Association between One-Hour Post-Load Plasma Glucose Levels and Vascular Stiffness in Essential Hypertension

Objectives

Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value ≥155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI).

Methods

We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index.

Results

Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h post-load plasma glucose <155 mg/dl (NGT<155) and 146 had 1-h post-load plasma glucose ≥155 mg/dl (NGT≥155). NGT≥155 had a worse insulin sensitivity and higher hs-CRP than NGT<155, similar to IGT subjects. In addition, NGT ≥155 in comparison with NGT<155 had higher central systolic blood pressure (134±12 vs 131±10 mmHg), as well as PWV (8.4±3.7 vs 6.7±1.7 m/s), AP (12.5±7.1 vs 9.8±5.7 mmHg) and AI (29.4±11.9 vs 25.1±12.4%), and similar to IGT. At multiple regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness.

Conclusion

Hypertensive NGT≥155 subjects, compared with NGT<155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile.     

The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition – A Randomized Control Trial

Background

Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.

Methods

We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.

Result

After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).

Conclusion

Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.

Trial Registration

ClinicalTrials.gov NCT00966615     

Soluble CD93 Levels in Patients with Acute Myocardial Infarction and Its Implication on Clinical Outcome

Background

Inflammation plays a key role in the pathogenesis of acute myocardial infarction (MI). However, it is unclear whether marker of immune activation will provide prognostic information in these patients. We hypothesized that circulating levels of soluble CD93 (sCD93), a soluble form of transmembrane glycoprotein CD93, is increased in acute MI patients and its level would be associated with clinical outcomes in patients with acute MI.

Methods

We measured circulating levels of sCD93 in 120 patients with acute MI (63±13 yrs, M∶F = 85∶35) and in 120 age, sex-matched control subjects. In patients with acute MI, clinical characteristics, echocardiographic and laboratory findings were assessed at the time of initial enrollment. The primary outcome was defined as all-cause and cardiovascular death.

Results

Circulating sCD93 levels were significantly higher in patients with acute MI than in control subjects (552.1±293.7 vs. 429.8±114.2 ng/mL, p<0.0001). Upon in vitro inflammatory stimulation, increased CD93 shedding was demonstrated in acute MI patients but not in control subjects. During follow up period (median 208 days, 3-1058 days), the primary outcome occurred in 18 (15%) patients (9 cardiovascular deaths). Circulating levels of sCD93 were associated with all cause (p<0.0001) and cardiovascular (p<0.0001) mortality in patients with acute MI. Multivariate Cox regression analysis revealed that initial sCD93 level was found to be an independent predictor of all cause (p = 0.002) and cardiovascular mortality (p = 0.033) when controlled for age and left ventricular ejection fraction.

Conclusions

Circulating levels of sCD93 are elevated in patients with acute MI and their levels were associated with adverse clinical outcomes.     

Elevated Plasma Soluble ST2 Is Associated with Heart Failure Symptoms and Outcome in Aortic Stenosis

B-type natriuretic peptide (BNP) is often used as a complementary finding in the diagnostic work-up of patients with aortic stenosis (AS). Whether soluble ST2, a new biomarker of cardiac stretch, is associated with symptomatic status and outcome in asymptomatic AS is unknown. sST2 and BNP levels were measured in 86 patients (74±13 years; 59 asymptomatic, 69%) with AS (<1.5 cm²) and preserved left ventricular ejection fraction who were followed-up for 26±16 months. Both BNP and sST2 were associated with NYHA class but sST2 (>23 ng/mL, AUC = 0.68, p<0.01) was more accurate to identify asymptomatic patients or those who developed symptoms during follow-up. sST2 was independently related to left atrial index (p<0.0001) and aortic valve area (p = 0.004; model R² = 0.32). A modest correlation was found with BNP (r = 0.4, p<0.01). During follow-up, 29 asymptomatic patients (34%) developed heart failure symptoms. With multivariable analysis, peak aortic jet velocity (HR = 2.7, p = 0.007) and sST2 level (HR = 1.04, p = 0.03) were independent predictors of cardiovascular events. In AS, sST2 levels could provide complementary information regarding symptomatic status, new onset heart failure symptoms and outcome. It might become a promising biomarker in these patients.     

Uric Acid Level Has a U-Shaped Association with Loss of Kidney Function in Healthy People: A Prospective Cohort Study

BackgroundThe relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people.ResultsThe following data was obtained: mean±SD age, male, 39.6±10.4 years, female 38.4±10.8 years; eGFR, male, 81.9±16.4 ml/min/1.73m2, female, 82.1±17.5 ml/min/1.73m2; serum uric acid level, male, 5.8±1.2 mg/dl, female, 4.1±0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male, <5 mg/dl; female, <3.6 mg/dl), multivariate linear mixed models showed that low serum uric acid levels were associated with eGFR decline in a time-dependent manner (male, p = 0.0001; female, p = 0.045).ConclusionThis study showed that low as well as high levels of uric acid are associated with the loss of kidney function. Hypouricemia is a candidate predictor of kidney function decline in healthy people.     

Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis

IntroductionCalprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA.MethodsA total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0–3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis.ResultsThe levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R² = 0.765, p < 0.001) than CRP (R² = 0.496, p < 0.001).ConclusionsThe serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.     

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Objectives

To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.

Methods

The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls.

Results

Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10⁻⁹), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels.

Conclusions

DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.     

Cumulative inflammatory burden is independently associated with increased arterial stiffness in patients with psoriatic arthritis: a prospective study

IntroductionThe aim of this study was to examine whether the cumulative inflammatory burden is associated with an increase in arterial stiffness in a prospective cohort of psoriatic arthritis (PsA) patients.MethodsIn total, 72 PsA patients were followed for a median of 6.5 years. Cumulative inflammatory burden was represented by the cumulative averages of repeated measures of erythrocyte sedimentation rate (ca-ESR) and C-reactive protein (ca-CRP). Brachial-ankle pulse wave velocity (PWV) was measured at the last visit. We also included 47 healthy controls for PWV assessment.ResultsPWV was significantly higher in PsA patients compared with healthy controls after adjustment for age, gender and body weight (1466 ± 29 cm/s versus 1323 ± 38 cm/s, P = 0.008). PsA patients were divided into two groups based on whether their PWV value is ≥1450 cm/s (High PWV group, N = 38) or <1450 cm/s (Low PWV group, N = 34). The High PWV group had a significantly higher ca-ESR (29 (19 to 44) versus 18 (10 to 32) mm/1st hour, P = 0.005) and ca-CRP (0.7 (0.3 to 1.4) versus 0.4 (0.2 to 0.7) mg/dl, P = 0.029). Using regression analysis, high ca-ESR (defined as ≥75th percentile: 37 mm/1st hour) was associated with a higher likelihood of being in the High PWV group (odds ratio (OR): 9.455 (1.939 to 46.093), P = 0.005, adjusted for baseline clinical and cardiovascular risk factors; and 9.111 (1.875 to 44.275), P = 0.006, adjusted for last visit parameters).ConclusionsCumulative inflammatory burden, as reflected by ca-ESR, was associated with increased arterial stiffness in PsA patients even after adjustment for cardiovascular risk factors, emphasizing the important role of chronic inflammation in accelerating the development of cardiovascular risks in PsA patients.     

Correlation of Perfusion MRI and 18F-FDG PET Imaging Biomarkers for Monitoring Regorafenib Therapy in Experimental Colon Carcinomas with Immunohistochemical Validation

ObjectivesTo investigate a multimodal, multiparametric perfusion MRI / ¹⁸F-fluoro-deoxyglucose-(¹⁸F-FDG)-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.ResultsRegorafenib significantly (p<0.01) suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min), PV (12.1±3.6 to 7.5±1.6%) and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min) as well as TTB (3.4±0.6 to 1.9±1.1) between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03) lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9) and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3) in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01) correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03) to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05).ConclusionsA multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and ¹⁸F-FDG-PET validated by immunohistochemistry.     

Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

We investigated in vivo changes in Schlemm’s canal and the trabecular meshwork in eyes with primary open angle glaucoma (POAG). Relationships between Schlemm’s canal diameter, trabecular meshwork thickness, and intraocular pressure (IOP) were examined. Forty POAG patients and 40 normal individuals underwent 80-MHz Ultrasound Biomicroscopy examinations. The Schlemm’s canal and trabecular meshwork were imaged in superior, inferior, nasal and temporal regions. Normal individuals had an observable Schlemm’s canal in 80.3% of sections, a meridional canal diameter of 233.0±34.5 μm, a coronal diameter of 44.5±12.6 μm and a trabecular meshwork thickness of 103.9±11.1 μm, in POAG patients, Schlemm’s canal was observable in 53.1% of sections, a meridional canal diameter of 195.6±31.3 μm, a coronal diameter of 35.7±8.0 μm, and a trabecular meshwork thickness of 88.3±13.2 μm, which significantly differed from normal (both p <0.001). Coronal canal diameter (r = -0.623, p < 0.001) and trabecular meshwork thickness (r = -0.663, p < 0.001) were negatively correlated with IOP, but meridional canal diameter was not (r = -0.160, p = 0.156). Schlemm’s canal was observable in 50.5% and 56.6% of POAG patients with normal (<21 mmHg) and elevated (>21 mmHg) IOP, respectively (χ = 1.159, p = 0.282). Coronal canal diameter was significantly lower in the elevated IOP group (32.6±4.9 μm) than in the normal IOP group (35.7±8.0 μm, p < 0.001). This was also true of trabecular meshwork thickness (81.9±10.0 μm vs. 97.1±12.0 μm, p < 0.001). In conclusion, eyes with POAG had fewer sections with an observable Schlemm’s canal. Canal diameter and trabecular meshwork thickness were also lower than normal in POAG patients. Schlemm’s canal coronal diameter and trabecular meshwork thickness were negatively correlated with IOP.     

Influence of Plasma Processing on Recovery and Analysis of Circulating Nucleic Acids

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer. However there is wide variation in blood processing and methods for isolation of circulating free DNA (cfDNA) and microRNAs (miRNAs). Here we compare the extraction efficiency and reproducibility of 4 commercially available kits for cfDNA and 3 for miRNA using spike-in of reference templates. We also compare the effects of increasing time between venepuncture and centrifugation and differential centrifugation force on recovery of CNAs. cfDNA was quantified by TaqMan qPCR and targeted deep sequencing. miRNA profiles were assessed with TaqMan low-density arrays and assays. The QIAamp^® DNA Blood Mini and Circulating nucleic acid kits gave the highest recovery of cfDNA and efficient recovery (>90%) of a 564bp spike-in. Moreover, targeted sequencing revealed overlapping cfDNA profiles and variant depth, including detection of HER2 gene amplification, using the Ion AmpliSeq™Cancer Hotspot Panel v2. Highest yields of miRNA and the synthetic Arabidopsis thaliana miR-159a spike-in were obtained using the miRNeasy Serum/Plasma kit, with saturation above 200 µl of plasma. miRNA profiles showed significant variation with increasing time before centrifugation (p<0.001) and increasing centrifugation force, with depletion of platelet associated miRNAs, whereas cfDNA was unaffected. However, sample replicates showed excellent reproducibility on TaqMan low density arrays (ρ = 0.96, p<0.0001). We also successfully generated miRNA profiles for plasma samples stored > 12 years, highlighting the potential for analysis of stored sample biobanks. In the era of the liquid biopsy, standardisation of methods is required to minimise variation, particularly for miRNA.     

Left Ventricular Dilation and Pulmonary Vasodilatation after Surgical Shunt for Treatment of Pre-Sinusoidal Portal Hypertension

ObjectiveThe aim of this study was to prospectively investigate the long-term cardiovascular and pulmonary hemodynamic effects of surgical shunt for treatment of portal hypertension (PH) due to Schistosomiasis mansoni.LocationThe University of São Paulo Medical School, Brazil; Public Practice.MethodsHemodynamic evaluation was performed with transesophageal Doppler and contrast-enhanced echocardiography (ECHO) on twenty-eight participants with schistosomal portal hypertension. Participants were divided into two groups according to the surgical procedure used to treat their schistosomal portal hypertension within the last two years: group 1—distal splenorenal shunt (DSRS, n = 13) and group 2—esophagogastric devascularization and splenectomy (EGDS, n = 15).ResultsThe cardiac output (5.08 ± 0.91 L/min) and systolic volume (60.1 ± 5.6 ml) were increased (p = 0.001) in the DSRS group. DSRS participants had a significant increase (p < 0.0001) in their left ventricular end-systolic and end-diastolic diameters as well as in their left ventricular end-diastolic and end-systolic volumes (p < 0.001) compared with the preoperative period. No statistically significant difference was found in the patients who underwent EGDS. ECHO revealed intrapulmonary vasodilatation (IPV) in 18 participants (64%), 9 DSRS and 9 EGDS (p > 0.05).ConclusionsThe late increase in the cardiac output, stroke volume and left ventricular diameters demonstrated left ventricular dilatation after a distal splenorenal shunt. ECHO revealed a greater prevalence for IPV in patients with schistosomiasis than has previously been described in patients with PH from liver cirrhosis.     

Early Vascular Aging in Young and Middle-Aged Ischemic Stroke Patients: The Norwegian Stroke in the Young Study

Background

Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients.

Methods

We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15–60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram.

Results

Patients were on average 49±10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = –0.10, all p<0.01) in multivariate linear regression analysis (multiple R² = 0.42, p<0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p<0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02–1.06; p<0.01), history of hypertension (OR 3.59; 95% CI 1.52–8.51; p<0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00–9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01–1.06; p<0.01) were associated with high for age PWV.

Conclusions

Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01597453","term_id":"NCT01597453"}}NCT01597453     

Trends in Cardiovascular Disease Risk Factor Prevalence and Estimated 10-Year Cardiovascular Risk Scores in a Large Untreated French Urban Population: The CARVAR 92 Study

Background

Surveys measuring effectiveness of public awareness campaigns in reducing cardiovascular disease (CVD) incidence have yielded equivocal findings. The aim of this study was to describe cardiovascular risk factors (CVRFs) changes over the years in an untreated population-based study.

Methods

Between 2007 and 2012, we conducted a screening campaign for CVRFs in men aged 40 to 65 yrs and women aged 50 to 70 yrs in the western suburbs of Paris. Data were complete for 20,324 participants of which 14,709 were untreated.

Results

The prevalence trend over six years was statistically significant for hypertension in men from 25.9% in 2007 to 21.1% in 2012 (p=0.002) and from 23% in 2007 to 12.7% in 2012 in women (p<0.0001). The prevalence trend of tobacco smoking decreased from 38.6% to 27.7% in men (p=0.0001) and from 22.6% to 16.8% in women (p=0.113). The Framingham 10-year risk for CVD decreased from 13.3 ± 8.2 % in 2007 to 11.7 ± 9.0 % in 2012 in men and from 8.0 ± 4.1 % to 5.9 ± 3.4 % in women. The 10-year risk of fatal CVD based on the European Systematic COronary Risk Evaluation (SCORE) decreased in men and in women (p <0.0001).

Conclusions

Over a 6-year period, several CVRFs have decreased in our screening campaign, leading to decrease in the 10-year risk for CVD and the 10-year risk of fatal CVD. Cardiologists should recognize the importance of community prevention programs and communication policies, particularly tobacco control and healthier diets to decrease the CVRFs in the general population.     

Effects of low calorie diet-induced weight loss on post-exercise heart rate recovery in obese men

[Purpose]

Heart Rate Recovery (HRR) after maximum exercise is a reactivation function of vagus nerve and an independent risk factor that predicts cardiovascular disease and mortality. Weight loss obtained through dietary programs has been employed as a therapy to reduce risks of cardiovascular disease and obesity.

[Methods]

Eighteen subjects of middle aged obese men (age 44.8 ± 1.6 yrs, BMI 29.7 ± 0.5 kg/m²) were selected for this study. As a weight loss direction, the nutritional direction of low-calorie diet mainly consisted of carbohydrate, protein, and fat has been conducted for 3 months. Blood pressure was measured after overnight fasting, and blood samples were collected from the antecubital vein before and after weight loss program. All the pre- and post-exercise ‘HRR decay constant’s were assessed by using values of HRR (heart recovery rate; 2 minutes) and HR measured after reached to the maximal oxygen uptake (VO₂max) exploited the bicycle ergometer.

[Results]

After the completion of weight loss program, body weight and BMI were significantly decreased, but the Heart Rate (HR) after maximum exercise and in steady state were not changed significantly (p > 0.05). The post-exercise HRR after the weight loss did not show significant changes in perspectives of 30 seconds (-16.6 ± 2.3 to -20.2 ± 2.1 beats/min, p > 0.05) and 60 seconds (-33.5 ± 3.4 to -34.6 ± 2.8 beats/min, p > 0.05) respectively but in perspectives of 90 seconds (-40.9 ± 2.6 to -48.1 ± 3.1 beats/min, p < 0.05) and 120 seconds (-48.6 ± 2.6 to -54.3 ± 3.5 beats/min, p < 0.05), they were decreased significantly. Pre-’HRR decay constant’s of 0.294 ± 0.02 %/second were significantly increased to post-values of 0.342 ± 0.03 %/second (p = 0.026). Changes in ‘HRR decay constant’ were significantly correlated with changes in blood glucose (r = -0.471, p < 0.05) and maximal oxygen consumption (VO₂max, r = 0.505, p < 0.05) respectively.

[Conclusions]

The low-calorie diet directed to obese middle aged men for 3 months significantly improved the HRR after maximum exercise, and this improvement in cardiovascular autonomic nerve system was estimated to be involved with improvements in blood glucose and maximal oxygen consumption.     

Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function

Background and Objective

Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.

Methods and Results

Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%). Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03) and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001). PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02) and improved endothelial functions (FMD 4.8±1.0%, p<0.0001).

Conclusion

We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.     

Irisin and the Metabolic Phenotype of Adults with Prader-Willi Syndrome

Context

Hyperphagia, low resting energy expenditure, and abnormal body composition contribute to severe obesity in Prader Willi syndrome (PWS). Irisin, a circulating myokine, stimulates “browning” of white adipose tissue resulting in increased energy expenditure and improved insulin sensitivity. Irisin has not been previously studied in PWS.

Objectives

Compare plasma and salivary irisin in PWS adults and normal controls. Examine the relationship of irisin to insulin sensitivity and plasma lipids.

Design and Study Participants

A fasting blood sample for glucose, lipids, insulin, leptin, adinopectin, and irisin was obtained from 22 PWS adults and 54 healthy BMI-matched volunteers. Saliva was collected for irisin assay in PWS and controls.

Results

Fasting glucose (77±9 vs 83±7mg/dl, p = 0.004), insulin (4.1±2.0 vs 7.9±4.7μU/ml, p<0.001), and triglycerides (74±34 vs 109±71mg/dl, p = 0.007) were lower in PWS than in controls. Insulin resistance (HOMA-IR) was lower (0.79±0.041 vs 1.63±1.02, p<0.001) and insulin sensitivity (QUICKI) was higher (0.41±0.04 vs 0.36±0.03, p<0.001) in PWS. Plasma irisin was similar in both groups, but salivary irisin (64.5±52.0 vs 33.0±12.1ng/ml), plasma leptin (33.5±24.2 vs 19.7±19.3ng/ml) and plasma adinopectin (13.0±10.8 vs 7.6±4.5μg/ml) were significantly greater in PWS (p<0.001). In PWS, plasma irisin showed positive Pearson correlations with total cholesterol (r = 0.58, p = 0.005), LDL-cholesterol (r = 0.59, p = 0.004), and leptin (r = 0.43, p = 0.045). Salivary irisin correlated negatively with HDL-cholesterol (r = -0.50, p = 0.043) and positively with LDL-cholesterol (r = 0.51, p = 0.037) and triglycerides (r = 0.50, p = 0.041).

Conclusions

Salivary irisin was markedly elevated in PWS although plasma irisin was similar to levels in controls. Significant associations with plasma lipids suggest that irisin may contribute to the metabolic phenotype of PWS.     

Increased frequency of micronuclei in the lymphocytes of patients chronically infected with hepatitis B or hepatitis C virus

In this study, we analysed the frequency of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) and evaluated mutagen-induced sensitivity in the lymphocytes of patients chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). In total, 49 patients with chronic viral hepatitis (28 HBV-infected and 21 HCV-infected patients) and 33 healthy, non-infected blood donor controls were investigated. The frequencies (‰) of MN, NPBs and NBUDs in the controls were 4.41 ± 2.15, 1.15 ± 0.97 and 2.98 ± 1.31, respectively. The frequencies of MN and NPBs were significantly increased (p < 0.0001) in the patient group (7.01 ± 3.23 and 2.76 ± 2.08, respectively) compared with the control group. When considered separately, the HBV-infected patients (7.18 ± 3.57) and HCV-infected patients (3.27 ± 2.40) each had greater numbers of MN than did the controls (p < 0.0001). The HCV-infected patients displayed high numbers of NPBs (2.09 ± 1.33) and NBUDs (4.38 ± 3.28), but only the HBV-infected patients exhibited a significant difference (NPBs = 3.27 ± 2.40, p < 0.0001 and NBUDs = 4.71 ± 2.79, p = 0.03) in comparison with the controls. Similar results were obtained for males, but not for females, when all patients or the HBV-infected group was compared with the controls. The lymphocytes of the infected patients did not exhibit sensitivity to mutagen in comparison with the lymphocytes of the controls (p = 0.06). These results showed that the lymphocytes of patients who were chronically infected with HBV or HCV presented greater chromosomal instability.     

Prognostic Impact of 9-Month High-Sensitivity C-Reactive Protein Levels on Long-Term Clinical Outcomes and In-Stent Restenosis in Patients at 9 Months after Drug-Eluting Stent Implantation

Introduction

The level of 9-month high-sensitivity C-reactive protein (hsCRP) in predicting cardiovascular outcomes is scanty in patients at 9 months after receiving drug-eluting stent (DES) implantations. This study aims to evaluate the relationship between 9-month follow-up hsCRP levels and long-term clinical outcomes in patients at 9 months after receiving DES.

Methods

A total of 1,763 patients who received 9-month follow-up angiography were enrolled and grouped according to hsCRP level 9 months after the DES implantation: group I (718 patients, hsCRP<1.0 mg/L), group II (639 patients, 1.0≦hsCRP≦3.0 mg/L), and group III (406 patients, hsCRP>3.0 mg/L).

Results

Group III patients had a lower cardiovascular event-free survival rate than group I or II patients during a follow-up of 64±45 months (64.5% vs. 71.6% vs. 72.8%, respectively, p = 0.012). Multivariate analysis showed that a follow-up hsCRP level <3.0 mg/L was an independent predictor of a major adverse cardiovascular event (cardiac death, reinfarction, target lesion revascularization, stenting in a new lesion, or coronary bypass surgery). Group III patients had a higher restenosis rate (11.3% vs. 5.8% vs. 6.6%, respectively, p = 0.002) and loss index (0.21±0.32 vs. 0.16±0.24 vs. 0.18±0.28, respectively, p = 0.001) than group I or II patients in 9-month follow-up angiography.

Conclusions

A high 9-month follow-up hsCRP level is an independent predictor of long-term clinical cardiovascular outcomes in patients at 9 months after DES implantation. It is also associated with a higher restenosis rate, larger late loss and loss index at 9 months after DES implantation.     

Research Activity and the Association with Mortality

IntroductionThe aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes.MethodsNational Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated.ResultsLow mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855–2,843], 5.9 patients/bed [2.7–9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864–1,357] p<0.0001, 2.6 patients/bed [1.7–3.5] p<0.0169) or, high (n = 42, 930 £/bed [683–1,177] p = 0.0001, 1.8 patients/bed [1.4–2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033–1.068] p<0.0001, recruitment 1.069 [1.052–1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024–1.055] p<0.0001, recruitment 1.085 [1.070–1.100] p<0.0001).ConclusionsResearch active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors.