Effectiveness of ultrasound treatment applied with exercise therapy on patients with ankylosing spondylitis: a double-blind,randomized, placebo-controlled trial

The aim of our study was to evaluate effectiveness of ultrasound treatment applied with exercise therapy in patients with ankylosing spondylitis. Fifty-two patients, who were diagnosed according to modified New York criteria, were aged 25–60, and have spine pain, were randomly assigned to two groups. Ultrasound (US) and exercise therapy were applied to treatment group (27); placebo US treatment and exercise therapy were applied to control group (25). Patients were evaluated before treatment, at the end of treatment, and 4 weeks after the treatment. Daily and night pain, morning stiffness, patient global assessment (PGA), doctor global assessment (DGA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire, Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR), and ASDAS C-reactive protein (CRP) were used as clinical parameters. In US group, all parameters showed significant improvements at 2 and 6 weeks, in comparison with the baseline. In placebo US group, significant improvement was obtained for all parameters (except tragus-to-wall distance and modified Schober test at 2 weeks and lumbar side flexion and modified Schober test at 6 weeks). Comparison of the groups showed significantly superior results of US group for parameters of BASMI (p < 0.05), tragus–wall distance (p < 0.05), PGA (p < 0.01), and DGA (p < 0.05) at 2 weeks as well as for the parameters of daily pain (p < 0.01), PGA (p < 0.05), DGA (p < 0.01), BASDAI (p < 0.05), ASDAS-CRP (p < 0.05), ASDAS-ESR (p < 0.01), lumbar side flexion (p < 0.01), the modified Schober test (p < 0.01), and ASQoL (p < 0.05) at 6 weeks. Our study showed that ultrasound treatment increases the effect of exercise in patients with ankylosing spondylitis.     

Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

Association Between CD4<Superscript>+</Superscript>, Viral Load,and Pulmonary Function in HIV

Purpose

The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4⁺, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally.

Methods

This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015.

Results

Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4⁺ <200 cells/μl was associated with significant diffusion impairment compared to CD4⁺ ≥200 cells/μl (DL_CO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DL_CO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4⁺ and VL correlated with DL_CO (r = +0.33; p = <0.01; r = ?0.26; p = <0.01) and no correlation was noted with FEV₁, FEV₁/FVC, or TLC. Current smoking and history of AIDS correlated with DL_CO (r = ?0.20; p = 0.03; r = ?0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03–19.4], p = <0.01) decrease in DL_CO. In Spearman’s Rank correlation, there was a negative correlation between change in VL and change in DL_CO over time (ρ = ?0.47; p = <0.01).

Conclusion

The presence of viremia in individuals with HIV is independently associated with impaired DL_CO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

     

Autoantibodies against interleukin-21 correlate with disease activity in patients with rheumatoid arthritis

The objective of this study is to investigate the levels of interleukin (IL)-21 and autoantibodies (AAbs) against IL-21 and their association with clinical characteristics and laboratory parameters in patients with rheumatoid arthritis (RA). One hundred twenty-six patients with RA, 69 patients with osteoarthritis (OA), and 88 healthy controls (HC) were included in this study. The levels of IL-21 and AAbs against IL-21 in the serum were measured using enzyme-linked immunosorbent assay (ELISA). The correlation between the levels of IL-21 and anti-IL-21 AAbs with clinical and laboratory parameters was evaluated. The results showed that the concentration of IL-21 was significantly higher in the serum of patients with RA (15.58 ± 3.22 ng/ml) than OA (1.80 ± 0.99 ng/ml) and HC (0.07 ± 0.03 ng/ml, p < 0.01). The levels of IL-21 in the serum correlated with erythrocyte sedimentation rate (ESR) in patients with RA (r = 0.435, p < 0.01). Anti-IL-21 AAbs could be detected in RA patients. The median AU value of AAbs against IL-21 was significantly higher in serum of RA (47.90) than in that of OA (15.17) and HC (8.19, p < 0.01). The titers of AAbs against IL-21 correlated with Disease Activity Score-28 (DAS28) (r = 0.449, p < 0.001), ESR (r = 0.386, p < 0.001), and CRP (r = 0.241, p = 0.03). Both IL-21 and AAbs against IL-21 are elevated in RA. The levels of AAbs against IL-21 correlate with disease activity, which suggests that anti-IL-21 AAbs may play a role in the pathogenesis of RA.     

Effect of physical activity on heart rate variability and carotid intima-media thickness in older people

We investigated the effect of physical activity on heart rate variability (HRV) and carotid intima-media thickness (IMT) in elderly subjects and the relationship between HRV and IMT. Thirty-two elderly sedentary subjects and 32 age-matched endurance athletes underwent ultrasonography of the carotid wall for measuring IMT, and 24-h ECG monitoring for measuring HRV. Elderly athletes had evidence of increased vagal activity in the time (SDANN, rMSSD, and pNN50; p < 0.01) and frequency domain (HF and LF/HF ratio, p < 0.01) with respect to sedentary subjects. Moreover, athletes showed lower IMT than control subjects (p < 0.01). In the whole population SDNN was inversely related to IMT, respectively (r = ?0.60 and r = ?0.58, p < 0.0001), while LF/HF ratio related positively to IMT. In conclusion, this study demonstrated that in aging HRV is negatively associated with IMT, a putative index of atherosclerosis, confirming cardiac autonomic neuropathy as part of the pathophysiological pathway for atherosclerosis. It confirms that the regular physical activity represents a valuable strategy to counter age-related impairments of cardiac autonomic activity and artery structural changes.     

Evaluation of the Greek TranQol: a novel questionnaire for measuring quality of life in transfusion-dependent thalassemia patients

The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19–58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p < 0.001 and r = 0.5, p < 0.001, respectively). There was also a moderately strong correlation between the physical health scale of TranQol and the relevant SF-36v2 scales, including physical functioning (r = 0.4, p < 0.001), role-physical (r = 0.6, p < 0.001), and bodily pain (r = 0.5, p < 0.001). TranQol also exhibited good internal consistency (Cronbach’s alpha coefficient = 0.9) and excellent test-retest reliability (intra-class correlation coefficient = 0.9). The subgroup of patients that reported a better QoL 1 week after transfusion also demonstrated a significant improvement in their TranQol score. These are the first data regarding the administration of the Greek TranQol in a single thalassemia unit. The psychometric properties of the Greek TranQol confirmed it is a valid, reliable, and responsive to change questionnaire, which can be incorporated into future clinical trials.     

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

Brazilian-Portuguese version of the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) in patients with ankylosing spondylitis: a translation,cross-cultural adaptation,and validation

To translate and cross-culturally adapt to the Brazilian-Portuguese language (BP), five items were added to Health Assessment Questionnaire (HAQ) to validate the resulting HAQ-S BP version for ankylosing spondylitis (AS). The items were translated into BP following translation and back-translation. To assess validity, 25 patients were evaluated using the HAQ, Bath AS Functional Index (BASFI), Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index (BASMI), and laboratory variables (erythrocyte sedimentation rate, C-reactive protein). One question required modification to adapt culturally to Brazilian conditions. The test–retest and interobserver correlation coefficients were 0.990 (p < 0.05) and 0.993 (p < 0.05), respectively. HAQ-S BP correlated to BASFI (r = 0.574; p < 0.05) and to HAQ (r = 0.963; p < 0.05), but not to BASDAI (r = 0.282), BASMI (r = 0.194), and laboratory variable. Individually, the fifth item referring to driving correlated highly to neck rotation (r = 0.900; p < 0.05), while the HAQ-S BP correlated to the neck rotation component (r = 0.303), but did not reach statistical significance. The HAQ-S BP version demonstrated adequate reproducibility, internal consistency and validity, confirming its utility in the research of AS in Brazil.     

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity,damage, and functional status

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = ?0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = ?0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = ?0.28, p = 0.06; r = ?0.25, p = 0.09 and r = ?0.25, p = 0.09, respectively). There is evidence of a possible influence of the ?308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.     

Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis

Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5?±?6.3 vs. 45.1?±?6.9 years, respectively, p?=?0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3?±?10.3 vs. 21.8?±?9.3 m/s, p?=?0.03), AIx@75 (10.2?±?2.3 vs. 9.2?±?1, %, p?=?0.01) and MPI (0.46?±?0.12 vs. 0.36?±?0.1, p?<?0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r?=?0.360, p?=?0.005; r?=?0.334, p?=?0.009; r?=?0.293, p?=?0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.     

Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease

Background

The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.

Methods

A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.

Results

Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = ?0.41, p < 0.001), and a weak but significant correlation (r = ?0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = ?0.637, p < 0.001) and claudin-1 and the baseline impedance (r = ?0.648, p < 0.001).

Conclusions

Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

     

Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe,Latin America,and Asia

Despite the demonstrated efficacy of etanercept for the treatment of ankylosing spondylitis (AS), sulfasalazine is often prescribed, especially in countries with limited access to biologic agents. The objective of this subset analysis of the ASCEND trial was to compare the efficacy of etanercept and sulfasalazine in treating patients with AS from Asia, Eastern/Central Europe, and Latin America. A total of 287 patients, 190 receiving etanercept 50 mg once weekly and 97 receiving sulfasalazine 3 g daily, from eight countries were included in this subset analysis. Differences in disease activity and patient-reported outcomes assessing health-related quality-of-life (HRQoL) parameters in response to treatment were analyzed using the Cochran–Mantel–Haenszel test for categorical efficacy endpoints and analysis of covariance model for continuous variables. At week 16, a significantly greater proportion of patients receiving etanercept achieved ASAS20 (79.0 %) compared with patients receiving sulfasalazine (61.9 %; p = 0.002). At week 16, treatment with etanercept also resulted in significantly better responses than sulfasalazine for ASAS40 (64.7 vs. 35.1 %; p < 0.001), ASAS5/6 (48.1 vs. 26.3 %; p < 0.001), proportion of patients achieving 50 % response in Bath AS Disease Activity Index (65.8 vs. 42.3 %; p < 0.001), partial remission (35.3 vs. 17.5 %; p = 0.002), and all HRQoL parameters. Both treatments were well tolerated. Etanercept was significantly more effective than sulfasalazine in the treatment of patients with AS from Asia, Central/Eastern Europe, and Latin America.     

Comparison of pulse wave velocity assessed by three different techniques: Arteriograph,Complior, and Echo-tracking

Arterial stiffness estimated by pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. Although recommended by the current guidelines, clinical applicability of this parameter is difficult, due to differences between the various techniques used to measure it and to biological variability. Our aim was to compare PWV assessed by 3 different commercially available systems. 100 subjects (51 ± 16 years, 45 men) were evaluated using the 3 methods: an oscillometric technique (Arteriograph, PWV-A); a piezo-electric method (Complior, PWV-C); and an high-resolution ultrasound technique implemented with an Echo-tracking system (Aloka, PWV-E). Conventional biological markers were measured. Correlations of PWV measured by the 3 methods were poor (r = 0.39, r = 0.39, and r = 0.31 for PWV-A vs. PWV-C, PWV-A vs. PWV-E, and PWV-C vs. PWV-E, respectively, all p < 0.05). By Bland–Altman analysis, mean difference (±SD) of PWV-A vs. PWV-C was ?1.9 ± 2.0 m/s, of PWV-A vs. PWV-E ?3.6 ± 1.9 m/s, and of PWV-C vs. PWV-E ?2.7 ± 1.9 m/s, with a wide coefficient of variation (22.3, 25.7, and 25.7 %, respectively). As expected, PWV-A, PWV-C, and PWV-E correlated with other arterial stiffness parameters, such as intima-media thickness (r = 0.22, r = 0.22, and r = 0.36, respectively), E _p (r = 0.37, r = 0.26, and r = 0.94, respectively), and augmentation index measured by Arteriograph method (r = 0.66, r = 0.35, and r = 0.26, respectively); all p < 0.05. Assessment of PWV is markedly dependent on the technique used to measure it, related to various methods for measuring traveled distance of the arterial wave. Our results suggest the urgent need to establish reference values of PWV for each of these techniques, separately, to be used in routine clinical practice.     

Left ventricular subclinical dysfunction associated with myocardial deformation changes in obstructive sleep apnea patients estimated by real-time 3D speckle-tracking echocardiography

Background

Previous studies have demonstrated that patients with obstructive sleep apnea (OSA) may develop left ventricular (LV) diastolic dysfunction. We aimed to study whether OSA patients have LV regional systolic dysfunction with myocardial deformation changes, despite a normal LV ejection fraction, using real-time 3D speckle-tracking echocardiography (Rt3D-STE).

Methods

Seventy-eight patients with OSA and no comorbidities were studied. They were divided into the following three groups according to the apnea–hypopnea index (AHI): 5~15/h as group I (mild OSA, 26 cases), 15~30/h as group II (moderate OSA, 29 cases), and ≥30/h as group III (severe OSA, 23 cases). Thirty gender–age-matched normal subjects were included as controls. The parameters of LV diastolic function were acquired with traditional echocardiography. The LV myocardial deformation parameters were obtained, including the longitudinal (LS), circumferential (CS), radial (RS), and area (AS) strains, with Rt3D-STE.

Results

LV global systolic function was normal in all patients, but diastolic function was impaired in groups II and III (E/E′ was 9.6?±?2.8 and 10.4?±?2.5, respectively, p?<?0.0001). The global LS and AS were significantly reduced in groups II and III compared with the controls and group I (LS 15.9?±?1.4 % and 14.8?±?1.5 % vs 18.2?±?1.7 % and 17.8?±?1.5 %; AS 27.4?±?1.8 % and 24.9?±?2.3 % vs 33.4?±?2.2 % and 32.7?±?2.9 %, respectively, p?<?0.0001), but the global CS and RS were significantly reduced only in group III (17.3?±?1.4 % and 43.1?±?6.5 % vs 19.6?±?1.6 % and 55.4?±?4.0 %, respectively, <0.0001). The severity of OSA was significantly associated with the LV global AS value (r?=??0.80, p?<?0.0001), LS (r?=??0.64, p?<?0.0001), CS (r?=??0.51, p?<?0.0001), and RS (r?=??0.62, p?<?0.0001).

Conclusions

Patients with moderate and severe OSA tended to have both LV diastolic dysfunction and abnormalities in regional systolic function with myocardial deformation changes, in spite of the normal LV ejection fraction. Myocardial strains of the LV were negatively correlated with the AHI. Rt-3DST had important clinical significance in the early evaluation of cardiac dysfunction in OSA patients.

     

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm²; p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.     

Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.     

Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure

While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = ?0.33, p < 0.05; r = ?0.28, p < 0.05, respectively), and HR (r = ?0.31, p < 0.05; r = ?0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.