 520 subjects developed metabolic syndrome, and Kaplan-Meier analysis showed a higher incidence of metabolic syndrome in the smoking cessation group than in the other groups. Smoking cessation was confirmed as an independent predictor of the new onset of metabolic syndrome by multivariate Cox proportional hazard analysis after adjustment. Subjects only from the smoking cessation group showed a significant deterioration in metabolic factors during the study in correlation with an increased waist circumference after smoking cessation. CONCLUSIONS: Smoking cessation without instruction could be followed by the development of metabolic syndrome, and the incidence of metabolic syndrome might reduce the benefit obtained from smoking cessation. Therefore, further educational outreach is needed to prevent the progression of metabolic syndrome during the course of smoking cessation.

Oxidative Stress is Closely Associated with Increased Arterial Stiffness, Especially in Aged Male Smokers without Previous Cardiovascular Events: A Cross-Sectional Study.

AIM: Cigarette smoking is one of the major risk factors for cardiovascular diseases and induces deleterious vascular damage. Oxidative stress is involved in vascular inflammation, the process of atherosclerosis. The purpose of the present study was to investigate whether the effects of oxidative stress on the arterial wall differ between smokers and non-smokers. METHODS: Male smokers and non-smokers without physical deconditioning who visited Enshu hospital for an annual physical check-up were enrolled in the study. To assess oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. The radial augmentation index (RAI) was measured using an automated device and was used as an index for arterial stiffness. RESULTS: Univariate and multivariate linear regression analysis showed that RAI was independently associated with d-ROM levels only in smokers. Moreover, RAI was significantly higher in smokers than in non-smokers. Logistic regression analysis with the endpoint of a higher RAI than the mean revealed that older age (＞65 years), hypertension, and smoking were independently associated with higher RAI. Similarly, logistic regression analysis with the endpoint of higher d-ROM levels than the mean showed that older age and smoking were independently associated with higher d-ROM levels. CONCLUSIONS: Increased RAI is significantly associated with smoking and, in smokers, with increased d-ROM levels. These results suggest that the effects of oxidative stress on arterial properties differ between smokers and non-smokers and that oxidative stress is closely associated with arterial stiffness, especially in smokers.

MicroRNA in atherothromobosis: is it useful as a disease marker?

Atherosclerosis is one of the major causes of death. Data from animal experiments suggest that atherosclerosis involves an inflammatory process of the vascular wall under hyperlipidemia. Atherothrombosis can become a serious complication of atherosclerosis leading to acute cardiovascular events such as myocardial infarction and stroke. Clinical applications to use this knowledge remain scarce. The plasma levels of vascular endothelium-enriched microRNA (miRNAs) in patients with atherosclerotic vascular disease could serve as a disease marker. In our laboratory vascular endothelium-enriched miRNA (miR-126) level was analyzed using quantitative RT polymerase chain reaction analysis (qRT-PCR) in plasma from patients with suspected coronary artery disease (CAD) according to the chest symptom or findings of electrocardiogram, or middle-aged male smokers. Endothelial function for peripheral small vessels was assessed using End-PAT 2000 and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. In patients with suspected CAD miR-126 was not significantly changed in CAD patients. However, miR-126 was decreased in CAD patients who also have high levels of low-density lipoprotein (LDL) cholesterol. Interestingly, miR-126 was increased when LDL cholesterol was high in patients who did not have evident CAD on coronary angiography even though they have risk factors for CAD. In smokers serum cotinine levels were inversely correlated with endothelial function expressed as RH-PAT index and positively correlated with levels of metabolic parameters such as non-high-density lipoprotein (HDL) cholesterol and insulin resistance. More than half of the smokers could not completely attain smoking cessation and, thus, the RH-PAT index was not improved 8 weeks after the instruction of smoking cessation. However, changes in the RH-PAT index showed a significant correlation with those in systolic blood pressure. In smokers who completely attained smoking cessation, both RH-PAT index and plasma miR-126 values were increased. Thus, among patients with suspected CAD or subjects with coronary risk factors plasma levels of endothelium-enriched circulating miR-126 could be substantially altered. The results suggest a potential usefulness of miR-126 as a sensitive biomarker in assessing endothelial damage. Measurement of microRNA may serve as a useful tool for laboratory assays to determine high-risk patients for atherothromobotic vascular diseases.

A case report of asymptomatic aortic thrombosis incidentally detected by computed tomography in apparently healthy subject with a history of cancer surgery.

BACKGROUND: Aortic thrombosis is a rare disease and only a few cases of the disease, especially associated with chemotherapy for malignant diseases and/or blood diseases, have been previously reported. Although Virchow's triad for thrombogenesis, namely hypercoagulability, blood flow stasis, and vessel wall injury, is the major factor promoting the formation of thrombosis, the detailed mechanism of the disease has not been well established. CASE PRESENTATION: We report a case of aortic thrombosis incidentally detected by computed tomography and then regressed by pharmacotherapy using warfarin. This case is an apparently healthy man in a postoperative state after lung cancer surgery with decreased protein-C activity. CONCLUSIONS: A case of aortic thrombosis without an obvious abnormality of the aorta was incidentally identified. A few cases of aortic thrombosis in healthy aortas have been reported to be associated with chemotherapy or blood diseases, however our present case did not had such a background. Although the detailed mechanism remains to be elucidated, this case suggests that aortic thrombosis can develop in apparently healthy subjects with a history of cancer surgery.

Serum levels of Mac-2 binding protein increase with cardiovascular risk and reflect silent atherosclerosis.

BACKGROUND AND AIMS: Mac-2 binding protein (M2BP) was reported to be a useful biomarker for liver fibrosis and malignant tumors. We hypothesized that expression of M2BP might also change in the process of atherosclerosis. METHODS: This study included subjects who visited our hospital for a physical checkup. RESULTS: The M2BP levels in subjects with hypertension, dyslipidemia, or abnormal glucose metabolism were higher than those in subjects without such risk factors. Moreover, the M2BP levels were associated with severity of cardiovascular risk. Subdivision of M2BP levels into quartiles revealed that M2BP was significantly associated with reactive oxygen metabolites, central systolic blood pressure, and radial augmentation index (AI). Logistic regression analysis with the endpoint of high radial AI (above mean value) showed that high radial AI was independently associated with high M2BP. CONCLUSIONS: Although the spectrum was narrow as compared to that in cases of hepatic fibrosis, serum M2BP may reflect silent atherosclerosis in apparently healthy subjects.

Use of Electrocardiography to Predict Future Development of Hypertension in the General Population.

Cardiac muscle responds to increased afterload by developing hypertrophy. During the early stages of hypertension, the heart can be transiently, but frequently, exposed to increased afterload. This study was designed to test the hypothesis that left ventricular hypertrophy (LVH) assessed by electrocardiography (ECG) can be used to predict future development of hypertension.Sokolow-Lyon voltage and Cornell product were calculated using ECG in 5770 normotensive participants who visited our hospital for a physical checkup (age 52.7 ±â€Š11.3 years). LVH was defined as a Sokolow-Lyon voltage of >3.8 mV or a Cornell product of >2440 mm × ms. After baseline examination, participants were followed up with the endpoint being the development of hypertension.During the median follow-up period of 1089 days (15,789 person-years), hypertension developed in 1029 participants (65.2/1000 person-years). A Kaplan-Meier analysis demonstrated a significantly higher incidence of hypertension in participants with LVH than in those without LVH as assessed by Sokolow-Lyon voltage or Cornell product (P < 0.0001 for both). The hazard ratios for incident hypertension in participants with LVH defined by Sokolow-Lyon voltage and Cornell product were 1.49 (95% confidence interval [CI] 1.16-1.90, P < 0.01) and 1.34 (95% CI 1.09-1.65, P < 0.01), respectively, after adjustment for possible risk factors. Furthermore, in multivariable Cox hazard analysis, where Sokolow-Lyon voltage and Cornell product were taken as continuous variables, both indices were independent predictors of future hypertension (P < 0.0001).Both Sokolow-Lyon voltage and Cornell product are novel predictors of future development of hypertension in the general population.

Dietary Sodium Consumption Predicts Future Blood Pressure and Incident Hypertension in the Japanese Normotensive General Population.

BACKGROUND: Although there is a close relationship between dietary sodium and hypertension, the concept that persons with relatively high dietary sodium are at increased risk of developing hypertension compared with those with relatively low dietary sodium has not been studied intensively in a cohort. METHODS AND RESULTS: We conducted an observational study to investigate whether dietary sodium intake predicts future blood pressure and the onset of hypertension in the general population. Individual sodium intake was estimated by calculating 24-hour urinary sodium excretion from spot urine in 4523 normotensive participants who visited our hospital for a health checkup. After a baseline examination, they were followed for a median of 1143 days, with the end point being development of hypertension. During the follow-up period, hypertension developed in 1027 participants (22.7%). The risk of developing hypertension was higher in those with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to 1.50). In multivariate Cox proportional hazards regression analysis, baseline sodium intake and the yearly change in sodium intake during the follow-up period (as continuous variables) correlated with the incidence of hypertension. Furthermore, both the yearly increase in sodium intake and baseline sodium intake showed significant correlations with the yearly increase in systolic blood pressure in multivariate regression analysis after adjustment for possible risk factors. CONCLUSIONS: Both relatively high levels of dietary sodium intake and gradual increases in dietary sodium are associated with future increases in blood pressure and the incidence of hypertension in the Japanese general population.

Circulating level of microRNA-126 may be a potential biomarker for recovery from smoking-related vascular damage in middle-aged habitual smokers.

BACKGROUND: Cigarette smoking promotes vascular endothelial damage and accelerates progression of atherosclerosis. The purpose of this study was to examine whether the circulating level of vascular endothelium-enriched microRNA-126 (miR-126), which is highlighted as a regulator of gene expression, would serve as a novel biomarker for recovery from smoking-related vascular damage. METHODS: Middle-aged male smokers (n = 30) were enrolled and instructed to stop smoking. Their clinical profiles and laboratory findings including expression of miR-126 were investigated before and after 8 weeks of smoking cessation. Serum levels of cotinine, metabolites of nicotine, were measured to confirm smoking cessation. Endothelial function for peripheral small vessels was assessed and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. The expression of miR-126 in plasma was analyzed by quantitative real-time PCR. RESULTS: At baseline, serum cotinine levels were inversely correlated with RH-PAT index (r = - 0.48, P < 0.01) and positively correlated with levels of metabolic parameters such as non-HDL cholesterol (r = 0.53, P < 0.01) and HOMA-IR (r = 0.52, P < 0.01). The RH-PAT index was not significantly changed after 8 weeks in all subjects, because only 13 subjects could attain smoking cessation. However, changes in the RH-PAT index showed a significant correlation with those in systolic blood pressure (r = - 0.54, P < 0.01). In smokers who completely attained smoking cessation (n = 13), RH-PAT index and plasma levels of miR-126 were significantly increased (P < 0.05, respectively). CONCLUSIONS: Endothelial damage was improved and plasma levels of circulating miR-126 were increased after 8 weeks of smoking cessation. These findings suggested a potential use of miR-126 as a biomarker for recovery from smoking-induced vascular damage.

Evaluation of risk for incident hypertension using glomerular filtration rate in the normotensive general population.

OBJECTIVES: The present study tested the hypothesis that glomerular filtration rate can predict the onset of hypertension in individuals with normal blood pressure in the general population. METHODS: Normotensive individuals (n = 7684) who visited our hospital for a routine physical examination were enrolled in the study (4907 men; mean age 52.1 ±â€Š11.1 years) and were followed up with the endpoint being the development of hypertension. The relationship between estimated glomerular filtration rate at baseline and the incidence of hypertension was evaluated. RESULTS: During the follow-up period (median 4.0 years; actual follow-up 30 624 person-years), hypertension developed in 2031 participants (66.3 per 1000 person-years). After adjustment for possible risk factors, the hazard ratio of incident hypertension (first tertile as reference) in the second and third tertiles was 1.03 (95% confidence interval 0.92-1.16) and 1.40 (95% confidence interval 1.26-1.57), respectively. Multivariate Cox proportional hazard regression analysis, in which estimated glomerular filtration rate was taken as a continuous variable and adjustments were made for known risk factors, also indicated that baseline estimated glomerular filtration rate independently predicted the onset of hypertension (P < 0.0001). Furthermore, multiple regression analysis revealed that a longitudinal increase in SBP was significantly associated with baseline estimated glomerular filtration rate after adjustment for known risk factors (P < 0.01). CONCLUSION: Estimated glomerular filtration rate in normotensive individuals is a good predictor of the onset of hypertension in the general population.

Randomized controlled trial of the effect of short-term coadministration of methylcobalamin and folate on serum ADMA concentration in patients receiving long-term hemodialysis.

BACKGROUND: Serum asymmetric dimethylarginine (ADMA) levels are increased in maintenance hemodialysis patients, and this abnormality may increase cardiovascular risk. We investigated whether combined administration of oral folate and intravenous methylcobalamin in such patients is more beneficial than oral folate alone at decreasing circulating ADMA levels. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Patients undergoing hemodialysis. INTERVENTION: 40 patients were randomly assigned to 1 of 2 groups. For 3 weeks, they received supplementation with either folate alone (15 mg/d; n = 20; folate group) or coadministered folate (15 mg/d) and methylcobalamin (500 mug after each hemodialysis treatment 3 times weekly; n = 20; methylcobalamin group). PRIMARY OUTCOMES: normalization of plasma homocysteine levels (<15 mumol/L), decrease in serum ADMA levels. SECONDARY OUTCOMES: change in augmentation index in the carotid artery and ratios of S-adenosylmethionine to S-adenosylhomocysteine (as a transmethylation indicator) and dimethylamine to ADMA (as an indicator of ADMA hydrolysis). MEASUREMENTS: Blood samples were collected under fasting conditions during the prehemodialysis procedure. RESULTS: The proportion showing normalization of plasma homocysteine levels was much greater in the methylcobalamin group (18 of 20 patients; 90%) than in the folate group (6 of 20; 30%; P < 0.001). The percentage of decrease in ADMA levels was greater in the methylcobalamin than folate group (25.4% +/- 10.2% vs 13.2% +/- 11.2%; P < 0.001). The increase in ratio of S-adenosylmethionine to S-adenosylhomocysteine was not different between the 2 groups; however, the ratio of dimethylamine to ADMA was increased in only the methylcobalamin group (P = 0.04). Augmentation index was decreased in only the methylcobalamin group (P = 0.03). LIMITATIONS: This study had an open-label nature and did not examine long-term effects of homocysteine-normalizing therapy (no clinical end points). CONCLUSION: Coadministration of intravenous methylcobalamin and oral folate in hemodialysis patients normalized hyperhomocysteinemia and decreased ADMA levels and arterial stiffness. We suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in such patients.

Combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin improves fulminant pseudomembranous colitis by reducing the elevated endogenous cannabinoids and inflammatory cytokines: report of a case.

This paper reports a case of fulminant pseudo-membranous colitis which did not lead to septic shock. The case was improved by combination therapy with direct hemoperfusion using polymyxin B-immobilized fiber and oral vancomycin. Direct hemoperfusion using polymyxin B-immobilized fiber has been demonstrated to have excellent therapeutic effects for the treatment of septic shock by removing circulating lipopolysaccharide. In the present case, the combination therapy dramatically improved clinical status of the patient. The clinical improvement occurred in parallel with a decrease in APACHE II score (from 20 to 14 points), serum levels of endogenous cannabinoids (anandamide and 2-arachidonylglycerol), and inflammatory cytokine (interleukin-6). Thus, direct hemoperfusion is strongly recommended in cases of fulminant pseudomembranous colitis, because direct hemoperfusion using polymyxin B-immobilized fiber reduces inflammatory cytokines by absorbing endogenous cannabinoids and, thereby, improves the patient's condition.

Carvedilol reduces elevated B-type natriuretic peptide in dialyzed patients without heart failure: cardioprotective effect of the beta-blocker.

Elevated plasma B-type natriuretic peptide (BNP) predicts future cardiovascular events in dialyzed patients without heart failure. We investigated whether carvedilol reduces the elevated BNP in these patients. Asymptomatic patients on chronic hemodialysis with elevated BNP but without clinical signs of heart failure were randomly assigned to receive either carvedilol (n = 10) or nothing (control group, n = 10). BNP and malondialdehyde-low density lipoprotein (MDA-LDL) were measured, and ultrasound cardiography was performed at baseline and at 3 months. Carvedilol reduced the concentrations of BNP (551 +/- 90 to 237 +/- 174 ng/L, P < 0.01) and MDA-LDL (174 +/- 63 to 85 +/- 23 U/L, P < 0.01) and increased the velocity ratio of E to A waves of the transmitral flow (E/A: 0.59 +/- 0.04 to 0.71 +/- 0.05, P < 0.05), while no such alterations were observed in the control group. The reduction in BNP concentration was correlated with that in MAD-LDL and the increase in the E/A. There was a significant correlation between the increase in the E/A and the reduction in MDA-LDL concentration. Thus, carvedilol reduces the elevated BNP by improving left ventricular diastolic function in dialyzed patients without heart failure, which may be attributable to the antioxidant property of the beta-blocker. Administering carvedilol may improve the prognosis in this population.

Association among C-reactive protein, oxidative stress, and traditional risk factors in healthy Japanese subjects.

BACKGROUND: Inflammation and oxidative stress play a key role in the pathogenesis of atherosclerosis. This study was designed to examine the interrelationships among C-reactive protein (CRP), oxidative stress, and traditional cardiovascular risk factors. METHODS: We conducted a cross-sectional analysis among 551 apparently healthy Japanese subjects not receiving medication (mean age, 53+/-11 years; males/females, 400/151). Subject underwent laboratory assessment of cardiovascular disease risk factors, and CRP and 8-isoprostane, a marker of oxidative stress, were measured. RESULTS: In unadjusted analyses, CRP was positively correlated with age, male gender, body mass index, blood pressure, smoking habit, creatinine, uric acid, triglycerides, an index of insulin resistance, and 8-isoprostane, and inversely correlated with high-density lipoprotein-cholesterol. 8-Isoprostane was positively correlated with age, pulse pressure, smoking habit, brain natriuretic peptide, and CRP. In multiple regression analyses, body mass index (r=0.177), high-density lipoprotein-cholesterol (r=-0.162), uric acid (r=0.141), and 8-isoprostane (r=0.097) were independently correlated with CRP (P<0.001), whereas smoking (r=0.341), age (r=0.217), and pulse pressure (r=0.091) remained independently correlated with 8-isoprostane (P<0.001). CONCLUSIONS: CRP levels are associated not only with clinical cardiovascular risk factors but also with oxidative stress. There are significant interrelationships among inflammation, oxidative stress, and traditional cardiovascular risk factors.