Nigeria is a developing country that is currently witnessing an upsurge in diabetes mellitus and obesity with its antecedent consequences. There is also a fairly high prevalence of asthma affecting an estimated 10.7% of the population. There is no data presently on the possible presence of metabolic syndrome in Nigerian living with asthma. The study was conceived to determine the prevalence of metabolic syndrome among a population of asthmatics seen in our practice. We also attempt to compare asthma severity, control and pulmonary function tests in asthmatics with metabolic syndrome and those without.This cross-sectional study was carried out at the asthma clinic of a tertiary teaching hospital. Ethical clearance was obtained from the research and ethics committee of the hospital. Written consent was obtained from the participants. Interviewer based questionnaire was used to obtain required information, anthropometric indices were recorded and clinical examinations done. Pulmonary function tests were carried out using desktop Alpha Spirometer model 6000 made by Vitalograph UK (2007). Blood pressure was measured using sphygmomanometer in mmHg. Fasting venous blood was taken for blood sugar and lipid profile. Metabolic syndrome was defined by the international diabetes Federation (IDF) criteria.One hundred and fifty eight (158) asthmatics participated in the study comprising of 63 (39.9%) males and 95(60.1%) females. The age range was 14-78 years with a mean of 46.48+/-17.00 years. The mean duration of asthma diagnosis was 13.95+/-12.14 years. The prevalence of hypertension was 29.1%. 17 (10.8%) had fasting blood sugar above 100 mg/dl. Abdominal obesity was present in 78 (49.5%). The mean total cholesterol was 192.63+/-40.7 mg/dl. HDL was low in 21(22%) of female and 3 (4.8%) male. The prevalence of metabolic syndrome was 17.7%, affecting 28 asthma patients. Asthma control was affected by the presence of metabolic syndrome. P < 0.05. The pulmonary function test was not significantly affected by presence of metabolic syndrome.Metabolic syndrome prevalence is high in the population of asthma patients studied. It is therefore important to screen patient with asthma for this condition and treat to improve outcome. Asthma affects an estimated 300 million people worldwide . It is aSeveral studies have associated obesity with asthma particularly central obesity which is an important component of metabolic syndrome. There is growing epidemiological evidence that obesity increases the risk of developing asthma. In some studies, insulin resistance or metabolic syndrome is a stronger risk factor than the body mass .The obese-asthma sub phenotype is thought to be characterized by paucity of inflammation but marked symptoms, poor response to glucocorticoids, and peripheral airway dysfunction. While obesity may predispose to increased Th2 inflammation or atopic tendencies, other mechanisms that are independent of inflammatory cells, need to be considered. There is growing evidence of the influence of hyperinsulinemia and insulin-like growth factors on airwaystructure and function -11.The metabolic syndrome is a cluster of risk factors that include hypertension, impaired glucose tolerance or diabetes mellitus, central obesity and dyslipidaemia. Nigeria is a developing country that is currently witnessing an upsurge in diabetes mellitus and obesity and the attendant sequelae. Against a background of a fairly high prevalence rate of asthma, the disease burden of these disorders may ultimately prove to be unacceptably high.Hitherto, there has been no data on the possible presence e of the metabolic syndrome in Nigerians living with asthma. Thus this study was carried out to determine the prevalence of metabolic syndrome among a population of asthmatics seen in our practice and also compare the asthma severity, control and pulmonary function amongst those with metabolic syndrome and those without the metabolic syndrome.This was a cross sectional study carried out at the asthma clinic of Lagos State University Teaching Hospital Ikeja. The hospital is one of the three tertiary hospitals in the megacity of Lagos with about 18 million residents. The hospital receives referral from secondary private and public health institutions in the state. The asthma clinic is conducted by Pulmonologists and resident doctors.Ethical approval was obtained from the hospital research and ethics committee. All participants gave written informed consent prior to enrolment in the study. Written informed consent was obtained from parents of willing patients who were below 18 years. Patients enrolled into the study were those on follow up at the asthma clinic with established diagnosis of bronchial asthma based on the pattern of symptoms (airways obstruction and hyperresponsiveness) and/or response to therapy (reversibility) over time [Asthma patients with an F score of < 8 recorded from a previous study on the prevalence of gastroesophageal reflux disease (GERD) among asthmatics were excluded . An infoInterviewer administered questionnaires were used to collect information on the bio data of the patients, the asthma symptoms, duration and asthma control. Anthropometric indices were determined by standard criteria and the blood pressure measured using a mercury sphygmomanometer with the systolic and diastolic blood pressures taken as the first and fifth korotkoff sounds respectively.The pulmonary function tests were done in the sitting position using desktop Alpha Spirometer model 6000 made by Vitalograph UK (year 2007) to measure the FEV1, FVC, PEFR and post bronchodilator responses following inhalation of 200ug salbutamol.Laboratory assessments included venous blood samples in a fasted state for the determination of components of the lipid panel  and blood glucose levels. The serum glucose was measured using the glucose-oxidase method and the lipid profile by the enzymatic-colorimetric method.The following operational definitions were utilized:1. Asthma was diagnosed based on episodic breathlessness, chest pain and wheeze with reversible airway obstruction [2. The presence of three or more of any of the following is a pointer to the metabolic syndrome. Waist circumference (WC) greater than 102 cm in men and 88 cm in women; serum triglycerides (TG) level of at least 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) level of less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of at least 130/85 mm Hg; or serum glucose level of at least 100 mg/dL (5.6 mmol/L) [3. Asthma control was defined according to GINA  Controlled asthma is said to be present if there is none or less than twice a week Daytime symptoms, No limitation of activities, no nocturnal symptoms or awakening, need none or less than twice a week need for reliever/rescue medications and the Lung Functions (Peak Expiratory Flow rate or Forced Expiratory volume in one sec FEV1) is normal. The asthma is said to be partly controlled if any of the following is present: More than twice per week daytime symptoms, any limitation of activity, nocturnal awakening needing more than twice/week rescue or reliever treatment and PEF or FEV1 less than 80% predicted. The asthma is uncontrolled if three or more of the partly controlled asthma is present [ is norma4. Asthma severity was classified into intermittent, mild persistent, moderate persistent and severe persistent using the symptoms and PEFR according to GINA guidelines .2), healthy/normal (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2), and obesity (30 kg/m2) [5. Cadre of BMI were classified as follows; Anthropometric indices were classified into underweight (<18.5 kg/m0 kg/m2) ,15.6. Lung function tests refer to the Forced Expiratory Volume in one second (FEV1), forced vital capacity (FVC) as well as the Peak Expiratory flow rate (PEFR).Data analysis was done using the SPSS version 17. Descriptive statistics was done and quantitative variable expressed as means ± SD. The qualitative data were expressed in ratio or proportions. Comparison of means were done using the student ‘t’ test and anova as applicable while categorical variables were compared with the chi square test. All tests were performed at 5% level of significance.A total of 158 asthma patients were enrolled into the study within the study period having fulfilled the enrolment criteria aforementioned and having given a written informed consent. There were 63 (39.9%) males and 95 (60.1%) females. The age range was between 14 and 78 years with a mean age of 46.5 ± 17.2 years. There was no significant gender difference in mean age of the participants: males were 44.9 ± 16.2 years and 47.6 ± 17.7 years for the females (p = 0.334). The females had a longer duration of asthma than the males with mean duration of 16.1 ± 13.4 years compared with 10.7 ±9.2 years for males, p = 0.006.Metabolic syndrome was present in 28 patients 17.7%) comprising of 13 males and 15 females. The socio demographic characteristics of asthmatics with metabolic syndrome and those without metabolic syndrome were compared in Table 7.7% compThere were 46 29.1%) asthmatics with hypertension. The prevalence of obesity according to BMI was 53.8% with 85 patients being obese. The distribution of patients according to BMI is shown in Figure % asthmatThe mean total cholesterol, mean high density lipoprotein cholesterol (HDL), mean triglyceride (TG), low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) of the patients were 192.6 ± 40.7 mg/dl, 52.9 ± 8.3 mg/dl, 62.5 ± 13.1 mg/dl, 122.2 ± 33.21 mg/dl and 13.3 ± 3.2 mg/dl respectively. Low level of HDL was present in 21(22.1%) of the females (HDL less than 50 mg/dl) while only 3 (4.8%) males had low HDL i.e. less than 40 mg/dl . All the patients had normal level of triglycerides.Table Inhaled corticosteroid and Long acting β agonist (LABA + ICS) were frequently used by the patients 126 (79.7) compared with 32 (20.3). The asthmatics without metabolic syndrome used 109 (83.8) used LABA + ICS significantly more compared with those without metabolic syndrome 17 (60.7) p < 0.05 similarly oral β agonist were used more in those with metabolic syndrome. P < 0.05 There was no statistical significant difference in the usage of other medications between the two groups. This is shown in Table Table Table The prevalence of diabetes was 4.4% with 7 patients having diabetes. Hypertension was present in 46(29.1%) of the patients. Allergic Rhinitis, allergic sinusitis, allergic conjunctivitis, and atopic dermatitis was present in 77(48.7%), 56 (35.4%), 66 (41.8%) and 6 (3.8%) respectively. Majority 114 (72.2) of the patients did not have family history of asthma.In this cross-sectional study of a subset of asthma patients, we found metabolic syndrome in 17.7% of the asthma patients studied. This is rather high and may be a reflection of the increasing prevalence of the metabolic syndrome in the population. Almost half of the asthmatics studied had abdominal obesity. This is quite worrisome as abdominal obesity remains one of the important components of the metabolic syndrome. In a similar study by Uzunlulu et al. the prevalence of metabolic syndrome in asthma patients was 36.7% which is higher than our own study but when compared with their own control they did not find any statistically significant difference . ObesityIn our study we found that the patients with metabolic syndrome co-existing with their asthma were much older than those having asthma without metabolic syndrome. This is not surprising as diseases like hypertension, Type 2 diabetes mellitus (Type 2-DM) and dyslipidaemia tends to occur more in the older age groups. The same cannot be said of obesity, an important component of the metabolic syndrome which is on the increase even among the younger age groups. The prevalence of obesity in this study is unacceptably high. This is not surprising because according to the World Health Organisation (WHO), obesity has reached epidemic proportions globally with more than 1 billion adults being overweight and at least 300 million of them clinically obese. Obesity is now recognised by WHO as a major contributor to the global burden of chronic diseases and disability . It is tThe relative increase in the prevalence of abdominal obesity in the females when compared with males is also in keeping with the literature since women have been documented to suffer a disproportionate burden of disease attributable to overweight and obesity. It is believed that female obesity has increased by 15% in the past decade and as a result has become more prone to diseases like diabetes and hypertension. Some of the reasons ascribed to this include low level of physical activity, genetic factors and endocrine factors among others .In this study, hypertension existed in a significant proportion of the asthma patient and this may be a reflection of the prevalence of hypertension in the population or a consequence of steroid therapy in use by the asthmatics. Although in our study we did not compare our findings to the general population or those without asthma, this is one of the limitations of our study. However an extensive study requiring larger number of asthmatics and matched with a control without asthma will be needed in the future to answer some of the questions.In our study we did not find any significant association between presence of metabolic syndrome and pulmonary function tests. This may be the consequence of the fact that our asthma patients are those previously diagnosed and already on treatment for asthma being followed up by specialist physicians this is at variance with Leone who found an independent relationship between lung function impairment  and metabolic syndrome in both sexes .In our study we could not exclude the potential role of obstructive sleep apnea on respiratory system in our obese asthmatics. This is because none of the obese asthmatics had any sleep studies done and we were unable to evaluate the adipokines and pro-inflammatory cytokines which are often up regulated in obese patients and could impact on the neural control of the upper airway in obstructive sleep apnoea. These are very important limitations in our study.The prevalence of metabolic syndrome is high among the asthma patients studied. We also recorded poorer asthma control in those with the metabolic syndrome. It is therefore important to screen patient with asthma for the components of metabolic syndrome and institute appropriate managements when indicated to improve overall outcome of asthma management.Olufunke O Adeyeye , Anthonia O Ogbera, Olayinka O Ogunleye, Ayodeji T Brodie-Mens, Folasade F Bolarinwa, Raymond T Bamisile, Babatunde O Onadeko. We have no competing interest.OO conceived of the study, and participated in its design and coordination as well as writing of the manuscript. OA involved in the drafting, conception, design, collection and analysis, writing of the manuscript. OO participated in its design data collection and analysis. AT analyse the biochemical parameters. FF carry out pulmonary function test on participants. RT collection of data, manuscript revision. BO involved in the drafting, conception, design and collection. All authors read and approved the final manuscript. The study was funded by the Authors.


P < 0.01) and new LVH . PP increased at a greater rate in the usual than in lower MAP groups , but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.Pulse pressure (PP), a marker of arterial system properties, has been linked to cardiovascular (CV) complications. We examined (a) association between unit changes of PP and (i) composite CV outcomes and (ii) development of left-ventricular hypertrophy (LVH) and (b) effect of mean arterial pressure (MAP) control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107 mmHg) or a lower MAP goal (≤92 mmHg) and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47,  Population and hospital-based studies , 2 have Investigations in hypertension have generally focused on the steady components of blood pressure, such as mean arterial pressure (MAP), which is determined by cardiac output and peripheral vascular resistance , 11. PulThe incidence of end-stage renal disease (ESRD) due to high BP has steadily increased over the years, and it disproportionately affects African Americans , 20. EpiThe African American Study of Kidney Disease and Hypertension (AASK), a multicenter clinical trial, was designed to evaluate the impact of two levels of mean BP control  and three antihypertensive drug regimens on the progression of hypertensive kidney disease –28. In t2 and with no other identified causes of renal insufficiency. Exclusion criteria included (i) diastolic BP (DBP) < 95 mmHg, (ii) known history of diabetes mellitus (fasting glucose ≥ 140 mg/dL or random glucose > 200 mg/dL), (iii) urinary protein to creatinine ratio greater than 2.5, (iv) accelerated and malignant hypertension within 6 months, (v) secondary hypertension, (vi) evidence of non-BP-related causes of renal disease, (vii) serious systemic disease, (viii) clinical congestive heart failure, or (ix) specific indication for or contraindication to a study drug or study procedure. The protocol and procedures were approved by the IRB of each center, and all participants read and gave written informed consent. Participants were enrolled between February 1995 and September 1998. Planned followup to the end of the study in September 2001 was 3 to 6.4 years.The 1094 randomized participants in the AASK study were self-identified African Americans with hypertension between 18 and 70 years of age, with initial GFR between 20 and 65 mL/min per 1.73 mn = 554) or a lower MAP goal defined as MAP ≤ 92 mmHg (n = 540) [n = 441), an ACE inhibitor, ramipril (n = 436) or a calcium channel blocker, amlodipine (n = 216). If the target BP could not be attained on the first line therapy, additional open label antihypertensive drugs were added sequentially . In this secondary analysis, patients requiring the addition of another medication or an increase in the current medication between months 9 and 35 were excluded in order to avoid a potential treatment effect on the rate of change in PP after they had stabilized at the onset of the analysis period.The AASK trial and study design have been described elsewhere –28. Brien = 540) –28. WithBlood pressure was assessed at protocol visits conducted at baseline, monthly during the first 6 months of followup, and every two months thereafter. Additional clinic visits with further blood pressure assessments were scheduled as needed to titrate the antihypertensive medications to bring the blood pressure level within the target range. At each blood pressure assessment three consecutive seated BP measurements were obtained using a Hawksley random zero sphygmomanometer after at least 5-minute rest, with the mean of the last 2 readings recorded. Pulse pressure was calculated as the difference between the average systolic and diastolic BP readings. A central laboratory measured serum and urinary levels of creatinine and protein as well as lipids. LVH was assessed at baseline and at 2-year intervals during followup by electrocardiography (EKG), using local readings based on the Cornell voltage criteria. A composite endpoint defined by the occurrence of cardiovascular death or the first cardiovascular hospitalization after randomization was designated as the main CV outcome for the trial. To determine the CV composite, events identified as potentially CV by the local clinical investigators, including hospitalizations and death from myocardial infarction, stroke, heart failure, revascularization procedures, and other cardiovascular events resulting in hospitalization, were reviewed, and a final classification was determined according to a prespecified protocol by a Cardiovascular Outcomes Committee that was blinded to randomization assignment. Because routine followup ceased once patients reached end stage renal disease (ESRD), only pre-ESRD CV events are included in the CV composite. In addition to the main CV composite outcome, disease progression of the heart is also evaluated in this paper by the development of EKG-based LVH at the 4-year assessment. The increase in PP from 9 months through the end of the patients' follow-up period is used as a surrogate of stiffening of the arterial system secondary to arteriosclerosis and/or CV remodeling.Univariate summaries of clinical and demographic characteristics included means and standard deviations or frequencies and percents, as appropriate. Multiple regression analysis was used to evaluate the cross-sectional relationship between PP and selected baseline variables, including age, gender, BMI, history of heart disease, lipid measures, and GFR.A series of exploratory analyses was performed to describe the association of selected CV and renal outcomes with baseline and follow-up BP indices. For these analyses, the mean follow-up systolic BP, diastolic BP, and PP were defined for each patient by the average of the BP parameter over all non-GFR BP assessments starting with the 4th month after randomization through the end of followup. In these analyses the BP indices were computed starting at the 4th month, rather than the 9th month, because in this case they are being evaluated as predictor variables rather than as response variables, so that it is advantageous to incorporate measurements early in follow-up. The analyses involving mean followup values of the BP indices were restricted to 1065 patients with at least one BP measurement after month 4.  Separate Cox regression analyses were performed to relate the main CV composite outcome to the baseline and mean follow-up values of the BP indices, with follow-up time censored at the occurrence of non-CV mortality, ESRD, or the end of the study. Finally, separate logistic regression analyses were performed to relate newly identified LVH at 4 years to the baseline and mean follow-up values of the three BP indices. The logistic regression analyses were conducted in a subgroup of 531 patients who remained in the study and provided EKG assessments at 4 years.Longitudinal mixed effects analysis was performed to estimate the effect of the randomized BP goal and drug treatments assignments on the rate of change of PP (PP slope) measurements obtained at protocol visits from 9 months after randomization through the end of followup. The mixed effects model assumed a random intercept plus a 1st order autoregressive error structure to account for the correlation in pulse pressure measurements in the same patients over time. Robust “sandwich” standard error estimates were used. The slopes were assessed using data after 9 months because most of the modifications in drug regimens required to attain target blood pressures under the AASK design had occurred by this time. Additional analyses were done including MAP, SBP, and DBP in the model in order to determine the effects of these BP components on the rate of change in PP. All analyses are performed using SAS Version 9 .P < 0.01 for each relationship). GFR, hematocrit, and level of educational attainment were no longer significantly associated with PP in the multivariable analysis. PP was not significantly associated with either gender or BMI in either the univariate or multivariable analyses.The 1094 randomized participants included 425 women (39%) and had a mean age of 55 years. Four hundred and twenty (38%) had LVH, 52% had a history of heart disease, and 29% were smokers. Additional baseline demographic and clinical characteristic of the study participants are displayed in P = 0.02) for every 10 mmHg increase in baseline PP and 28% greater  for every 10 mmHg increase in mean follow-up PP. Composite CV outcomes were not significantly associated with baseline MAP but with mean follow-up MAP. The CV composite outcome was not significantly associated with either baseline DBP or mean follow-up DBP after adjustment for baseline factors.P = 0.02) (P = 0.01) but neither with DBP nor MAP. Baseline BP indices were not associated with newly identified LVH at 4 years. These analyses of LVH were restricted to the subgroup of 531 patients who remained in the trial and provided an EKG reading at the 4-year assessment. Results of logistic regression models showed that a 10 mmHg higher mean followup PP was associated with a 26% increase in risk of a new indication of LVH by EKG between the baseline and 4-year assessments  . There wβ) ± SE) was significantly higher in the usual MAP goal compared to the lower MAP goal group . Averaging across the two MAP groups, the mean rates of increase of PP in the 3 antihypertensive treatment groups were, respectively, 0.85 ± 0.15, 0.68 ± 0.17, and 0.71 ± 0.27 mmHg per year for ACE, BB, and CCB and did not differ significantly by drug treatment assignment, that is, no interaction between MAP goal and drug treatment assignment. The mean SBP declined significantly in the lower MAP group , while there was no significant change in the usual MAP group (mean slope +0.21 ± 0.19 mmHg per year). The mean rates of change of DBP were negative and slightly steeper in the low than in the usual MAP groups, though not significantly different . This observation is important, because it shows that the effort of the study protocol to influence the MAP did not influence the BP components and subsequently PP.While the mean PP increased after 9 months in both MAP groups, after averaging across the three drug groups, the rate of increase (mean slope (P = 0.01). The larger increase in PP in the usual compared to the lower BP groups may have resulted from the larger difference between BP groups in the mean SBP slope than in the mean DBP slope.The mean rates of change of mean MAP were also negative and significantly steeper in the low than in the usual MAP groups,  the PP, an integrated result of the pulsatile flow and arterial system interaction, is a real-time representation of the in vivo hemodynamics of hypertension and not just a mathematical mean as is the MAP; (b) the PP, an observed BP component, may be more sensitive for detecting vascular changes from hypertension than the randomized MAP, even at small BP differences; and (c) a better understanding of the shape and rate of increase in amplitude of the PP may improve the prevention and treatment of hypertension.R = +0.25, P < 0.001), indicating that efforts to modify MAP may have also unintentionally modified PP to a limited extent and by the continued decline in SBP after 9 months in the lower but not in the usual MAP groups (see Two limitations must be acknowledged. First, because MAP was the independent variable in the trial, it is difficult to rule out the possibility that slower increase in PP after 9 months in the lower may have resulted from continued efforts of study personnel to bring MAP in the lower goal patients to ≤92 mmHg. We do not believe that was the case because there is always a close relationship among BP components except when the PP increases as a result of an increase in SBP and decrease in DBP. This possibility is suggested by the positive correlation of mean MAP with PP during the follow-up period (Pearson oups see . HoweverIn conclusion, this study demonstrates an independent association of PP with cardiovascular outcomes and showed that PP progression over time was less when a lower BP goal was targeted compared to usual BP goal.


To assess the relationships between progression of target-organ damage and cardiovascular, cortisol and coping responses in black urban Africans.n = 200) aged 21–62 years from the Sympathetic Activity and Ambulatory Blood Pressure in Africans study were stratified into normotensive and hypertensive groups. Resting and reactivity Finometer blood pressure, fasting sodium fluoride glucose and salivary cortisol values were obtained before and after applying the Stroop and cold pressor tests. Coping strategies were determined and high-resolution ultrasound carotid intima–media scans were done to determine progression of target-organ damage.Urban black African gender groups (A trend of high-normal resting cortisol values during sampling time 1 was demonstrated in all hypertensive men. Both hypertensive gender groups showed increased vascular responses during both mental stressors. During the cold pressor test, vascular responses predicted sub-clinical atherosclerosis in all hypertensive men, independent of sampling time.Early morning vascular responses in all the hypertensive men could have occurred secondarily to the permissive effect of cortisol on norepinephrine secretion, with subsequent α-adrenergic vasoconstriction. Their α-adrenergic vascular responses during the cold pressor test, however, predicted sub-clinical atherosclerosis, independent of sampling time and cortisol level. Exposure to chronic stress is a good predictor of future cardiovascular disease (CVD),3Psychological appraisal of stress could contribute to cardiovascular dysregulation through endothelial dysfunction and changes in vascular function.10et al.et al., revealing that Caucasian individuals who coped by problem engagement and seeking social support had lower cortisol levels and possibly lower CVD risk.14Malan et al. suggested that resting rather than cortisol stress responses plays a permissive role in sympathetically driven cardiovascular stress responses.17Chronic stress can lead to dysregulation of the HPAA with resultant increased circulating adrenocorticotropic hormone (ACTH), cortisol, corticosterone, impaired feedback regulation of the axis and impaired glucocorticoid receptor binding in the hippocampus.Since stress and related health impairments have become major problems in human life, investigation of the psychobiological pathways that link stress and disease are of major importance in black Africans with a high prevalence of hypertension.n = 101 men, n = 99 women) will be referred to as Africans. Exclusion criteria for the study were: pregnancy, lactation, temperature above 37ºC and users of alpha- and beta-blockers. Participants included had not donated blood or been vaccinated in the previous three months.The SABPA study was a target-population study that included a sample of 200 black African teachers, aged 21 to 62 years, in the Dr Kenneth Kaunda educational district, North-West Province. Hereafter, the black Africans (Permission to participate was granted by the North-West Education Department and support ensured from the South African Democratic Teachers’ Union. The ethics committee of the North-West University approved the study (00036-07-S6) and the study protocol conforms to the revised ethical guidelines of the Declaration of Helsinki, 2004. A standard subject information sheet was given to the subjects at their screening visit, and an informed consent form was signed prior to the start of the study.Every morning during the working week, physical activity meters were fitted to four of the 200 teachers between 07:00 and 08:00. Anthropometric measures, i.e. height and weight were taken into consideration for activating the software of the Acticals® activity monitor . The educators then resumed their normal daily activities and were transported at 16:30 to the Metabolic Unit research facility of the North-West University. At 17:00, they were welcomed and the four teachers each received his/her own private bedroom and was familiarised with the experimental setup to lessen anticipation stress.19Pre-counselling for HIV/AIDS was done under supervision by a trained registered nurse. They commenced with the first part of the psychosocial battery at 17:30 under supervision of registered psychologists. A standardised dinner  was provided at 18:00 and the last part of the psychosocial battery was completed after dinner. Participants were advised to go to bed at 22:00 and instructed to refrain from consuming food, alcohol, caffeine, smoking, exercising and tooth brushing eight hours prior to saliva and blood sampling.12At 05:45 the following morning, the participants were awakened and anthropometric measurements were taken in triplicate by registered anthropometrists according to standardised procedures. We collected blood pressure measures, and saliva and blood samples for cortisol assays from the teachers in semi-Fowlers position in two identical blood pressure stations at two different times .Procedures in the two identical blood pressure stations were as follows: blood pressure measurements according to the Rocci/Korotkoff method were taken, followed by resting Finometer blood pressure, and saliva and blood sampling for cortisol determinations. Blood pressure responses were obtained during stressor application while blood sampling was done 10 minutes after stressor exposure. Cortisol saliva responses were sampled 30 minutes after stressor exposure. The same procedure was followed for the second stressor. The two identical blood pressure stations followed exactly the same protocol (± 1.5 hours) under supervision of a registered nurse and doctor. Ultrasound scanning for carotid intima–media thickness (CIMT) followed. Immediate feedback was given on available data and post-counselling regarding HIV status and referrals were made. Thereafter, they received incentives and breakfast, and went back to school.Height was measured with an Invicta Stadiometer  to the nearest 0.1 cm while the participant’s head was in the Frankfort plane. Heels were together, with the buttocks and upper back touching the stadiometer. Mass was measured to the nearest 0.1 kg on a KRUPS scale with the participant wearing minimal clothing and with the weight evenly distributed. Height and mass were used to calculate body mass index (BMI). Waist circumferences (WC) were measured with the participant in a standing position . The WC was taken at the midpoint between the lower costal border and the iliac crest, perpendicular to the long axis of the trunk.Participants were in semi-Fowlers position in the blood pressure stations. After a five-minute rest period, two Riva-Rocci/Korotkoff blood pressure measurements were obtained, with a five-minute rest period between measurements. A suitable cuff size was applied to the non-dominant arm. The second measurement classified participants as hypertensive according to the cutoff points of the European Society of Hypertension Guidelines (Korotkoff sound I: resting SBP ≥ 140 mmHg and/or Korotkoff sound V: resting DBP ≥ 90 mmHg).Resting salivary cortisol levels were obtained 45 minutes after awakening, avoiding the cortisol awakening response (CAR).Participants were subjected to mental stressors for one minute in a counterbalanced design, including the Stroop color–word interference task (CWC) and the cold pressor test (CPT), which involved the immersion of the left foot up to the ankle in ice water (4°C).A high-resolution ultrasound carotid intima–media scanThe Coping strategy indicator (CSI) of Amirkhan,A registered nurse sampled fasting blood from brachial vein branches with a winged infusion set, for serum oestrogen as well as sodium fluoride (NaF) glucose levels. Analyses were done with the sequential multiple analyser computer, KonelabTM 20i, Finland. Salivette® cortisol analyses were done with a high-sensitivity enzyme-linked immunosorbant assay (ELISA). The intra- and inter-assay coefficients of variation for cortisol were 7.7 and 9.8%, respectively. The antibody test to indicate positive HIV status was done for each participant, including the First response kit  and Confirmatory Pareekshak test (Bhat Bio-tech India (P) LTD, Bangalore, India).A 2 × 2 analysis of covariance (ANCOVA) adjusted for age, BMI and resting values (blood pressure and cortisol) was conducted to determine interaction between the main effects, i.e. gender and blood pressure status and each of the different variables. Gender groups were stratified according to the ESH guidelines (RivaRocci Korotkoff 2nd measurements) into BP = 120–139/80–89 mmHg and BP ≥ 140/90 mmHg,p ≤ 0.05, r ≥ 0.35 and adjusted R2Multivariate regression analyses were done. Firstly, partial correlations, adjusting for age, BMI and resting values (blood pressure and cortisol), identified independent variables for forward stepwise regression analyses. Secondly, in forward stepwise regression analyses we determined associations in two separate models, i.e. model 1 (for each sampling time) and model 2 . CIMT was the dependent variable, and independent variables included age, resting and reactivity blood pressure and cortisol values. Multivariate regression values with p = 0.05] and TPR responses during the CWC test . In p = 0.001) during cortisol sampling time 1: 06:00–07:00, than during sampling time 2: 08:30–09:00, in all men and women.A single 2 × 2 ANCOVA showed significant interactions on the main effects for low problem solving [df  = 4.01, From p = 0.01) compared to their normotensive counterparts. No significant associations for hypertensive women existed to predict progression of sub-clinical atherosclerosis.In The aim of the study was to assess the relationship between cardiovascular, cortisol and coping responses in urban Africans. More men than women were hypertensive  with no differences in their CIMT levels. As their CIMT levels did not exceed 0.9 mm, which is the cut-off point for diagnosed sub-clinical atherosclerosis, we only indicated trends in the progression of sub-clinical atherosclerosis.25et al. demonstrated that a shift from central to more vascular blood pressure responses could be due to uncontrollability of psychosocial stress experienced by Africans.et al. added that hypertensives have been found to have a more reactive cardiovascular system than normotensives, and that they show a greater mean DBP reactivity when stressed.et al., indicating that Africans exhibit peripheral resistance responses at rest and when exposed to stressful situations.27From Glucose and salivary cortisol levels in both the normotensive and hypertensive men and women were high-normal (International Diabetes Federation, 5.6 mmol/l; 0.76–2.94ng/ml,29Results of urine analyses for cortisol, collected over eight to 24 hours and indicating chronic stress31Both hypertensive men and women demonstrated higher levels of stress, as indicated by high-normal resting cortisol and glucose values, as well as increased vascular responsiveness during mental stress in cortisol sampling time 1. It was also apparent that in men and women, independent of blood pressure status, their high-normal blood glucose levels, which were above 4.9 mmol/l, could imply increased cardiovascular risk.32In developing countries where cultural disruptions are apparent, such as experienced by black South Africans, this could increase stress and therefore accentuate their CVD risk. This could especially hold true in black Africans with an inherent predisposition to increased salt sensitivity and sympathetic nervous system hyperactivity.The mechanism proposed to be active in the hypertensive men is as follows: the resting high-normal cortisol and glucose levels and vascular responses due to acute mental stress could be enhanced via the permissive effect of cortisol on the catecholamines and subsequently vasoconstriction, inhibiting insulin production and vasodilating responses.A typical α-adrenergic vascular pattern was seen in both genders during stressor application, also suggesting a more avoidance/passive coping pattern.Limitations and weaknesses of this study included groups that were too small when different coping strategies were considered within the existing blood pressure stratification. Small groups could have caused the psychological aspect of this study to lose its strength. An additional stress-related hormone such as norepinephrine could have clarified the mechanistic approach. Strengths of the study included the well-controlled psychophysiological design of the study as well as the novelty of data on salivary cortisol levels and associated vascular responses in black South Africans.Early morning vascular responses


Background. Postoperative acute kidney injury (AKI) is associated with high mortality and substantial cost after aortocoronary bypass graft (CABG) surgery. We tested the hypothesis that intraoperative systolic blood pressure variation is associated with postoperative AKI. Methods. We gathered demographic, procedural, blood pressure, and renal outcome data for 7,247 CABG surgeries at a single institution between 1996 and 2005. A development/validation cohort methodology was randomly divided . Peak postoperative serum creatinine rise relative to baseline (%ΔCr) was the primary AKI outcome variable. Markers reflective of intraoperative systolic blood pressure variation were derived for each patient including (1) peak and nadir values (absolute and relative to baseline) and (2) excursion episodes beyond selected thresholds . Each marker of systolic blood pressure variation was then separately evaluated for association with AKI using linear regression models with adjustment for several known risk factors . Results. An association was identified between systolic blood pressure relative to baseline and postoperative AKI (P < 0.006). Conclusions. In CABG surgery patients, intraoperative systolic blood pressure decrease relative to baseline systolic blood pressure is independently associated with postoperative AKI. It is commonly purported that poor perioperative hemodynamic control during cardiac surgery leads to postoperative acute kidney injury (AKI) –9. SystoWhereas a large rise in serum creatinine ≥100%) over baseline has been shown to portend a doubling of in-hospital mortality, it has also been shown that even the small relative increases in creatinine, used as a sensitive index of AKI after aortocoronary bypass graft (CABG) surgery, can be associated with higher mortality and substantial additive cost 0% over b.  Cardiac surgery-associated AKI appears mechanistically to be related to preexisting renal dysfunction, diabetes and glucose intolerance, ventricular dysfunction, older age, preexisting hypertension, micro- and macroembolic processes, inflammatory mediators, prolonged duration of cardiopulmonary bypass (CPB), sensitivity to sympathetic stimulation, and perturbations of renovascular resistance and flow , 19–23.  Although preoperative characterizations of blood pressure such as systolic hypertension and widened pulse pressure are already known to be predictors of ischemic postoperative events including AKI , 24–31, http://www.sts.org/) criteria [With Institutional Review Board approval, we retrospectively studied a cohort of 7247 consecutive patients undergoing primary nonemergent CABG surgery procedures performed at Duke University Medical Center between September 1st, 1996, and December 30th, 2005. Demographic, perioperative, and renal outcome data, including patient characteristics, were accessed from the prospectively collected Duke Databank for Cardiovascular Diseases. The Databank is prospectively compiled from contemporaneous medical records, custom datasheets, and records of laboratory results. Database quality assurance involves random chart review for data confirmation and assessment of data completeness. In-hospital complications were classified using the Society of Thoracic Surgeons  at 50–80 mm Hg. Mean arterial pressure was adjusted during CPB using intravenous vasoconstrictors and dilators by bolus and/or infusion as required. The pump was primed with crystalloid, and arterial blood gases were measured every 15 to 30 minutes to maintain arterial carbon dioxide partial pressures of 35 to 40 mm Hg, unadjusted for temperature (α-stat), and oxygen partial pressures of 150 to 250 mm Hg. Use of agents with potential renal effects  was not regulated. The CPB circuit was primed with mannitol (50 gm of 20% solution), crystalloid solution , and 500 mL albumin/hetastarch and packed red blood cells as required. Typically, acceptable hematocrit ranged from 22 to 24% during bypass, with red blood cell transfusion usually occurring when values below 20% were observed. Anterograde and retrograde blood cardioplegia delivered between 6 and 8°C was the myocardial protection strategy of choice.Anesthesia was managed per the attending anesthesiologist's preference. All patients underwent nonpulsatile hypothermic (30°–32°C) CPB. Perfusion was maintained at pump flow rates of 2 to 2.4 L·minμmol/L (0.5–1.5 mg/dL). Preoperative creatinine was obtained within one week prior to surgery and defined as the value recorded closest to but not on the day of surgery. The peak postoperative creatinine value was the highest of the daily in-hospital postoperative creatinine values. Preoperative to peak postoperative change in serum creatinine was the relative difference between preoperative and peak postoperative values (%ΔCr).Preoperative and daily postoperative serum creatinine values were measured until hospital discharge as per institutional protocol. If more than one creatinine per day was measured, then the first measurement was used. Serum creatinine was measured using a dry slide enzymatic reflectance technique  with a normal range of 44–133 Following radial arterial line placement, intraoperative blood pressure measurements were captured every 30 seconds for all patients as part of their electronic medical record. In total nearly 1.5 million  blood pressure data points were evaluated. Rules were used to exclude implausible blood pressure values and those suggestive of artifact such as line occlusion or open-to-air. Systolic blood pressure values beyond 299 mm Hg or below 25 mm Hg were excluded from analysis. Blood pressure measurements during CPB were also excluded since nonpulsatile CPB perfusion pressure variation is dissimilar to blood pressure variation unrelated to CPB, and several studies including one from the study institution,  have fai baseline blood pressure was defined as the median of the first 5 intraoperative recorded values, occurring while the patient was awake and mildly sedated but prior to anesthesia induction. Peak and nadir variables were calculated from the most extreme intraoperative fluctuations in systolic blood pressure (SBP) compared to baseline blood pressure. Excursion episodes beyond various systolic threshold criteria  were characterized by their occurrence frequency , duration , and “area under curve” (AUC), as reflected by an integral of degree and duration calculated in mm Hg·min units , as previously described [For study purposes,escribed , 37.P < 0.05 was considered significant. The study was conceived and designed by Solomon Aronson; the data gathered and analyzed by Solomon Aronson, Mark Stafford Smith, and Barbara Phillips-Bute. The paper was written by Solomon Aronson and Mark Stafford Smith and edited by Solomon Aronson, Jeffrey Gaca, Manuel Fontes, Joseph P. Mathew, and Mark F. Newman. Patient characteristics were described using percentages for categorical variables and medians and interquartile ranges (IQR) for continuous variables. Assessment for associations between AKI (%ΔCr) and each derived measure of systolic blood pressure variability was then investigated using separate multivariable linear regression models, adjusted for aprotinin use, age, CHF, previous MI, baseline creatinine, bypass time, diabetes, weight, valve surgery, gender, and preoperative pulse pressure. No adjustment was made for multiple comparisons in these development analyses since all inquiries were considered exploratory. After thorough investigation in the development dataset, a single primary hypothesis was generated for testing in the validation dataset. Preoperative hematocrit and intra-aortic balloon pump utilization were tested separately as interactive variables with intraoperative systolic hypotension for an association with postoperative AKI. Secondary  analyses of the combined development and validation dataset were employed to further explore the validated significant associations. All analyses were performed using SAS statistical software . a priori criteria for exclusion, including 482 values above 299 (0.03%) and 11,839 below 25 mm Hg (0.79%), from a total 1,495,289 systolic blood pressure determinations. A priori it was decided that values above 300 and below 25 represent an artifact and were excluded. In contrast, values between 250 and 299 mm Hg were rare (0.1%) but fell within a normal distribution of systolic blood pressure values and were therefore not excluded.Final development and validation samples included 4864 and 2383 patients, respectively, with complete blood pressure and renal data . There wr2 value in the developmental sample, a marker of systemic hypotension relative to baseline was identified as the single best predictor of % delta creatinine . This measure was calculated as systolic blood pressure drop from baseline to nadir, expressed as a percentage of baseline. Therefore, this single measure (% drop) was selected for validation in the validation sample.Measures of systolic blood pressure variability  were eacP < 0.0016) in the validation data set. Descriptive data, P values, and model r-square values for all of the tested measures are presented in P = 0.44) for the effect of SBP on renal function across the range of preoperative HCT values as well as utilization of an intraoperative aortic balloon pump (P = 0.25), In a multivariable linear regression analysis using the validation sample, an association between percent systolic blood pressure change below baseline and %ΔCr was validated , but the small sample size of both off-bypass and valve procedures precludes this. This hypothesis sought to primarily explore the association of intraoperative systolic blood pressure variability with postoperative changes in creatinine. These data only represent intraoperative pulsatile blood pressure and exclude static mean arterial pressure (MAP) during cardiopulmonary bypass (CPB). While we acknowledge that blood pressure management during CPB is an important and interesting variable, we chose not to include the MAP index during CPB in this analysis because data regarding MAP during CPB and postoperative outcomes are unclear. Whereas Fischer et al.  reported


Systolic blood pressure (SBP) decline has been reported in octogenarians. The aim was to study if it could be observed while measuring SBP with two methods: Korotkoff (K-BP) and Strain-Gauge-Finger-Pletysmography (SG-BP), and which of them were more reliable in expressing vascular burden.A cohort of 703 men from a population of Malmö, Sweden, were included in "Men born in 1914-study" and followed-up at ages: 68 and 81 years. 176 survivors were examined with K-BP and SG-BP at both ages, and 104 of them with Ambulatory Blood Pressure at age 81/82. Ankle Brachial Index (ABI) was measured on both occasions, and Carotid Ultrasound at age 81.From age 68 to 81, mean K-BP decreased in the cohort with mean 8.3 mmHg, while SG-BP increased with 13.4 mmHg. K-BP decreased in 55% and SG-BP in 31% of the subjects. At age 81, K-BP was lower than SG-BP in 72% of subjects, and correlated to high K-BP at age 68 . SG-BP at age 81 was correlated with mean ambulatory 24-h SBP , daytime SBP , nighttime SBP , and daytime and nighttime Pulse Pressure . KB-BP correlated moderately only with nighttime SBP , and daytime and nightime pulse pressure . Increasing SG-BP from age 68 to 81, but not K-BP, correlated with: 24-h, daytime and nighttime SBP, and mean daytime and nighttime Pulse Pressure. Increasing SG-BP was also predicted by high B-glucose and low ABI at age 68, and correlated with carotid stenosis and low ABI age 81, and the grade of ABI decrease over 13 years.In contrast to K-BP, values of SG-BP in octogenarians strongly correlated with Ambulatory Blood Pressure. The SG-BP decline in the last decade was rare, and increasing SG-BP better than K-BP reflected advanced atherosclerosis. It should be aware, that K-BP underdetected 46% of subjects with SG-BP equal/higher than 140 mmHg at age 81, which may lead to biased associations with risk factors due to differential misclassification by age. Several studies have reported that in aging, blood pressure (BP) takes a shape of inverted parabola with initial BP-increase up to a seventh decade, and thereafter a subsequent decline ,2. BP deIn healthy hypertensive elderly, attempts to treat high BP gave positive results concerning the rate of stroke, heart failure, cardiovascular death and dementia ,20. In aTo avoid the pitfalls connected with auscultation and to increase reliability of BP measurement in labolatories, a strain gauge technique has been developed - where BP is recorded objectively by a curve . This meConcerning the possible pitfalls during blood pressure measurement using Korotkoff technique in the elderly, we aimed to study if aging-related changes in BP could be observed in the same extent by Korotkoff as Strain gauge technique, and which of them was best correlated to Ambulatory Blood Pressure Monitoring. Thanks the opportunity to examine BP with both Korotkoff and strain gauge technique in the cohort of elderly men twice during their life, we could compare the time-change in BP with vascular risk factors, as well as with established markers of vascular disease. The null hypothesis was that there would be no difference between age-related BP decline examined with these two methods.A prospective population study "Men born in 1914" has been in progress since 1968. 809 men born in even months in 1914 in Malmö- Sweden were invited, and 703 of them took part in the first examination. At first follow-up, at age 68, 500 agreed to participate in a new examination. At the second follow-up, 281 men who were at life and reached 81 years, were invited 185 agreed to participate (66%). BP measurements according to the protocol below were done in 176 subjects. Additional examinations were done at age 68, including laboratory analyses and circulation in lower extremities estimated by ankle-brachial pressure index (ABI). At age 81, except repeated medical examination, a medical history was retrieved from a questionnaire, spouses and/or relatives, and carotid ultrasound was performed, as well as ABI was estimated again.Upper right arm systolic and diastolic BP was measured sphygmomanometrically at age 68 and at age 81, after 15 min of rest, using a calibrated mercury manometer and a standard rubber cuff (12 × 35 cm). For obese patients, 15 cm cuff were used. All measurements at age 81 were made by one and the same physician. Additionally, at both follow-ups, BP has been measured by Strain Gauge Pletysmography Technique (SG). This method has been mainly used for labolatory measurements, e.g. for peripheral pressure measurements in arms, legs, ankles and toes, for the last four decades . The valAnkle BP was estimated by placing a cuff at the ankle level and using Doppler signal on tibial posterior artery or dorsal foot artery. Reference pressure in the arm was calculated using SG-BP method as above. The arithmetic average of duplicate recordnings in supine position was used. Ankle-brachial pressure index (ABI) was calculated by dividing the ankle systolic BP with the highest upper arm systolic BP.The examination of carotid arteries was performed using computed sonography system  with a 7 MHz B-mode real-time linear scanner. A 5 MHz pulsed, color-coded Doppler was used to localize areas with high flow velocities in the internal carotid artery, and the maximum flow velocity (m/s) was measured.Ambulatory blood pressure monitoring was performed during the first year after the last follow-u, using Micro AM Recorder, Model KI5600 . Readings at 20 min intervals during a day (from 06.20 AM to 09.40 PM) and at 60 min intervals at night (from 10.00 PM to 06.00 AM) were performed. Monitoring was performed in patient's private environment without specific advices regarding physical activity. The ambulatory BP data were obtained primary by the auscultatory method and in case of failure repeated with oscillometric method. The accuracy of KI5600 was confirmed by a simultaneous measurement with a standard mercury sphygmomanometer, and accepted if they were within 10 mmHg of standard method. The exclusion of patients was made according to the quality criteria: deficit in measurement time intervals at least 6 h accumulated during a daytime or more than 3 h accumulated at nighttime, or more than 3 h consecutively during a daytime or at least 2 h consecutively during a nighttime. Pulse pressure daytime and nighttime, an established vascular disease marker, was estimated as a mean of individual difference values between SBP and DBP, and used for analysis. 136 subjects agreed to participate, but 104 fullfiled the quality criteria and were chosen to statistical anlysis.P value of less than 0.05 was considered statistically significant. Local ethical committee at Lund University accepted the study, and informed consent was obtained from all participants.Summary values are expressed as mean ± standard deviation. Correlation analyses were performed using Pearson correlation test. Differences in vascular risk factors/markers were calculated with Mann-Whitney Rank Sum Test. All data analysis has been performed using SPSS  statistical package. A two tailed The baseline data in 176 study subjects of the study are presented in table At age 68, an arithmetic difference between values of K-BP and SG-BP in each subject was calculated and the mean value in the whole cohort was 5.2 mmHg SD 12.9). K-BP and SG-BP measurements were strongly correlated to each other . In that age, 33% of subjects had lower K-BP than SG-BP. At age 81, a mean of arithmetic differences between K-BP and SG-BP was -16.5 mmHg (SD 23.0), and the correlation between those measurements was significant  , but no correlation was observed between SG-BP values at 68 and 81  . Contrary, SG-BP changed over time with an increase with mean 13.4 mmHg (SD 31.5). At an individual level, K-BP decreased over time in 55.1% of the subjects, while SG-BP decreased only in 31.3% of the subjects. K-BP at age 68 correlated negatively with K-BP at age 81  and negatively with SG-BP at age 81  .Fasting b-glucose levels at age 68 predicted increasing SG-BP, but not K-BP Table . Low valSG-BP at age 81 was correlated with mean 24-h SBP , daytime SBP , nighttime SBP , mean daytime variability (SD-SBP) , and mean daytime and nighttime pulse pressure . Systolic KB-BP at age 82 did not correlate with either 24-h SBP, daytime SBP, or SBP variability, but correlated with nighttime SBP , and daytime and nightime pulse pressure .Increasing SG-BP from age 68 to 81 (i.e. arithmetic difference SG-BP age 81-68) correlated with 24-h SBP, daytime SBP, nighttime SBP, mean daytime variability (SD-SBP), and mean daytime and nighttime pulse pressure  if measured with K-BP method . However, SG-BP was significantly higher in the drop-out subgroup than in those who participated in the follow-up at 81 .Drop-out analysis compared pressure data between those study subjects who died between follow-ups or did not agree to participate, mainly due to the poor health (307 subjects) and those who reached the last follow up at age 81 (176 subjects). Systolic and diastolic K-BP did not differ significantly between those groups (SBP mean ± SD: 154 ± 22 and 151 ± 21 respectively, In our study, K-BP and SG-BP measurements correlated with each other in both ages, but the correlation was weaker at age 81. At that age, the vast majority of subjects had lower K-BP than SG-BP. During the 13-years-long observation period, blood pressure decreased in a large part of the sample, but the proportion of subjects with declining pressure was nearly double when measured by Korotkoff method, compared to SG-BP. An important finding was that, paradoxically, those subjects who had highest K-BP at age 68, had also lowest K-BP values 13 years later. That was not observed using SG-BP method. The difference between K-BP and SG-BP at age 81 was mainly explained by growing SG-BP, and to a lesser extent by decreasing K-BP.Ambulatory blood pressure monitoring, even if performed only in the two thirds of the sample, could be used as a reference point for the two methods. SG-BP correlated strongly with 24-h, both daytime and nighttime SBP values, and reflected by higher SBP-variability. Contrary, K-BP was only correlated and in a moderate grade with nocturnal SBP. It suggests that SG-BP is a much more reliable method in octogenarians to estimate high systolic BP levels.The clinical validity of SG-BP, contrary to K-BP, was also tested by correlating their time-change with markers of vascular disease and vascular risk factors. Growing SG-BP, from 68 to 81, in the best way reflected the established markers of atherosclerosis at age 81: low ABI, high daytime and nighttime Pulse Pressure, and carotid stenosis. Aggravating atherosclerosis, i.e. decreasing ABI during follow-up, was also best correlated with increasing SG-BP level.The role of values from the drop-out group, i.e. subjects who died before reaching age 81, had higher SG-BP than K-BP at age 68, which suggests that SG-BP reflects in a better way the cardiovascular burdon which lead to early death in the study. The data on the relationship between increasing SG-BP and aggravated atherosclerotic process emphasize that BP decline could be overestimated by Korotkoff method.The validity of auscultatory Korotkoff method was examined in the 1950-70-ties, showing generally lower systolic K-BP than intra-arterial BP with -0, 4 to -24 mmHg and a range from -70 to + 48 mmHg . In a poMeasurement of SG-BP was introduced in 1960-ies for detection of peripheral arterial disease in legs and toes . Its valWhat could be the possible explanation of the underestimated BP with Korotkoff method in the oldest old? It should not be possible that vascular pressure wave reaches distal vessels before the brachial artery itself, and that we detect a pulse signal in the finger before we hear the Korotkoff sound. If we try to explain that artefact, we must understand, that in aging, hypertension is a combination of arterial stiffening, early wave reflection and central BP. In the elderly, the amplitude of the brachial and radial pulse pressure is nearly equal to that in ascending aorta due to the back-reflection of the forward pressure wave, transmitted from the central aorta by high-resistance arterioles. The pulse wave is then amplified toward the periphery at any point of the impedance discontinuity, such as arterial branches. Therefore, the pressure waveform in the brachial artery is a sum of the forward pressure wave generated by the heart and the forward reflected pressure wave from the body. In the elderly, the reflected pressure wave returns during early systole in ascending aorta, through the fact that arterial stiffness augments the aortic pulse pressure, similarly as the brachial. It leads to a low amplification. In younger subjects, the reflected wave doesn't augment aortic and brachial pulse pressure, because it returns during late systole or early diastole in the artery and cannot contribute to high pulse pressure. It leads instead to higher amplification . The pheAnother mechanism for measurement pitfall could be the pulse wave velocity, which increases with age, atherosclerosis, and BP, and is dependent upon vessel elasticity, as well as an independent risk factor for cardiovascular disease . It coulThere can be three sources of error in the indirect measurement of BP: observer bias, faulty equipment, and failure to standardize the techniques. At both follow-ups, K-BP was examined by experienced physicians, aware of the measurements pitfalls in elderly, and all measurements at age 81 were made by one and the same physician. SG-BP was a standardized method from the same labolatory. Selective mortality of individuals at high risk has not influenced on the results. However, 105 invited subjects chose not to participate, mainly for health reasons, expressing higher frequency of vascular disease as their SG-BP was higher 13 years earlier. Changing exposure to risk factors and changing therapy regime during the follow-up could be another source of bias.Both cross-sectional and longitudinal data of this study point out a significant underestimation of BP with Korotkoff technique and underdetection of hypertension in men over 80-ty, leading to biased associations with risk factors due to differential misclassification by age. Systolic blood pressure values on Ambulatory Blood Pressure Monitoring were highly correlated with SG-BP, and not with K-BP, at age 81. Peripheral vascular disease, and its dynamics, were stronger related to increasing SG-BP during the 13 years follow-up. The clinical relevance of these observations seems to be substantial since only 54% of subjects with systolic BP level equal or above 140 mmHg, according to Strain gauge method, were detected with the Korotkoff method. This phenomenon should be made aware for clinicians and researches treating octogenarians or designing future treatment studies.The authors declare that they have no competing interests.ASL was involved with data analysis and manuscript preparation. SE was involved with data collection and manuscript preparation. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2318/11/57/prepub


Chronic heart failure (CHF) is the leading cause of hospitalization and death in industrialized countries. CHF is frequently associated with humoral and metabolic disturbances, including reduced bioavailability of the important signalling molecule nitric oxide (NO), which has vasodilating properties. Several studies reported high plasma levels of asymmetrical NG, NG-dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO production, in CHF, contributing to endothelial dysfunction. The Dynamic Vessel Analyzer (DVA) enables dynamic analyses of retinal vessels. NO is a mediator of retinal vasodilator response to flicker light. Reduced response of retinal arterioles to flicker light may be an attractive technique to non-invasively assess endothelial dysfunction. The aim of the study was to test the hypothesis that retinal vessel response to flicker light is reduced in patients with CHF and correlates inversely with serum ADMA levels.16 patients with non-ischemic cardiomyopathy and 22 healthy volunteers were included. Retinal arteriolar flicker response as percent change from baseline and serum ADMA level were measured.Retinal arteriolar flicker response was significantly reduced in CHF patients compared to the healthy control group . ADMA levels tended to be higher in CHF patients . Noteworthy, we observed a highly significant inverse correlation between retinal arteriolar flicker response and ADMA levels .Our findings suggest that analysis of retinal vessels could be an attractive non-invasive method to quantify endothelial dysfunction in CHF.


Cardiovascular disease (CVD) is a common comorbidity in patients with chronic airway obstruction, and is associated with systemic inflammation and airway obstruction. The aim of this study was to evaluate the predictors of CVD in two different conditions causing chronic airway obstruction, asthma and COPD.Lung function tests, clinical and echocardiographic data were assessed in 229 consecutive patients, 100 with asthma and 129 with COPD. CVD was classified into: pressure overload (PO) and volume overload (VO). Sub-analysis of patients with ischemic heart disease (IHD) and pulmonary hypertension (PH) was also performed.1 and MEF50 and those of VO were age, VC and MEF50. In asthma, the predictors of CVD were VC, FEV1, FEV1 /VC%, and PaO2, those of PO were VC, FEV1 and FEV1 /VC%, while for VO there was no predictor. In COPD the predictors of CVD were age, GOLD class and sex, those of VO age, VC and MEF50, and that of PO was BMI. Sub-analysis showed that IHD was predicted by COPD, age, BMI and FEV1, while PH (found only in 25 COPD patients), was predicted by VO (present in 80% of the patients) and FEV1. In subjects aged 65 years or more the prevalence of CVD, PO and VO was similar in asthmatic and COPD patients, but COPD patients had higher prevalence of males, smokers, IHD, PH, lower FEV1 and higher CRP.CVD was found in 185 patients (81%: 51% COPD and 30% asthmatics) and consisted of PO in 42% and of VO in 38% patients. COPD patients, as compared to asthmatics, had older age, more severe airway obstruction, higher prevalence of males, of smokers, and of CVD (91% vs 68%), either PO (46% vs 38%) or VO (45% vs 30%). CVD was associated with older age and more severe airway obstruction both in asthma and COPD. In the overall patients the predictive factors of CVD were age, COPD, and male sex; those of PO were COPD, BMI, VC, FEVThe results of this study indicate that cardiovascular diseases are frequent in patients with chronic obstructive disorders, particularly in COPD patients. The strongest predictors of CVD are age and airway obstruction. COPD patients have higher prevalence of ischemic heart disease and pulmonary hypertension. In the elderly the prevalence of PO and VO in asthma and COPD patients is similar. Asthma and chronic obstructive pulmonary disease (COPD) are the most common airway disorders with a high morbidity and mortality ,2. Accor1) is ranked second to smoking and above blood pressure and cholesterol as a predictor of all-cause and cardiovascular mortality [1 combined with smoking history better predicts cardiovascular mortality than cholesterol [Both asthma and COPD are characterized by inflammation, which in asthma, particularly the eosinophilic phenotype, is predominantly confined to the airway, while in COPD the inflammation may spill-over from the lungs to the systemic circulation and initiate systemic inflammation, as a consequence of exposure to indoor or outdoor air pollution, cigarette smoke, or diesel exhaust fumes . A recenortality . In thislesterol .The aim of this study was to evaluate prevalence and predictors of CVD in two common airway obstructive diseases with quite different phenotypes, asthma and COPD.Consecutive adults outpatients with asthma and COPD, diagnosed according to international guidelines ,2, were Patients underwent recording of demographic data including age, full smoking history , recording of symptoms and medication use, clinical examination, assessment of lung function tests, arterial blood gas analysis and venous blood sampling for serum determination of CRP. Body mass index was calculated on the basis of height and weight (BMI) . Asthma Coexistent cardiovascular disease was assessed on the basis of history, clinical and echocardiographic data. CVD included: prior myocardial infarction and cardiovascular accidents, documented ischaemic heart disease, pulmonary or systemic arterial hypertension, heart valve disease, echocardiographic diagnosis of pulmonary hypertension.According to the criteria of the American Heart Association , heart d– pressure overload (PO), causing diastolic dysfunction with preserved systolic function, including all the conditions causing concentric left ventricle hypertrophy, such as systemic arterial hypertension and aortic valve disease– volume overload (VO), including all the conditions causing left ventricle dilatation and systolic dysfunction, such as mitral or aortic incompetence and ischemic heart disease.Sub-analysis was done on patients with ischemic heart disease (IHD) and pulmonary hypertension (PH).1), and their percentage ratio (FEV1/VC%), and maximum expiratory flow at mid VC (MEF50) were computed and expressed as percentage of the predicted value, according to the European Respiratory Society guidelines [Lung function tests were measured using the Baires System . The values of vital capacity (VC), forced expiratory volume in one second (FEVidelines .2 and PaCO2 respectively) were measured using the analyzer GEM 4000 PREMIERE (Instrumentation Laboratory Lexington USA).Arterial blood gases, that is oxygen and carbon dioxide partial pressures , age, sex, BMI, smoking habits, GINA or GOLD class, prebronchodilator lung function tests, PaO2, CRP. The same models were used to evaluate predictors for asthma and COPD separately and for the sub-analysis of patients with IHD or PH.Data were analyzed using the SPSS software package, version 20.0  for Windows. Discrete variables are presented as counts and percentages. Continuous variables are presented as means ± SEM, as appropriate. Comparisons between asthmatics and COPD patients, and between patients with predominant chronic bronchitis and predominant emphysema were performed by the unpaired Student's Statistical significance was assumed at p < 0.05.2 and PaCO2 was found between the two groups.The subjects enrolled were 100 asthmatic patients and 129 COPD patients. CVD was found in 185 patients (81%), and consisted of pressure overload in 97 (42%) and of volume overload in 88 (38%). IHD was found in 58 patients (25%), 8 asthmatics and 50 COPD, and PH in 25 (11%), all with COPD. The general characteristics of asthmatic and COPD patients are compared in Table The comparisons among subgroups with no cardiovascular disease (No CVD), with PO and VO in the overall patients, in asthma and in COPD are reported in the Tables 1, FEV1/VC and MEF50 and higher CRP. The same associations (apart from CRP) were found in asthmatic patients  and FEV1.As shown in Table The distributions of PO and VO by severity of asthma (GINA) and COPD (GOLD) are reported in Figure 1, higher CRP and of IHD and PH. The results of linear regression analysis in these older patients are reported in Tables As one of the stronger predictors of CVD was age, we made a sub-analysis on subjects with an age equal to 65 years or higher. As shown in Table 1, as previously suggested [The results of this study show that patients with chronic airway obstructive disorders, either asthma or COPD, have increased prevalence of cardiovascular diseases as compared to the general population of similar age . The comuggested ,23. The uggested -24, and 1 and volume overload, suggesting that both airway obstruction and post capillary mechanisms participated in increased pulmonary vascular resistance. Actually, VO was present in 80% of patients with PH.As mentioned above, age and COPD were the strongest predictors of CVD, but the two factors were closely linked each other, as COPD patients were significantly older than asthmatics. To clarify this point, we performed a sub-analysis on patients with an age equal to or higher than 65 years. As shown in Table In conclusion, the results of this study indicate that cardiovascular disease are frequent in patients with chronic obstructive disorders, particularly COPD. The strongest predictors of CVD are age and severity of airway obstruction. In older patients the prevalence of CVD is similar in asthma and COPD, apart from ischemic heart disease and pulmonary hypertension, which are strongly associated with COPD.COPD: Chronic obstructive pulmonary disease; CVD: Cardiovascular disease; FEV1: Forced expiratory volume in one second; IHD: Ischemic heart disease; MEF50: Maximum expiratory flow at mid VC; PH: Pulmonary hypertension; PO: Heart pressure overload; VO: Heart volume overload; VC: Vital capacity.The authors declare that they have no competing interests.BC, BM and MM conceived and designed the study and contributed to drafting the manuscript, BM, MM, CA, CS, VA, BM contributed to acquisition and analysis of data, TR provided critical revision of the manuscript. All authors read and approved the final manuscript.


Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP), pentraxin 3 (PTX3), interleukin-1β (IL-1 β), and soluble type II receptor of IL-1 (sIL-1RII) were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥50 years and with ≥10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70) or stable CHF (n=124) were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects). Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05). None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation. Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are important causes of morbidity and mortality worldwide, particularly in the elderly ,2. DespiCigarette smoking is the major risk factor for COPD and cardiovascular diseases. It causes systemic inflammation, oxidative stress, increased circulating concentration of inflammatory cytokines, and changes in endothelial functions. Low-grade systemic inflammation has been proposed to be the common substrate of chronic diseases such as COPD and CHF, and thus it is a possible link between these diseases and their comorbidities .C-reactive protein (CRP) is the most established marker of systemic inflammation, plays an important role in COPD , and is Recognition of comorbid heart failure in COPD patients and of COPD symptoms in CHF patients is hampered by similarities in signs and symptoms, in particular, dyspnea. Moreover, even though it is well known that spirometry is essential to establish the diagnosis of COPD, and echocardiography is essential for the diagnosis of CHF, epidemiological data suggest an under-use in clinical practice of both measurements in smokers . Indeed,This was a two-center observational study.A total of 218 subjects were studied: 70 COPD patients, 124 CHF patients, and 24 healthy smokers. Patients aged ≥50 years who had a smoking history of ≥10 pack years were enrolled at the Respiratory Unit of the University Hospital of Modena and at the Heart Failure Centre of the University Hospital of Ferrara, respectively, between July 2009 and September 2010. The control group of 24 age-matched healthy smokers (≥10 pack years) had no known cardiac or respiratory diseases or symptoms and were recruited from the same outpatient clinics.COPD patients had been free from exacerbations for 4 weeks, and CHF patients had been on stable medication for 3 months.ClinicalTrials.gov number, NCT01114386).The study conformed to the Declaration of Helsinki and was approved by the institutional ethics committees of each participating university hospital . All participants provided signed informed consent before recruitment , spirometry, Charlson comorbidity index, 6-min walk test (6MWT), basic biochemistry, N-terminal pro-hormone brain natriuretic peptide (NT-proBNP), HsCRP, PTX3, IL-1 β, and sIL-1RII were obtained from all study participants. COPD and CHF patients also underwent electrocardiography and echocardiography. Subsets of data collected from patients with CHF were reported previously .g for 10 min at 7 °C. Plasma aliquots were stored at -80 °C until assayed.Blood samples were obtained from all study subjects for assessment of plasma concentrations of PTX3, IL-1 β, and sIL-1RII. Blood samples were centrifuged at 1,500 x Spirometry  and the 6MWT were performed according to current international guidelines ,14.Echocardiography was carried out by following a standard protocol that included the measurements and the validated diagnostic criteria recommended by the European Society of Echocardiology .Plasma levels of PTX3 and sIL-1RII were measured by in-house sandwich ELISA as previously described ,16. DetePlasma level of IL-1 β was determined using commercially available kits . Sensitivity was 0.057 pg. /ml.The concentration of all cytokines was determined by comparison with a standard curve, following the manufacturer's instructions.The Shapiro–Wilk test was used to test the normal distribution of continuous variables. When continuous variables were normally distributed, the results were expressed as mean ± SD; otherwise, median and interquartile range  were reported. Categorical variables were summarized as counts and percentages. Continuous variables were compared among groups  by ANOVA if normally distributed and by the Kruskal-Wallis test if non-normally distributed, with Bonferroni corrections for multiple testing. Categorical variables were compared among groups by the chi-square test or Fisher’s exact test, when appropriate. Correlation between continuous variables was assessed by using Spearman's rho. An ANOVA on ranks was constructed to compare IL-1β and sIL-1RII values among groups by considering potential confounders. P values <0.05 (two sided) were considered significant. Statistical analyses were performed using Stata version 12 .2) was higher and partial arterial pressure of carbon dioxide (PaCO2) was lower in CHF than in COPD . It is noteworthy that, while all the COPD patients underwent this measurement, 40% of the patients with CHF refused to perform it.Seventy COPD patients, 124 CHF patients, and 24 healthy smokers (control subjects) were studied  and 2. CHypertension (98%), myocardial infarction (58%), and hypercholesterolemia (35%) were the three most common comorbidities in CHF patients, whereas hypertension (50%), osteoporosis (14%), and diabetes (13%) were most common in COPD patients.The plasma levels of PTX3 were similar in the three groups studied; in contrast, circulating IL-1 β was higher in COPD patients than in both CHF patients and control subjects . Plasma levels of IL-1 β did not differ between CHF patients and control subjects . LikewisThe potential correlations of PTX3, IL-1 β, and sIL-1RII with clinical variables  were checked. PTX3 and sIL-1RII did not show clinically meaningful associations with any of those parameters. IL-1 β correlated negatively with NT-proBNP , FEV1 (% predicted) , and FEV1/FVC , and correlated positively with Hs-CRP .Finally, an ANOVA on ranks was constructed to compare either IL-1 β or sIL-1RII values among groups, considering potential confounders such as age, smoking, pack years, NT-proBNP, Hs-CRP, FEV1 (% predicted), FEV1/FVC, and statin, inhaled bronchodilator and inhaled steroid medication. IL-1 β, but not sIL-1RII, remained significantly higher in COPD patients than in CHF patients and healthy smokers [1.43 (0.57-2.16) vs. 0.48 (0.34-0.88) and 0.47 . Because the CHF subjects we examined were stable and were all smokers, we feel rather confident that the risk of misdiagnosis in this group of patients with CHF is limited.Spirometry may be difficult to assess in elderly patients with CHF, and diagnosis of COPD may be under- or over-estimated in these patients. Spirometric abnormalities of the restrictive type may be present in patients with stable heart failure, and airflow limitation may develop in patients with decompensated heart failure . Also, FWe did not observe any overt LV systolic dysfunction (ie LVEF ≤40%) in COPD patients. Also LV end-diastolic size and LV end-systolic size were not abnormal in any but one patient with COPD, who had definitively increased LV end-diastolic and end-systolic diameters, according to the normal values indicated in the European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure . The preThe high LVEF (%) observed in our COPD might be explained by the following reasons: 1) patients with COPD were recruited in tertiary pulmonary referral centers, and were all on regular COPD pharmacologic treatment, and thus most likely patients with COPD and chronic heart failure were excluded from the recruitment; and 2) patients with COPD were all treated with long-acting bronchodilators associated or not with inhaled steroids, and thus the hemodynamic effects of the bronchodilator therapy may have contributed to the high values of LVEF. In fact both inhaled antimuscarinic and beta 2 agonist bronchodilators increase ejection fraction and stroke volume , 3) the It has been hypothesized that chronic low-grade systemic inflammation is a “common soil” for pulmonary and cardiovascular diseases, particularly COPD and CHF, and that aging, smoking, and obesity, the major risk factors for complex chronic disorders, cause systemic inflammation.The results presented here show that the serum level of Hs-CRP was significantly higher in COPD patients than in CHF patients and control subjects, which did not differ from each other. The association between stable COPD and increased blood CRP is well established and helps to explain the presence of systemic inflammation in this chronic pulmonary disease . In contCRP is a member of the pentraxin superfamily. In recent years, another pentraxin, PTX3, has been investigated in both CHF and COPD. In CHF, PTX3 is related to more severe disease and worse outcomes, such as all-cause mortality, cardiovascular mortality, and hospitalization for decompensated heart failure . Our stuIL-1 β, a proinflammatory cytokine, is increased in airway secretion during exacerbation of COPD ,25 and cRecent studies indicate that decoy receptors act as a general strategy to fine-tune the action of primary inflammatory mediators. The decoy receptor paradigm describes a receptor that is capable of recognizing its ligand with high affinity and specificity, but that is structurally incapable of signaling . SolubleCirculating IL-1 β and sIL-1RII levels did not differ between our CHF patients and control subjects. This was not completely unexpected, as the inflammatory network in CHF is still debated. In particular, previous studies have reported that IL-1 β systemic levels in heart failure are either unchanged , increasIn conclusion, this report shows that airflow limitation is common and unrecognized in smokers with CHF, whereas a consistent impairment of LV function is not always detectable in well-characterized patients with COPD. In contrast to CHF patients, COPD patients show evidence of low-grade systemic inflammation, as demonstrated by an increase in CRP, IL-1 β, and sIL-1RII plasma levels. Better clinical and functional characterization of elderly smokers with chronic diseases, and identification of the key inflammatory mediators involved, may help to improve the treatment and management of these patients.


Uncontrolled asthma is a risk factor for pregnancy-related complications. Hyaluronic acid (HA), a potential peripheral blood marker of tissue fibrosis in various diseases, promotes eosinophil survival and plays a role in asthmatic airway inflammation as well as in physiological processes necessary to maintain normal pregnancy; however the level of circulating HA in asthma and asthmatic pregnancy is unknown. We investigated HA levels in asthmatic patients  N = 16; asthmatic non-pregnant (ANP) N = 36) and tested their relationship to asthma control. Serum HA level was lower in AP than in ANP patients ; the difference attenuated to a trend after its adjustment for patients’ age (p = 0.056). HA levels and airway resistance were positively , HA levels and Asthma Control Test (ACT) total score inversely  associated in ANP patients; these relationships remained significant even after their adjustments for age. The potential value of HA in the determination of asthma control was analyzed using ROC analysis which revealed that HA values discriminate patients with ACT total score ≥20 (controlled patients) and <20 (uncontrolled patients) with a 0.826 efficacy  when 37.4 ng/mL is used as cut-off value in ANP group, and with 0.78 efficacy  in the whole asthmatic cohort. In conclusion circulating HA might be a marker of asthma control, as it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease of HA level in pregnancy may be the consequence of pregnancy induced immune tolerance. Asthma is a chronic inflammatory disease of the airways characterized by variable and recurring symptoms, local inflammation, reversible airflow obstruction, and bronchospasm Airway inflammation, a major element of asthma pathophysiology, has been described to be related to asthma severity Asthma is one of the most frequent potentially serious medical conditions complicating pregnancy, occurring in 3.7 to 8.4 percent of pregnant women During last decades elevated serum level of hyaluronan , a major extracellular matrix component, was reported in several pathological conditions characterized by systemic inflammation and activation of immune system ; however its suitability as a systemic inflammation marker in asthma has not yet been investigated. HA is a glycosaminoglycan forming non-covalent complexes with extracellular matrix proteoglycans Recently HA was shown to be implicated in asthma pathophysiology by contributing to the two main characteristics of the disease: airway inflammation and remodeling. Elevated levels of HA have been reported in bronchoalveolar lavage fluid of persistent asthmatic patients HA also plays a role in maintaining healthy pregnancy Therefore, present study aimed to investigate serum HA levels in patients with asthma and asthmatic pregnancy. Furthermore, in order to define the utility of HA as a screening tool in the evaluation of asthma control in asthmatic pregnant and non-pregnant patients, we also investigated the relationship between HA and asthma control determinants.Written informed consent was obtained from all subjects, and our study was reviewed and approved by an independent ethical committee of the institution . Laboratory studies and interpretations were performed on coded samples lacking personal and diagnostic identifiers. The study was adhered to the tenets of the most recent revision of the Declaration of Helsinki.The study had a cross-sectional design. 36 asthmatic non-pregnant (ANP) women and 16 asthmatic pregnant (AP) patients were enrolled. Asthmatic patients were assessed at their regular visit at the outpatient clinic of the Department of Pulmonology, Semmelweis University. They had persistent disease and asthma had been diagnosed according to the current guidelines (at least 6 months prior to the study) Plasma was isolated from EDTA anticoagulated fasting blood samples and stored at −80°C until measurement. Serum hyaluronan was determined by enzyme-linked binding protein assay .Lung function was measured by means of electronic spirometer  according to the American Thoracic Society guidelines t-test for comparisons between the study groups with Welch correction for the adjustment for age. In case of not normally distributed data, Mann–Whitney U-test was performed. In the case of HA, the adjustment for age was done with Quade’s rank analysis of covariance. Correlations between HA and lung function parameters were determined with Spearman rank correlation. To adjust correlation between HA and Raw and between HA and ACT for patients’ age, partial rank correlation was used. AUC values of Receiver-Operating Characteristics (ROC) were carried out using standard methods and data are presented as AUC ROC (95% CI). p values <0.05 were considered significant in each calculation.Statistical analysis was performed using Graph Pad Prism software 5 , correction for age was made by SPSS Statistics V21 . Data distribution was analyzed by D’Agostino-Pearson normality test. Data are expressed as median [interquartile range] except for the normally distributed values of age which are presented as the mean with standard deviation (SD). We used unpaired Student’s Median age of asthmatic patients (N = 52) was 35 [29–43.75] years, whereas FEV1 (% of predicted) 92 [82.5–102], PEF (% of predicted) 90 [75.25–100], and Raw (% of predicted) 127 [102–165]. ACT total score of 21 Median circulating HA level in all asthmatic patients (N = 52) was 34.8 [25.6–46.48] ng/mL, and was related to age . HA values were lower in AP than in ANP subjects . After adjusting for age, significance changed to a trend (p = 0.056) .A significant correlation was revealed between HA levels and Raw .According to current asthma guidelines ACT total score ≥20 is the main determinant of well-controlled asthma. The potential value of HA in the determination of asthma control was analyzed using ROC analysis. ROC analyses of HA data were performed in subgroups of AP, ANP patients and also of all asthmatic patients with ACT total score above (controlled) and below (uncontrolled) 20. Statistical significance was proved in the case of HA with ACT score above and below 20 in the ANP group and in the whole asthmatic cohort.The area under the receiver operating characteristics curve for predicting asthma control was 0.826 (95% CI: 0.686–0.966) in the ANP group. The cut-off value of HA to discriminate between ANP patients with an ACT score above and below 20 was 37.4 ng/mL (sensitivity% (95% CI): 80 (51.91–95.67), specificity% (95% CI): 78.95 (54.43–93.95); p = 0.001) .ROC analysis of HA values in the whole asthmatic patient group with Asthma Control Test total score above and below 20 yielded an AUC of 0.78 (95% CI: 0.65–0.92) with the 37.4 ng/mL cut-off value of HA to discriminate between patients with controlled and not controlled asthma : 70.00 (45.72–88.11), specificity% (95% CI): 82.76 (64.23–94.15) .The aim of this study was to assess serum HA levels in asthmatic non-pregnant and asthmatic pregnant patients, and to reveal the possible relationship between HA and asthma control determinants in both groups. To our knowledge, this study was the first to investigate circulating HA values in asthmatic pregnancy.The normal circulating concentration of HA may vary from 10 to 100 µg/L Interestingly, lower level of circulating HA was found in asthmatic pregnant women compared to asthmatic non-pregnant patients in this study. Although the difference failed to reach statistical significance after correction for age, a trend still remained. Despite the well-known role of HA in morphogenesis, data on serum HA during pregnancy are not fully concordant. Kobayashi et al. observed increased serum HA levels in the third trimester of human pregnancy, especially close to term and a further increase was seen in labor suggesting an association with cervical ripening During tissue injury, repair, fibrosis and inflammation, HA levels elevate both in serum and tissue fluids The potential value of circulating HA measurement in the determination of asthma control was analyzed using ROC analysis. We found that a cut-off level of 37.4 ng/mL is suitable to discriminate with acceptable sensitivity and specificity between patients suffering from well-controlled or uncontrolled asthma and thus help to identify patients with impaired asthma control; however the diagnostic yield of HA for the detection of uncontrolled asthma was much lower in asthmatic pregnancy.In summary, circulating HA seems to be a marker of disease control in asthma, as it correlates with airway resistance and effectively discriminates between well-controlled and uncontrolled asthma. The best utility of HA serving as a screening tool in the evaluation of asthma control was detected in non-pregnant patients. Decreased level of HA in asthmatic pregnant women is presumably the result of pregnancy induced immune tolerance and attenuated systemic inflammatory responses which weaken the probable value of serum HA as a marker of asthma control during pregnancy.