Analysis of the relationship between the amplitude of aortic wall motion and heart function.

PURPOSE: Because the posterior wall of the aorta and left atrium are interlocked, the amplitude of motion of the aortic wall (AMAW) may reflect cardiac and vessel functions. This study examined the relationship between cardiac and vessel functions and AMAW. METHODS: Patients with cardiovascular diseases or patients undergoing health examinations who visited a participating hospital and underwent echocardiography and brachial-ankle pulse-wave velocity (baPWV) examinations were registered. The correlations between echocardiographic indices, ankle-brachial index, and baPWV and AMAW on M-mode echocardiography were analyzed. RESULTS: Overall, 184 patients were enrolled. Heart rate (r = - 0.1587), ejection fraction (EF; r = 0.3240), wall thickness (r = - 0.1598), peak early diastolic mitral annular velocity (E) to peak early diastolic mitral annular velocity ratio (e'; r = - 0.2463), and baPWV (r = - 0.1928) significantly correlated with AMAW. In the stratified multiple regression analysis, E/e' (standardized partial regression coefficients = - 0.1863) and mean baPWV (standardized partial regression coefficients = - 0.1917) in patients with an EF of ≥ 60% (n = 114) significantly correlated with AMAW. In patients with an EF of < 60% (n = 70), E/e' (standardized partial regression coefficients = - 0.2443) significantly correlated with AMAW. CONCLUSION: Because E/e' correlated with AMAW in patients with an EF of < 60% or ≥ 60%, AMAW might be an indicator of left atrial pressure elevation. Moreover, because AMAW correlated with baPWV in patients with an EF of ≥ 60%, changes in the restricted left atrial volume might influence diastolic dysfunction. AMAW may be related to cardiac and vessel functions.

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.

Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF)α, interleukin (IL)-6, and IL-17. Effective treatments, including pathogenesis-based biological agents against psoriasis, are currently under development. Although the role of reactive oxygen species (ROS) in the pathogenesis of psoriasis has been investigated, it remains to be fully elucidated; ROS-targeted therapeutic strategies are also lacking at present. Therefore, the objective of the present study was to assess whether H2, a ROS scavenger, has a therapeutic effect on psoriasis-associated inflammation by reducing hydroxyl radicals or peroxynitrite in the immunogenic psoriasis cascade. Three methods were used to administer H2: Drop infusion of saline containing 1 ppm H2 (H2-saline), inhalation of 3% H2 gas, and drinking of water containing a high concentration (5-7-ppm) of H2 (high-H2 water). Treatment efficacy was estimated using the disease activity score 28 (DAS28) system, based on C-reactive protein levels, and the psoriasis area and severity index (PASI) score, determined at baseline and following each H2 treatment. Furthermore, levels of TNFα, IL-6, and IL-17 were analyzed. The DAS28 and PASI score of the three patients decreased during H2 treatment, regardless of the administration method. The psoriatic skin lesions almost disappeared at the end of the treatment. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. In conclusion, H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.

Consumption of water containing over 3.5 mg of dissolved hydrogen could improve vascular endothelial function.

BACKGROUND: The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical. OBJECTIVES: To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function. METHODS: The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline. RESULTS: FMD increased in the high-H2 group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (P<0.05) in the high-H2 group compared to the placebo group. CONCLUSION: H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.

Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.

The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Patients were randomized 1:1 to receive 500 ml of either H2-saline or placebo-saline, which was drop infused intravenously (DIV) daily for 5 days. The disease activity score in 28 joints (DAS28) was measured at baseline, immediately post infusion, and after 4 weeks. Therapeutic effects of H2-saline on joint inflammation were estimated by measuring serum biomarkers for RA, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and urinary 8-hydroxydeoxyguanosine (8-OHdG). In the H2-infused group, average DAS28 decreased from 5.18 ± 1.16 to 4.02 ± 1.25 immediately post infusion and reached 3.74 ± 1.22 after 4 weeks. No significant decrease in DAS28 was observed in the placebo group throughout the study. IL-6 levels in the H2 group significantly decreased in 4 weeks by 37.3 ± 62.0% compared to baseline, whereas it increased by 33.6 ± 34.4% in the placebo group. TNFα levels did not change remarkably in the H2 or placebo groups in 4 weeks post-infusion compared to baseline. The relative ratio of 8-OHdG in the H2 group also significantly decreased by 4.7%. After 4 weeks, MMP3 was significantly reduced by 19.2% ± 24.6% in the H2 group, and increased by 16.9% ± 50.2% in the placebo group. Drop infusion of H2 safely and effectively reduced RA disease activity.

Postprandial increase in plasma concentrations of remnant-like particles: an independent risk factor for restenosis after percutaneous coronary intervention.

Postprandial increase in remnant lipoprotein concentrations has been suggested as an important atherogenic factor. However, the influence of these remnants on the development of restenosis after percutaneous coronary intervention (PCI) remains to be examined. The present study was designed to address this point. In 60 consecutive patients with successful PCI, the influences of possible risk factors on the development of restenosis, including remnant-like particles (RLP) cholesterol (RLP-C) and triglyceride (RLP-TG), were examined. While mean concentrations of RLP-C and RLP-TG were normal in fasting state, postprandial change in RLP-C concentrations was a significant and independent risk factor for restenosis after PCI. The calculated cut-off index (COI) for the change was +64%. When the patients were divided into 2 groups according to this COI, minimal lumen diameter (MLD) and reference coronary diameter were comparable before and immediately after PCI between the high- (COI < 64%) and the low- (COI < 64%) responders. However, follow-up coronary angiography 3 to 6 months after PCI demonstrated that MLD, late loss, and loss index were all worse in the high responders compared with the low responders. These results indicate that post-prandial increase in RLP-C concentrations is an independent risk factor for restenosis after successful PCI, even in patients with normal fasting RLP-C levels.

Role of prehypertension in the development of coronary atherosclerosis in Japan.

BACKGROUND: Hypertension is an important risk factor of coronary heart disease. A new guidelines for hypertension prevention and management in The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the United States recommended lifestyle modification or medical treatment for subjects with prehypertension. However, whether prehypertension increases the risk of coronary atherosclerosis in the Japanese population is still unknown. METHODS: A cross-sectional study in a clinical setting was conducted. The subjects were 705 patients (417 males and 288 females) aged 30 years and older who underwent a first-time coronary angiography for suspected or known coronary heart disease at 5 major cardiology departments in the Fukuoka metropolitan area between September 1996 and August 1997. RESULTS: Compared to subjects with normal blood pressure, those with prehypertension had an increased risk of coronary atherosclerosis even after adjusting for other factors. CONCLUSION: Prehypertension may be an important clinical entity which requires treatment in the Japanese population.

Comparative study of dobutamine stress echocardiography and dual single-photon emission computed tomography (thallium-201 and I-123 BMIPP) for assessing myocardial viability after acute myocardial infarction.

Discordance between the (123)I-labelled 15-iodophenyl-3-R, S-methyl pentadecanoic acid (BMIPP) and (201)Tl findings may indicate myocardial viability (MV). This study compared dobutamine stress echocardiography (DSE) and single-photon emission computed tomography (SPECT) using the dual tracers for assessment of MV and prediction of functional recovery after acute myocardial infarction (AMI). DSE and dual SPECT were studied in 35 patients after AMI, of whom 28 underwent percutaneous coronary intervention in the acute stage. Dual SPECT was performed to compare the defect score of BMIPP and (201)Tl. The left ventricular wall motion score (WMS) was estimated during DSE and 6 months later to assess functional recovery of the infarct area. The rate of agreement of MV between dual SPECT and DSE was 89% (p<0.01), and the sensitivity and specificity of DSE for dual SPECT in MV assessment was 86% and 93%, respectively. The positive and negative predictive values for functional recovery by dual SPECT were 76% and 67%, respectively, and by DSE were 90% and 79%, respectively. Four of 5 patients with positive MV by dual SPECT, but without functional recovery, had residual stenosis of the infarct-related artery. The WMS and defect scores of BMIPP and (201)Tl were significantly smaller in patients with functional recovery than in those without. Assessment of MV using DSE concords with the results of dual SPECT in the early stage of AMI. DSE may have a higher predictive value for long-term functional recovery at the infarct area. However, a finding of positive MV by dual SPECT, without functional recovery, may indicate residual stenosis of the infarct-related artery, although the number of cases was small. Combined assessment by dual SPECT and DSE may be useful for detecting MV and jeopardized myocardium. Furthermore, the results suggest that functional recovery of dysfunctional myocardium may depend on the size of the infarct and risk area.

Coronary disease morphology and distribution determined by quantitative angiography and intravascular ultrasound--re-evaluation in a cooperative multicenter intravascular ultrasound study (COMIUS).

Although previous studies have demonstrated that even quantitative coronary angiography (QCA) can not provide accurate disease morphology, there has not been a systematic comparison of disease morphology determined by QCA and intravascular ultrasound (IVUS), particularly in Japanese patients. Therefore, the present study prospectively examined patients in a multicenter cooperative study. A total of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11 years) who underwent coronary interventions were enrolled. The target lesions (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and lesion length were determined. The minimal (min) and maximal (max) distances from the center of the stenotic lesion to the outline of the vessel wall were measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA, lesion length was determined by measuring the distance between the proximal and distal shoulders of the lesion. When the lesions were observed by IVUS with a motorized pull-back system, the length was calculated by multiplying the time for observation of the disease and 0.5 or 1 mm/s. Although the severity of the stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and the correlation did not improve when lesions with remodeling, enlargement (n=176) or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography significantly misinterprets disease morphology in terms of severity, eccentricity and length, in part because of vessel remodeling that can be accurately determined only by IVUS.

Relation between type A behavior pattern and the extent of coronary atherosclerosis in Japanese women.

This study examined the relation of Type A behavior pattern and its components to angiographically documented coronary atherosclerosis in 198 Japanese women. A questionnaire-based interview elicited psychosocial and other factors. Type A behavior pattern was measured by 12 questions. Significant coronary stenosis was defined when a 75% or greater luminal narrowing occurred at one or more major coronary arteries or 50% or greater narrowing occurred at the left main artery. Gensini's score also was calculated. Logistic regression analysis was used to calculate odds ratios and 95% confidence intervals with adjustment for traditional coronary risk factors and the presence of a job. Global Type A behavior pattern showed no material association with the severity of coronary atherosclerosis assessed by both Gensini's score and the presence of significant coronary stenosis. However, its subcomponents, enthusiasm and competitiveness, were positively related to the severity of coronary atherosclerosis, whereas self-confidence and perfectionism were negatively related. These findings suggest overall a null association between global Type A and coronary atherosclerosis as well as the presence of toxic or beneficial components of Type A behaviors in Japanese women.

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).

OBJECTIVES: This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. BACKGROUND: Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). METHODS: A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. RESULTS: Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). CONCLUSIONS: Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.