Recent community-based research has linked aortic stiffness to the development of atrial fibrillation. We posit that aortic stiffness contributes to adverse atrial remodeling leading to the persistence of atrial fibrillation following catheter ablation in lone atrial fibrillation patients, despite the absence of apparent structural heart disease. Here, we aim to evaluate aortic stiffness in lone atrial fibrillation patients and determine its association with arrhythmia recurrence following radio-frequency catheter ablation.We studied 68 consecutive lone atrial fibrillation patients who underwent catheter ablation procedure for atrial fibrillation and 50 healthy age- and sex-matched community controls. We performed radial artery applanation tonometry to obtain central measures of aortic stiffness: pulse pressure, augmentation pressure and augmentation index. Following ablation, arrhythmia recurrence was monitored at months 3, 6, 9, 12 and 6 monthly thereafter.th percentile) of peripheral pulse pressure, central pulse pressure and augmentation pressure had higher atrial fibrillation recurrence rates . Only central aortic stiffness indices were associated with lower survival free from atrial fibrillation using Kaplan-Meier analysis.Compared to healthy controls, lone atrial fibrillation patients had significantly elevated peripheral pulse pressure, central pulse pressure, augmentation pressure and larger left atrial dimensions . During a mean follow-up of 2.9±1.4 years, 38 of the 68 lone atrial fibrillation patients had atrial fibrillation recurrence after initial catheter ablation procedure. Neither blood pressure nor aortic stiffness indices differed between patients with and without atrial fibrillation recurrence. However, patients with highest levels (≥75Aortic stiffness is an important risk factor in patients with lone atrial fibrillation and contributes to higher atrial fibrillation recurrence following catheter ablation procedure. Atrial fibrillation (AF) has been recognized as an emerging epidemic. Increased focus on its prevention is thereby warranted given the limitations with current therapeutic options . RecentlHowever, peripheral derived blood pressures are known to overestimate true central hemodynamic indices . In partIn this study, we aim to further investigate the role of aortic stiffness in AF by analyzing the central pulse wave of lone AF patients who have no apparent structural heart disease or conditions that predispose them to the arrhythmia. Recently, it has been demonstrated that lone AF patients have an abnormal atrial electrical and structural substrate -10. We pThe Research Ethics Committee of the Royal Adelaide Hospital, Australia approved this study. From a total of 115 consecutive lone AF patients who underwent initial catheter ablation procedure at our institution for symptomatic AF between August 2005 and September 2010, 72 agreed to participate in this study. Due to the presence of AF during applanation tonometry in 4 patients, we only included data from the remaining 68 patients for analysis. Lone AF was defined as previously described by: absence of structural heart disease or stroke based on history, physical examination, chest X-ray, routine blood chemistry, and echocardiography; coronary artery disease was excluded by clinical, ECG or stress test criteria; pulmonary disease, hypertension, hyperthyroidism and diabetes were eliminated by appropriate tests [Measurements of blood pressure and radial artery applanation tonometry were performed in a quiet, temperature controlled room (22°C) with subjects in a recumbent position after 10 minutes of rest. All subjects were instructed to refrain from alcohol and caffeine consumption for 1 day prior to these measurements. Brachial blood pressure was the average of the last 2 readings (out of 3) measured in each subject at 5-minutes interval using a mercury sphygmomanometer and appropriately sized arm cuff.Radial artery pressure waveform was acquired using a high fidelity applanation tonometer on the same arm . The system has real-time monitoring of waveform quality  allowingClassification of AF was in accordance with expert consensus statement . ParoxysElectrophysiological procedures were performed with patients in the fasting state and under conscious sedation using midazolam and fentanyl. The ablation technique utilized at our institution has been previously described . In brieThe ablation strategy included wide-encircling pulmonary vein ablation with an endpoint of pulmonary vein isolation in all patients. Further substrate modification was performed for patients with AF episodes lasting longer than 48 hours. This included linear ablation at the left atrial roof with endpoint of conduction block and/or electrogram-guided ablation at highly fractionated sites with abolition of fractionated signals as endpoint. Typically, radiofrequency power of 30W was used for pulmonary vein ablation and up to 35W for substrate modification while irrigation rate was fixed at 30 ml/min.2 score ≥2. Procedural success was determined as the absence of any atrial arrhythmia longer than 30 seconds without anti-arrhythmic drug use after a blanking period of 6 weeks.Patients were reviewed 3 monthly for the first year after ablation and 6 monthly thereafter. At each review, AF recurrence was ascertained from ambulatory 7-day Holter monitoring, 12-lead ECG and patients’ symptoms. All patients were treated with flecainide or sotalol for the first 6 weeks following the ablation procedure. Ongoing anti-arrhythmic drug use was at the discretion of the treating physician. Warfarin anti-coagulation was routine in all patients for a period of 3 months following ablation and continued in those with a CHADSContinuous variables were expressed as means ±SD or median with inter-quartile range accordingly using the Shapiro-Wilks test of normality. Data were compared using the unpaired Student’s t-test or Wilcoxon rank-sum test as appropriate. Categorical data were expressed as numbers and percentages, and compared using Fisher’s exact test. Kaplan-Meier survival analysis with log-rank testing was applied to compare post ablation AF recurrence. Statistical significance was established with two-tailed P value less than 0.05.Patient characteristics are presented in The various peripheral and central blood pressure parameters are detailed in During a mean (±SD) follow-up of 2.9±1.4 years, 38 of the 68 lone AF patients had recurrence of AF at 31±27 weeks after single ablation procedure. As shown in th percentile) had higher AF recurrence rates when compared to those with values less than the 75th percentile . Importantly, corresponding analysis of those with highest levels of central or peripheral systolic, diastolic and mean blood pressure (≥75th percentile) showed no relationship to higher AF recurrence rates. Likewise, left atrial dimensions  and inter-ventricular septal thickness (≥75th percentile) were not significantly associated with higher AF recurrence . In addition, only central aortic stiffness indices were associated with lower survival free from AF using Kaplan-Meier statistics .Even though no differences were seen in both mean peripheral and central pressures, patients with highest levels of aortic stiffness  was evident in lone AF patients as compared to controls;2Measures of aortic stiffness demonstrated stronger association with AF recurrence following catheter ablation than standard brachial blood pressure measures and conventional echocardiographic parameters;3Lone AF patients had larger left atrial dimensions than controls.Therefore, this study implicates aortic stiffness as a silent contributing factor in the development of lone AF. Elevated aortic stiffness, by leading to abnormal atrial remodeling, creates a path to development of the substrate that develops apparently “lone” AF.Studies in lone AF patients have alluded to several underlying atrial abnormalities thereby pointing to the possibility of as yet unrecognized risk factors. These abnormalities include: increased inflammation, diastolic dysfunction, increased fibrosis and microvascular dysfunction -18. MoreThe causes of aortic stiffness remain incompletely understood. The lack of association between aortic stiffness and conventional cardiac risk factors other than hypertension and aging has been well documented -21. OtheTheoretically, central pressure is more patho-physiologically relevant to the heart than their peripheral counterparts as its proximity will exert greater strain leading to increased afterload and impaired relaxation . A recenThis study affirms aortic stiffness as a novel modifiable risk factor for AF. It can be used to identify “high-risk” pre-hypertensive patients with subclinical atrio-myopathy. Further studies are necessary to determine whether targeting of aortic stiffness with anti-hypertensive medications may modify the burden or progression of AF. Of note, agents with central blood pressure effects such as inhibitors of the renin angiotensin system have also been shown to reduce the occurrence of AF in various patient groups including normotensive lone AF patients ,32.We did not have longitudinal measures of central pulse wave analysis. Inclusion of pulse wave velocity measurements would have strengthened our findings. Pulse wave analysis ideally requires stable artery waveforms, which is difficult when a subject is in AF.Lone AF is associated with greater aortic stiffness; which contributes to higher AF recurrence following catheter ablation procedures. Active monitoring and targeting of this novel risk factor may improve outcomes in patients with AF.


P < 0.05) without decline in estimated glomerular filtration rate. Concerning parameters of vascular function, the combination therapy significantly improved both brachial-ankle pulse wave velocity (baPWV) and central systolic BP (cSBP) . Collectively, these results suggest that the combination therapy with amlodipine and atorvastatin may exert additional beneficial effects on renal and vascular damages as well as BP profile in addition to BP lowering in hypertension with CKD.Both strict blood pressure (BP) control and improvements in BP profile such as BP variability are important for suppression of renal deterioration and cardiovascular complication in hypertension and chronic kidney disease (CKD). In the present study, we examined the beneficial effects of the single pill-based combination therapy of amlodipine and atorvastatin on achievement of the target BP and clinic BP profile, as well as markers of vascular and renal damages in twenty hypertensive CKD patients. The combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased clinic BP, and achievement of target BP control was attained in an average of 45% after the combination therapy in spite of the presence of no achievement at baseline. In addition, the combination therapy significantly decreased the within-visit BP variability. With respect to the effects on renal damage markers, combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased albuminuria (urine albumin-to-creatinine ratio, 1034 ± 1480 versus 733 ± 1218 mg/g-Cr,  Chronic kidney disease (CKD) patients are reportedly increasing in number, and cardiovascular complications are the most common cause of death in these patients. Thus, it would be a considerable advance in the management of this condition to elucidate the mechanisms involved in the renal deterioration and the cardiovascular events associated with hypertension complicated by CKD and to identify therapeutic approaches to treat them. Accumulated results of clinical trials also showed that strict control of blood pressure (BP) is essential to prevent target organ damage and to reduce cardiovascular mortality in hypertensive CKD patients , 2. The In addition, therapies that lower lipid levels also slow the progression of atherosclerosis and reduce morbidity and mortality in patients with hypertension or atherosclerotic disease. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) demonstrated an additive benefit of combined antihypertensive and lipid-lowering therapy on the prevention of cardiovascular complication in high-risk hypertension . Vasculahttp://www.umin.ac.jp/ctr/). All of the patients provided written informed consent prior to the start of the study.This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committees of Yokohama City University Hospital  = 194 × serum creatinine−1.094  × age−0.287  × 0.739  [Hypertensive patients with CKD who have already been treated with antihypertensive therapy were eligible for the study if they could not achieve the BP goal (clinic systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg), and their low-density lipoprotein (LDL) cholesterol levels were 100 mg/dL or more. CKD was diagnosed by the presence for more than 3 months of albuminuria , proteinuria , or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m female) . The excAfter the run-in period, eligible patients were given a single pill of amlodipine/atorvastatin tablet  for 16 weeks. The starting dose of the single amlodipine/atorvastatin tablet was determined according to each physician's choice, and it was titrated up as needed to achieve the BP and lipid goal . If patients had already been treated with another calcium channel blocker or statin before the start of the study, they were switched to the single amlodipine/atorvastatin tablet of same dose during the run-in period. If the BP and lipid goal could not be achieved by maximum doses of amlodipine and atorvastatin (10 mg/day and 20 mg/day), another antihypertensive drug and lipid-lowering drug were considered to be added. The doses of other drugs such as oral glucose lowering agents and anticoagulant agents were not changed during the treatment period.The clinic BP was measured in sitting position using a calibrated standard mercury sphygmomanometer and the recommended cuff size . Three mThe central systolic blood pressure (cSBP) and augmentation index (AI) were measured using an HEM-9000AI  with an automatic tonometry probe wrapped onto the wrist to record radial waveforms, which were calibrated against the contralateral arm cuff brachial BP taken immediately after tonometry. An algorithm based on a linear regression model was then applied to estimate the cSBP from the “late systolic shoulder” (pSBP2) of the radial pulse waveform, which has been shown to closely agree with the cSBP –18. ThisThe baPWV values were determined by a PP analyzer , as described previously –21. The Blood and urine sampling were performed in fasted state at baseline and after a period of 16-week treatment, respectively. All parameters were determined by routine methods in the Department of Clinical Chemistry, Yokohama City University School Hospital.t-test. Univariate and multivariate linear regression analyses were performed to identify the factors affecting the changes in cSBP and UACR. The independent variables entered into the multivariate model were those that were significantly associated in the univariate analyses or were significantly different after a period of 16-week treatment. Analysis was performed using SPSS version 19.0 (IBM Corporation), and a value of P < 0.05 was considered statistically significant.All data were presented as the mean ± SD or as a percentage. For the statistical analysis of the difference between baseline and 16 weeks of treatment, analysis of variance was compared by a paired comparison n = 11), diabetic nephropathy (n = 6), chronic glomerulonephritis (n = 2), and obstructive nephropathy due to urinary tract stones (n = 1). None of the enrolled patients discontinued participation in the study. Mean age was 67.7 ± 12.4 years, and the number of males and females was 14 and 6, respectively. Body mass index was 26.8 ± 4.9 kg/m2, suggesting that the participants correspond to obese hypertensive patients as a whole. With respect to BP control, clinic BP did not at all achieve the target BP level according to the JSH2009 guideline (clinic SBP/DBP 151 ± 15/81 ± 8 mm Hg) [8 mm Hg) .As a whole, the combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased clinic SBP and DBP , and cliWith respect to the glucose and lipid metabolism, the combination therapy with amlodipine and atorvastatin significantly lowered total and LDL-cholesterol levels, without evident changes in parameters of glucose metabolism and inflammation . In addiP < 0.05). In addition, the reduction of UACR by the combination therapy was not accompanied with decline in eGFR (2). Concerning parameters of vascular function, the combination therapy with amlodipine and atorvastatin for 16 weeks significantly improved both baPWV and cSBP .Combination therapy with amlodipine and atorvastatin for 16 weeks significantly decreased UACR (Multivariate regression analysis of the independent variables, which showed significant correlations in the univariate analyses or were significantly different after a period of 16-week treatment, indicated that there were significant associations between the changes in cSBP and those in SBP and total cholesterol and changes in UACR and those in serum creatinine and total cholesterol .The main finding of this study was that the single pill-based administration for combinatorial antihypertensive and LDL cholesterol-lowering therapy with amlodipine and atorvastatin successfully decreased clinic BP so as to improve the achievement of target BP in hypertensive CKD patients already being treated before the start of the combination therapy. In addition, the combination therapy was able to significantly reduce UACR without decrease in eGFR and resulted in significant improvements in vascular function and lipid metabolism. These pleiotropic therapeutic effects by combination therapy with amlodipine and atorvastatin on biomarkers of renal and vascular damage deserve further discussion.Recent clinical guidelines for hypertensive patients recommend combination therapy such as renin-angiotensin system inhibitors and CCB or diuretics, and, in this study, the combination therapy with amlodipine and atorvastatin was effective for efficient lowering of clinic BP and inhibition of within-visit BP variability in Japanese hypertensive CKD patients. With respect to BP-lowering efficacy of amlodipine, we previously showed that the amlodipine add-on group exerted greater reductions of clinic BP and home BP than the ARB add-on group .Accumulated evidence indicates that renin-angiotensin system inhibitors such as ARB and ACE inhibitors are able to improve albuminuria better than CCB such as amlodipine through the reduction of intraglomerular pressure . HoweverA previous study showed that the decreases in BP significantly contributed to the decreases in albuminuria by CCB in hypertensive and CKD patients , 29. AltThe combination therapy with amlodipine and atorvastatin exhibited a significant improvement in vascular functional parameters such as baPWV and cSBP in this study. A previous study showed that the add-on amlodipine therapy had benefits in terms of the vascular function and vascular structure of hypertensive patients already treated with renin-angiotensin inhibitors, which were independent of its depressor effects but with a concomitant decrease in ambulatory BP variability . Also, tRecently, parameters of BP variability obtained by clinic BP measurement are suggested to be associated with target organ damage including CKD and cardiovascular complication –39. VariA recent study showed that alteration of vascular function is an important factor in the correlation between clinic BP variability and cardiovascular disease , and cliIn the present study, pulse rate was significantly decreased by combination therapy of amlodipine and atorvastatin in spite of BP reduction. It has been reported that amlodipine tends to increase pulse rate via the reflex stimulation of sympathetic nervous system . On the There are several limitations in the present study. Firstly, the present study is not randomized parallel-group control trial, and the numbers are small. Secondly, the patient's adherence was not examined in the present study. Since there are several previous studies suggesting that single-pill amlodipine/atorvastatin rather than 2-pill regimen may reduce cardiovascular events by improving the patient's adherence , 49, theIn summary, the results of the present study suggest that the combination therapy with amlodipine and atorvastatin may exert additional beneficial effects on renal and vascular damages as well as BP profile in addition to BP lowering in hypertension with CKD.


Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. Therefore it seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. As opposed to nitric oxide donors, magnesium has both endothelium-dependent and non-endothelium-dependent vasodilatory pathways.In a single-center open label study we evaluated the effects of magnesium sulphate (MgS) infusion on the sublingual microcirculation perfusion in fluid resuscitated patients with severe sepsis and septic shock within the first 48 hours after ICU admission. Directly prior to and after 1 hour of magnesium sulphate (MgS) infusion (2 gram) systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, were obtained.2 = 0.270, p = 0.057). The correlation between baseline Mg concentrations and the change in MFI pre- and post MgS infusion was non-significant .Fourteen patients  with a median APACHE II score of 20 were enrolled. No significant difference of the systemic hemodynamic variables was found between baseline and after MgS infusion. We did not observe any significant difference pre and post MgS infusion in the primary endpoint microvascular flow index (MFI) of small vessels: 2.25(1.98-2.69) vs. 2.33(1.96-2.62), p = 0.65. Other variables of microcirculatory perfusion were also unaltered. In the overall unchanged microvascular perfusion there was a non-significant trend to an inverse linear relationship between the changes of MFI and its baseline value (y = -0.7260 × + 1.629, rIn the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time.ClinicalTrials.gov NTC01332734. Microcirculatory dysfunction in sepsis is crucial in the pathogenesis of organ dysfunction and consists of a cascade of mechanisms, which involves many cells, such as endothelial cells, smooth muscle cells, red blood cells and leukocytes . New micTherefore, other strategies that aim to attenuate microcirculatory dysfunction directly at the level of the microcirculation, have been tested. According to Poiseuille's Law, blood flow through a vessel is directly proportional to the driving pressure along the vessel and its radius to the fourth power, and inversely proportional to the length of the vessel and the dynamic blood viscosity. Theoretically, vasodilators should be able to increase blood flow via a change in vessel diameter at the entrance of the microcirculation and recruit microcirculatory perfusion in volume resuscitated patients . StimulaStudies with magnesium (Mg) and magnesium sulphate (MgS) have shown a peripheral (predominantly arteriolar) vasodilator effect with preserved cardiac function, within a large safety margin -13, not However, up to date the effect of MgS infusion on microvascular perfusion in septic patients, is unknown. Our study aims to test the hypothesis that MgS infusion may improve sublingual microcirculatory perfusion in patients with severe sepsis and septic shock.The study was performed during an 8-months period in 2010 in a closed-format 15-bed mixed ICU in a university hospital. It was designed as a prospective, single-centre, open-label trial. Patients were included with less than 48 hrs duration of severe sepsis or septic shock as defined by the International Sepsis Definition Conference [2) ≥ 65% or central venous saturation (S(c)vO2) ≥ 70%. Red blood cell transfusion trigger was a haematocrit < 25%. Sedation and analgesia was provided with midazolam and fentanyl.All patients were equipped with an arterial line and central venous catheter or a pulmonary artery catheter . Prior to the start of MgS infusion, all patients followed a strict protocol to optimize systemic hemodynamic parameters in accordance with international guidelines for management of sepsis . PatientAfter achieving these therapeutic endpoints, MgS infusion was started at a rate of 2 g over 1 hour. For safety reasons, a sustained MAP < 65 mm Hg during infusion despite protocolized treatment constituted a reason to stop MgS infusion permanently.The following data were recorded at baseline: general characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, calculated over the first 24 hrs following ICU admission and Sequential Organ Failure Assessment (SOFA) score, calculated at study time. Directly prior to and within 10 minutes after cessation of MgS infusion systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, including arterial and central/mixed venous blood gasses were obtained. ICU and hospital length of stay (LOS) and mortality were registered afterwards.®, Microvision Medical, Amsterdam, the Netherlands) [Images of the sublingual microcirculation were obtained with SDF videomicroscopy (Microscanerlands) . After gerlands) . Vesselserlands) .p value < 0.05 was considered significant.Primary outcome is sublingual MFI of small vessels. We anticipated a standard deviation in difference of response of 0.5. We calculated a sample size of 14 patients to detect a absolute difference of 0.4 in a two-sided test with 0.05 type I error and a 80% probability. The Statistical Package for Social Sciences  was used for statistical analysis. With respect to small numbers data are presented as the median (25th-75th percentiles) and analyzed with non-parametric Wilcoxon signed rank test and Spearman's rho for correlations. A Fourteen patients (12 with septic shock and 2 with severe sepsis) with a median APACHE II score of 20 were enrolled, within 24 hours after the initial sepsis resuscitation. Baseline characteristics are summarized in Table 2 = 0.270, p = 0.057, Figure s = -0.165, p = 0.67).No significant difference in systemic hemodynamic variables was found between baseline and after MgS infusion Table . FurtherTo our knowledge, this is the first study in which the effect of Mg on the human microcirculation is visualized directly in patients with sepsis. The main finding of our study is that MgS infusion had no effect on both sublingual microvascular perfusion and systemic hemodynamic variables in this setting. This is not in line with previous observations, that evaluated the effect of MgS on microcirculatory perfusion under non-septic conditions. In vivo plethysmography of the forearm in healthy volunteers during intra-arterial MgS infusion revealed a marked increased in blood flow. In an animal model with direct in-vivo microscopy of the microcirculation, both topical and intravenous application of Mg-compounds demonstrated vasodilatory effects in mesenteric arterioles (10-20 μm) and venules (15-30 μm), that could not be blocked by cyclo-oxygenase inhibition . This efThe discrepancy between these results and our observations may in part be explained by a difference in technique. Plethysmography incorporates artiolar, capillary and venular blood flow. In sepsis however, a heterogeneous distribution of altered capillary blood flow is observed, often despite maintenance of both artial and venular blood flow. In contrast to plethysmography, SDF enables discrimination between these different vascular compartments. Furthermore, sublingual SDF imaging may not necessarily reflect microvascular perfusion abnormalities in vascular beds of other organs . WhetherThe classical response to overcome microvascluar perfusion abnormalities in shock has always been to raise arterial pressure by means of vasopressors, in order to increase the net perfusion pressure over the microvascular compartment. However, according to physiological theory, the drop in perfusion pressure prior to the microcirculation is equal to the increase in artiolar resistance, thus reducing its pro-microcirculatory flow effect . Recent Our study has a number of limitations. Due to the open label setting and relatively small numbers a modest effect of MgS infusion on microcirculatory perfusion may have remained unnoticed. Baseline MFI was decreased despite resuscitation, but only to a moderate extend. Although this may have blunted a potential pro-microcirculatory effect of MgS, we only observed a non-significant and weak correlation between baseline MFI and change in MFI in response to therapy. It must be stated however, that post-hoc linear regression analysis itself is limited by the narrow range of variables. We deliberately chose this strategy, since we consider it key not to replace therapeutic macro-hemodynamic strategies by micro-hemodynamic strategies, but to add micro-hemodynamic strategies in case of remaining microcirculatory abnormalities, despite optimal macro-hemodynamic resuscitation. In our study we used a continuous fixed dose of MgS without bolus due to safety reason, since some data show, that higher doses of MgS may inhibit catecholamine release ,33. EndoIn the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time.2: mixed venous saturation; S(c)vO2: central venous saturation; APACHE: Acute Physiology and Chronic Health Evaluation; SOFA: Sequential Organ Failure Assessment; LOS: length of stay; MFI: microvascular flow index; PPV: proportion of perfused vessels; PVD: perfused vessel density total vessel density (TVD)OPS: orthogonal polarization spectral; SDF: sidestream dark field; NO: nitric oxide; Mg: magnesium; MgS: magnesium sulphate; MAP: mean arterial pressure; SvOThe authors declare that they have no competing interests.AP conceived the study, performed SDF imaging and wrote the first draft; NV analyzed SDF images; VP participated in the design of the study; MK was responsible for data acquisition; CB performed statistical analysis and wrote the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2253/11/12/prepub


Objective: This study aimed to determine the effects of mat Pilates on resting heart rate, resting blood pressure and fasting blood glucose, cholesterol and triglycerides in elderly women.Methodology: Fifty sedentary, apparently healthy females aged 60 and older were randomly assigned into a control  or an intervention  group. The IG took part in an eight-week progressive mat Pilates exercise program, three times weekly while the CG did not take part in any structured exercises throughout the eight-week period. All subjects underwent pre- and post-tests in which cardiometabolic parameters were assessed.Results: In the eight-week mat Pilates program, the IG only demonstrated a significant (p ≤ 0.05) decrease in systolic BP (p = 0.040) from 135.84 ± 14.66mmHg to 128.80 ± 16.36mmHg and a significant increase in blood glucose (p = 0.000) from 5.07 ± 0.46mmol.L-1 to 5.83 ± 0.57mmol.L-1, whereas resting HR (p = 0.148) (from 68.80 ± 12.58beats.min-1 to 73.20 ± 11.46beats.min-1), resting diastolic BP (p = 0.342) (from 75.64 ± 10.10mmHg to 77.44 ± 9.32mmHg), blood TC (p = 0.073) (from 5.37 ± 0.99mmol.L-1 to 5.67 ± 1.04mmol.L-1) and blood TG (p = 0.384) (from 1.77 ± 0.88mmol.L-1 to 1.92 ± 0.87mmol.L-1) did not produce any significant changes.Conclusion: Due to the contradictory nature of the cardiometabolic variables (except systolic BP) with the findings of previous studies, it is difficult to establish a case for using Pilates as a substitute for more conventional forms of exercising when exclusively attempting to favourably alter cardiometabolic parameters at least among the elderly women in our sample. Glucose intolerance can be caused by changes in hormones involved in the increase uptake and suppression of glucose usage such as glucagon, growth hormone and pancreatic hormones.9 With ageing, there is also a tendency to increased total body weight and increased distribution of adipose tissue in the abdominal area, which mainly influence glucose tolerance by causing insulin resistance.8,9Ageing can also be seen as one of the largest factors affecting glucose homeostasis. According to Elahi and Muller and Stout,10 found that the prevalence of dyslipidemia increases with age, however, there has been much debate whether cholesterol increases are the result of a natural process of intrinsic ageing or whether it is due to age-associated anthropometrics and/or lifestyle changes.10 Schubert et al.11 found that age is an important independent predictor for LDL-C and TC in men and TC in women, but it is not as influential as body composition and lifestyle on HDL-C and TG in men and women and LDL-C in women. Regardless of the link between overweight and cholesterol levels Nakagawa et al,12 found that intramyocellular lipid content also increases with age in lean elderly. This might be related to blood lipid and lipoprotein profiles, with a decrease in HDL-C and might affect health risks and muscle attenuation with age in lean elderly.With regards to lipids, Gostynski et al.13 Pilates results in various physical improvements such as, increases in flexibility, bone density and dynamic balance as well as favourable changes in body mass index and have a positive effect on muscular strength and endurance.14-17 Correct breathing during Pilates can also prevent excessive stress on the heart, result in total body relaxation and mental calmness.16 This reduction in stress as a result of Pilates can reduce other serious complications. It may directly or indirectly result in an improvement in cardiometabolic parameters, especially in the elderly, resulting in reduced risk of developing coronary artery disease (CAD).18 However, little literature is available on the effects of Pilates on cardiometabilic parameters, therefore creating a need for scientific evidence on the beneficial effects of Pilates on cardiometabolic parameters.The weakening of the cardiovascular system associated with ageing, could be countered by increasing levels of physical activity and functional fitness.A sample of 50 elderly female subjects (≥ 60 years of age), selected from caring facilities within Pretoria, Gauteng Province, South Africa were randomly assigned into one of two groups using a random numbers table; with 25 subjects undergoing an eight-week mat Pilates program (IG), while the other 25 subjects participated as a non-exercising control group (CG). The research protocol was approved by the Institutional Review Boards of the Tshwane University of Technology, Pretoria, South Africa and was endorsed by the International Physical Activity Projects (IPAP). Permission to conduct the study at the caring facilities was obtained from the relevant care facilities and all subjects signed a written informed consent form indicating all the advantages and risks involved of participation in the study. All subjects were required to obtain medical clearance prior to commencement of pre-testing procedures. Both groups took part in identical pre- and post-tests. Subject demographics at baseline are shown in 2 Resting BP was measured by means of a sphygomanometer and a stethoscope . The subject was required to be supine for five minutes and the tested arm was supported and the cuff was wrapped securely around the right arm at heart level. The stethoscope was placed below the cuff and the cuff inflated to approximately 180 millimeters mercury (mmHg). The pressure was then slowly released and different heart sounds were heard. The first sound heard was used as the systolic blood pressure (heart contraction) value and the sound heard when the tone changed or disappeared was used for the diastolic blood pressure (heart relaxation) reading.2 Fasting blood glucose, total cholesterol (TC) and triglycerides (TG) were measured by means of using the Reflotron system  after an eight-hour fast. A multiclix lancing device was used to prick the subjects’ finger. A drop of blood was then placed on a Reflotron testing strip and the test strip placed in the Reflotron. The glucose, cholesterol and triglycerides readings were then digitally displayed.All subjects were required to undergo cardiometabolic testing prior to and at completion of the eight-week treatment period. Each subject’s resting heart rate was measured in a seated position (after five minutes rest) by means of manually applying mild pressure. Pressure was applied to the radial artery on the lateral side of the anterior forearm just proximal to the wrist.19 in order to compile the mat Pilates exercise program. A session was allocated to explain the basics of mat Pilates, before commencement of the program. This session included an explanation of the neutral position of the spine and also the correct breathing techniques used during Pilates. After the introductory session the eight-week mat Pilates exercise program commenced. The program consisted of three non-consecutive sessions a week, 60 minutes in duration, for eight-weeks with increasing intensity. All sessions started with breathing, followed by a flowing system from standing, to sitting, to lying down exercises and ended with the rest position. Mat Pilates exercises were derived from Worthpost-hoc analysis. Data was analyzed using commercial software  Version 17, Chicago, IL) and statistical significance set at p ≤ 0.05.Statistical analysis consisted of basic statistics to determine pre- and post-test means and standard deviations. A paired samples t-test was used to determine if a significant change took place in the measurements at post-test. Differences in measurements were compared using a one-way analysis of variance (ANOVA) using a Dunnett T3 -1 to 5.83 ± 0.57mmol.L-1, whereas resting HR (p = 0.148) (from 68.80 ± 12.58beats.min-1 to 73.20 ± 11.46beats.min-1), resting diastolic BP (p = 0.342) (from 75.64 ± 10.10mmHg to 77.44 ± 9.32mmHg), blood TC (p = 0.073) (from 5.37 ± 0.99mmol.L-1 to 5.67 ± 1.04mmol.L-1) and blood TG (p = 0.384) (from 1.77 ± 0.88mmol.L-1 to 1.92 ± 0.87mmol.L-1) did not produce any significant changes following the eight-week exercise programme. Despite the CG demonstrating no significant difference in resting systolic BP (p = 0.705), resting diastolic BP (p = 0.471), blood TC (p = 0.054), blood TG (p = 0.321), the CG did demonstrate significant changes in resting HR and blood glucose from pre- to post-test  . At pre-test, the groups were, however, homogenous for resting systolic BP (p = 0.736), resting diastolic BP (p = 0.143), fasting blood glucose levels (p = 0.319), blood TC (p = 0.754) and blood TG (p = 0.474). Following the eight-week mat Pilates program, the IG only demonstrated a significant (p ≤ 0.05) decrease in systolic BP (p = 0.040) from 135.84 ± 14.66mmHg to 128.80 ± 16.36mmHg and a significant increase in blood glucose (p = 0.000) from 5.07 ± 0.46mmol.Lctively) .20 It was however, stated that exercise has major benefits for the cardiovascular system  and metabolism .21 Results obtained from the present study, however, indicate that eight-weeks of mat Pilates did not produce improvements in any of the cardiometabolic variables tested except systolic BP, which is a desirable finding as hypertension is one of the most significant risk factors for cerebrovascular and CVD.22As individuals age, physiological functioning decreases and most of the elderly develop at least one of the following chronic diseases: hypertension (49%), arthritis (36%), heart disease (31%), cancer (20%) and/or diabetes (15%).14 regarding diastolic BP by indicating that no significant changes occurred in diastolic BP at post-test. In this regard, Jago et al.14 found non-significant changes in systolic and diastolic BP , following four-weeks of Pilates training in girls. Even though no significant change occurred in diastolic blood pressure (BP), the present study demonstrated a significant reduction in systolic BP. Brandaorondon et al.23 found that exercise significantly decreases BP in hypertensive elderly and provokes a decrease in BP that lasts for 22 hours, the moderately hypertensive pre-test systolic BP value should not be neglected. This reduction found in BP after exercise in elderly hypertensive individuals can be associated with a decrease in stroke volume and left ventricular end-diastolic volume.23 The reduction in BP can also be attributed to a diet high in cholesterol or fat that might result in fatty deposits called plaques to clot the arteries, thus resulting in narrowing of the arteries and increasing pressure. However, this cannot be confirmed in the present study since no dietary analyses were conducted. Exercise also exerts beneficial effects on blood lipids, but since the separate measures of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were not assessed, the vascular remodeling of existing arteries can also not be confirmed in the present study. In general, obesity and overweight are considered controllable risk factors for hypertension,18 but with a more thorough investigation24 found that body mass index (BMI), WHR, and skinfolds adiposity have some independent effect on the risk of elevated BP, where waist and hip circumferences are most important variables in women for obesity and BP. As such, it can be assumed that the decrease found in BP after completion of the eight-week mat Pilates programme in the present study can be as a result of the decrease found in waist circumference (WC) from 83.50 ± 12.79mm to 81.44 ± 9.90mm at post-test. Another influential mechanism in the decrease in systolic BP could have been due to total body relaxation and mental calmness as a result of correct breathing during the mat Pilates intervention,16 as mental or emotional stress activates nervous and endocrine responses, such as an increase in epinephrine and norepinephrine stimulation that results in an increase in BP, while preparing the body for physical activity.2,25The present study correlates with the findings of Jago et al.26 Based on this statement, a decrease in blood glucose in the IG would have been expected as the present study demonstrated a significant (p = 0.006) increase in lean body mass (LBM) (from 46.67 ± 6.33kg to 48.04 ± 7.52kg) in the IG. However, this was not the case, instead both the control group (CG) and the IG demonstrated a significant increase in blood glucose. The mean fasting glucose levels are significantly higher during the colder than warmer months.27 The present study was conducted during the transition from a warmer to a colder season, hence the possibility of the increase in blood glucose observed in the present study. The significant increase in glucose from pre- to post-test can also possibly be due to different instead of fixed nutritional consumption followed by each subject, several days prior to testing.Skeletal muscle is the primary site of glucose disposal, therefore by increasing skeletal mass might be an effective way to improve insulin action.28 and favourable changes from pre- to post-test was observed in body fat percentage (BF%) (from 33.85 ± 6.67% to 32.23 ± 5.82%), WC (from 83.50 ± 12.79 millimeters to 81.44 ± 9.90 millimeters), fat mass (FM) (from 25.03 ± 9.53 kilograms to 23.69 ± 8.06 kilograms) and LBM (from 46.67 ± 6.33 kilograms to 48.04 ± 7.52 kilograms) (data not shown). A possible reason might have been due to an increase in HDL-C without a corresponding decrease in LDL-C, but as the CG also showed an increase in TC, this could not be a reasonable assumption. Uncontrollable factors affecting lipids are genetics, age and gender,29 but as only elderly women were used in the study age and gender could not have influenced the outcome. Boardley et al,29 however, indicated that dietary intake also influences blood lipids. As such, the observation might also be, as in the case of glucose, attributed to different instead of fixed nutritional consumption followed by each subject several days prior to testing. However, again this cannot be confirmed since no dietary analyses were conducted.The present study found no significant changes in TC and TG after completion of an eight-week mat Pilates programme. The results found on blood lipids in the present study was not attributable to any of the anthropometric variables as the majority of TG are stored in adipose cellsThe present study demonstrated that eight-weeks of Pilates is sufficient to produce a significant improvement in systolic BP, however, due to the contradictory nature of the other cardiometabolic variables with the findings of previous studies, it is difficult to establish a case for using Pilates as a substitute for more conventional forms of exercising when exclusively attempting to favourably alter cardiometabolic parameters in elderly women.


Elevated plasma total homocysteine (tHcy) acts synergistically with hypertension to exert a multiplicative effect on cardiovascular diseases risk. The aim of this study was to determine the relationship between tHcy concentration and blood pressure, and to evaluate the role of plasma tHcy in arterial stiffness and wave reflection in hypertension.In this cross-sectional study, a community-based sample of 1680 subjects (mean age 61.6 years) was classified into four groups according to tHcy level (<21.6 vs. ≥21.6 µmol/l) and blood pressure (hypertensive vs. normotensive). Levels of plasma tHcy and other biochemical parameters  were determined. Central arterial blood pressure, reflected pressure wave, and carotid-femoral pulse wave velocity (cf-PWV) were assessed by tonometry within 2 days of obtaining the blood specimen.Neither peripheral nor central blood pressure differed according to tHcy levels in normotensive and hypertensive subjects. Differences in cf-PWV according to tHcy were observed only in hypertensive subjects; differences in cf-PWV in normotensive subjects were not significant after adjusting for confounding factors. Central augmentation index did not differ according to tHcy level in either normotensive or hypertensive subjects. Results of univariate analysis revealed significant correlations between blood pressure parameters and tHcy concentration only among normotensive subjects; however, these correlations were not significant in a partial correlation analysis. Results of multiple regression analysis showed that plasma tHcy levels were independently correlated with cf-PWV in hypertensive subjects . The independent relationship between tHcy and central augmentation index was not significant by further multiple analyses in normotensive or hypertensive individuals.Plasma tHcy level is strongly and independently correlated with arterial stiffness measured as cf-PWV only in hypertensive subjects. Thus, hypertension is a major link between tHcy and aortic arterial stiffness. Recent studies have reported that elevated tHcy may be deleterious in individuals with hypertension or other risk factors , with which it acts synergistically to exert a multiplicative effect on cardiovascular disease (CVD) risk The pathological mechanisms underlying the interaction between hypertension and hyperhomocysteinemia in CVD and cerebrovascular diseases are not fully understood but may include their similar effects on the vascular system or oxidative stress The purpose of this study was to investigate the following in a large community-based sample from China: (1) relationship between hypertension complicated by hyperhomocysteinemia with increased arterial stiffness and wave reflection; (2) relationship between tHcy and peripheral, central arterial blood pressure (BP); (3) influence of plasma tHcy and other risk factors on arterial stiffness and wave reflection by measuring pulse wave velocity (PWV) and augmentation index (AIx) in hypertensive and normotensive individuals.This community-based cross-sectional study was carried out in the Pingguoyuan area of Shijingshan district, Beijing, China. A total of 1859 community residents reporting for a health examination in two communities were randomly recruited to the study. We excluded 31 individuals with severe systemic diseases including collagenosis, endocrine and metabolic diseases other than diabetes mellitus (DM), inflammation, neoplastic disease, or severe liver or renal disease. We attempted to assess arterial stiffness in the remaining 1828 subjects; however, adequate tonometry was either not attempted or not obtained in 86 participants. Another 37 participants were excluded because of missing data . An additional 25 participants were excluded because of missing covariate data needed for multivariable analysis. The remaining 1680 participants were eligible for analysis. This study was approved by the ethics committee of People’s Liberation Army General Hospital, and written informed consent was obtained from all participants.All participants were interviewed and completed a standardized questionnaire that included questions about prevalent diseases, family history of CVD, medication use, and lifestyle factors. Physical examinations and interviews were carried out by trained medical doctors. Self-reported smoking status was categorized as current, former, or never. Height and weight were measured in a standing position without shoes. Body mass index was calculated as weight in kilograms divided by the square of height in meters. Peripheral BP was measured two times in the right brachial artery; measurements were taken at 5-min intervals, and the average systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were used for analysis and further calculation. Mean arterial blood pressure (MAP) was calculated as DBP+[1/3 × (SBP – DBP)]. Hypertension was defined exclusively by the peripheral BP measurement.All subjects underwent full laboratory evaluation . After a 12-h fasting , blood was collected from the antecubital vein between 8 a.m. and 10 a.m., with the subject in a sitting position.2) = 175 × standard creatinine (mg/dl)−1.234 × age (year)−0.179 × . Plasma tHcy level was determined by high-performance chromatography with fluorometric detection, with a lower limit of detection of 0.5 µmol/l, and inter-assay variation of 4.1%.Biochemical variables of all blood specimens were measured with an automated analyzer  in the same laboratory, following the criteria of the World Health Organization Lipid Reference Laboratories. All participants without a history of DM underwent the standard 75-g oral glucose tolerance test (OGTT). The estimated glomerular filtration rate (eGFR) was calculated using the Chinese modification of diet in renal disease (C-MDRD) equation Measurement of arterial properties was conducted in the morning, in a quiet environment, at a stable temperature. The subjects were asked to abstain from caffeine, smoking, alcohol, and taking vasoactive medication for at least 12 h before this assessment.Central arterial BP and wave reflection were assessed using a SphygmoCor pulse wave analysis system . The probe was placed at the site of the strongest radial artery pulse to record a stable pulse wave. After 20 sequential waveforms were acquired, a validated, generalized transfer function was used to generate the corresponding central aortic pressure waveform. The central blood pressures  were automatically calculated. Augmentation indices of the central waveform were measured as indices of wave reflection; AIx  was defined as augmented pressure divided by pulse pressure and expressed as a percentage After participants rested in the supine position for 5 to 10 min, PWV was determined using a Complior SP device , which allows online pulse wave recording and automatic calculation of PWV. Two transducers were used: one positioned at the base of the neck over the common carotid artery, and the other over the femoral artery. Two different pulse waves were obtained simultaneously at two sites, the measurement was repeated over 10 different cardiac cycles, and the mean value was used for the final analysis. PWV was calculated from the pulse transit time and distance traveled by the pulse between the two recording sites (measured on the surface of the body in meters), according to the following formula: PWV (m/s) = distance (m)/transit time (s) Essential hypertension was defined as (i) systolic blood pressure (SBP) ≥140 mmHg, and/or (ii) diastolic blood pressure (DBP) ≥90 mmHg, and/or (iii) self-reported use of antihypertensive medication A subject with any of the following was considered to have DM: (i) fasting venous blood glucose ≥7.0 mmol/l, (ii) 2-h plasma glucose ≥11.1 mmol/l during an OGTT, (iii) symptoms of hyperglycemia and casual plasma glucose ≥11.1 mmol/l, or (iv) the subject was taking antihyperglycemic medication Results are expressed as percentages for dichotomous variables, and mean±SD or median (interquartile range) for continuous variables; tHcy level and other biomarkers were normalized by natural logarithm transformation, as necessary. Plasma tHcy levels were categorized as quartile 1 , quartile 2 , quartile 3 , and quartile 4 . Quartiles 1 to 3 were defined as low tHcy (<21.6 µmol/l), and quartile 4 was defined as high tHcy (≥21.6 µmol/l). Arterial properties included in the analyses were brachial BP, central arterial BP, cf-PWV, and heart rate-corrected AIx. Subjects were classified into four groups according to BP (hypertensive vs. normotensive) and tHcy level (<21.6 vs. ≥21.6 µmol/l).The four groups were compared by one-way ANOVA test (continuous variables) and chi-square test . A general linear model univariate analysis post hoc multiple comparison with Bonferroni’s correction was used to compare cf-PWV and AIx among the groups after adjustment for covariates. Pearson and partial correlation coefficients were used to determine the relationship between tHcy and BP in normotensive and hypertensive subjects after adjusting for age, gender, body mass index, ratio of total to high-density lipoprotein (HDL) cholesterol, blood glucose, current cigarette smoking, eGFR, and prior diagnosis of CVD. Independent determinants of cf-PWV and central AIx were identified by multiple linear stepwise regression analysis .All analyses were conducted using SPSS software for Windows, version 13.0J . P values <0.05 were considered statistical significant.Of the 1680 subjects included in the analysis, 709 were male (42.2%), and the mean age was 61.55±10.90 years (range 24–96 years). Of these, 847 had hypertension (50.4%), 362 had DM (21.5%), and 420 were current smokers (25.0%). The median value of plasma tHcy concentration was 17.2 µmol/l.Participants were divided into four groups based on blood pressure and plasma tHcy level: 672 were normotensive with low tHcy (<21.6 µmol/l), 161 were normotensive and high tHcy (≥21.6 µmol/l), 587 were hypertensive with low tHcy, and 260 were hypertensive with high tHcy . All CVDPeripheral blood pressures  and central arterial blood pressures  did not differ significantly according to tHcy level among either normotensive or hypertensive subjects . Among nIn bivariate analyses, correlations between plasma tHcy and BP parameters were significant only among normotensive subjects; no statistically significant correlations were observed among hypertensive individuals . In normTo determine independent predictors of cf-PWV, multiple regression analysis was performed using the stepwise procedure . The anaPlasma tHcy was not an independent predictor of central AIx among either normotensive or hypertensive individuals . Gender,Several important findings emerged from our study evaluating central arterial BP and indices of arterial stiffness in a large community-based sample from China. First, we detected a significant positive association between plasma tHcy and arterial stiffness, measured as cf-PWV (aortic PWV), only among hypertensive subjects. Second, plasma tHcy was not an independent predictor of central AIx, and tHcy concentration was not associated with peripheral or central BP. To the best of our knowledge, this is the first study to include both normotensive and hypertensive individuals to evaluate the relationships between circulating tHcy level and BP and arterial stiffness.The main finding of this study was that plasma tHcy is positively associated with cf-PWV only in hypertension. This finding suggests a potential role for tHcy in arterial wall remodeling in hypertension, leading to arterial stiffness. PWV is a known marker of arterial stiffness and indicator of vascular damage The mechanisms underlying the relationship between Hcy and arterial stiffness are not entirely clear but may include endothelial dysfunction The second important finding of this study is that tHcy was not independently associated with central AIx in hypertension or normotension. These results are consistent with those reported by the B-PROOF study Finally, this study did not detect an association between tHcy concentration and peripheral or central BP. The association of tHcy levels with high BP has been reported in some but not all prior studies. The Framingham Heart Study did not find a relationship between baseline tHcy with hypertension incidence or with longitudinal blood pressure progression There are several potential limitations of our study. First, all participants were from Beijing; therefore, conclusions drawn from our study cannot be generalized to other ethnic groups. Second, because of the cross-sectional design of our study, we have no direct evidence for a cause–effect relationship. The role of elevated tHcy in increased aortic stiffness requires further investigation by interventional prospective studies. Third, the multiple comparisons may increase the likelihood of type I error. To address this limitation, Bonferroni procedure was used for correction of multiple testing.In conclusion, we found that plasma tHcy level is independently associated with arterial stiffness  in hypertensive subjects only. This study raises the possibility that reducing plasma tHcy may decrease arterial stiffness in hypertensive individuals.


The concept of control of chronic rhinosinusitis (CRS) has only recently been introduced by the EPOS expert panel following the concept of control in allergic rhinitis and asthma. The aim of this study was to examine the degree of control of CRS at a mean period of 3-5 years after endoscopic sinus surgery (ESS) and to correlate the new criteria of control of CRS to VAS  for sinonasal symptoms and the SNOT-22 questionnaire. Another aim was to find out if patients changed from controlled to partly controlled or uncontrolled following nasal endoscopy.All adult patients who had a bilateral ESS procedure for bilateral inflammatory sinonasal disease at the University Hospitals Leuven between January 2008 and December 2010 were contacted by classic mail. They were asked to complete a survey including sinonasal symptoms according to EPOS criteria, VAS scores, SNOT-22 and SF-36 questionnaires and general questions regarding asthma, smoking habits, allergies and current medication intake. They were invited to the out-patient clinic for nasal endoscopy.The response rate was 54.5% (n = 297). 19.8% were well controlled, 39.3% partly and 40.9% uncontrolled. There was no significant difference between the CRSwNP and CRSsNP groups. These results only depended on the self-reported symptoms, without taking into consideration endoscopic examination. Sixty patients underwent endoscopic examination of which 10% were controlled, 30% partly and 60% uncontrolled. The results of the examination showed that 18 patients had signs of recurrence (30%). In 77.8%, the endoscopic findings did not change the degree of control as defined by the questionnaire. 16.7% changed from partly to uncontrolled and 5.6% from controlled to partly controlled. The average global VAS scores of the controlled, partly and uncontrolled groups were 0.8, 2.7 and 5.7 respectively. The average SNOT-22 scores were 9.7, 22.2 and 44.8 respectively.The percentage of partly and uncontrolled CRS greatly overshadows the 19.8% of well controlled CRS. In 77.8% of cases, endoscopic investigation did not change the degree of self-reported control. The sensitivity of the EPOS questionnaire is 94.4% and the specificity is 14.3%. Therefore, endoscopy is useful in lowering the number of false positives. However, as the goal of treatment is the control of symptoms, the value of nasal endoscopy in defining control is one that is debatable.


Arterial blood gas (ABG) analysis is routinely performed for sick patients but is fraught with complications, is painful, and is technically demanding.2, pO2, and bicarbonate levels in sick patients with cardiopulmonary disorders in the valley of Kashmir in the Indian subcontinent, so as to use venous gas analysis instead of arterial for assessment of patients.To ascertain agreement between the arterial and peripheral venous measurement of pH, pCOSher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, a 650-bedded tertiary care hospital in North India located at an altitude of 1584 m.2) saturation. Data were analyzed using Pearson correlation and bias (Bland Altman) methods.One hundred patients who required ABG analysis were admitted. Peripheral venous blood was drawn within 5 min of an ABG measurement, and the samples analyzed immediately on a point of care automated ABG analyzer. Finger pulse oximetry was used to obtain oxygen  although the arterial saturation and finger oximetry revealed a good degree of agreement with clinically acceptable bias.The venous measurements of pH, pCOPeripheral venous blood gas assessment in conjunction with finger pulse oximetry can obviate the routine use of arterial puncture in patients requiring ABG analysis. Acid base analysis is an essential tool in acute care medicine, yielding valuable information about a diverse group of disorders. Arterial blood gas (ABG) is the gold standard method for acquiring this information. Although used to evaluate many respiratory and metabolic conditions, ABG analysis is not without drawbacks. Blood sample for ABG is obtained by arterial puncture. The risks associated with this procedure include pain, hematoma, aneurysm formation, thrombosis or embolization, needle stick injuries to health care providers, and sometimes even reflex sympathetic dystrophy.–4 The prvia an arterial puncture into a heparinized syringe. Simultaneously, venous blood in another heparinized syringe was also sampled via antecubital vein without application of any tourniquet. Venous and arterial blood samples were taken within 5-min of each other. In addition, the measurement of oxygen saturation (SpO2) was obtained from a finger pulse oximeter (Nonin pulse oximeter). Blood was analyzed immediately for values of acid-base, oxygenation and electrolyte status. The ABG and VBG analyzes were run on an immunoradiometric assay point-of-care blood gas analyzer that is operated by the Department of Biochemistry . The assay is routinely used for analyzing blood gases in patients, and its accuracy is validated daily.This prospective study was conducted in the Department of Internal and Pulmonary Medicine of Sher-i-Kashmir Institute of Medical Sciences, a 650-bedded tertiary care university hospital facility in the Northern Indian State of Jammu and Kashmir. A total of 100 randomly selected patients, who were adjudged to require ABG analysis by the treating physician, were enrolled. The patients included 63 cases admitted with chronic obstructive pulmonary disease (COPD) and exacerbation, 20 cases with community acquired pneumonia/sepsis, 11 cases with congestive heart failure, 5 cases with interstitial lung disease, 3 cases with post-tubercular fibrosis, and 1 patient with obstructive sleep apnea. All patients had arterial blood sampled which was drawn P value of <0.05 for means and Pearson r was considered significant. Informed consent for participation in the study was obtained from all the participants, and the study was approved by the Institute Postgraduate and Ethics Committee.All the documented data were analyzed using Med Cal Statistical Software version 10.4). The mean and 95% confidence intervals were calculated for each arterial and venous variable and for difference between them. The strength of the relationship between the arterial and venous gas values was assessed with the Pearson product–moment correlation coefficient test. The Bland–Altman limits of agreement were determined by plotting the difference between two paired values  against their mean, thus creating a bias plot. The 95% limits of agreement represents the mean difference between each pair of venous and arterial values ±1.96 SD, and they estimate by how much a venous value is likely to differ from the criterion standard, the arterial value. This is the accepted method for assessing the agreement between two tests and represents a clinically relevant measure of comparison..4. The m A P valu2, venous pCO2, arterial and venous bicarbonate, and arterial and venous pO2. In addition, the oxygen saturation as determined by ABG analysis (SaO2) and by digital pulse oximetry (SpO2) is depicted in r = 0.88, 95% confidence limits of r = 0.82-0.92, P < 0.001). There was a strong correlation between the arterial and venous pCO2, bicarbonate values , and pO2 levels . A significant correlation was also observed between SaO2 and SpO2.A total of 100 patients who required ABG analysis were enrolled in this study, and 200 sets of blood gas values were analyzed. The mean age of the subjects was 44 ± 19.63 and the patients included 63 males and 37 females. 2 was –4.05 , and in bicarbonate levels 086 . Although the arterial and venous pO2 were significantly correlated with each other , the bias between the two was –22.34 . However, the bias between measured oxygen saturation (SaO2) and digital pulse oximetry (SpO2) was low , these results thus demonstrate an acceptably low bias with excellent agreement between the arterial and peripheral venous values.Bland Altman bias plots of the average of the arterial and venous measurements, and the difference between them are depicted in Figures 2, and bicarbonate level with a high degree of agreement and clinically acceptable difference on Bland Altman difference plotting. Although there is a significant correlation between the arterial and venous measurements of pO2 level, the difference of -22.34 ± 15.23 is not clinically acceptable enough to support uniform usage of venous pO2 instead of arterial measurements in clinical situations. However, SaO2 and SpO2 were highly correlated and demonstrated excellent agreement and a clinically acceptable difference (-1.44 ± 8.82). Caution is required for using correlation coefficients to describe the agreement between two quantitative variables. A high correlation is definitely required but does not necessarily imply agreement, for which the line of agreement should be a 45° (x = y) line. Bland Altman plots are used instead to describe the agreement between two quantitative variables, the difference of the paired two observations plotted against the mean of two measurements and 95% of the data points recommended to lie within ±2D of the mean difference.[Our data have demonstrated a high level of correlation between the arterial and venous measurements of pH, pCOfference.2 content.[et al.[Several researchers have looked at the possibility of using the venous or capillary data instead of ABGs and have reported differing results. Gambino compared “arterialized” capillary blood with arterial samples from the brachial artery in patients undergoing pulmonary function tests and found no difference in pH and CO content. Subseque content. examinedt.[et al. emphasizt.[et al.17 while t.[et al. have rest.[et al.19 and vet.[et al.2 among supine, sitting, and standing positions in asymptomatic patients of different age-groups or in patients with COAD[2 in patients with COPD, body position should be noted for ABG measurements and should be kept constant for valid comparison of serial measurements.[All the samples of the patients in our study were taken in the supine position. In a study comparing the effect of various body positions on the ABGs, there were essentially no significant differences in pOwith COAD even as urements.2 of moist inspired gas is (380-47) + 0.2093 = 70 mmHg . In spite of hypoxia associated with high altitude, some 15 million people live at elevations over 3050 m depicting a remarkable degree of acclimatization at these altitudes. The permanent residents who live at these altitudes have a degree of hyperventilation that compensates for the degree of hypoxia, but at the expense of decreased PCO2. The hyperventilation results from the hypoxic stimulation of the peripheral chemoreceptors. Graham and Houston[2 retention) tolerate high altitudes of up to 2000 m well, complaining of fatigue only.[The majority of our patients had lung disorders with COPD forming the commonest condition. Earlier COPD patients on mechanical ventilation and thosd Houston have repgue only.25 This e2, and bicarbonate values with clinically acceptable differences between the arterial and the venous values. Although there is a high correlation between the arterial and venous pO2 values, the difference is large for total clinical agreement and thus suggesting that one cannot be swapped for the other without loss of important detail. However, SaO2 and SpO2 have high degree of correlation and high degree of agreement with clinically acceptable difference. Thus if venous pH is combined with routine finger pulse oximetry, the ABG analysis might be minimized to a great degree in cardiopulmonary patients. Additional studies may be necessary to address the feasibility and reproducibility of such testing.We used peripheral venous blood in our study for VBG assessment. While analysis of central venous blood has been previously used for data comparison of VBG versus ABG1526 samp1557


The aim of this study was to see how acupressure at distal acupuncture points of a specific meridian affects heart rate variability (HRV) and oxygenation of the trapezius muscle. Forty-one female participants were randomly allocated to three groups. Subjects in the Stomach Meridian acupuncture point (ST) group received acupressure at ST 34, ST 36, and ST 41, subjects in the Large Intestinal Meridian acupuncture point (LI) group received acupressure at LI 4, LI 10, and LI 11, and subjects in the control group did not receive any stimuli. HRV and oxygenation of the trapezius muscles were measured. The high frequency components of HRV in the control and LI groups tended to be higher than those in the ST group. Total hemoglobin in the control and LI groups eventually reached significantly higher levels than in the ST group. While oxyhemoglobin (ΔO Distal traditional acupuncture points, “Hegu” LI 4), “Shousanli” LI 10), and “Quchi” (LI 11), are contained in the Large Intestinal Meridian and have been suggested to be the particular points for improving neck-shoulder-arm disorder. Chronic neck and shoulder pain is a very common symptom especially in females. Subjects with neck and shoulder pain showed impaired regulation of microcirculation in the trapezius muscle 0, and “Q and impa, “ShousaWe hypothesized that distal acupuncture points in each meridian would have specific effects, thereby differently influencing autonomic nervous activity and muscle blood flow and oxygenation. The aim of the present study was to see how acupressure at distal acupuncture points of a specific meridian affects heart rate variability (HRV) and oxygenation of the trapezius muscle in healthy female subjects.This study used a single-blind, randomized controlled trial. After receiving approval from the Nagoya Gakuin University Board of Ethics and obtaining written informed consent, 41 female participants were recruited for the present study. The subjects were randomly allocated to three groups. Exclusion criteria were conditions such as neck or shoulder pain, cardiovascular or neurological disease, diabetes, menstruation, or administration of sedatives, analgesics, or other medication.Subjects in the Stomach Meridian acupuncture point (ST) group received acupressure at three distal acupuncture points, “Liangqiu” (ST 34), “Zusanli” (ST 36), and “Jiexi” (ST 41) , subjectμM of oxyhemoglobin (ΔO2Hb), deoxyhemoglobin (ΔHHb), and total hemoglobin (ΔTHb = ΔO2Hb + ΔHHb) from baseline [All measurements were performed in the afternoon. Oxygenation of the trapezius muscles was measured using near-infrared spectroscopy (NIRS)  bilaterally. Probes were placed at the transverse section on both sides of the upper trapezius muscles at the midpoint between the spinous process of the seventh cervical vertebra and the acromion. Measurements were given as concentration change in baseline , 9. The P value < 0.05 was considered statistically significant.For data evaluation, the areas under the curve (AUC) of NIRS and HRV values were measured for the first rest period, each set of acupressure, and the second rest period , 10. Dat2Hb in the control and LI groups did not change, ΔO2Hb in the ST significantly decreased temporarily and returned to the baseline level during the acupressure manipulation  has been used as a biomarker of autonomic nervous system function. HRV is a reliable method to obtain information on sympathetic and parasympathetic contributions to heart rate, and several studies have shown that pain increases sympathetic activity . FrequenIn the present study, the HF component of HRV in the ST group was lower than in the other groups and the LF/HF ratio of HRV had a tendency to increase in the ST group in contrast to the other groups, which means that sympathetic nervous activity increased in the ST group. We thus believe that acupressure at three distal acupuncture points in the Stomach Meridian, “Liangqiu” (ST 34), “Zusanli” (ST 36), and “Jiexi” (ST 41), led to sympathetic nervous activation. However, there is a possibility that stimulation caused by acupressure per se might have induced a sympathomimetic effect. In contrast, the HF component in the LI group was higher than that in the ST group and the LF/HF ratio in the LI group did not tend to increase, as observed in the control group, which means that parasympathetic nervous activity increased in the LI group. We thus believe that acupressure at three distal acupuncture points in the Large Intestinal Meridian, “Hegu” (LI 4), “Shousanli” (LI 10), and “Quchi” (LI 11), led to parasympathetic nervous activation in spite of acupressure stimuli.2Hb in the ST group significantly decreased temporarily during acupressure manipulation, while ΔO2Hb in the control and LI groups did not change. These data indicate that these three distal acupuncture points in the Stomach Meridian did not influence blood flow of the trapezius muscle but rather reduced oxygenation of the muscle. In contrast, these three distal acupuncture points in the Large Intestinal Meridian increased blood flow of the trapezius muscle and maintained oxygenation of the muscle.ΔTHb in the control and LI groups eventually reached significantly higher levels than in the ST group. Furthermore, ΔOAcupuncture is an important component of traditional Chinese medicine . Over loThere is a limitation to the present study. The dermatomes of the thoracic region of the upper limb have their neuronal cell bodies in the same dorsal root ganglia and synapse on the same second order neurons in the spinal cord segments as the general visceral sensory fibers from the heart. The responses induced by acupuncture-like stimulation are reflexes in which cutaneous and/or muscle somatic afferent nerve fibers of the afferent limb, autonomic efferent nerve fibers of the efferent limb, and the spinal cord and/or the brain stem of the reflex centers work in a complex way . Thus, sIn conclusion, acupressure at three distal acupuncture points, LI 4, LI 10, and LI 11, maintained higher level of the HF components of HRV and blood flow and oxygenation of the trapezius muscle, compared with acupressure at three distal acupuncture points, ST 34, ST 36, and ST 41.


We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).We examined 491 patients with systolic CHF . Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up  after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes. Endothelin-1 (ET-1) is a potent vasoconstrictor peptide secreted mainly by endothelial cells It is presumed that the assessment of circulating ET-1 might represent a marker of disease progression and prognosis in patients with CHF Increased circulating levels of ET-1 have been demonstrated in patients with CHF We hypothesized that measurement of plasma CT-proET-1 would carry additional prognostic value in a population of patients with CHF, beyond other generally accepted prognostic markers, including clinical measures of CHF severity and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP).We tested the aforementioned hypothesis in 491 patients with systolic CHF enrolled at 4 European centers: Verona , Wroclaw , London , and Athens . The criteria for inclusion in our study were: 1) a ≥3 months documented history of CHF; 2) left ventricular ejection fraction (LVEF) ≤45% as assessed by echocardiography; 3) clinical stability and unchanged medications for at least one month preceding the study. The following exclusion criteria applied: a) revascularisation and/or acute coronary syndrome within 3 months preceding the study; b) circulatory decompensation within 1 month preceding the study; 3) lack of informed written consent. Inclusion and exclusion criteria were uniform in all participating centers.In 11 additional cases , plasma CT-proET-1 levels were not available for technical reasons. Clinical characteristics of all studied patients are presented in In all patients with CHF, venous blood samples were taken in the morning following an overnight fast and after supine rest of at least 15 min. After centrifugation, plasma was collected and frozen at −80°C until being analysed. Plasma levels of CT-proET-1 (pmol/L) were assessed using a chemiluminescence sandwich immunoassay that used 2 polyclonal antibodies to amino acids 168–212 of pre-proET-1  as previously described Plasma levels of NT-proBNP (pg/mL) were determined by an electrochemiluminescence immunoassay on the Elecsys 1010/2010 System .Patients were regularly seen by the study investigators with a follow-up duration of at least 12 months in all who survived. Information regarding survival was obtained directly from patients or their relatives, from the CHF clinic database, or from the hospital system. No patient was lost to follow-up. The primary end-point for the analysis was 12-month cardiovascular mortality. Cardiovascular mortality was defined as death due to myocardial infarction, sudden cardiac death, due to the progression of CHF, or death related to strokes.2 test, or one-way ANOVA as appropriate. Plasma CT-proET-1, NT-proBNP and serum creatinine had skewed distributions and were therefore log10 transformed before analyses. They were expressed as medians with interquartile ranges (IQR). The inter-group differences were tested using the Mann-Whitney U test, the Pearson χ2 test, or the Kruskal-Wallis test as appropriate. Spearman's rank correlation and multivariable regression analyses using ordinary least squares were applied to establish variables plasma CT-proET-1 levels in patients with CHF.Continuous variables were expressed as mean ± standard deviation (SD). The inter-group differences were tested using Student's t-test, the χ2  are given. The predictive value of each model was assessed by the model likelihood ratio χ2 statistic. In addition, to describe and compare the predictive performance of each multivariable model, the concordance index (c index) was calculated using a Harrel's method 10 transformation.The associations between analysed variables and survival were assessed using Cox proportional hazards analysis (both single predictor and multivariable models). In the multivariable analyses, we included age, New York Heart Association (NYHA) class, LVEF, and creatinine, as well as plasma levels of neurohormonal markers . NYHA class was included as a categorized variable. Due to the low number of patients in NYHA class I and a similar mortality rate in NYHA classes I and II, both groups were combined and were used as reference group. The assumptions of proportional hazards were tested for all the covariates. For continuous variables, hazard ratios (HR) per interquartile range (IQR) are reported (standardized HR). 95% confidence intervals (CI) for risk factors and significance levels for χhttp://www.r-project.org). All authors had full access to the data and took responsibility for the integrity and accuracy of the analyses.In order to illustrate the effect of plasma CT-proET-1 on 12-month cardiovascular mortality rates, Kaplan-Meier curves for cumulative survival were constructed. For continuous variables, subsequent quartiles were used. Differences in survival rates were tested using the Cox-Mantel log-rank test. Receiver-operating characteristic (ROC) curves for prediction of 12-month mortality were constructed and the area under the curve (AUC) with a 95% confidence interval were calculated. To further contrast the prognostic accuracy of biomarkers, statistical comparison of ROC curves was performed using the method of paired ROC curves described by Hanley and McNeil Plasma levels of CT-proET1 were evaluated in 491 patients with systolic CHF. For the additional 11 samples , valid CT-proET-1 levels could not be determined due to a complete degradation. The median level of plasma CT-proET-1 was 63.6 pmol/L (IQR: 49.5–87.1 pmol/L).10) correlated positively with age (r = 0.33), serum creatinine  and plasma NT-proBNP . In single predictor regression analyses, plasma CT-proET-1 (log10) was inversely related to hemoglobin level , BMI  and LVEF . Higher plasma CT-proET-1 levels were found in patients with ischemic CHF in comparison to subjects with non-ischemic CHF (p = 0.0002).Median levels of plasma CT-proET-1 increased with increasing NYHA class . In sing10) was related significantly to NYHA class , serum creatinine  and plasma NT-proBNP . The model explained 32.9% (adjusted R2) of total variance of plasma CT-proET-1 in patients with CHF.In a multivariable regression model based on all parameters included in univariate models, plasma CT-proET-1  deaths, and 12- month mortality rate was 14%,. Mean time to death was 139±110 days . The proportionality assumption and the assumption of a log-linear relationship between the prognosticators and the hazard function were fulfilled for all tested variables.In single predictor Cox proportional-hazards models, the following variables were related to increased 12-month cardiovascular mortality in patients with CHF : high plTwelve-month survival rates were 93% (95% CI: 86–96%), 93% (95% CI: 86–96%), 90% (95% CI: 83–93%) and 68% (95% CI: 58–75%) for those patients with plasma CT-proET-1 in ascending quartiles . Whilst In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for plasma CT-proET-1 and plasma NT-proBNP (AUC = 0.724 (CI 0.682–0.763) and 0.751 (CI 0.710–0.788), respectively; p>0.4).In multivariable models that included LVEF, NYHA, age, NT-proBNP and creatinine, high plasma CT-proET-1 remained an independent predictor of increased 12-month cardiovascular mortality in patients with CHF .2 statistic. A model adjusted for LVEF, age, serum creatinine, and NYHA class was defined as a base model. This model was compared with models including CT-proET-1, NT-proBNP or both biomarkers. Using the likelihood ratio χ2 test for nested models, CT-proET-1 and NT-proBNP were shown to add a significant prognostic value to the base model . CT-proET-1 added prognostic value to the base model including NT-proBNP (p = 0.02), and NT-proBNP added predictive value to a model that includes the variables of the base model plus CT-proET-1 (p = 0.045)  .Here we demonstrate that high plasma CT-proET-1 predicts increased 12-month cardiovascular mortality in patients with CHF, independently of clinical disease severity and plasma NT-proBNP.The ET-1 system plays a crucial role in the pathophysiology of CHF So far, the prognostic value of plasma CT-proET-1 measurements has been proven only in patients during the acute phase of myocardial infarction In some analyses, high plasma big ET-1 Some limitations of this analysis deserve discussion. First, the study population consisted mainly of male patients, and it is unknown whether these findings can be directly extrapolated to female patients. Moreover, the number of patients in NYHA class I was relatively small (9%) and novel surrogate biomarkers usually perform better in high-risk populations than in low-risk subjects or unselected populations. Finally, the study group represents a population with a high risk of cardiovascular events. These facts have to be kept in mind when the data are being interpreted.Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF, independently of disease severity and plasma NT-proBNP.