Psychiatric comorbidities are prevalent in patients with chronic somatic disorders such as asthma. But, there is no clear evidence regarding the effect of atopic status and the type of sensitized allergen on emotional status. The aim of the present study was to investigate the effects of house dust mites and pollen allergies on emotional status, asthma control and the quality of life in patients with atopic asthma.The study included 174 consecutive patients who were diagnosed with asthma accoring to the GINA criteria and who did not receive therapy for their allergy. All patients underwent a skin prick test. The asthma control, quality of life, and emotional status were evaluated using the ACT (asthma control test), AQLQ , and HAD .Atopy was detected in 134 (78.7%) patients. Of those patients: 58 (33.3%) had anxiety and 83 (47.7%) had depression. There was no relationship between emotional status, atopic status, and the type of indoor/outdoor allergen. Furthermore, there was no relationship between atopy and asthma severity, asthma control, and the quality of life. The anxiety and depression scores were significantly higher and the quality of life scores lower in the uncontrolled asthma group. The ACT and AQLQ scores were also lower in the anxiety and depression groups.It was concluded that anxiety and depression are prevalent in patients with uncontrolled asthma, and atopic status did not affect the scores in ACT, AQLQ, and emotional status tests. Asthma is a chronic health problem that encompasses the patient’s entire lifetime, and causes significant mental and social problems in addition to physical symptoms. It is; therefore, considerably important to evaluate the quality of life of the patients in addition to the symptoms in order to gather full information about the health status of the patients .Psychiatric comorbidities are frequently observed in patients suffering from chronic somatic disorders. These psychiatric comorbidities have a significant negative impact on the quality of life of the patients . EmotionThe allergens are well-known to cause asthma exacerbations and sustained symptoms ; howeverThe secondary aim of the present study was to assess the emotional status of patients with asthma. Main purpose of our study was to investigate the effects of house dust mites and pollen allergies on emotional status, asthma control and the quality of life in patients with atopic asthma.The consecutive 174 patients, who were new diagnosed with asthma according to GINA criteria in Sakarya University Hospital (Turkey) in March-September 2012 period and who have not received at least last one month an antihistamines and immunotherapy for allergy and any inhaled or oral therapy for asthma were included in the present study. The patients who were receiving a therapy for psychiatric disease or those with a chronic disorder  that could affect emotional status were excluded from the study.A detailed medical history was obtained, and all patients underwent physical examinations. All pulmonary function tests were performed by the same technician on the SpiroAnalyser ST-300 instrument. The severity of asthma was determined based on Global Initiative for Asthma (GINA) criteria . The patThe patients were administered a 5-item questionnaire assessing their asthma symptoms, use of rescue medications, and the impact of asthma on daily life . In asthThe AQLQ assessed the scores of the patients regarding their symptoms (12 questions), restriction of activity (11 questions), emotional function (5 questions), and environmental exposure (4 questions). The total score was recorded as the average of the scores in 32 questions . The ansThe assessment of emotional status was measured by using the HAD questionnaire. The Hospital Anxiety and Depression Scale was developed in 1983 by the Zigmond and Snaith and the validity and reliability were performed . It inclThe purpose of the scale is not to diagnose, but to determine the risk group by scanning anxiety and depression in physically ill patients in a short amount of time. The scale can also be used in the follow up of changes in the patient’s emotional state. Although the scale uses the word “hospital”, it can also be used in the field or in a study performed in outpatient settings. To the aim was to minimize the effects of the existing somatic disease on the scale results in the HAD scale.For this reason, it does not include any physical signs. In the preparation of scoring, “0 to 1” was recognized as normal, “2” was recognized as borderline symptomatic, and “3” was recognized as having prominent symptoms. It has been proven that the HAD scale is a useful assessment tool, and its score range provides results so as to minimize the false-positive and false-negative data . It has Turkish adaptation study of HAD scala has been made by Aydemir et al. According to this study, for the anxiety sub-scale cut-off score has been found 10 and more, and depression subscale cut-off score has been found 7 and more . MeasureA skin test  was performed using 20 different aeroallergens in order to determine atopic status of the patients. The test media contained a mixture of Dermatofagoides farinea, D. pteronyssinus, storage mite, cockroaches, latex, hair, fungi, wheat, oak, olive, trees, mixture of weeds, cat hair, dog hair, grass mixture, and grass-wheat mixture. Histamine was used as a positive control and saline was used as a negative control. The test site was evaluated after 15 minutes, and the result was considered positive if the edema was more than 3 mm in diameter. The house dust mites were considered indoor allergen, and pollens were considered outdoor allergen .The SPSS for Windows 21.0 (IBM) software package was used in the statistical analysis of the study. In the present study, the continuous variables were expressed with mean value, standard deviation, maximum and minimum values. The Shapiro-Wilk test was used for the normality test of continuous variables. Normally distributed continuous variables were compared by means of variables were evaluated with samples t test, nonparametric variables between the two groups were made by Mann–Whitney U test, categorical variables were compared by Chi square test.A total of 174 patients were included in the study. The characteristics of the patients are presented in table The skin prick test was found to be positive for at least one allergen in 137 patients (78.7%), with 45 patients (25.9%) having only a pollen allergy, 32 patients (18.4%) having only a mite allergy, and 60 patients (34.5%) having both pollen and mite allergies. In total, 105 patients (60.3%) had pollen allergies and 92 patients (52.9%) had mite allergies.The mean anxiety score was 8.07 + 4.42, the mean depression score was 7.00 + 4.54, and the mean HAD score was 15.07 + 7.97. When the cutoff for anxiety and depression was taken as 10 and 7, respectively, 58 patients (33.3%) had anxiety, and 83 patients (47.7%) had depression.The mean ACT score was 18.32 + 5.1. Of the patients, 19 (10.9%) had fully controlled disease, 65 (32.4%) had controlled disease, 78 (44.8%) had partially controlled disease, and 12 (6.9%) had uncontrolled disease. When the cut-off for asthma control was taken as 20, 89 patients (51.1%) had uncontrolled asthma, and 85 patients (48.9%) had controlled asthma.The mean total AQLQ score was 4.30 + 1.24, the mean symptom score was 4.76 + 1.38, the mean activity score was 4.04 + 1.27, the mean emotional score was 4.50 + 1.57, and the mean environmental exposure score was 3.61 + 1.64.There was no significant difference between patients who had versus who did not have mite and pollen allergy in terms of asthma control, quality of life, anxiety, and depression level Table .Table 2Of the patients, 105 had pollen allergies, 92 had mite allergies, and 60 had both mite and pollen allergies. When analyzed by the type of allergens, there was no significant difference in terms of asthma control, quality of life, anxiety, and depression level Table .Table 3Independent from the type of allergen, the patients with an anxiety score greater than 10 and depression score greater than 7 had significantly worse asthma control and lower quality of life Table .Table 4Atopic patients did not significantly differ in terms of spirometric measurements, BMI, age of asthma, and number of exacerbations; however, prick test positivity was significantly higher among male patients with rhinitis Table .Table 5The general characteristics and spirometric measurements were comparable between the two groups. The number of episodes was the only parameter that differed between patients with and without anxiety (p = 0.039), while the number of episodes (p = 0.002), and asthma severity (p = 0.013), were the two parameters that significantly differed between patients with and without depression.The patients with uncontrolled asthma achieved significantly worse scores in emotional status and quality of life domains Table .Table 6The present study evaluated the effects of the atopic trait and the type of allergy on the level of anxiety, depression, quality of life, and asthma control. When atopic patients with positive skin prick test were compared to non-atopic patients, no significant difference was found in terms of anxiety and depression scores, asthma control, and quality of life. There was also no significant difference in terms of the types of pollen and mite allergies.The exposure to allergens is a well-established cause of asthma episodes and sustained symptoms in atopic patients ,20. In tThe major strength of the present study was its cross-sectional design and inclusion of patients with a recent diagnosis that have not received a previous allergic therapy. In studies that are based on the review of patient charts, treatment effect appears as a confounder, in that, therapy may have minimized the effects of allergy. Consequently, the studies that evaluated the effects of therapy have shown improvement in the quality of life score after the therapy in comparison to pre-treatment scores . AnotherThere are a very limited number of studies in the literature regarding allergic sensitization and emotional status. Among these studies, Kohlbeck evaluated 182 atopic and 63 non-atopic children with asthma and reported a 3-fold higher rate of emotional disorders in the asthma group. Similarly to the present study, they did not find any significant differences between atopic asthma group and non-atopic group. In addition, they did not report a relationship between emotional disorders and age, gender, BMI, and frequency of rhinitis .In the study by Barone et al. that evaluated 217 patients, the total Anxiety Sensitivity Index score was significantly higher in the atopic group when compared to the non-atopic group; however, no significant differences were found between atopic and non-atopic asthmatics in terms of their scores in Beck Depression Inventory-II. The spirometric measurements and severity of asthma were comparable between the two groups .As a secondary outcome of the present study, ACT and ACLQ scores were found to be significantly lower in patients with anxiety and depression. Our study confirmed that both the prevalence and severity of emotional disorders are related to the degree of asthma control and quality of life. These results are consistent with the works of other authors. Janson observed a correlation between the prevalence of anxiety and depression and the occurrence of asthma symptoms.  In anoth1, FVC, and PEF values were similar in patients with anxiety and depression. However, the number of exacerbations were higher in the anxiety group, and the number of exacerbations and asthma severity were higher in the depression group. This discrepancy complicates the interpretation of the results. If these parameters were similar between the groups, this would provide convincing evidence that emotional status has negative effects on asthma control and the quality of life. In our opinion, anxiety and depression are more common in uncontrolled asthma group and the statistical significance of this relationship is stronger. Thus, it is more plausible to suggest that emotional disorders are the result of poor asthma control.Is the asthma control and quality of life worse in those with a psychiatric disorder, or may it be that emotional status is worse in patients with uncontrolled asthma? There is not a straightforward answer to this question as the present study has not been designed as to address this casual relationship. Age, BMI, presence of rhinitis, and as the basic parameters of asthma FEVOf the patients in the study group, 78.7% had rhinitis. The prevalenece of house dust mite and pollen allergy was higher in patients with rhinitis. Only 18 patients (13%) had rhinitis combined with a negative prick test. Consistent with the current results, previous studies reported a rate of positive prick test in patients with allergic rhinitis that ranged from 81% to 62.5% -35. No rAnother major strength of the study is the use of objective skin prick tests to determine atopic status. And these tests were conducted at the same time with the asthma control, quality of life and psychological status evaluation.Our study has its limitations; firstly, we used questionnaires to evaluate emotional status, and no actual physician diagnosis was used. Secondly, this study was a single center study, and it is not capable of evaluating various ethnic and sociocultural differences, thus preventing the generalized use of the study results.The present study is the first, to our knowledge, to systematically investigate the association between emotional status, quality of life, and indoor-outdoor type of atopy in patients with asthma. Finally, it was concluded that house dust mite and pollen allergies did not influence the scores in ACT and AQLQ; therefore, they did not increase the prevalence of anxiety and depression. It was concluded that emotional impairment is prevalent in patients with uncontrolled asthma, and holistic treatment approach should include psychological support and patient education in addition to the provision of medical therapy.


Studies on the blood pressure lowering effect of renal denervation (RDN) in resistant hypertensive patients have produced conflicting results. Change in medication usage during the studies may be responsible for this inconsistency. To eliminate the effect of medication usage on blood pressure we focused on unmedicated hypertensive patients who underwent RDN.p = 0.04]. Mean change in office SBP was −13.1 mmHg . No changes were observed in other variables, such as eGFR, body–mass-index and urinary sodium excretion.Our study reports on a cohort of patients, who were not on blood pressure lowering drugs at baseline and during follow-up, from eight tertiary centers. Data of patients were used when they were treated with RDN and had a baseline office systolic blood pressure (SBP) ≥140 mmHg and/or 24-h ambulatory SBP ≥130 mmHg. Our primary outcome was defined as change in office and 24-h SBP at 12 months after RDN, compared to baseline. Fifty-three patients were included. There were three different reasons for not using blood pressure lowering drugs: (1) documented intolerance or allergic reaction (57 %); (2) temporary cessation of medication for study purposes (28 %); and (3) reluctance to take antihypertensive drugs (15 %). Mean change in 24-h SBP was −5.7 mmHg [95 % confidence interval (CI) −11.0 to −0.4; This explorative study in hypertensive patients, who are not on blood pressure lowering drugs, suggests that at least in some patients RDN lowers blood pressure.The online version of this article (doi:10.1007/s00392-016-0984-y) contains supplementary material, which is available to authorized users. Sympathetic overactivity and kidney injury are major contributors in sustaining high blood pressure (BP) levels . PercutaThe study was designed to evaluate a cohort of patients that underwent RDN and who were either without blood pressure lowering drugs at baseline and follow-up, or, whose medication was withdrawn according to protocol. Our primary outcome was defined as change in office and 24-h SBP at 12 months after RDN, compared to baseline. Eight international centers  participated in this initiative . These centers delivered patient records that met the following inclusion criteria: the patient was ≥18-year-old, treated with catheter-based RDN and had a baseline office SBP ≥140 mmHg and/or 24-h SBP ≥130 mmHg. Patients were excluded if they were using medication for their hypertension or when no BP data were available at baseline or during follow-up visits. Local medical ethics committees approved the primary study in which the patient originally participated, in accordance with the Declaration of Helsinki.Twenty-four-hour BP and office BP measurements were collected at baseline and at 6 months and/or 12 months post RDN. Twenty-four-hour BP was calculated as the mean of the readings at least every 30 min at daytime and every hour at nighttime. Office BP was calculated as the mean of three measurements obtained with a noninvasive automatic blood pressure measuring device with at least 5 min resting between each BP reading. All BP measurements were performed in accordance with the European guidelines and with recommended devices , 18. In We collected physical  and biochemical parameters  to explore lifestyle and other potentially relevant factors at baseline and follow-up. We report on body mass index, kidney function and 24-h urinary sodium excretion. Serum creatinine was determined as standard care at each study site (Jaffé or Enzymatic method). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Modification of Diet in Renal Diseases (MDRD) equation , 21. MeaTM catheter  or EnligHTNTM Ablation catheter . Ultrasound RDN was performed with the use of PARADISETM technology . The treating physician decided which renal arteries to treat, which device to use and how many ablations could be performed.Study sites selected patients for RDN according to their own study protocol . Percutaneous radiofrequency ablation was performed with SymplicityResults are presented as the mean difference between baseline and 12 months with corresponding standard error and 95 % CI interval, unless otherwise stated. When the 95 % CI does not contain the zero value, the difference is considered statistically significant. Our primary outcome was change in BP 12 months after RDN. For missing data, we used the 6-month BP data carried forward. The rationale for this approach was to increase the number of individuals with an outcome variable. This was considered to be reasonable based on previous reports showing that over time the magnitude of the RDN effect does not seem to attenuate between 6 and 12 months, if anything an increase in RDN effect is expected . To stud2. Three patients (6 %) had moderately reduced kidney function (eGFR <60 ml/min/1.73 m2). Forty-two patients were treated with the Symplicity catheter, ten with the EnligHTN catheter and one was treated with ultrasound RDN. Baseline characteristics of the three groups of patients, according to the reason for not using blood pressure lowering drugs, are shown in Table 5 .Fifty-three records of patients, who complied with our inclusion criteria, were included. There were three different reasons for not using BP lowering drugs: 1) documented intolerance or allergic reaction (57 %); (2) temporary cessation of medication for study purposes (followed by immediate resumption of drug treatment after study visits), using a highly standardized stepwise program (28 %); and (3) reluctance to take antihypertensive drugs (15 %) , 24. Fou documentp = 0.04] and −4.0 mmHg , respectively. Office SBP and DBP decreased significantly after RDN by −13.1 mmHg  and −4.4 mmHg , respectively  . BP changes at 6 and 12 months are separately presented in Table 7 . Based on a systematic review, a selective pooling of previous studies was performed to assess the effect of participating in a trial on BP levels. Mean change in office SBP in the placebo controlled group was −4.0 mmHg (95 % CI −7.5 to −0.4) and the change in 24-h SBP −0.9 mmHg (95 % CI −2.1 to 0.2) .Twenty-four-hour BP and office BP data were available in 43 and 47 patients, respectively . In the whole group, 24-h SBP and diastolic BP (DBP) reduced after RDN as compared to baseline by −5.7 mmHg . There was a significant relation between baseline office SBP and change in SBP after RDN  for every mmHg increase in baseline office SBP).We observed a relation between percentage dipping at baseline and change in SBP after RDN . All univariable analyses are presented in Table Univariable analysis showed no significant relation between baseline 24-h SBP and change in 24-h SBP after RDN [mean change in 24-h SBP is −0.22 mmHg  be due to other mechanisms, including lifestyle improvement, the effect of taking part in a trial and also the ‘regression to the mean’ phenomenon. Our data suggest no major changes in potentially relevant factors, such as BMI, eGFR and urinary sodium excretion. It is highly implausible that ‘regression to the mean’ can be responsible when observing sustained BP reductions 12 months post RDN. Furthermore, most patients already have a long history of hypertension. To overcome the limitation of having no control group, we assessed the BP lowering effect in the placebo arm of hypertension trials in patient populations not on antihypertensive drugs, based on a recently published systematic review.  , 29–38. This study has some other limitations as well. Firstly, our study may consist of a highly selected population. However, when compared to earlier studies, our population did not differ in mean levels of predictors of response to RDN , 22, 39.In conclusion, this explorative study suggests a beneficial effect of RDN on blood pressure in patients with hypertension, independent of medication change during the study. Furthermore, this supports the rationale to investigate the effects of RDN in a patient population not on blood pressure lowering drugs , 41.Supplementary material 1 (DOCX 176 kb)Below is the link to the electronic supplementary material.


In persons 15 years and above in South Africa the prevalence of pre-diabetes and diabetes has been estimated at 9.1% and 9.6%, respectively, and the prevalence of systolic prehypertension and hypertension, 38.2% and 24.6%, respectively. Elevated blood glucose and elevated blood pressure are prototype of preventable chronic cardiovascular disease risk factors.Lifestyle interventions have been shown to control high normal blood pressure and/or high normal blood glucose.This study proposes to evaluate the efficacy of a community (church)-based lifestyle intervention programme to control high normal blood pressure and/or high normal blood glucose in church members in a randomized controlled trial in Gauteng, South Africa. The objectives are to: (1) measure non-communicable diseases profile, including hypertension and diabetes, health behaviours, weight management and psychological distress of church members; (2) measure the reduction of blood glucose and blood pressure levels after the intervention; (3) prevent the development of impaired glucose tolerance; (4) compare health behaviours, weight management and psychological distress, blood glucose and blood pressure levels between intervention and control groups, and within group during 6, 12, 24 and 36 months during and post intervention. The study will use a group-randomized design, recruiting 300 church members from 12 churches. Churches will be randomly assigned to experimental and control conditions.Lifestyle interventions may prevent from the development of high blood pressure and/or diabetes. The findings will impact public health and will enable the health ministry to formulate policy related to lifestyle interventions to control blood pressure and glucose.PACTR201105000297151 In the first South African National Health and Nutrition Examination Survey SANHANES-1) [ [1] of 2Lifestyle interventions have been shown to ameliorate or prevent the progression of prediabetes and prehypertension to diabetes and hypertension ,4. Such To have a significant public health impact, benefits of proven lifestyle interventions have to be translated into community settings ,16. EvidThe aim of this study is to study the efficacy of a community (church) -based lifestyle intervention programme to control high normal blood pressure and/or high normal blood glucose in church members in a randomized controlled trial in Gauteng, South Africa.1. To measure non-communicable disease profile, including hypertension and diabetes, health behaviours, weight management and psychological distress of church members;2. To measure the reduction of blood glucose and blood pressure levels after the intervention;3. To prevent the development of impaired glucose tolerance and hypertension;4. To compare health behaviours, weight management and psychological distress, blood glucose and blood pressure levels between the intervention and control groups, and within group during 6, 12, 24 and 36 months during and post intervention.The study is a cluster randomized controlled evaluation of a group-based programme, implemented and reported in accordance with the requirements of the CONSORT statement  and its • Individuals receiving lifestyle intervention will have a greater reduction in systolic blood pressure, compared with the individuals receiving a health education leaflet only (control group).• Individuals receiving lifestyle intervention will have a greater reduction in blood glucose levels, compared with the individuals receiving a health education leaflet only (control group).Churches Churches having a church building and having at least 100 church members in the locations of Ga-Rankuwa and Soshanguve will be included in the study.Church members Males and females, aged from 40–65 years, who visit the church, and having been diagnosed with pre-diabetes and/or prehypertension will be included in the study.Church members Church members under the age of 40 and above 65 years will not be included. In addition, all individuals with previous diagnosis of heart diseases, previous diagnosis of hypertension and/or type 2 diabetes, unstable pulmonary disease, history of alcoholism, drug abuse, or other psychiatric problems that are likely to limit compliance to the study, orthopaedic or rheumatologic disease (i.e. severe rheumatoid arthritis), already enrolled in a clinical research trial, and having kidney disease will be excluded.A list of the names of churches in each village/ward will be obtained. The church sites will be randomized into intervention and control sites to prevent contamination. Randomisation will be conducted using a secure remote randomization service. We believe that there will not be any contamination between the experimental and control groups since religious leaders and small group church members will stay nearby their church area. The control and intervention churches will not be matched. There are about 452 Christian churches in Soshanguve and Ga-Rankuwa . In moreChurch leaders will be informed that their assignment to conditions is random, and that different churches will receive different types of interventions. Random assignment will occur prior to the baseline assessment to assure that recruitment and assessment staff (research assistant nurses) remains blind to condition assignments.After randomization, baseline measurements will occur. Recruitment of the programme participants will take place in 12 churches by specially trained research assistant nurses. Church members will be screened for prehypertension and prediabetes by the research assistant nurses.Inclusion Criteria: 1) age from 40–65 years, 2) willingness to participate in the screening programme.All church members will pass brief pre-screening questions to meet the The participants will be recruited on Saturday and Sunday after the worship activities. Research assistant nurses will be trained for 1 week on risk factors, data collection and research process. They will screen church members in the church area , using a diabetes risk screen and blood pressure assessment after informed consent has been taken for study participation. Prehypertension will be defined as blood pressure between 120-139/80-89 mmHg . Blood pAfter completion of the face-to-face administered diabetes risk screen, the research assistant nurse will calculate the risk score and provide the results to the client. Likewise, church member’s blood pressure will be measured by a research assistant nurse and the results provided to the client. Clients who score less than 15 on the diabetes risk screen are provided with a lifestyle education pamphlet in English and SeTswana explaining the benefits of a healthy diet and exercise. Likewise, clients with a normal blood pressure are provided with a lifestyle education pamphlet explaining the benefits of a healthy diet and exercise.Clients who score 15 or more on the diabetes risk screen have elevated diabetes risk. Likewise, clients with a blood pressure between 120-139/80-89 mmHg are at elevated risk for hypertension. The research assistant nurse will take informed consent for participation in the study (Step II). The appointment will be made for the following week at the churches and fasting procedures are explained.nd inform consent (for intervention)). Patients with type 2 diabetes and/or hypertension exit the study and are referred for medical management  and collect fasting venous blood samples from the participants for fasting plasma glucose (FPG) and Lipid profile test. An appointment will be made to receive their results after one week and to recruit into the trial. The Eligibility for Step III are: had high normal blood pressure determined as a seating resting systolic blood pressure between 120 and 139 mmHg and/or a diastolic blood pressure of 80–89 mmHg, and/or a fasting glucose level between 6.1 and 6.9 mmol/l and agreed to participate over a 36-month period .Consent to participate will be obtained in a 3-stage process. Research assistant nurses will initially ask for informed consent to conduct a health screen (diabetes risk screen and blood pressure test) and collect basic information and check eligibility to take part. No identifiable information will be collected at this stage. Patients who score positive on the diabetes risk screen and/or have high normal blood pressure, will have the study explained to them verbally and in writing (using the patient information sheet). Informed consent will now be obtained for stage 2 of the study for confirmatory testing of pre-diabetes and/or pre-hypertension. At this second stage, which will include permission to give the contact details to the research assistant nurses staff, and participate in the experimental or control condition and follow ups.All the church members randomized and allocated to the control group will complete the baseline and follow-up measures, receive standard care and a lifestyle education pamphlet on healthy diet and exercise benefits.In the 6 lifestyle intervention study churches two lay health promoters per church will be trained for two weeks with a standardized training programme, training manuals, and practical exercises. In each church the lay health promoter(s) is expected to start and run 4–5 support groups (6–8 members per group) over the project period. The intervention model used is based on a Finnish diabetes prevention implementation study ,34 and iAssessment and intervention quality assurance procedures ensure that project activities are standardized across the churches and across the cohorts and that assessment and intervention process data are collected accurately. To achieve this, standardized protocols, procedures, and training manuals are prepared, and the staff is systematically trained in their use. In addition, the performance of the assessors and programme implementers is routinely monitored by the research coordinators. This will require the development of mechanisms for determining that adequate levels of competence have been attained by those who have received training and that their continuing performance does not fall below these levels. A random sample of group session interactions will be tape-recorded and analysed for that purpose. Feedback will be provided to the field work staff and protocol deviations or other problems addressed and corrected in a timely manner.The primary outcomes and measures include 1) the reduction in systolic blood pressure after the intervention and 2) the reduction in blood glucose levels after the intervention.The secondary outcomes and measures include 1) anthropometric measures: body weight, height (for BMI) and waist-to-hip-ratio; body composition 2) lipid levels: total cholesterol, LDL- and HDL-cholesterol, triglycerides; 3) behavioural measures ; and 4) blood lipid profiles. Measurements will occur at baseline, 6-months, 12-months and 36-months post intervention  evaluation framework for complex implementation trials will be utilized to analyze the reach, effectiveness, adoption, and implementation of the intervention . NutritiThe statistical analysis will include differences among the subjects’ characteristics in clinical, behavioural, and physiological outcome measures using analysis of variance (ANOVA). Interactions and/or a specific age, gender, or clinical variable differences will be examined using Tukey’s post hoc analyses. If a group difference between a potentially confounding variable is observed at limit differences in a key outcome, analysis of covariance (ANCOVA) will be performed with the potentially confounding variable serving as the covariant. Relations of interest will be initially identified by univariate correlation analysis. Independent correlations among the dependent variables will be determined using partial correlation analyses and/or conventional multivariate step-wise regression analysis. In all cases, probability levels will be p < 0.05.We have received ethical approval from the University of Limpopo MEDUNSA Research and Ethics Committee (Project number: MREC/H236/2012:IR).The study will run for a period of 46 months beginning in January 2014 to October 2017.This integrative lifestyle intervention trial for both the reduction of diabetes and hypertension risk offers the unique opportunity to evaluate the effect of a community (church) -based intervention delivered by trained lay health promoters targeting a high risk population. The integration of a lifestyle intervention for both the reduction of diabetes and hypertension risk and evaluating the effectiveness of this intervention in a community-based setting is both innovative and can facilitate research translation into primary health care practice. Moreover, this intervention utilizes community health workers to enhance lifestyle modification for the reduction of both diabetes and hypertension risk through group sessions, which can be easily adapted in real world settings. This study will present a new analysis of the effectiveness a community (church)-based lifestyle intervention programme to control high normal blood pressure and/or high normal blood glucose in a low and middle income setting. If data confirm our hypothesis, this may help policy makers to increase resources in prevention rather than treatment. It is important to consider that the study data will be collected from a real life community setting.BP: Blood pressure; CHD: Coronary heart disease; DASH: Dietary approaches to stop hypertension; DPP: Diabetes prevention programme; FBS: Fasten blood sugar; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance.The authors declare that they have no competing interests.SP and KP were the main contributors to the conceptualization of the study and also contributed significantly to the first draft of the paper. All authors contributed to the subsequent drafts and finalization. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/14/568/prepub


Pulmonary artery hypertension (PAH) is a disorder of elevated resistance in the pulmonary arterial vessels, reflected by elevation of measured pulmonary artery pressure (PAP), and presenting with breathlessness and, if untreated, progressing to right heart failure and death. The heightened prevalence of PAH in populations with underlying systemic autoimmune conditions, particularly scleroderma and its variants, is well recognised, consistent with the proposed autoimmune contribution to PAH pathogenesis, along with disordered thrombotic, inflammatory, and mitogenic factors. Rheumatoid arthritis (RA) is one of a group of systemic autoimmune conditions featuring inflammatory symmetrical erosive polyarthropathy as its hallmark. This study explored the prevalence of PAH in a population of unselected individuals with RA, using exercise echocardiography (EchoCG). The high prevalence of EchoCG-derived elevation of PAP (EDEPP) in this population (14%) suggests that, like other autoimmune conditions, RA may be a risk factor for PAH. Patients with RA may therefore represent another population for whom PAH screening with noninvasive tools such as EchoCG may be justified. The heightened prevalence of PAH in individuals with scleroderma, combined with the arrival of specific therapies which improve PAH prognosis, has led to widespread screening for PAH in this patient subgroup in accordance with published guidelines . SubsequRheumatoid arthritis (RA) is an autoimmune condition which affects the rheumatological system but may involve the vasculature, eyes, lungs, and other organs. The shared pathogenesis between rheumatoid and other autoimmune conditions has raised the question of whether patients with RA may also display a heightened prevalence of PAH , althougThe Stress Associated Pulmonary Hypertension in Rheumatoid Evaluation (SAPHIRE) study was conducted to explore the prevalence of pulmonary hypertension in individuals with rheumatoid arthritis (RA) using stress echocardiography (SE) as a screening tool.The Autoimmune Resource and Research Centre (ARRC) was established in 1990 to provide education and support for individuals with systemic and organ-specific autoimmune syndromes. Using the ARRC database and individuals seen by the Rheumatology Clinic of the Royal Newcastle Centre, 177 subjects with American College of Rheumatology (ACR) criteria confirmed rheumatoid arthritis (RA) were randomly invited to participate in the study. Recruited patients were evaluated via stress echocardiography. Inclusion criteria included age ≥ 18 years, weight ≥ 40 kg, and ability to undergo informed consent; individuals with total lung capacity (TLC) < 60% of predicted volume were excluded, as were patients with previous pulmonary thromboembolism. Predetermined withdrawal criteria included worsening rheumatoid inflammation precluding further participation or leading to death or change in inclusion criteria status . The study proceeded in accordance with the 1983 revision of the 1975 Helsinki Declaration and in keeping with guidelines for good clinical practice. The trial protocol was reviewed by the Hunter Area Research Ethics Committee.Patients were asked to complete the World Health Organisation (WHO) functional class assessment, standardised six-minute walk test (6MWT), and formal pulmonary function testing (PFT) including carbon dioxide diffusing capacity (DLCO). WHO functional assessments are classified as follows: Class I (unlimited during activity); Class II (some breathlessness with extreme exertion); Class III ; and Class IV (breathlessness at rest).Patients were assessed for raised PASP  at rest and following exercise using SE; if unable to exercise, they underwent resting echocardiography only. Based upon literature review , it was Analysis of biochemical markers, such as B type natriuretic peptide and troponin I, was not included in the study design. C-reactive protein (CRP) plasma concentrations were measured with an ultrasensitive latex immunoassay  and antibodies to cyclic citrullinated peptide (CCP) were measured by enzyme immunoassay (EIA)  according to the manufacturer's details.V2 + right atrial (RA) pressure, with RA pressure assumed as 10 mmHg in keeping with previously published data when employing exercise stress echocardiography in patients with autoimmune disease [Patients undertook exercise stress testing using a modified Naughton protocol with standard 12 lead electrocardiogram (ECG) and noninvasive blood pressure monitoring. All echocardiograph studies were performed by a single sonographer and interpreted by a single experienced cardiologist, blinded to full clinical case details. Echocardiograph measures of left ventricular function were also performed before and after exercise. Continuous wave Doppler interrogation of the tricuspid regurgitant (TR) jet was used to estimate peak systolic pulmonary artery pressure (PASP), which is considered to be the most accurate echocardiographic method. TR jet interrogation allows estimation of the peak right ventricle to right atrium gradient using the modified Bernoulli equation  .Primary endpoints were prevalence of EDEPP in patients with rheumatoid arthritis, and, where possible, confirmation of PAH. Two outcomes were analysed: (i) PAH prevalence as determined by PASPr > 35 (EchoCG) and/or mean pulmonary artery pressure (MPAP) > 25 mmHg at rest (RHC) and (ii) PAH prevalence as determined by PASPe > 40 (EchoCG) and/or mean PAP > 30 with exercise (RHC).t or Mann-Whitney-Wilcoxon tests where appropriate for continuous variables and the chi-square test (or exact test where appropriate) for categorical variables.Clinical and measured variables are summarized as means ± SD (or median with range where appropriate) for continuous data and as frequencies (with percentages) for categorical data. Differences between these summary statistics are analysed using the Student p < 0.05 (two-sided) is considered significant. Analyses were performed using Stata version 11 .A probability value of 177 patients were invited to participate in the SAPHIRE study, of whom 100 patients responded and were accepted. A final number of 80 were included in the study; 7 people withdrew, and 13 were excluded based upon predefined exclusion criteria. All patients declining involvement in the study expressed concern surrounding potential performance of invasive RHC studies in the context of subjectively good functional capacity and lack of clear therapeutic gain.80 patients were studied, displaying a mean age of 60 , dominantly falling into WHO Class II functional class. Overall mean values for key variables are listed in The diagnosis of PAH was based predominantly on echocardiographic findings, reflecting patient reluctance to undergo invasive testing with RHC .p < 0.05); PASPe (mmHg): 42.5 (with PAH) versus 28.2 (without PAH) (p < 0.05)). There was no significant difference between subgroups for the exercise-induced rise in PASP (REEP), reflecting resting PA pressure as an important discerning echocardiographic parameter. There were no significant differences in the serological markers CRP and CCP across patient groups with and without PAH. Significant reductions in DLCO  and 6MWD  were also noted in patients with EDEPP as compared to those without. These significant relationships are represented graphically in Figures In patients diagnosed with PAH, as expected, PASP (as determined by EchoCG) was significantly higher compared to those without PAH. Resting and postexercise PASP values were approximately 15 mmHg greater in the PAH groups versus those without this condition (PASPr (mmHg): 40.8 (with PAH) versus 25.5 (without PAH) , increasing to 21% when elevations in SE derived pulmonary pressures are considered. Of the small number of RA patients who agreed to proceed to right heart catheterisation studies, 2 out of 6 (33%) were diagnosed with PAH .The prevalence of pulmonary hypertension in RA is not well reported, with some authors stating it is rare , 10, 16 PAH is often silent, with the development of clinical symptoms often signalling the presence of advanced disease, associated with poor survival. With available therapeutic options  endothelin blockade) and given the irreversibility of advanced pathology associated with PAH, an impetus is provided for earlier detection of PAH in at-risk populations, with exercise proposed as a useful stress tool, albeit a method yet to possess clear normal cutoff ranges.For screening to be justified, a condition must be common enough in the at-risk population to warrant the inconvenience, false positives, medicalisation, and potential costs of the screening strategy. Pulmonary hypertension screening has been associated with improved survival displayed in the subgroup of scleroderma patients in whom earlier PAH detection was secured . The preScreening tools such as EchoCG, whilst imperfect in terms of sensitivity and specificity against the “gold standard” of RHC, are still useful with high pretest probability, such as in screening high risk groups including scleroderma, systemic lupus erythematosus, and now possibly rheumatoid arthritis. Given the inherent limitations of any single parameter in determining the likelihood of pulmonary hypertension in a given individual, expert consensus is increasingly moving towards multiparametric approaches incorporating more than one predictor variable to refine determination of pulmonary hypertension risk. In our study, the prevalence of PAH was increased with the incorporation of SE, although the clinical relevance and specificity of these findings require further study. The use of assumed right atrial pressure may potentially overestimate the true prevalence of pulmonary hypertension in this population. This overly sensitive result may be appropriate in terms of screening to avoid false negative results, given the deleterious effects of late diagnosis. The use of DLCO represents an additional modality with previously published data demonstrating that the prevalence of PAH was enriched approximately fivefold when testing incorporated a DLCO < 55% , 20.It is acknowledged that the diagnostic gold standard test for defining PAH is the right heart catheter and that the key parameters in this condition include pulmonary vascular resistance and right heart function, as well as exclusion of coexisting left heart disease by measurement of pulmonary capillary wedge pressure. Whilst RHC determines mean PAP (mPAP), the EchoCG-derived value estimates only peak systolic PAP, as calculated from tricuspid regurgitant jet velocity. Lack of systematic right heart catheterisation is a limitation of this study and is reflected in previous reports which have highlighted the imperfect correlation between PASP as derived from EchoCG and mean PAP measured during RHC. However, echocardiographically based screening as an initial approach in these patient populations is advocated because (i) RHC is impractical as a tool for identifying PAH tendencies in at-risk populations, where noninvasive strategies are required; (ii) although linear correlation between PASP (Echo-derived) and mPAP (from RHC) is imperfect, the agreement between methods is acceptable when a higher threshold for EchoCG-derived PASP is employed ; and (iip < 0.001) was confirmed in a recent study [Whilst the proposed study protocol was designed to clarify abnormal EchoCG-derived PAP measurements, the decision to proceed to RHC was contingent upon patient and clinician agreement; reluctance was expressed in the study group surrounding potential performance of invasive RHC studies in the context of subjectively good functional capacity, potential RHC risks, and lack of clear therapeutic gain  is still contentious ). Using nt study . Of notent study .It has been proposed that some of the pulmonary vascular pathology underlying PAH may reflect a similar phenomenon to the peripheral vascular hyperreactivity seen in Raynaud's phenomenon, possibly reflecting similar vasoconstrictor-mediated pathophysiology. Due to a lack of patients affected by Raynaud's phenomenon in our patient cohort (only two patients with Raynaud's phenomenon), this question could not be addressed in this study.The clinical significance of exercise-induced EDEPP is controversial, with consensus guidelines having suggested that exercise EchoCG not be employed routinely in the absence of normative values . It is nThe shared clinical, serological, and epidemiological features seen in both PAH and other autoimmune conditions led us to explore the possible roles of autoimmunity and inflammation in our disease subset with abnormal PASP. Whilst the patients with and without PAH displayed no significant difference in CRP or CCP values, the heightened prevalence of EDEPP and PAH in our cohort of RA patients fits well within an autoimmune paradigm for PAH pathogenesis.This study screened a population of patients with RA, irrespective of the presence of breathlessness at baseline, with rest and stress echocardiography to assess the prevalence of PAH in this group. We demonstrated that there is a significant prevalence of EchoCG-defined PH in patients with RA, with 14% of RA patients displaying elevation of resting PASP > 35 mmHg.The demonstration of an increased prevalence of PAH in this population of RA patients suggests that RA may be considered along with other systemic autoimmune conditions  for which periodic clinical and further assessment for PAH needs to be regularly considered. Whilst this proposed 14% prevalence of PAH is inferred largely from noninvasive data using an established threshold for pulmonary hypertension based on echocardiography, it warrants further replication and, ideally, exploration with routine RHC to confirm the presence of PAH.


CD300LG was recently found to be associated with fasting HDL-cholesterol and triglyceride levels. The polymorphism has not been detected in hypertension GWAS potentially due to its low frequency, but CD300LG has been linked to blood pressure as CD300LG knockout mice have changes in blood pressure. Twenty-four-hour ambulatory blood pressure was obtained in human CD300LG CT-carriers to follow up on these observations.The genetics of hypertension has been scrutinized in large-scale genome-wide association studies (GWAS) with a large number of common genetic variants identified, each exerting subtle effects on disease susceptibility. An amino acid polymorphism, p.Arg82Cys, in CD300LG rs72836561 CT-carriers matched for age and BMI with 20 healthy male CC-carriers. Office blood pressure, 24-hour ambulatory blood pressure, carotid intima-media thickness (CIMT), and fasting blood samples were evaluated. The clinical study was combined with a genetic-epidemiological study to replicate the association between blood pressure and CD300LG Arg82Cys in 2,637 men and 3,249 women.Twenty healthy male CD300LG genotype was detected in the genetic-epidemiological study.CT-carriers had a higher 24-hour ambulatory systolic blood pressure  and diastolic blood pressure  compared with CC-carriers. There were no differences in CIMT between the two groups. Metalloproteinase-9 level was higher in CT-carriers than in CC-carriers (P<0.01). However, no association between office blood pressure and CD300LG rs72836561 CT-carriers was higher than in CC-carriers, this did not translate into significant differences in office blood pressure in a larger cohort. This discrepancy which may reflect differences in methodological approach, underlines the importance of performing replication studies in a larger clinical context, but a formal rejection of a relation between blood pressure and CD300LG requires measurement of 24-hour ambulatory blood pressure in a larger cohort.Although 24-hour blood pressure, measured with a sensitive method, in a small sample of  CD300LG  with a minor allele frequency of 3.5% was selected for replication in stage 2 and 3 of the study due to its annotation as a missense mutation in stage 1 of the study. In stage 2 and 3 of the study, the polymorphism was associated with a decreased fasting HDL-cholesterol level and an increased fasting triglyceride level. The protein encoded by CD300LG is a membrane-bound protein expressed on vascular endothelial cells in a broad range of human tissues with the highest expression in placenta, adipose tissue and skeletal muscle CD300LG are not well characterized, but CD300LG knockout (KO) mice have osteopenia and decreased systolic blood pressure . In the present study, aspects of the cardiovascular phenotype were characterized in healthy male heterozygous carriers of the CD300LG rs72836561 polymorphism to address the hypothesis that CD300LG has effects on blood pressure regulation as suggested in studies of the CD300LG KO mice.Hypertension constitutes an important public health challenge due to its association with cardiovascular diseases CD300LG rs72836561 CT-carriers and 20 age and BMI matched CC-carriers (controls) were recruited from Biobank Vejle CD300LG T-allele, but in the present report only data on the cardio-vascular phenotype were included. Only males were included in the study to avoid the effect of the menstrual cycle on the metabolic variables. The study subjects gave a written informed consent prior to study participation. The study protocol was approved by the regional ethical committee  and the studies were conducted according to the principles of the Helsinki declaration.Twenty healthy male After an overnight fast, body composition was evaluated by DXA-scan (Hologic QDR 2000). An intravenous catheter was inserted into a cubital vein for sampling of peripheral blood. Blood samples were drawn after 90 minutes of bed rest. 24-hour blood pressure and heart rate were obtained using an oscillometric blood pressure monitor . Blood pressure and heart rate were recorded every 20 minutes for 24 hours and classified into daytime or nighttime recordings according to information from the study subjects. Carotid intima-media thickness (CIMT) was obtained by ultrasonography. Two radiologists used the same protocol to obtain bilateral B-mode images during the cardiac diastole of the far wall of the common carotid artery and in the bulb of the internal carotid artery using dedicated software . The radiologists were blinded to the genotype of the study subjects.Pro-Brain natriuretic peptide (pro-BNP) was analyzed using an immunometric method. V-CAM1, I-CAM1, metalloproteinase-9 (MMP-9), high-sensitive C-reactive protein (HsCRP), aldosterone, and renin were analyzed by ELISA using commercially available kits . Plasma free metanephrine and normetanephrine were analyzed using a commercially available enzyme immunoassay .CD300LG CC-carriers, 157 CT-carriers, and 5 TT-carriers. As blood pressure changes had been observed in female CD300LG KO mice, we also tested the association between CD300LG Arg82Cys and office blood pressure in women using data from the original genetic-epidemiological study. Data were available for 3,028 female CD300LG CC-carriers, 218 CT-carriers, and 3 TT-carriers.With the aim of replicating the results from the clinical study, a post-hoc analysis of the blood pressure data from the original Danish genetic-epidemiological study of 15,989 Danish individuals was performed Statistical analyses were performed using SPSS 21.0 and R 2.12. Results are presented as mean +/- 95% confidence interval or median +/− interquartile range. A Students t-test was applied to compare the two genotype groups. The Kolmogorov-Smirnov test was used to test whether data were normally distributed. P-values <0.05 was considered significant. A multiple regression model was applied to adjust blood pressure measurements for age and fasting triglyceride level (TAG). The analyses of CIMT included adjustment for age and 24-hour systolic blood pressure. Bivariate associations of continuous variables were tested using Pearson's coefficient of correlation. Variables were omitted from the regression model if P>0.1. A Fisher's exact test was used to test for association between dichotomous variables. In a post hoc power calculation with the 24-hour systolic blood pressure as endpoint, the statistical power was 80% to detect a difference of 7,5 mmHg with 20 subjects in each study group. In the genetic-epidemiological replication study a linear regression analysis was performed applying an additive genetic model adjusted for age. Outcome variables were rank normalized before analysis. The choice of an additive genetic model was arbitrary as we had no prior knowledge of the effect of the minor allele on risk transmission.Clinical characteristics of the study subjects are presented in Study subjects from the CT-group had significantly higher 24-hour and daytime ambulatory blood pressure compared to the controls in the CC-group. Nighttime measurements displayed the same trend with higher blood pressure in the CT-group, but the differences were not statistically significant. Adjusting blood pressure for age and fasting triglyceride level did not change the results. There were no differences between the two groups in heart rate, circadian variation in heart rate, pulse pressure or nighttime dipping (results not shown). One subject from the CT-group was excluded from the analyses due to manifest hypertension (24-hour average 161/100) to avoid skewing of the data.There were no differences in CIMT measures between the CT-group and the CC-group . AdjustiTo explore the physiological mechanisms underlying the higher blood pressure levels in the CT-group, a biochemical profile relevant to the cardiovascular phenotype was obtained. The panel of vascular endothelial markers revealed significantly higher levels of MMP9 in the CT-group than in the CC-group (P<0.01). There was a tendency to higher aldosterone/renin ratio in the CT-group than in the CC-group, but this difference was not statistically significant (P = 0.10).CD300LG genotype; in the linear regression, the beta-coefficient for systolic blood pressure was 0.003 (p = 0.75) and for diastolic blood pressure −0.005 (p = 0.56) in men and the beta-coefficient for systolic blood pressure was −3.17*10−5(p = 1.00) and 0.004 for diastolic blood pressure in women (p = 0.95), respectively.The findings of the clinical study were not confirmed in the replication study of office blood pressure versus CD300LG rs72836561 CT-carriers had higher levels of 24-hour and daytime systolic and diastolic ambulatory blood pressures than age and BMI matched CC-carriers. CD300LG rs72836561 was originally identified in a genetic-epidemiological study CD300LG and office blood pressure was detected. The cohorts used for the genetic-epidemiological study included subjects with obesity and diabetes and both sexes were included in the analyses. After finding the effect of CD300LG on 24-hour blood pressure in the clinical study, the data from the original genetic-epidemiological study was filtered with the aim of re-analyzing data with inclusion of only men with a phenotype resembling the men in the clinical study. In this analysis we found no association between CD300LG and systolic office blood pressure (p = 0.75) nor diastolic office blood pressure (p = 0.56). Unfortunately, 24-hour ambulatory blood pressure measurements were unavailable in the genetic-epidemiological data, but the high number of study subjects potentially compensated for the less precise methodology. In the clinical study, systolic office blood pressure correlated well with 24-hour ambulatory systolic blood pressure  whereas the correlation was weaker for ambulatory diastolic blood pressure , but in larger studies both systolic and diastolic office blood pressure have been shown to correlate well with ambulatory blood pressure (r = 0.66) CD300LG minor allele in the clinical study and in the genetic-epidemiological study only a total of 8 homozygotes were included. Consequently, with the present data we were unable to reliably assess the effect of homozygosity for the CD300LG minor allele on blood pressure level. In the present study only the potential association between this specific variant in CD300LG and blood pressure level was tested. The results may have been influenced by other rare variants in the gene or variants in genes not tested in the present study. Consequently, a formal rejection of a relation between blood pressure and CD300LG would require measurement of 24-hour ambulatory blood pressure in a large study cohort.In the present study, healthy male CD300LG polymorphism on blood pressure becomes manifest with increasing age, then this age difference could potentially mask an effect on blood pressure in the genetic-epidemiological study. Consequently, we performed a sub-analysis in the genetic-epidemiological cohort with inclusion of participants with a similar median age . This did however not change the results. Likewise, we observed no association between age and blood pressure in the clinical study. The observed differences in blood pressure between the genotype groups were statistically significant. The large differences in blood pressure could, however, be a consequence of recruitment bias with study subjects in the CC-group with 24-hour blood pressure in the lower range of normal blood pressure and/or study subjects in the CT-group with 24-hour ambulatory blood pressure in the higher range of normal 24-hour ambulatory blood pressure. Furthermore, incidental recruitment of an unhealthy CT-group could potentially lead to similar results. With respect to body composition, fasting glucose, and fasting lipid profile we observed no differences between the groups and as such the CT-group seemed at least as healthy as the controls in the CC-group. We assessed the level of physical activity of the study subjects at work and in the leisure time by use of a questionnaire and we observed no clear differences between the study groups.The participants in the genetic-epidemiological study were slightly younger than the participants in the clinical study. If the potential effect of the CD300LG KO model, female mice had decreased systolic blood pressures, but presumably no changes in blood pressure were observed in male mice. We included an analysis of office blood pressure in 3,249 women and tested its association to the CD300LG polymorphism. As in men, again we found no association between office blood pressure and CD300LG genotype. The effects on protein function of the amino acid change in CD300LG has not been characterized, and the observed discrepancy between human carriers of the CD300LG polymorphism and the CD300LG KO mice may relate to different expression patterns of CD300LG and/or a functional difference between having a CD300LG with an altered amino acid sequence and having no CD300LG protein. We sought to explore the underlying physiology of the observed blood pressure differences by obtaining a biochemical profile. The level of MMP9 was higher in CT-carriers than in CC-carriers and we observed a trend towards a higher aldosterone to renin ratio among CT-carriers whereas the remaining biochemical markers were at the same level in the two groups. MMP9 is involved in remodeling of the extracellular matrix (ECM), physiological processes that act to maintain structural stability of the ECM, due to its ability to degrade collagenCD300LG variant on fasting HDL-cholesterol and triglyceride was subtle in the genetic-epidemiological gene-discovery study, the effect of the gene variant on fasting HDL-cholesterol was higher than all but one of the previously GWAS-identified HDL-cholesterol-associated variants In the murine Carotid intima-media thickness is widely used in clinical and epidemiological research for detection of early cardiovascular disease CD300LG, we found a higher level of 24-hour and daytime systolic and diastolic ambulatory blood pressure in CT-carriers compared with CC-carriers. We combined the clinical study with a genetic-epidemiological study based on a post-hoc analysis of office blood pressure in 2,637 men and 3,249 women. In this large group of subjects, the association could not be confirmed. The findings of the present study underscore the importance of replicating findings from clinical studies in larger and external study cohorts, but a formal rejection of an association between CD300LG and blood pressure would require use of a precise methodology such as 24-hour ambulatory blood pressure in a large cohort.In this study of blood pressure level in carriers of the Arg82Cys polymorphism in Table S1Data on the study subjects according to CD300LG rs72836561 CC and CT genotype.(DOCX)Click here for additional data file.Table S2Carotid intima-media thickness (CIMT) in the common carotid artery (CCA) and internal carotid artery (ICA) according to CD300LG rs72836561 CC and CT genotype (in mm).(DOCX)Click here for additional data file.


Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome.We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers . All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded.648 patients  days) were included between March 2011 and May 2013. Two NSTEMI patients  experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased.In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon. The myocardial fractional flow reserve (FFR) assesses the physiological significance of a coronary stenosis and is expressed as the ratio of maximal blood flow in a stenotic artery to maximal flow if theoretically the artery was unobstructed. FFR-guided management is evidence-based in patients with stable coronary artery disease DEFER  and has Intravenous adenosine induces hyperemia through interactions with A2A receptors. However, due to the ubiquitous expression of adenosine receptors, adenosine is also associated with unwanted off-target side-effects. For example, interaction with bronchial A2B receptors can lead to mast cell degranulation and bronchoconstriction Intracoronary adenosine may also be used therapeutically for the treatment of no-reflow in STEMI In November 2013 the United States (US) Food and Drug Administration (FDA) issued a safety announcement on the risk of myocardial infarction (MI) and death in patients receiving Adenoscan (adenosine) for stress testing We aimed to prospectively assess the safety of guidewire based measurement of coronary physiology using intravenous adenosine amongst patients with acute or recent myocardial infarction (MI). Based on our prior experience with intravenous adenosine in this setting 22.1We simultaneously conducted two prospective studies involving assessments of coronary physiology in patients with acute or recent MI. The first was a study of the natural history of coronary microvascular function in patients with acute STEMI undergoing emergency PCI  The exclusion criteria for administration of intravenous adenosine included evidence of 2nd or 3rd degree heart block on the ECG, long QT syndrome, cardiogenic shock, or a history of asthma concurrently treated with bronchodilators 2.2The clinical and catheter laboratory management followed contemporary guidelines for STEMI 2.3In patients with STEMI, infarct artery microvascular function (IMR) was measured at the end of the primary or rescue PCI . Thus weThe patient's response to adenosine administration was a pre-defined safety outcome An SAE was defined as an event that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is otherwise considered medically significant by the investigator.Major adverse cardiac events (MACE), were defined as the occurrence of death, myocardial infarction, or hospitalization for heart failure 2.4Continuous data with a normal distribution were summarized with the mean ± standard deviation (SD). Paired t-tests were used to assess hemodynamic data before and during adenosine administration. Significance was defined as a p value < 0.05. The statistical analyses were performed using the SPSS statistical software package 14.0 for Windows .33.1648 patients  were included between March 2011–May 2013. Their clinical characteristics are presented in In the patients with STEMI, evidence of hemodynamic instability on arrival in the cardiac catheter laboratory was common. Thirty-three (11.1%) patients had a systolic blood pressure (BP) of < 90 mm Hg, 20 (7.2%) patients had ventricular fibrillation (VF) or ventricular tachycardia (VT) before or during PCI but prior to adenosine administration, and 4 (1.4%) patients received intra-aortic balloon pump (IABP) counterpulsation therapy during the PCI. In the patients with NSTEMI there were no patients with VF/VT during the procedure and only 1 (0.3%) patient required IABP.3.2During adenosine infusion, 255 (85.6%) STEMI patients reported symptoms including chest discomfort, dyspnea and facial flushing, all of which resolved immediately after the infusion ceased. There were no other symptoms reported. No MACE, atrial or ventricular arrhythmias occurred in association with intravenous adenosine administration. There were no SAEs related to adenosine.In the STEMI cohort, MACE occurred in 3 (1.0%) patients within 24 h of the PCI. One patient experienced an acute stent thrombosis associated with a dissection at the distal end of the stent; one patient with severe left ventricular dysfunction experienced ventricular fibrillation in the coronary care unit; one patient died suddenly from myocardial rupture that was confirmed at autopsy. All of these events occurred in the coronary care unit and none of these events were temporally associated with the adenosine infusion in the catheter laboratory. In the STEMI cohort there were no pressure-wire related dissections and no SAE related to arrhythmias.In the NSTEMI cohort, no MACE occurred in association with the adenosine infusion. There were 2 (0.6%) cases of coronary dissection related to the guidewire. There were 4 cases of in-hospital adverse events, including 3 (0.9%) cases of contrast nephropathy and 3 (0.9%) cases of major bleeding but none related to adenosine infusion. There were no SAE related to bradyarrhythmias or tachyarrhythmias and FFR was measured in all subjects.3.33.3.1In 330 patients with complete hemodynamic data , aortic systolic blood pressure was reduced during adenosine administration (systolic BP (rest vs. adenosine): 124.5 (26.0) mm Hg vs. 111.7 (24.7) mm Hg (n = 330)  p < 0.001]) as was diastolic BP (67.0 (12.8) mm Hg vs. 60.5 (13.2) mm Hg (n = 330)  p < 0.001]). Heart rate increased to 64.7 (13.0) bpm from 58.3 (12.1) bpm [95% CI 6.3  p < 0.001]. The proximal aortic pressure (Pa) was also reduced during adenosine administration (systolic BP (rest vs. adenosine): 119.7 (26.6) mm Hg vs. 104.2 (25.0) mm Hg (n = 351)  p < 0.001]) as was the distal coronary pressure (64.7 (14.4) mm Hg vs. 55.2 (14.4) mm Hg  p < 0.001]).3.3.2In the STEMI cohort (n = 298), non-invasive hemodynamic data (blood pressure and heart rate) were available for all study participants . Complet3.3.3In the NSTEMI cohort (n = 350), complete aortic hemodynamic data were available for 144 NSTEMI patients with distal coronary (Pd) hemodynamic data recorded in 165 NSTEMI patients. The mean (SD) non-invasive aortic systolic BP reduced from 130.3 (28.8) mm Hg under resting conditions to 118.5 (27.0) mm Hg during adenosine infusion [95% CI 11.8  p < 0.001]. Aortic diastolic BP was also reduced by adenosine infusion (65.9 (11.9) mm Hg vs. 60.0 (12.7) mm Hg [95% CI 5.9  p < 0.001]). Heart rate increased to 58.1 (11.0) bpm from 52.1 (8.8) bpm (n = 144) [95% CI 6.0  p < 0.001] and distal coronary (Pd) pressure was reduced also .4We report the largest study to date of guidewire-based measurements of FFR and/or IMR in patients with acute coronary syndromes. Our study is the first to report information on a pre-specified outcome relating to the safety of intravenous adenosine in patients with an acute STEMI or recent NSTEMI, who were prospectively enrolled simultaneously in parallel studies. The main findings of our multicenter study are that, first, coronary dissection due to the guidewire was rare (≤ 0.3%). Second, brief intravenous adenosine infusion in MI patients for diagnostic purposes was commonly associated with symptoms but these symptoms were brief and self-limiting and were not associated with any SAEs; most importantly, the use of adenosine was safe and not associated with any SAEs during routine emergency care.Only 2 guidewire-related coronary dissections occurred in 698 prospectively enrolled MI patients undergoing emergency or urgent invasive management. This result represents evidence for the safety of guidewire-based assessments of coronary physiology. Guidewire dissections were less common than in previous studies  In our study, predictable symptoms associated with intravenous adenosine occurred in the majority of patients and can be explained by the pharmacological effects of this naturally occurring vasodilator Systolic and diastolic blood pressures were reduced with intravenous adenosine consistent with an A2A receptor-mediated response. However, a rise in heart rate of > 10% or a fall in systolic BP > 10% occurred in less than half of the STEMI and NSTEMI patients in our study. These observations could be explained by the fact that the patients already had tachycardia due to STEMI, and they had been treated with vasoactive drugs, which attenuate the systemic reflex sympatho-excitation response . It is also possible that there was an attenuated sympathetic response due to beta blocker treatment.Of the 6 hospitals in the FAMOUS-NSTEMI trial In STEMI patients, guidewire-based measurement of coronary microvascular function with intravenous adenosine is mainly used in clinical research studies (as was the case here in the STEMI group). IMR in the infarct-related artery has prognostic value when measured invasively at the end of primary PCI In our study invasive measurements of FFR and IMR can be safely obtained in patients with acute or recent MI. IMR has been shown to be a biomarker of severe microvascular injury and has prognostic value in identifying the highest risk patients at an early stage, potentially enabling triage of higher risk patients to intensification of therapy. FFR measurement in the acute setting, especially in non-culprit disease, has much promise and is undergoing ongoing evaluation in clinical trials.Avoid using these drugs (Lexiscan or Adenoscan) in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions” Adenosine is an established drug for use in pharmacological stress testing. Adenoscan has been marketed from 18 May 1995. From this date until 10 April 10 2013 the FAERS database accrued 26 reports of myocardial infarction (MI) and 29 deaths with regadenoson and 6 reports of myocardial infarction and 27 deaths reported with Adenoscan. There were two case reports of MI associated with Lexiscan administration but none with Adenoscan In contrast to the FDA recommendations, our findings are supported by the results from similar studies in other centers, in which intravenous adenosine has been used in patients with acute MI 5Our study has several limitations. First, we do not have information on other hyperemic drugs, such as regadenoson. Second, although safety assessments were performed and recorded in all of the patients at the time of the procedure, symptom reporting was incomplete. The available results confirm that symptoms typically occur with intravenous adenosine. Third, complete hemodynamic recordings were not available in all of the participants because resting arterial pressure is not required for IMR. Fourth, pressure wire studies were restricted to the infarct-related artery rather than the non-infarct artery in the STEMI cohort study. Nonetheless, we provide comprehensive hemodynamic data and information on symptoms from prospective evaluations in individual patients who were enrolled in studies that had been designed with an open approach to enrolment of ‘all-comers’. We think our observations are representative of ‘real-world’ clinical practice.6Guidewire-based measurement of coronary microvascular function involving intravenous adenosine infusion was feasible and safe during emergency or urgent PCI for STEMI and NSTEMI. The symptoms related to adenosine were predictable, self-limiting and not associated with adverse events. Finally, coronary dissection in MI patients was noted to be a rare phenomenon.British Heart Foundation (BHF) (Project Grant PG/11/2/28474), Chief Scientist Office (CSO), Scottish Diabetes Research Network (SDRN), Medical Research Scotland and the Scottish Funding Council (SFC).Our research is supported by grants from the All authors participating have disclosed potential conflicts of interest. Professor Berry has been Principal Investigator on institutional research grants supported by St Jude Medical and he has acted as a consultant to St Jude Medical with reimbursement to his employer, the University of Glasgow. Professor Oldroyd and Professor Curzen have acted as consultants to Volcano Corporation and St Jude Medical. None of the other authors have conflicts of interest to declare.


To assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age.Analysis of data collected from a prospective cohort study.Community-based investigation in Southampton, UK.761 children with valid blood pressure measurements, born to women participating in the Southampton Women’s Survey.Anthropometric measurements were collected at 0, 6, 12, 24 and 36 months and conditional changes between the time points calculated. Blood pressure was measured at 36 months. Factors possibly influencing the blood pressure were assessed using linear regression. All independent variables of interest and confounding variables were included in stepwise multiple regression to identify the model that best predicted blood pressure at 36 months.Greater conditional gains in abdominal circumference (AC) between 0–6 and 24–36 months were associated with higher systolic and diastolic blood pressures at 36 months (p<0.001). Subscapular skinfold and height gains were weakly associated with higher blood pressures, while greater weight gains between 0–6, 12–24 and 24–36 months were more strongly associated, but the dominant influences were AC gains, particularly from 0–6 to 24–36 months. Thus one SD score increases in AC between 0–6 and 24–36 months were associated with 1.59 mm Hg (95% CI 0.97 to 2.21) and 1.84 mm Hg (1.24 to 2.46) higher systolic blood pressures, respectively, and 1.04 mm Hg (0.57 to 1.51) and 1.02 mm Hg  higher diastolic pressures, respectively.Conditional gains in abdominal circumference, particularly within 6 months of birth and in the year preceding measurement, were more positively associated with blood pressure at 36 months than gains in other anthropometric measures. Above-average AC gains in early childhood may contribute to adult hypertension and increased cardiovascular disease risk. This is one of few studies that have investigated detailed anthropometric changes in relation to blood pressure in early age and examined conditional changes between different age points.Key confounding risk factors were adjusted for in the models, including maternal education attainment and smoking during pregnancy.A large number of children from a cross-section of socioeconomic backgrounds were included in the study.We were not able to include all the children born in the course of the cohort study as blood pressure measurements were not available for all children, but the study sample was found to be similar to the larger group at 36 months of age.Abdominal girth at this young age may only represent a gross measure of central fat deposition and differences between individuals may represent genetically/prenatally determined differences in physique.Low birth weight and rapid postnatal weight gain have been linked to increased risk of cardiovascular disease,6It is thought that there may be critical periods at specific time points early in life when accelerated growth predisposes to hypertension later in life.6Therefore, insight into whether postnatal alterations in body composition influence blood pressure in early childhood is relevant to the development of preventative strategies to reduce the risk of cardiovascular disease in later life. Our aim was to assess how gains in adiposity, fat distribution and body size between birth, 6, 12, 24 and 36 months relate to the blood pressure of children at 36 months.The SWS is a large prospective cohort study which started in 1998.There were 1981 singleton live births to women in the SWS by the end of 2003. After exclusion of infants with major congenital abnormalities (n=2) and neonatal deaths (n=6), 1973 SWS infants remained for postnatal follow-up.When each child was 24-months-old, the occupations of its mother and her partner were recorded and the highest ranking of these used to define the child's social class. The social class scale was: Professional (I), Management and technical (II), Skilled non-manual (IIIN), Skilled manual (IIIM), Partly skilled (IV) and Unskilled (V). For 10 children whose parental occupations were missing at this time, employment status recorded during early pregnancy was used. Educational attainment of the mother recorded before pregnancy was defined in six groups, from ‘none’ to ‘degree or above’.Anthropometric measurements were taken by trained researchers at birth, 6, 12, 24 and 36 months. Apart from those at birth, all measurements were taken in the children's homes. Infant crown-heel length was measured with a neonatometer . Child height was measured with a portable stadiometer . Skinfold thicknesses were measured using Holtain skinfold callipers (Holtain Ltd) at specified sites and abdominal circumference was taken at the end of expiration using a blank tape measured against a fixed scale. Strict monitoring of the nurses’ measurement techniques was performed by the senior research nurse and regular inter-observer variation studies were conducted.Blood pressure was measured using a Critikon DINAMAP 1846 SX automated blood pressure deviceRegression coefficients (β), with associated 95% CIs, were used to assess the strength of association between body size indicators . z-Scores were calculated for body weight and length/height using the 1990 British growth references for time points 6, 12, 24 and 36 months.Factors reported to be associated with blood pressure were assessed using linear regression, including age, social class, maternal education attainment, smoking in late pregnancy (an indicator of smoking throughout pregnancy) and crying of the child during blood pressure measurement. Factors that were univariately associated with blood pressure at age 36 months were retained for inclusion in regression models, namely crying, smoking and education.Multiple regression analysis was performed by entering all independent variables of interest into the model, in addition to the confounding variables. A stepwise multiple regression analysis was used to identify the growth variables that were most strongly associated with blood pressure at 36 months. Statistical analyses were performed using SPSS PASW Statistics Release V.18 , and Stata V.12.0 .At 36 months of age, 1640 children (83% of the 1973 available for follow-up) were followed-up. Birth weights and blood pressure measurements at age 36 months were available for 773 infants. Seven children with missing height and weight data at age 36 months and five with systolic pressures more than three SDs from the mean were excluded, leaving 761 in the analysis. Children in this study were similar to the larger population sample of SWS children seen at 36 months . Owing tThe greatest relative and absolute increases in body weight, height/length, abdominal circumference and subscapular skinfold thickness occurred between birth and 6 months , with thAge, gender and social class were not associated with blood pressure, but the 45 infants who cried during measurement had higher systolic (p=0.004) and diastolic pressures (p=0.001). Smoking in late pregnancy was associated with higher systolic (p=0.067) and diastolic pressures (p=0.005). Lower educational attainment (p=0.024) was associated with higher diastolic pressure.Initially, the four anthropometric measurements were considered separately . Each moThe results of the final regression models are presented in Our data indicate that conditional gains in abdominal circumference between birth and 6 months, as well as in the 12 months prior to blood pressure measurement, were associated with systolic and diastolic blood pressure at 36 months of age. Changes in weight were also associated with blood pressure, particularly systolic pressure, but to a lesser extent. In the multivariate regression model, a one SD gain in abdominal circumference z-score between 24 and 36 months was associated with a 1.66 mm Hg increase in systolic blood and a one SD increase between birth and 6 months with 1.56 mm Hg.There was considerable variability in the gains of abdominal mass at the time interval most predictive of blood pressure (24–36 months), with 39% of children experiencing an increase, suggesting the impact of environmental factors. It is possible that dietary intake and/or physical activity levels during this early period could alter abdominal circumference gain early in life, or it may be related to differences in growth trajectories,It is of note that subscapular skinfold thickness change, an indicator of subcutaneous fat deposition, had much weaker associations with blood pressure than abdominal circumference, which is an indicator of abdominal or visceral fat deposition. The finding that abdominal circumference gain between 0 and 6 months was more strongly associated with blood pressure at age 36 months than gains during 6–12 and 12–24 months could reflect the proposed critical period for childhood adiposity in the first 2 months of life,As summarised earlier, a strength of this study is the large sample size drawn from the general population. A post hoc power calculation  indicated there was 80% power to detect a regression coefficient of 0.88 mm Hg per one SD of an independent variable at 5% level of significance. Our study was thus sufficiently large to detect effect sizes of clinical relevance. In addition, we have assessed conditional growth, accounting for measurements at previous ages (thus ensuring independence of growth summaries between age periods), and have adjusted for relevant confounding factors.Few studies have collected such detailed anthropometric measurements with the methodological rigour to provide indicators of fat distribution in the early postnatal period, encompassing the transition from milk only to a mixed diet at the age of 36 months.It is clear from the data that the strongest association with blood pressure from all the anthropometric measurements is the gain in abdominal circumference; however, we acknowledge that when building a multivariate regression model of best fit, there is an element of chance as to which variables are included, even when they are not highly correlated.A limitation of the study is the inability to measure blood pressure in all children in the cohort, although there do not appear to be noteworthy differences between those who were measured and the remainder.Central adiposity and a large waist circumference have been associated with higher blood pressure in adults, but there are few reports for children. In one study, children with accelerated weight gain in the first 2 years of life were fatter and had more central fat distribution at 5 years of age than other children.There is considerable debate as to whether there are specific age periods early in life during which weight gain and/or fat deposition are more influential in predicting cardiovascular risk. Our findings are similar to a report that weight gain between 24 and 36 months was positively associated with systolic blood pressure.Our data support a developmental contribution to the origin of elevated blood pressure in childhood, and therefore potentially in later adulthood. Indeed, we have previously demonstrated that higher fetal liver blood flow is strongly correlated with greater fat mass at birth and at 4 years, indicating that influences on body composition operate very early in life.It is not clear whether postnatal interventions would be effective in limiting growth in abdominal circumference, and any interventions to limit abdominal circumference gains would likely also reduce the rate of growth. However, there is accumulating evidence that accelerated early growth has long-term adverse physiological effects in later life, increasing cardiovascular risk factors, including high blood pressure.We have demonstrated that although conditional gains in body weight and height during specific age periods are associated with systolic and diastolic blood pressure, as previously recognised, conditional gains in abdominal circumference  have the strongest association with blood pressure at 36 months of age. This is especially true for the first 6 months of life and between 24 and 36 months . Therefore, central deposition of fat in early childhood, indicated by abdominal circumference, may contribute to an increased risk of developing hypertension later in life. Follow-up blood pressure measurements for the study group may enable confirmation of this at a later date.