The diagnosis of orthostatic hypotension (OH) requires blood pressure (BP) readings while supine and upright, either during active standing or during a tilt-table test, to determine the presence of a sustained orthostatic fall of at least 20 mmHg systolic or 10 mmHg diastolic BP. BP and heart rate should be measured after the patient has been supine for several minutes and after standing still (or passively tilted) for 1–3 min. The changes in heart rate on standing help to determine whether the OH is neurogenic in origin. In patients with neurogenic OH (nOH) the increase in heart rate upon standing up is usually <20 bpm. Marked increases in heart rate suggest that the OH is non-neurogenic  is useful for the diagnosis of nOH in patients who do not have a fall in BP during an office visit, and to identify post-prandial hypotension and nocturnal hypertension  Fig. 2)2).Fig. 2The goal of treatment is not to normalize standing BP, but to reduce symptom burden, and to improve quality of life. The steps in management include: (1) correcting aggravating factors, (2) implementing non-pharmacological measures, and 3) drug therapies . Patients and their families or caregivers should understand the basics of nOH pathophysiology and the importance of non-pharmacologic methods. In many situations, educational materials may be helpful for both the patient and the caregiver Table . PhysicaThe selection of one drug over the other is related not only to the severity of the patient’s symptoms, but also, in certain situations, based on the clinician’s preference and experience with a certain drug Table .Table 3PHypertension in the supine occurs in ~50% of patients with nOH. There are no controlled clinical trials on its treatments. In patients with nOH experiencing supine hypertension [systolic blood pressure (BP) of 160–180 mmHg or diastolic BP of 90–100 mmHg], there is agreement that sleeping with the head of the bed raised at least 30°–45° should be recommended. If patients are experiencing sustained severe supine hypertension (systolic BP of >180 mmHg or diastolic BP of >110 mmHg) even after sleeping in the semi-sitting position, some experts advocate using short-acting an antihypertensive agent before bedtime (Table


To compare the values of central and brachial systemic blood pressure (SBP) between women and men over 60 years of age with systemic arterial hypertension. This study was a quantitative, descriptive, cross-sectional study with elderly patients admitted to and selected from spontaneous and scheduled demand at basic health units in Uberlândia, Minas Gerais, Brazil, between March 2013 and March 2014. We included 69 study participants and compared central and brachial SBP using a Sphygmocor® XCEL device . Significant differences were found in the blood pressure values of the whole population in the central versus brachial systolic blood pressure (SP) [140(21) versus 153(23) mmHg] and in the central versus brachial pulse pressure (PP) [55(18) versus 70(18) mmHg]. Additionally, females exhibited higher blood pressure levels than males . Elderly women exhibited higher blood pressure values than elderly hypertensive men. Systemic blood pressure (SBP) changes with ageing. Systolic blood pressure (SP) rises progressively, whereas diastolic blood pressure (DP) rises until the 6th decade of life and then stabilizes or gradually decreases –4.SBP levels measured indirectly through cuffs placed either on the upper limbs or at the aortic root [the central SBP levels (SBPc)] constitute independent factors for cardiovascular risk (CVR) , 6. EvidEpidemiological studies have confirmed that the physiological hormonal changes that occur in women during and after menopause affect the systemic circulation, thereby increasing SBP and consequently CVR. Additionally, CVD is the leading cause of mortality in postmenopausal women, with a prevalence equal to or higher than the prevalence in men due to low plasma oestrogen levels, among other factors –20.As good markers of CVR, central and peripheral blood pressure values could diverge in the same patient and behave differently in elderly female patients. Therefore, the objective of the present study is to compare the central and brachial SBP values between women and men over 60 years of age with systemic arterial hypertension (SAH).n = 69; (II) women: 71 ± 7 years, n = 39; and (III) men: 68 ± 6.5 years, n = 30. All patients were active, stable, and conscious.This study was a quantitative, descriptive, cross-sectional study with elderly patients ≥60 years of age who were admitted and selected from the spontaneous and scheduled demand at basic health units (BHUs) in the municipal network of Uberlândia, Minas Gerais, Brazil, from March 2013 to March 2014. The first 69 hypertensive participants were included in the study and were divided into three groups of patients as follows: (I) overall study population: 70 ± 7.3 years, This study was conducted in accordance with the attributes defined in Resolution CNS 466/12 and approved by the Ethics Committee in Research of the Federal University of Uberlândia under opinion number 224,540 and CAAE 37440114.3.0000.5152.Patients with SAH, a SBPb ≥ 140/90 mmHg, or a SBPb ≤ 140/90 mmHg with the use of one or more antihypertensive drugs (controlled) were considered.A Sphygmocor XCEL applanation tonometry device  was used to measure both SBPb and SBPc simultaneously and noninvasively. The components of the SBP surveyed were the SP, DP, PP, and mean arterial pressure (MAP) . All values are expressed in mmHg. The SBPc and SBPb measurement procedure was performed only once and was based on a previous description .t-test was applied to compare the values of the SBPc and SBPb components according to the normality of the sample. Differences were considered significant when P < 0.05. Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 20 for Windows.The results for the continuous variables shown in Tables The clinical characteristics of the overall study population and the population according to sex are shown in Cross-sectional and longitudinal studies have confirmed a higher prevalence of hypertension in elderly postmenopausal women –19, 22 aIn the present study, all patients were randomly included. We observed that women presented high SPc and PPc mean values, whereas men remained within the limits considered normal , 26. We P < 0.05).Both SP and PP increase with age, mainly due to the decrease in elasticity of the large vessels as a consequence of their respective structural modifications , 4, 20. Son et al.  conducteKim et al.  also shoThe AIx@75 (heart rate-corrected augmentation index) is considered as a composite marker of reflection waves and arterial stiffness. In this sense, it was evidenced that postmenopausal women had higher arterial stiffness when compared to elderly hypertensive men  30]..30].To the best of our knowledge, Brazilian studies demonstrating and comparing the components of central and brachial SBP in postmenopausal women with elderly hypertensive men via applanation tonometry are rare. Notably, this study is a preliminary study with the inclusion of the first 69 hypertensive patients, which will help guide future research.This study is a cross-sectional study with the inherent limitations of this type of design. The study patients used several classes of antihypertensive drugs, including beta-adrenergic blockers , which do not effectively reduce central pressure levels –13, 31. Significant differences were found in both the central and brachial SP and PP values between women and men. The elderly women presented higher blood pressure values than those of the elderly hypertensive men.


The effects of seasonality on blood pressure (BP) and cardiovascular (CV) events are well established, while the influence of seasonality and other environmental factors on arterial stiffness and wave reflection has never been analyzed. This study evaluated whether seasonality (daily number of hours of light) and acute variations in outdoor temperature and air pollutants may affect carotid-femoral pulse wave velocity (PWV) and pressure augmentation.10, O3, CO, N2O) exposure on the same day.731 hypertensive patients  were enrolled in a cross-sectional study during a 5-year period. PWV, central BP, Augmentation Index (AIx) and Augmentation Pressure (AP) were measured in a temperature-controlled (22–24°C) room. Data of the local office of the National Climatic Data Observatory were used to estimate meteorological conditions and air pollutants , CO , N2O . In multiple linear regression analysis, adjusted for confounders, PWV remained independently associated only with daylight hours . No significant correlation was found between pressure augmentation and daylight hours, mean temperature or air pollutants. The relationship was stronger in untreated patients and women. Furthermore, a positive, independent association between O3 levels and PWV emerged in untreated patients  and in women .PWV  was related to age , body mass index , central systolic  and diastolic BP , daylight hours , mean outdoor temperature , O3 levels may acutely reduce arterial stiffness in hypertensive women and in untreated patients.PWV showed a marked seasonality in hypertensive patients. Environmental O The seasonality of cardiovascular (CV) disease is well known, with acute events occurring more frequently during winter months than in the summertime ,3,4,5,6.2, for example, mainly derived by the heating system of the buildings, shows the highest peak during winter, whilst ozone (O3), linked to photochemical smog, reaches the highest concentration during summer and the central hours of the day [2.5) [Another possible factor influencing the increase of BP and CV events during winter is the variation in the levels of air pollutants. Air pollution in urban areas is characterized by both seasonal and daily fluctuations. SO the day . The maiay [2.5) ,22,23, way [2.5) ,25,26. Hay [2.5) . To our The aim of the present study is to investigate, in a cross-sectional study, whether variations in seasonality (daily number of hours of light) and environmental variables  may acutely affect the gender-specific assessment of carotid-femoral PWV and central BP augmentation.For this cross-sectional, retrospective study, data from 731 hypertensive patients aged 30–88 years, 314 untreated (184 men) and 417 treated with antihypertensive drugs (241 men) seeking medical consultation in our outpatient clinic for cardiovascular risk stratification and target organ damage evaluation during a 5-year period (2006–2011) and performing arterial tonometry measurements on the same day, were analyzed.Inclusion criteria were: age ≥ 18 years; arterial hypertension, defined as blood pressure (BP) ≥ 140/90 mmHg in two previous separate occasions or current antihypertensive treatment; written informed consent. Exclusi2. Weight and height were measured and a complete clinical examination was performed; obesity was defined as a body mass index (BMI) >30 kg/m2. Current use and dosage of cardiovascular drugs was recorded, as well as medical and pharmacologic history in order to identify cardiovascular risk factors and disease.After enrollment, patients were asked to come to the Hypertension Outpatient Unit after an overnight fasting. A blood sample was drawn for routine examinations , according to standard laboratory procedures. Hypercholesterolemia, hypertriglyceridemia and diabetes mellitus were defined according to current guidelines  or in thArterial measurements were performed with subjects in supine position in a quiet air-conditioned room (24°C). BP was measured after 10 minutes of rest for three times at 30 seconds intervals by an automatic device (OMRON 950) at the dominant arm. The mean value was calculated from the last 2 measurements .A non-invasive measurement studying the structural characteristics of large arteries was performed. Carotid-femoral PWV (cf-PWV) was assessed by arterial tonometry recording waveforms at the femoral and carotid site, sequentially, using a SphygmoCor device . A hand-held probe was placed on the selected artery in order to record 10–15 subsequent images. PWV was calculated as the ratio of surface distance between the two recording sites (subtracted distance) to wave transit time calculated by simultaneously recorded electrocardiogram (ECG). In a suA hand-held probe was placed on the radial artery from the wrist of the dominant arm and 10 to 15 subsequent images were recorded, as previously described . A validData on air quality were taken from the European air quality database (airbase v7)  maintainX2 test for categorical variables. One-way ANOVA was used for the analysis of monthly changes across the year in PWV, AIx and central systolic BP values. Univariate analysis (Pearson coefficient) was performed. In order to analyze factors independently associated with PWV, AIx and central systolic BP, multiple linear regression analysis was performed. Subgroup analysis  was also conducted. A P value < 0.05 was considered significant.Statistical analysis was performed using NCSS8 . The results were expressed as mean ± SD for normally distributed continuous variables and as mean and interquartile range for non-normally distributed variables. Discrete variables were represented as frequency with percentage and counts. Gender differences in the clinical characteristics were analyzed by Student’s test or Wilcoxon Rank Sum test for continuous variables and Clinical characteristics of the study population are presented in Arterial parameters are reported in 3 showed a positive correlation with daylight hours (r = 0.763 p<0.0001), indicating higher levels in summer. The following showed a negative correlation with daylight hours: PM10 (r = -0.304 p<0.0001), CO (r = -0.316 p<0.0001), NO2 (r = -0.524 p<0.0001), benzene (r = 0.360 p<0.0001), NOx (r = -0.424 p<0.0001), toluene (r = 0.189 p<0.0001) indicating higher levels in winter. Ethylbenzene and oxylene showed no clear seasonality.Among the air pollutants studied, OCf-PWV showed an inverse correlation with daylight hours . In particular, median monthly cf-PWV value reached the highest values in winter (9.28±2.04 m/s in January and 9.18±2.35m/s in November) and the lowest values in summer (7.99 ±1.47 m/s in June and 8.03±2.02 in July). In the subgroup of patients in which the parameters were available, nor cr-PWV neither aortic-brachial PWV ratio exhibited any clear seasonality , though there was a significant increase in its levels in October and November (1.03 ± 0.26 and 1.05 ± 0.26 respectively) in comparison to May and June (0.88 ± 0.15 and 0.90 ± 0.17 respectively).Brachial and central systolic BP, AP and AIx were not significantly associated with daylight hours. Interestingly, HR showed an inverse correlation with daylight hours  and outdoor temperature , but not with any of the air pollutants measured. The highest HR values were registered in February (69.3 ± 11.4 bpm) and the lowest in May (63.3 ± 10.8 bpm).In the univariate analysis, brachial systolic BP was not correlated with any of the environmental variables, while among clinical variables it showed a slight association with low-density lipoprotein (LDL) cholesterol .2 full model 0.09).Among environmental variables, the univariate analysis demonstrated a positive correlation between central systolic BP and CO . Among clinical characteristics, central systolic BP was positively associated to age , heart rate , and LDL cholesterol . A multiple regression analysis, performed including the above-mentioned clinical variables, also adjusted for sex, antihypertensive drugs use, outdoor temperature and daylight hours, showed no significant association between CO and central systolic BP . CO , N2O , and NOx  showed a positive correlation with PWV.In the univariate analysis, cf-PWV was directly related to age , BMI , central systolic BP  and diastolic BP . Furthermore, cf-PWV was increased in the presence of hypertriglyceridemia , IFG/DM  and CKD . Additionally, the following environmental variables were inversely related to cf-PWV: daylight hours , mean outdoor temperature  and O3) in addition to female sex, BP-lowering drugs, heart rate, hypertriglyceridemia, IFG/DM, CKD, antihypertensive treatment and N2O. This analysis revealed that cf-PWV values were independently and directly associated with age, BMI, central systolic BP, heart rate and CKD. Among environmental variables, only the number of daylight hours resulted independently and inversely associated to cf-PWV , accounting for 1.2% of the cf-PWV variance (full model r2 = 0.417).A multiple linear regression model  was creaAmong environmental variables, cr-PWV was directly related with CO in the univariate analysis . However, the association was no longer significant  in a multiple linear regression model including those variables significantly associated with cr-PWV in the univariate analysis as confounders .3 in the univariate analysis . The association lost significance  in a multiple linear regression model including those variables significantly associated with aortic-brachial PWV ratio in the univariate analysis as confounders .Among environmental variables, aortic-brachial PWV ratio was inversely related with OThe same variables included in the multiple linear regression analysis created for the overall population were included in the analysis of the subgroups, with cf-PWV considered as the dependent variable Figs  and 2.3 were directly associated to cf-PWV values   was shown, being responsible for 2.7% of the variance of cf-PWV . Furthero 0.034) . Age, ceo 0.034) .3 were directly associated to cf-PWV values   . Dayligho 0.045) . Other io 0.045) .The univariate analysis showed no correlation between AIx and environmental factors. Clinical variables correlated with AIx were age , BMI , brachial SBP (r = 0.116 p = 0.003), central systolic BP , total cholesterol , high-density lipoprotein (HDL) , creatinine , MDRD (r = -0.093 p = 0.027). Furthermore, AP  was related to age , BMI , central SBP , heart rate , total cholesterol , LDL , HDL , estimated glomerular filtration rate .No significant correlation was found between AIx, AP and daylight hours, mean temperature and air pollutants, neither in the univariate analysis, nor in the multiple regression analysis adjusted for confounders.3 concentrations and cf-PWV emerged in untreated hypertensive patients, an association occurring regardless of the shown seasonal variations of both parameters. Furthermore, in women a significant and positive association between aortic stiffness and outdoor O3 concentrations was found, suggesting that this subgroup might be more vulnerable to the effects of acute exposure to air pollution.This cross-sectional analysis aimed at detecting variations in seasonality (expressed as daily number of hours of light) and environmental variables  in a population of hypertensive patients and how they may affect carotid-femoral PWV and central augmentation. The main result of the study is that the daily number of hours of light independently affect measurements of cf-PWV in hypertensive patients. The association was stronger in women and in untreated patients. Among air pollutants, a positive and significant association between outdoor O2D3, possibly leading to a reduction in arterial stiffness [The seasonality of CV disease has been attributed to variations in BP, secondary to changes in outdoor temperature and other environmental variables . Our dattiffness . Howevertiffness ,39,40.3 levels, which was especially evident in untreated hypertensive patients and in women. A number of studies [2 and SO2 was associated to a significant increase in cf-PWV and AIx [3 levels may induce endothelial dysfunction in in rat coronary arteries [3 on large artery stiffness has been shown for the first time by this analysis. Antihypertensive therapy might have masked this effect, since most antihypertensive drugs affect arterial stiffness, directly or indirectly [Another interesting finding of our study is that cf-PWV was inversely associated to O studies ,25,26 ha studies ,22,23; u and AIx . Indeed, and AIx . Since e and AIx , it is larteries , whereasarteries . To our directly . Furtherdirectly . On the directly . These cTo our knowledge, this is the first study investigating the impact of seasonality and air pollutants on carotid-femoral PWV in a population of hypertensive patients, both treated and untreated with BP-lowering drugs. An adequate sample size is another strength of the study.The main study limitation is the cross-sectional design of the study. Prospective studies are required in order to firmly demonstrate the role of cf-PWV in determining the higher rate of cardiovascular events during winter. Furthermore, the study did not include objective measurements of 24h-BP, which might have revealed a relationship between arterial stiffness and circadian BP pattern, which is peculiarly influenced by seasonality ,11. Unfo3 concentrations on cf-PWV suggested by our analysis, and elucidate mechanisms of its gender-specific effect.Seasonality affects carotid-femoral PWV in hypertensive patients. Arterial stiffness, evaluated as cf-PWV, is considered as a form of subclinical hypertensive organ damage according to current guidelines for hypertension management  and it m


Although the prevalence of chronic kidney disease (CKD) and diabetes mellitus (DM) is increasing globally, information on Chinese CKD patients with DM is lacking. A total of 3499 pre-dialysis CKD patients from across China were enrolled in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) between November 2011 and April 2016. We divided the C-STRIDE patients into CKD with DM and CKD without DM groups and compared their clinical, demographic, and laboratory data in this cross-sectional study. CKD patients with DM were older, had a higher male-to-female ratio, and had more complications than CKD patients without DM. Age, smoking, and 24-h urinary protein levels were associated with co-occurrence of CKD and DM. Less than 50% of patients in either group took antilipemic, cardiovascular, cerebrovascular, or anti-anemic drugs. In addition, only 18.38% of CKD patients with DM had undergone a renal biopsy, and diabetic nephropathy was confirmed in 35.4% of them. Our findings suggest that several types of medication and renal biopsies should be used more frequently in the treatment of Chinese CKD patients with DM. International Diabetes Federation Diabetes Atlas (7th edition) reports that 415 million people suffered from DM in 2015. By 2040, an estimated 642 million people will have DM globally, which equates to approximately 1 in 10 adults. In mainland China, 109.6 million adults have DM; China had more adults with DM than any other countries or territories in the world in 2015 [Incidences of diabetes mellitus (DM) have increased rapidly around the world because of changes in human environments, behaviors, and lifestyles –3. The IA total of 3499 pre-dialysis CKD patients were included in the study, of which 2066 were males (59.05%) and 1433 were females (40.95%) (Table P < 0.001). Percentages of patients who used alcohol did not differ between the groups. CKD patients with DM were generally less well-educated.Male-to-female ratio and mean age were higher in the CKD with DM group. In addition, a larger proportion of CKD patients with DM were smokers (48.86%) compared to CKD patients without DM . Diastolic blood pressure was similar in both groups. Mean BMI was higher in CKD patients with DM (25.44 ± 3.39) than in those without DM . CKD patients with DM were also more likely to have a history of hypertension, myocardial infarction, arrhythmia, cerebrovascular disease, and peripheral artery disease (P < 0.005).CKD patients with DM had more severe kidney disease as indicated by CKD stages Table . SystoliP < 0.001). Hemoglobin, total protein, serum albumin, and high-density lipoprotein cholesterol levels were lower in CKD patients with DM than in those without DM (P < 0.001). Total cholesterol was lower in CKD patients with DM than in those without DM (P < 0.05).The main laboratory findings are shown in Table P < 0.001) Figure .Multivariable logistic regression analysis revealed that age, 24-h urinary protein, alkaline phosphatase, CKD-3a and CKD-3b stages, BMI, hypoalbuminemia, anemia, hypertension, smoking, and vascular disease history were positively associated with CKD with DM. However, level of education, C-reactive protein, and hyperuricemia were negatively associated with CKD with DM. Gender, CKD-2 and CKD-4 stages, hyperlipidemia, malignant tumor, urologic surgical procedures, frequency of alcohol use, and total protein were not associated with CKD with DM (Table P < 0.001). Renal biopsy reports were available for 99 CKD patients with DM , while 1180 42.91%) of the 2864 CKD patients without DM underwent a renal biopsies; this difference was significant  had diabetic nephropathy; 62 (60.6%) patients had non-diabetic renal disease (NDRD) and 2(2%) had NDRD with diabetic nephropathy. In a previous study, 45.5% of biopsied type 2 DM patients were diagnosed with NDRD . AnotherIn general, NDRD is relatively common in CKD patients with DM, and renal biopsies are therefore crucial for correctly diagnosing and monitoring renal diseases. However, out of the 635 Chinese CKD patients with DM included in this study, only99 (18.38%) had undergone a renal biopsy. Clinicians in China should perform renal biopsies more often to help identify etiologies of CKD more effectively, thus avoiding misdiagnosis and mistreatment. The results of this cross-sectional study should be explored further in prospective studies of CKD patient populations.3499 pre-dialysis CKD patients between the ages of 18 and 74 were enrolled in the C-STRIDE cohort between November 2011 and April 2016. C-STRIDE is a multicenter cohort of Chinese CKD patients from 39 clinical centers located in 28 cities in 22 provinces of China. Briefly, patients within the age range with specific estimated glomerular filtration rates (eGFR) were included, regardless of etiology. Severe heart failure, systemic inflammatory illness, autoimmune disease, and some other factors served as exclusion criteria; C-STRIDE criteria have been described in detail previously  were incThe study was approved by the ethics committees of all 39 centers involved and was conducted in accordance with the principles contained within the Declaration of Helsinki. All participants gave written informed consent before data collection.Data were collected on demographic information, clinical characteristics, laboratory examinations, complications, and concomitant medication. Renal biopsy reports were collected for enrolled patients who had undergone a renal biopsy. Demographic and clinical information and laboratory examinations included gender, age, education level, body mass index (BMI), systolic blood pressure, diastolic blood pressure, eGFR (using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation), smoking and drinking history, and 24 h urine albumin.Hypertension was defined by systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, and/or use of antihypertensive drugs within the past 2 weeks. Hyperlipidemia was defined by total cholesterol ≥6.22 mM, triglycerides ≥2.26 mM, high-density lipoprotein <1.04 mM, and/or use of antilipemic drugs within the past 2 weeks. Anemia was defined by hemoglobin <120 g/L for males and <110 g/L for females and/or use of erythropoietin, chalybeate, or another anti-anemic treatment within the past 2 weeks. Hypoalbuminemia was defined by plasma albumin <30 g/L or vascular diseases, including cardiovascular disease, cerebrovascular disease, and peripheral angiopathies. Antihypertensive, antilipemic, anti-anemic, and vascular disease drugs were considered when collecting information on drug use. Frequency of alcohol use over the past year was scored as follows: “Occasionally” indicates use 1–3 times/month and 1–2 times/week; “Frequently” indicates 3–5 times/week, almost once/day, and more than once/day. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, diuretic hydragogue, α-acceptor blocker, β-acceptor blocker, αβ-acceptor blocker, and centrally-acting antihypertensive treatments were considered hypotensive drugs. Statins and fibrates were considered antilipemic drugs. Ferralia, folacin, and erythropoietin were considered anti-anemic drugs. Antiplatelet and anticoagulant drugs were considered vascular drugs.T-tests or Mann–Whitney nonparametric tests were used for comparisons between groups. Categorical variables are presented as frequencies and percentages and were compared using chi square tests.Continuous variables are presented as means ±SD or as medians with interquartile ranges, as appropriate. To mitigate the effects of missing data, we performed multiple imputation for missing data values using a fully conditional specification method in SAS. For each patient with missing data, all available data values were included as predictors in the imputation procedure for the prediction of missing data values; the original scale or categories were used before being further categorized in the regression analysis. We used a regression method to impute missing values for continuous variables that were normally distributed, a predictive mean matching method for continuous variables that were not normally distributed, and a logistic regression method for categorical variables of a binary or ordinal nature. Five imputed data sets were generated and analyzed separately, and the results obtained from the separate complete data sets were then combined.We analyzed associations between demographic, clinical, and laboratory data from the CKD with DM group and the relevant covariates using logistic regression models. Independent variables were screened first by using variables identified in previous studies that might be closely related to CKD with DM as independent variables in the regression analysis. The independent variables were then screened based on experts’ clinical and research experience. Univariable and multivariable adjusted odds ratios (ORs) with 95% CIs are reported. The following covariates were included in the multivariable logistic regression models: age, sex, education completed, 24 h urinary protein, C-reactive protein, total protein, alkaline phosphatase, CKD stage1-4, BMI, hypoalbuminemia (yes vs. no), anemia (yes vs. no), hypertension (yes vs. no), hyperlipidemia (yes vs. no), hyperuricemia (yes vs. no), vascular disease history (yes vs. no), malignant tumor (yes vs. no), urologic surgical procedures (yes vs. no), smoking (yes vs. no), and alcohol use.P-values < 0.05 were considered statistically significant. SAS statistical software  was used for statistical analyses.Multivariable logistic regression analysis was used to identify factors related to CKD with DM. Results from regression analysis are presented as odds ratios with 95% confidence intervals.


It is well known that hematoma volume and expansion is associated with poor outcomes in patients with spontaneous intracerebral hemorrhage (sICH). The factors associated with hematoma volume and possible expansion include the use of anticoagulant medications, autoimmune or bacterial diseases that reduce platelet production, and genetic defects of Von Willebrand factor causing inhibition or reduction of platelet aggregation.However, little is known about the role of elevated systolic blood pressure (SBP) on hematoma volume and its ultimate role on sICH when identified in the prehospital setting. Our objectives were to determine the prevalence of elevated SBP among diagnosed sICH patients transported by emergency medical services (EMS), and to explore possible associations between prehospital elevated SBP and hematoma volume.This is a hypothesis-generating study for which we used a retrospective observational design. The subjects included 243 adult patients who were seen and treated for sICH in an emergency department serving a county hospital in a large metropolitan city. Elevated SBP in the setting of sICH was defined as ≥140 mm Hg. A univariate analysis was performed to investigate associations between patient demographics, elevated SBP, and sICH characteristics with the pre-determined outcome of hematoma volume. We then performed a multivariable logistic regression model to determine if elevated prehospital SBP remained associated with hematoma volume.The number of subjects with a hospital-based diagnosis of sICH was 243. Of those, 193 (79%) were transported by an ambulance. Among those transported by ambulance, 180 (93%) had a documented prehospital SBP; out of those patients with a documented SBP, 173 (96%) showed an elevated SBP of ≥140 mm Hg, and 82 (46%) had a hematoma volume of ≥30 mL.Our univariate analysis showed that sICH patients with an elevated prehospital SBP of ≥140 mm Hg were associated with hematoma volume. The multivariable regression model showed that elevated prehospital SBP (≥140 mm Hg) was associated with larger hematoma volumes (odds ratio (OR) 3.86 95% confidence interval (CI) 1.02-4.60).Prehospital elevated SBP is associated with larger hematoma volume in patients with sICH. Future studies should confirm these findings in a larger cohort of patients. Spontaneous nontraumatic intracerebral hemorrhage (sICH) is a neurovascular emergency and constitutes about 10% of all strokes . PrognosHematoma expansion is known to occur in the first hour after a baseline CT scan in a third of patients with sICH and is associated with significant neurodeterioration, a predictor of morbidity and mortality -7. A litInhospital association between elevated SBP and neurodeterioration has been studied, ,9, and aThe multicenter observational pilot study 'Antihypertensive Treatment of Acute Cerebral Hemorrhage-I' (ATACH I), and the 'Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage-I' (INTERACT I) pilot trial showed that early and aggressive lowering of blood pressure was feasible and reasonably safe, but ultimately did not result in any appreciable decrease in the rate of death, severe disability, or hematoma growth -11. AnalThese trials formed the basis for the randomized Phase III clinical trial ATACH II, which sought to determine the efficacy of early and intensive blood pressure lowering treatment administered within three hours of sICH onset and continued for the next 24 hours. Similar to the ATACH I and INTERACT I and II studies, recently published results have shown no appreciable decrease in the rate of death, or disability , 15-16.We aim to identify the prevalence of prehospital elevated SBP as defined by ≥140 mm Hg and determine if an association exists between elevated prehospital SBP and hematoma volume. This study, while exploratory in nature, may shed light on the contribution of prehospital factors in ultra-early management of sICH and its associated outcomes, as well as expand the horizon of possible factors that could contribute to improved outcomes in sICH patients.This is a three-year retrospective observational cohort study of patients admitted through a single emergency department with a new diagnosis of sICH confirmed via computed tomography (CT) scan in the hospital. Subject enrollment and data acquisition are described previously -18. All We included all ambulance-transported subjects with a final inhospital diagnosis of sICH. Interhospital transfers were excluded.The patient demographic variables used for analysis included date of birth, gender, ethnicity, and race. The baseline variables included SBP recording and pre-sICH functional status and baseline characteristics, including modified Rankin Score (mRS) and use of anticoagulants. Post-sICH characteristics recorded include hematoma volume, location of the hemorrhage, and presence of intraventricular hemorrhage. The patient outcomes during and following hospitalization were available for analysis.The hematoma volume and outcomes associated with prehospital SBP of ≥140 mm Hg were analyzed. Although data on other prehospital vital signs were available, we chose to focus solely on SBP and Glasgow Coma Scale (GCS). This selective approach was done to prevent inaccurate risk estimates resulting from the use of too many independent variables in a model with a small sample size.The primary outcome measure was hematoma volume upon initial CT at the emergency department (ED) Table . The secThe patients were initially categorized by hematoma size (≥30 mL and <30 mL) . The demIn our multivariate model we sought to determine if an independent association existed between components of prehospital SBP and hematoma size at initial CT when controlling for demographic characteristics, baseline functional status of the subject, and sICH characteristics. A p-value of 0.05 was considered significant. Statistical analysis was performed using STATA Version 10.0 .The subjects included 243 adult patients who were seen and treated for sICH in an emergency department serving a county hospital in a large metropolitan city. Out of those 243 subjects, 193 were transported by ambulance and had a mean age of 66 years (SD+/-14.5). Nintey-eight (51%) were male. A total of 180 (93%) patients had a documented prehospital SBP, out of which 173 (90%) showed an elevated SBP of ≥140 mm Hg, and 82 (43%) had a hematoma volume of ≥30 mL. The mean hematoma volume according to the CT scan on admission was 41 mL (SD=47 mL)  was associated with a trend towards larger hematoma volume (OR 3.86 95% CI 1.02- 4.60). No statistically significant associations were noted between prehospital SBP and 30-day mortality (OR 0.10 95% CI 0.2-4.97), severe disability (OR 3.64 95% CI 1.01-13.06), and prehospital neurodeterioration (OR 1.22 95% CI 0.39-5.20)  lowering) within six hours of sICH onset . HoweverAn interesting study by Fan, et al. (2015) showed that compared to inhospital blood pressure readings, increased on-scene systolic, diastolic, and mean arterial pressures were all independently and more strongly associated with increasing neurologic deterioration as defined by ≥2 decrease in GCS within 24 hours after ED admission .Differing results between other studies described could be attributed to differences in demographics of the patient population and study settings. The main limitation for this study was our small sICH cohort size as evidenced by wide confidence intervals.ICH is seldom diagnosed in the prehospital setting due to lack of imaging modalities. CT equipped ambulances are available in parts of Europe and the United States and may play an increasing role in prehospital stroke care in the future. While we acknowledge these limitations, this is one of the few studies exploring the impact of prehospital SBP on sICH patient outcomes. Based on our findings, we hope to provide valuable information and spur investigation into possible future diagnostic and treatment modalities for sICH patients in the prehospital setting.Prehospital elevated SBP is associated with larger hematoma volume on ED arrival in patients with spontaneous intracranial hemorrhage. While these findings are limited by the size of the cohort and unmeasured variables such as prehospital hematoma volume in the early phase of care, future studies using larger sample size, accounting for further prehospital variables, and using a cumulative dose of hypertension  rather than episodic elevations in SBP are likely to shed more light on the association between prehospital SBP and sICH patient outcomes.


Although oxygen is generally administered in a liberal manner in the perioperative setting, the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion have not been fully unraveled. Our aim was to study the acute hemodynamic and microcirculatory changes before, during and after arterial hyperoxia in mechanically ventilated patients after coronary artery bypass grafting (CABG) surgery.This was a single-center physiological study in a tertiary care ICU in the Netherlands. Twenty-two patients scheduled for ICU admission after elective CABG were enrolled in the study between September 2014 and September 2015.2) of 90% allowing a 15-min wash-in period. Various hemodynamic parameters were measured using direct pressure signals and continuous arterial waveform analysis at three sequential time points: before, during and after hyperoxia.In the ICU, patients were exposed to a fraction of inspired oxygen (FiO2) of 90%, the partial pressure of arterial oxygen (PaO2) and arterial oxygen saturation (SaO2) were significantly higher. The systemic resistance increased (P < 0.0001), without altering the heart rate. Stroke volume variation and pulse pressure variation decreased slightly. The cardiac output did not significantly decrease (P = 0.08). Mean systemic filling pressure and arterial critical closing pressure increased (P < 0.01), whereas the percentage of perfused microcirculatory vessels decreased (P < 0.01). Other microcirculatory parameters and cerebral blood flow velocity showed only slight changes.During a 15-min exposure to a fraction of inspired oxygen (FiOWe found that short-term hyperoxia affects hemodynamics in ICU patients after CABG. This was translated in several changes in central circulatory variables, but had only slight effects on cardiac output, cerebral blood flow and the microcirculation.Clinical trial registration Netherlands Trial Register: NTR5064 During and after coronary artery bypass grafting (CABG), patients are supported with mechanical ventilation and supplemental oxygen. Despite its lifesaving characteristics and key role in the treatment of vasodilatory shock, oxygen therapy may harbor considerable risks given the relationship between prolonged hyperoxia, lung injury and adverse outcome –5. The eAchieving hemodynamic stabilization is an important clinical prerequisite for early extubation and dismissal from the intensive care unit (ICU) after cardiothoracic surgery. Any intervention that influences hemodynamics and blood flow to the bypassed myocardial territories may impact functional recovery and requires optimal fine-tuning to achieve the best outcome. Although oxygen is generally administered in a liberal manner in the perioperative setting, the unraveling of the effects of oxygen administration on dynamic cardiovascular parameters, filling status and cerebral perfusion may provide novel insights in the pathophysiological mechanisms involved in hyperoxic exposure. Our aim was to study the acute hemodynamic and microcirculatory changes during increased oxygen supply in mechanically ventilated ICU patients after CABG surgery.Adult patients with symptomatic coronary artery disease without recent myocardial infarction scheduled for ICU admission after coronary artery bypass surgery were screened for eligibility. Patients with congestive heart failure, severe arrhythmias, intracardiac shunts, extensive peripheral arterial occlusive disease, symptomatic pulmonary disease, aortic aneurysm and/or significant valvular disease were not considered for inclusion. Patients with signs of severe hemodynamic instability  during ICU admission were excluded. Study approval was granted by the local medical ethics committee (LUMC P14.046), and all patients signed informed consent. The study was registered with the Netherlands Trial Register, number NTR5064, registration date February 2015.2 was 0.4, and a positive end-expiratory pressure of 5 cm H2O was applied. Directly after surgery, patients were admitted to the ICU and received standard postoperative care. Continuous infusion of propofol and sufentanil was maintained for all patients, and no bolus medications  were administered.Anesthesia during surgery was maintained with propofol and sufentanil. Ventilation was adjusted to achieve normocapnia. FiOMean arterial blood pressure (MAP) was measured via a 20-G radial arterial catheter inserted by Seldinger technique. Central venous pressure (CVP) was measured with a central venous catheter inserted in the right internal jugular vein . Pressure transducers  for the arterial and central venous signals were referenced to the intersection of the anterior axillary line and the fifth intercostal space. The airway pressure was measured at the entrance of the endotracheal tube and balanced at zero level against ambient air. Standard electrocardiogram leads were used to monitor heart rate. Body temperature was measured using a rectal temperature probe.plus monitor .Beat-to-beat values of cardiac output (CO), stroke volume, stroke volume variation (SVV), pulse pressure variation (PPV) and heart rate (HR) were obtained by Modelflow using continuous arterial waveform analysis as previously described , 19. HemBefore starting the protocol, the mechanical ventilation in volume-controlled mode was switched to airway pressure release ventilation (APRV), with settings adjusted to achieve the same minute ventilation, which allows for external control of the ventilator . A computer program was used to control the ventilator as described previously . During At least three videos of ten sequences (40 frames each) visualizing different sites of the sublingual microcirculation were recorded per patient per time point by the same dedicated researcher using sidestream dark field (SDF) imaging with the MicroScan Video Microscope . The three best quality videos from representative multiple site imaging were analyzed, and calculated parameters were averaged. Previously suggested key points for optimal image acquisition were considered, and maximal efforts were undertaken to avoid pressure artifacts and eliminate secretions . SDF imaBlood flow velocity (BFV) in the right middle cerebral artery (MCA) was measured at an insonation depth of 50–52 mm by transcranial Doppler (TCD) monitoring using a Pioneer TC 4040. When the optimal TCD signal was achieved, a 2-MHz TCD transducer probe was fixed over the temporal window using an adjustable headset .2 was titrated to a level targeting a partial pressure of arterial oxygen (PaO2) between 67.5 mmHg (9 kPa) and 82.5 mmHg (11 kPa) and a complete set of hemodynamic measurements was performed. The intervention (T2) commenced by increasing the FiO2 to 0.9, and after a 15-min wash-in period, all hemodynamic measurements were repeated. Thereafter (T3), the FiO2 was decreased by targeting baseline PaO2 levels, and after 15-min wash-out period, the final control measurements were completed. Before, during and after the intervention, arterial blood gas samples were analyzed to determine arterial oxygenation.Approximately one hour after ICU admission the experimental procedures were initiated. All measurements were performed with patients in supine position at three sequential time points: pre-intervention, during intervention and post-intervention. Before the intervention (T1), FiO2O as previously reported [Pmsf). Similarly, the ventricular output curve was fitted through the values of MAP and CO, where the regression line crosses the zero flow intercept at the critical closing pressure (Pcc) [Four 12-second inspiratory hold maneuvers were applied using ventilator plateau pressures of 5, 15, 25 and 35 cm Hreported . Each sue (Pcc) .Rsys) was calculated as the ratio of the pressure difference between MAP and mean CVP, and CO. The resistance at the arterial and venous side of the circulation was also separately calculated as resistance for ventricular output Rvo = (MAP − Pcc)/CO and resistance for venous return Rvr = (Pmsf − CVP)/CO [The resistance of the systemic circulation ( CVP)/CO .As this was an exploratory physiological intervention study studying multiple hemodynamic parameters, we did not specifically rely on sample size calculation for one single outcome.hyperoxia) and post-intervention measurements  were compared to baseline  measurements, using a paired t tests or Wilcoxon signed-rank test, depending on the underlying distribution.The intervention  and hemoglobin (Hb).Multivariate linear mixed models with random effects per patient were used to compare the exposure (T2) with the non-exposure (T1 and T3) measurements, to account for within-subject correlation and were adjusted for age, temperature, the administered dose of propofol and norepinephrine, and the achieved levels of arterial carbon dioxide .−1) and sufentanil (range 5–25 µg h−1). Two patients additionally received norepinephrine (0.02 and 0.04 µg kg−1 min−1) at a constant rate in order to keep the blood pressure in a similar range (MAP higher than 65 mmHg) as the other included patients during the experimental procedure. This was accounted for in the multivariate linear mixed model, and excluding these patients did not materially change the magnitude or direction of our univariate findings.Patients were screened for eligibility from September 2014 until September 2015. Four patients were excluded due to severe postoperative hemodynamic or respiratory instability in the ICU. Baseline characteristics of the twenty-two included patients are listed in Table 2 levels pre- and post-hyperoxia matched well with the targeted levels. Also, pre- and post-hyperoxia arterial oxygen saturation (SaO2) was similar. During hyperoxia PaO2 and SaO2 were significantly higher.Arterial blood gas values at the three different time points are shown in Table 2 decreased over time, whereas hemoglobin, hematocrit, glucose and lactate levels did not change.PaCORsys increased (P < 0.0001), without altering the heart rate. SVV and PPV decreased slightly. CO did not significantly decrease (P = 0.08).Hemodynamic values at the three different time points are shown in Table Pmsf and the slope of the venous return curve (Slopevrc) increased  did not change. Rsys and Rvr increased because of the higher MAP and Pmsf at constant CO. Rvo did not change because MAP and Pcc increased similarly.During the hyperoxia period sed Fig. . Pcc inP = 0.01). No changes in vascular density were detected for either large or small vessels.We did not find any reduction in cerebral blood flow and only slight shifts in microcirculatory scores were noted. The percentage of perfused vessels decreased during hyperoxia  and change in Rvr and baseline heart function, as observed before [Rvo) did not change, we must realize that our description of the circulation is not complete. We cannot describe the part between the site where Pcc exists and the site where Pmsf exists. Therefore, there is a missing part of the circulatory circuit, i.e., the distal arterial compartment, where control of the peripheral circulation is performed by the pre-capillary sphincters.The increase in stressed volume and propofol , 32. We plus monitor that showed a similar pattern compared to the Modelflow technique in our study. Furthermore, the determination of Pmsf is not dependent on the accuracy of the Modelflow technique. Indeed, extrapolation of the venous return curve to flow zero is independent of absolute cardiac output. The ability to follow changes in cardiac output within a patient has been clearly demonstrated before [A recent study with an alternative cardiac output monitor of the arterial pressure wave showed a poor correlation with the thermodilution obtained CO values while changing norepinephrine doses . Howeverd before . We alsod before .Acknowledging that our findings are to be reproduced in a larger cohort and different clinical settings, the following study aspects should be considered. First, the small sample size and the specific subgroup of patients do not warrant a broad generalizability for the observed effects. Hemodynamics in the current patient group may be affected by the effects of the recent bypass and the potential mediators of ischemia reperfusion and inflammation. Other subsets of critically ill patients may respond differently than patients in our cohort who were in a relatively stable condition before starting study procedures. Two patients received small doses of norepinephrine during the experiment to keep the blood pressure in the same order of magnitude as the other included patients but showed stable hemodynamics and the dose was not changed throughout the experiment. Also, excluding these patients from our analyses showed virtually no change in our results.There may be a time effect in which recovery and stabilization of patients in the ICU after surgery may influence hemodynamics. However, assuming that the effect of hyperoxia was transient and respecting a 15-min time gap between the two exposures, the carryover effect was minimized and each case served as its own control (self-matched) . Adjuste2, are therefore not a likely explanation for the hemodynamic changes as seen during the experiment. While a short period of supraphysiological arterial oxygenation may disturb the hemodynamic balance, the effects of long-term exposure to hyperoxia are still uncertain but may be essential regarding patient-centered outcomes.Since we could not detect large differences between the outcomes of univariate and multivariate statistical models accounting for repeated measurements, the observed effects may be predominantly attributed to hyperoxic ventilation, rather than to concomitant changes in other parameters. Other covariates that were considered, such as PaCOShort-term hyperoxia after cardiac surgery induces significant alterations in systemic circulation mainly by vasoconstriction of both the venous and arterial circulation and an increase of mean systemic filling pressure. The increase in stressed volume and systemic filling pressure by hyperoxia resembles the effects of administering a fluid bolus or norepinephrine. This may have clinically important consequences in critically ill patients when hemodynamic and microcirculatory changes are vital, but the effects were not clearly linked to relevant changes in cardiac output and cerebral blood flow.


Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients.This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis.p = 0.002), greater severity of asthma , at least one previous episode of pneumonia , and lower levels of FeNO . The NOPES score was developed on the basis of these variables , and it ranges from 0 to 4 points, where 0 means “no risk” and 4 corresponds to “high risk”. The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%.A total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49–5.84; Almost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma. Asthma is a heterogeneous condition characterized by chronic inflammation of the pulmonary airways  that curBronchiectasis (BE) is defined as bronchial dysfunction secondary to an infectious, inflammatory or reparative process in the airways that permanently damages the bronchial walls and causes irreversible enlargement of the airways. Although the real prevalence of BE is unknown, it has been estimated as being anywhere between 42 and 566 cases per 100,000 people and it particularly affects women and the elderly, but a significant trend toward under-diagnosis has also been acknowledged , 4. HoweAsthma and bronchiectasis are different conditions that frequently coexist. Furthermore, in our experience, a diagnosis of bronchiectasis in asthma patients could lead to modifications to both therapy and prognosis (as in the case of COPD patients –9). Mostn = 432) with UMSA . We classified patients as moderate or severe: moderate if they need at least 100 μg fluticasone propionate equivalent per day and additional controller drugs, or at least 250 μg fluticasone propionate equivalent per day without additional controller drugs; and severe if they need at least 1000 μg fluticasone propionate equivalent per day and required additional controller drugs.This prospective study included consecutive patients ( 4 and 5 ) during We used a standardized protocol to try to improve the control of these patients. This was designed to ensure patients’ adherence to both the therapy and the appropriate inhaler procedures, provide health education, adjust the treatment and rule out other comorbidities. If, after all this, and after at least a year of follow-up (as required for inclusion in the study), the disease was still not satisfactorily under control, then a high-resolution computed tomography chest scan (HRCT) was carried out to evaluate other pathologies, in accordance with the main guidelines for asthma , 20. SeeAt the following appointment, one to three months after inclusion in the study, those patients diagnosed as having BE by means of HRCT underwent a complete examination, following specific guidelines , to invePrevious episodes of pneumonia reported by patients or their medical records were recorded. Patients with a previous diagnosis of bronchiectasis, smokers, and former smokers of more than 10 packs per year were excluded (to avoid the possibility of concomitant COPD diagnosis). On inclusion, patients were required to have been in a stable phase for at least 8 weeks (no respiratory tract infection), and all the tests were performed in this phase. Written informed consent was obtained from all participants. The study was approved by our hospital’s Ethics Committee.A chest HRCT scan was performed on all the patients, and bronchiectasis was diagnosed according to the criteria established by Naidich et al. . The extFull clinical histories from diagnosis to inclusion in the study were compiled in a database. A standardized protocol was applied for the prospective collection of sociodemographic data , clinical profile  was measured with a conventional chemoluminescence analyser  using the online standardized single-breath technique, following international guidelines . SpiromeModerate-to-severe exacerbations were recorded according to standard guidelines . All the3 was set for the identification of abnormal cultures positive for PPM, following published methods [All patients underwent a monthly microbiological analysis of spontaneous morning sputum during the first 6 months. Instructions were given to ensure that sputum was collected correctly, with low percentages of saliva recorded . Diluted methods –39. The  methods .All data were analyzed using R commander  and exprk value) was calculated for assessment of inter-reader agreement for qualitative radiological variables .The kappa statistic , as well as those variables that presented statistically significant differences in bivariate analysis, were included as independent variables in the first step. The forward technique  was used to remove variables with a p > 0.1 from the logistic model (conditioned by selecting the model with the fewest variables and strongest goodness of fit), as well as to evaluate any possible interactions between independent variables. ORs and 95% CIs were calculated for independent variables. Together with the above-mentioned risk indicators, the goodness of fit was assessed using the Hosmer-Lemeshow test, and the variance of the model was explained by Nagelkerke R2.Bivariate analysis based on Student Receiver operating characteristic (ROC) curves were obtained to elucidate the clinical functions of FeNO in the diagnosis of bronchiectasis in asthmatic patients. An AUC-ROC≥0.70 is established as a suitable diagnostic performance , and theP < 0.05 was considered significant.Finally, in order to evaluate the effectiveness of the NOPES score as regards the presence of bronchiectasis for the cut-off points of ≥1, ≥2 and ≥ 3, the basic indicators , 44 of tp < 0.001).A total of 432 patients with UMSA were recruited consecutively and prospectively during the study period. Fifteen patients refused to participate, 13 were excluded because they presented bronchiectasis secondary to another disease, and six were lost to follow-up  was developed, using logistic regression  .Another predictor of bronchiectasis in UMSA is asthma severity. The results obtained are consistent with the literature , 18, 46 Our study’s contribution is the correlation found between higher FeNO levels and a lower probability of bronchiectasis. FeNO is a non-invasive biomarker of the inflammation of the airways in asthma; high levels are associated with eosinophilic inflammation of the airways –54. Its However, some studies of FeNO levels in BE have presented contradictory results. Thus, Kharitonov et al.  showed tIn fact, few studies have assessed FeNo in subjects with asthma and bronchiectasis. In a recent retrospective study, Chen et al  measuredAs FeNO is not available in all centers, we made a score with three variables (excluding FeNO but retaining the other three variables), but it proved to be of little value in comparison with the score with four variables (AUC-ROC 0.648 and Nagelkerke’s R Square 0.08 vs AUC-ROC 0.7 and Nagelkerke’s R Square 0.145) and was therefore discarded.We therefore propose the NOPES score as a clinically valuable, easy-to-use tool for predicting bronchiectasis in patients with uncontrolled asthma.The strength of this study is its use of the largest prospective study of patients subjected to HRCT. It provides real data on the prevalence of bronchiectasis in patients with uncontrolled asthma, without biases such as smoking, ABPA, or other diseases causing bronchiectasis, as these conditions were excluded.n was 4; consequently, this probability can be underestimated in the former case and overestimated in the latter. Furthermore, induced sputum is unfortunately unavailable in our center, and so we were unable to establish our patients’ inflammatory phenotypes. Another limitation is that all the patients were treated in the same center, so a multicenter study would be required to confirm the results.One limitation of this study, despite its large sample, is that patients were grouped according to the presence or absence of different variables, leaving some study arms with very few patients, as in the cases of subjects likely to develop bronchiectasis according to a NOPES score of 0% and 100%, where the highest The prevalence of bronchiectasis in UMSA is high. The severity of asthma, chronic expectoration, and a history of previous pneumonia can be independent predictive factors for bronchiectasis in subjects with UMSA, and high FeNO levels are related to a lower presence of bronchiectasis. We propose an easy-to-use predictive tool for bronchiectasis in these patients.


Recurrent syncope — abrupt loss of consciousness — can have a serious impact on patients’ quality of life, comparable with chronic illnesses. Vasovagal syncope (VVS) is a specific reflex syncope, in which an inappropriate reaction of the autonomic nervous system (ANS) plays a key role in the pathophysiology. In syncope diagnosis, an ideal diagnostic method should positively identify vasovagal sensitive patients, without the need to perform a specialised head-up tilt table (HUTT) test. We apply a novel methodology of multistructure index (MI) statistics for seamlessly evaluating the size spectrum of the asymmetry properties of magnitudes of neural reflexes responsible for maintaining the homeostatic dynamics of autonomic control. Simultaneous evaluation using the MI of the effects on heart rate and blood pressure involved in achieving homeostasis of contrasting properties of the dynamics of slow and fast neural regulation reveals a clear distinction between vasovagal patients and healthy subjects, who are/are not susceptible to spontaneous fainting. Remarkably, a healthy cardiovascular response to the HUTT test is indeed evident prior to the test, making the MI a robust novel indicator, clearly distinguishing the cardiovascular autonomic regulation of healthy people from that of vasovagal patients without the need to perform an actual HUTT test. The autonomic nervous system (ANS) mediates these processes to maintain the body’s homeostatic state2. Methods evaluating changes in the time intervals between consecutive heart contractions, called heart rate variability (HRV)3, and beat-to-beat variation of the level of blood pressure, called blood pressure variability (BPV)4, have been proposed to assess the ANS control. These approaches have been successful both in extending our knowledge about cardiovascular regulatory mechanisms and also in enabling the design of clinically important measures of risk prediction3.The physiological mechanisms responsible for heart rate accelerations and decelerations and for rises and falls in blood pressure are distinct8. The upright posture induces downward displacement of about 500 to 1000 ml of blood and the major part of this redistribution occurs within the first ten seconds. During the following minutes, an additional 700 ml of fluid gradually relocates into the interstitial space. Therefore, various regulatory mechanisms have to be involved in maintaining a proper blood supply for the vital organs, including the brain. A decrease in blood pressure is sensed by arterial baroreceptors, which first results in the decreased activation of the vagal branch of the ANS and in the subsequent rise of the heart rate within one or two following heartbeats. Then, after 1–3 seconds the rise in the sympathetic ANS branch activity increases both the heart rate and heart muscle contractility, and induces the constriction of small arteries and arterioles6. In addition, local vasoconstrictor mechanisms are activated. In contrast, vasovagal patients in the upright position may experience vasodilation and/or bradycardia resulting in hypotension, a decrease in brain perfusion, and finally, the loss of consciousness7.Disorder of the autonomic regulation is considered to be the main reason for vasovagal syncope (VVS) — a transient loss of consciousness resulting from the orthostatic stress5.Although vasovagal syncope is very common, its pathophysiology is not fully understood. Several concepts have been developed, including ventricular theory, baroreflex dysfunction theory, reduced blood volume theory, neurohumoral theories and active vasodilation theory. The roles of respiration and cerebral blood flow deregulation have also been considered. However, many of the attempts made to explain the various mechanisms involved in vasovagal syncope have led to contradictory results7. Patients are initially placed in a supine position on a special-purpose table, and are subsequently titled to the upright position. During all the parts of the test, continuous recording of heart rate and beat-to-beat blood pressure is performed and is subsequently analysed to determine the type of the main mechanism leading to a loss of consciousness. Spectral methods of heart rate and blood pressure variability analysis have been extensively used to describe cardiovascular rhythms and the role of the ANS activity during vasovagal syncope9. However, the results obtained have contained numerous discrepancies5. Moreover, while considerable research has been devoted to ANS dysfunction assessment by HRV and BPV analysis, less attention has been paid to revealing other mechanisms responsible for syncope by using heart rate and blood pressure variability investigations.A simple and non-invasive method, referred to as a head-up tilt test (HUTT), is usually used to provoke vasovagal syncope in laboratory conditions16. Moreover, it has been proposed that this difference could be related to the rate19, and the pattern of breathing20. Also by studying BPV, differences between rises and falls in systolic blood pressure have been identified21. Indeed, interbeat time series do not exhibit time reversal symmetry22 — decelerations in original time series become accelerations in the series with the inverted temporal axis/time, and vice versa. This suggests that asymmetric time patterns characterize the underlying dynamics12, and might be used for better understanding of complex responses provoked by the HUTT.Recently, there has been growing interest in asymmetric features of cardiovascular parameters. HRV analyses have revealed a difference in the short-term organization between heart decelerations and accelerationsAdditionally, various methods have been proposed to assess long-range characteristics in time series data in general, and in heartbeats in particular; see, e.g., refs Here we develop an approach extending the methodology of the structure function to explicitly address asymmetry properties across the entire range of effects of large and small fluctuations. Technically, the novelty of our approach consists of splitting fluctuations into increments and decrements. Then we investigate the balance between the increments and decrements (both separately and cumulatively), from the smallest to the largest changes. In particular, the present proposition — to be referred to as a multistructure index (MI) — reveals the structure of the asymmetry between increments and decrements by studying the participation of positive increments in the pool of all changes. We hypothesize that fluctuations of various sizes might characterize distinct mechanisms of cardiovascular regulation.Therefore, by investigating similarities and differences in MI between healthy individuals and patients suffering from VVS, in a supine position and in three separate time windows during tilting, we can observe and compare coordinated activities of basic mechanisms responsible for cardiovascular homeostasis. Remarkably, we obtain differentiation between all the groups investigated, from healthy to pathological — VVS patients, not only in the three windows of tilting, but in the actual initial condition — supine position prior to tilting. This capability of the MI index to provide precursory insight into the syncope mechanism by means of investigating time series asymmetry constitutes the main innovation of this work.The paper is organized as follows. The Methods section contains a description of the subject data, together with a full explanation of the methodology of signal acquisition, pre-processing, and the statistical analysis used. The definition of the MI-index and an introduction to its capacity as an index of asymmetry is provided in the Methods section. The Results section presents graphical MI(q) plots of groupwise responses to tilting for both RR and SBP increments. A discussion of the results and conclusions close the manuscript.The study comprised signals obtained from 112 vasovagal patients who experienced vasovagal syncope in their everyday life and 29 healthy individuals with no history of fainting. All clinical data came from the Department of Cardiology and Electrotherapy, Medical University of Gdansk, Poland. The experimental protocol complied with the Declaration of Helsinki and was approved by the Bioethics Committee of the Medical University of Gdansk. All the subjects gave their informed written consent to participating in the study.The study group was recruited from patients managed in the outpatient syncope evaluation clinic. Inclusion criteria were: the occurrence of at least 2 episodes of syncope within the last 6 months, a typical history suggesting vasovagal fainting, and age 18–50 years. Patients with a history or physical examination findings suggesting mechanisms of syncope other than vasovagal were excluded. The control group (CG) consisted of healthy volunteers matching the study group in age and sex. None of the subjects were medicated. A demographic description of the groups studied is presented in Table The HUTT tests were performed in all the study participants between 7 and 11 am, after an overnight fast. The subjects rested in a supine position on a special table for 30 min and then the table was tilted to 60°. The study participants remained in the tilted position for 20 minutes or until the occurrence of syncope. If fainting did not occur, the subject was administered 400 micrograms of nitroglycerine  and the test was continued for 10 minutes or until syncope occurred. During the tests, all the subjects were asked to synchronize their breathing rhythm with recorded, verbal instructions to breathe in and out at a frequency of 0.25 Hz, in the physiological breathing pattern, namely with a 1:2 ratio between the inspiration and expiration time.26. If the blood pressure fell, followed by an increase in the RR-intervals to less than 1.5s , the syncope was classified as being of mixed type and was denoted as VVS1. If the RR-intervals increased to an asystole of more than 3s , the syncope was described as cardioinhibitory and was denoted as VVS2 type.The results of the HUTT test were interpreted according to the modified VASIS criteriaCG - control group ; NEG - patients with a history of syncope who did not faint during HUTT; VVS1 - patients with a history of syncope who experienced mixed type vasovagal syncope during HUTT; VVS2 - patients with a history of syncope who experienced faint of cardioinhibitory type during the test.As the various types (results) of vasovagal syncope are related to different pathophysiological backgrounds, we decided to analyze their data separately. Therefore, our study groups were as follows: Initially, the study group consisted of 50 healthy subjects, 100 patients with a positive result for the HUTT test and 50 patients with negative result for HUTT (no syncope during the test). Subjects who fainted before nitroglycerine administration were not included in the present study (8 patients). Additionally, 14 healthy subjects who experienced syncope during HUTT (despite having no history of syncope) were also excluded from our study.Surface ECG (lead II) and beat-to-beat pressure were simultaneously recorded using the Task Force Monitor System . Data were sampled at 1 kHz. All the patients were examined in the same room at the same temperature. The Task Force Monitor System is a device for continuous noninvasive assessment of cardiovascular regulation. .Despite all the attempts to obtain signals of the best quality, in 7 subjects in the control group and 30 vasovagal patients, the ECG and/or blood pressure recording was not satisfactory to obtain reliable results  and we had to exclude these individuals from the groups studied. As a result, the present paper is based on data from 112 patients and 29 healthy volunteers.RRi and SBPi, where i indexes subsequent normal heart contraction events. Then RR-increments are defined as changes in the length between the adjacent RR-intervals, i.e., The values of RR-intervals and SBP levels will be denoted, respectively, as In Fig. horizontal) contains recordings which ended one minute before tilting, when the subject was still in the supine position. Subsequently, one minute after tilting, two windows of 300 beats were selected, to be referred to as an early tilt phase T1 , and the actual tilt phase T2. The final, late tilt phase window of 300 beats, referred to as T3, entails beats recorded one minute before nitroglycerine administration.The procedure of tilting results in nonstationarity of the signals. In order to facilitate the investigation of the dynamical effects after the onset of tilting, each signal was divided into windows consisting of 300 beats. The first window (named H for i) a change between the adjacent i and i − 1 values of either the RR-intervals or the values of SBP. Moreover, let q, the MI is defined as follows:Let us denote as Δ(MI(q) measures the total effect of the positive changes with respect to all changes in the signal, when the influence of the changes of a particular size is selectively magnified (enhanced or suppressed) by the particular value of the control parameter q. Note, that if for each size of the change there is a balance between positive and negative changes then MI(q) = 0.5 independently of q. However, if there are event sizes where prevalence or deficiency of Δ+s occurs, then depending on the size of Δ+, small/mid-size/large, values different from 0.5 occur at different intervals of q, namely for negative/around 0/positive values of q, respectively.The function MIRR(q) refer to the multistructure index of RR-increments. Then MIRR(q) estimates the proportion of decelerations Δ+s in all changes of the heart rhythm. Similarly, let MISBP(q) refer to the multistructure index of SBP-increments. Then MISBP(q) measures the role of rises in SBP Δ+s with respect to all non-zero SBP-increments.Let MI(q). This implies that the value of MI(q) for large negative q is determined by whether or not the smallest positive and negative values are balanced. Similarly, the ratio between positive and negative the biggest values determines MI(q) for large q. Similar proportions for other signal values influence the q-spectrum of MI(q) when q moves from large negative to large positive values. However, the relation between small, mid-size and large events is logarithmic, which implies that with this distinction, we separate dynamics of different timescales.From the mathematical point of view, the smallest and biggest increments in a signal function as anchors stabilizing the limit values of MI(q) observed for q < −2 as referring to the ‘smallest changes’, and for q > 2 as referring to the ‘largest changes’ in the signal. The features obtained for −2 ≤ q ≤ 2 will be considered as ‘mid-size events’. Therefore, the smallest changes can be interpreted as referring to the slow dynamics, and the largest changes as describing the fast dynamics. Note that in the case of RR-intervals and SBP signals, the probability of a change sharply decreases with the increase in the size of the event. Therefore, the smallest changes are the most probable changes, whilst the largest changes correspond to ‘rare events’.In the following, we consider the properties of q values can be related to the moments of the probability distribution of increments. Accordingly,q = 0, then MI is the ratio of the total number of positive changes of any size to the total number of all changes. Hence, MIRR(0) answers the question about which events happen more frequently, decelerations or accelerations. Similarly, MISBP(0) tells whether falls or rises in SBP are more frequent.If q = 1, then MI provides the ratio of the total sum of Δ+s to the total sum of all changes. In this way, MI(1) provides information about whether there is a trend in the signal or not, whether the values of the signal, RR-intervals or SBP levels are increasing or decreasing. MIRR(1) is directly related to the Porta index PI12, as MI(1) = 1 − PI.If q = 2, then MI estimates the ratio of fluctuations of Δ+s to the total of all fluctuations in the signal. Therefore MI(2) provides information about the overall variability of Δ+s with respect to the variability of the signal. MIRR(2) is known as the Guzik index GI11, MIRR(2) = GI.If q = 3, the MI explores the skewness of the probability distribution of increments. In this way, MI(3) can provide characterization equivalent to the skewness index S1 considered in ref. If In contrast, non-negative and integer MIRR(q) and MISBP(q) functions were calculated for each signal with RR-intervals and with values of SBP, respectively, in each time window separately, for q = 0.1. Then by pooling the results corresponding to the same group of subjects and the same time window, we obtained the group mean The Formula (1) makes it possible selectively to amplify singular unbalanced extremes – minimal and maximal changes in the signal. However, minimal changes are usually related to the properties of the equipment used rather than to the physiological properties recorded. Also maximal changes may be more related to individual characteristics of a subject than representative of the features of the group. Therefore our calculations were performed under the following restrictions to extremal values:Applying these thresholding criteria, the spectrum of quantified events spreads over three clearly separated logarithmic timescales. Estimates performed with different limits potentially modify the significance of the smallest, and largest events. The effect might potentially also affect the properties of mid-size events, which could, for example, be less pronounced since the specific features would accumulate in the mid-size events due to noise from extreme values. With these study limitations in mind, we nevertheless consider the thresholding criteria applied to be reasonably conservative.q, type of the signal) on the mean of the function MI was studied by four-way analysis of variance. The interactions among pairs of factors were taken into account. Analysis was performed for different sets of q, starting from classical {1, 2} to represent the Porta and Guzik indices alone. Based on the anovan results, multiple comparisons (multicompare) were performed for pairwise comparison of the group means.The numerical and statistical validation of the group means was performed with MATLAB and its Statistics Toolbox R2016b (The MathWorks Inc.). The overall effect of the four factors , we represent the group results as their means and standard errors of the means. The asymmetry of MI, i.e., the validity of the distinction of the MI(q) value from 0.5 was tested by two-sided t-test. The statistical significance of the differences between two groups was verified by t-test for either paired data (in the case of the same group of patients) or independent data (in the case of different groups of patients). The figures were prepared with SigmaPlot V13.0 (Systat Software Inc.).We applied the Lilliefors test to assess the normality for each q = 1, 2, the MI response to each factor  of the statistical analysis is proven to be statistically significant with p-values , respectively. However, only the interaction of the time window and q index has had a statistically significant (p = 0.0384) impact on the mean of MI. By adding −0.5, 0, 0.5 to the set of q values, we obtained not only better statistics for the impact of all the groups [p-value: ] but also all the pairs of interactions were statistically significant with the exception of the pair . A statistically significant impact of this pair was obtained when large q negative values were considered. For example, for q = −5.0, −0.5, −0.2, 0.2, 0.5, 1.0, 1.5, 2.0 all factors and also all pair interactions reached the p-value less than 0.05.If q for all the groups of the signals studied are jointly plotted in Figs q values for which the normality test has been passed (thick line) — which validates our use of the means in presenting group properties. Then, the next lines up show the ‘significance’ (thick line) of the detection of asymmetry — i.e. the test if the actual MI(q) value is significantly distinct from 0.5. Finally, the top lines refer to the significance of the difference with respect to the results obtained for the CG group. The results of this test support our investigations of pathological cardiovascular regulation of homeostasis in VVS patients.The dependence of entclass1pt{minimaPlots of entclass1pt{minimaq < 2, both the indices + is distinct from the domination observed for the RR-intervals, Δ−. Additionally, there is a noticeable transition in the predominance in both signals, SBP and RR-intervals, when q is changing from the negative q values to positive q values. These two properties together make the plots of the indices MI(q) = 0.5 and with respect to the point  when compared with each other.For small and mid-size increments, i.e. for q < 2 (approximately).We observe the slight domination among the most probable events, i.e., accelerations in the case of RR-intervals and rises in the case of SBP, related to the events of the smallest size. The prevalence of rare events is likely to be related to large decelerations in the heart rate and large falls in the blood pressure. It is worth noting that the domination of accelerations extends to all RR-increments except the largest RR-increments, because MI(q) = 0.5, but there is no symmetry with respect to the point . The indices of the VVS1 and VVS2 groups are not mutually symmetrical either along the line MI(q) = 0.5 or at the point .Only the indices of the NEG group are mutually symmetric and along the line There is an evident distinction in the prevalence of the most probable events for SBP between healthy people and vasovagal patients. In vasovagal patients, the most probable events, the smallest ones, exhibit the domination of falls in SBP, while in the case of the healthy people, rises in SBP dominate over falls. This distinction among the smallest events and in some of the mid-size events is statistically significant.q considered.In the case of RR-interval dynamics, for all groups there is a slight domination of accelerations among the mid-size RR-increments. Considering large changes, the signals from the healthy group display a significant prevalence of decelerations, while the signals from the vasovagal groups do not show such a strong prevalence. However, the values of The functions entclass1pt{minimaThe results for the mean values T1  separated by m steps in time. Negative and positive q values respectively emphasize the collective effect of small and large fluctuations in xi values. In ref. Our proposition of MI for quantification of events according to their sizes and directions follows a popular approach of the structure function used in the estimates of long-range dependencies in time series {However, the influence of these relationships is assessed following a multiscaling approach, meaning that the results do not necessarily progress smoothly from the smallest to the biggest values, but rather tend to exhibit strong non-linear increases/decreases over scales. Hence, by the suitable choice of the minimal and maximal increments we can directly not only identify, but also separate the scales of interest, such as, for example, accelerations and decelerations larger than 50 ms commonly associated with vagal activity, from smaller ones which are usually considered as following the sympathetic activation.RR and ΔSBP. Therefore, baroreflex couplings can be qualified by symmetries between asymmetries in 27. Note, that such an approach avoids the problem of delays between RR-interval and SBP beat-to-beat interactions.During the study, the subjects were initially in supine rest. Head-up tilting then triggered the autonomic provocation. Our aim was to characterize the dynamics of the short-term regulation of the two basic physiological rhythms: changes in RR-intervals and changes in SBP. It is commonly believed that RR-intervals and the values of SBP are entangled with each other, which leads to beat-to-beat variations in the length of RR-interval and in the value of SBP. The so-called feed-forward mechanical pathway (Starling law and diastolic runoff) is responsible for the effect of the actual RR-interval on SBP, and baroreflex feedback induces the variation in RR-intervals in response to SBP change. The baroreflex loop is assumed to be crucial in maintaining the proper blood perfusion in distant organs. Investigation of baroreflex effects demands at least bi-variate signals. Our signals with RR and SBP were indeed bi-variate signals, but we estimated properties of RR and SBP separately. However, in a rough approximation, the baroreflex sensitivity assumes linear dependence between Δ29. Typically, heartbeats are shortened (heart rate accelerates) during inspiration, and prolonged (heart rate decelerates) during expiration. However, the exact phase relationship happens to be dependent on the respiration rate30. Therefore, a paced breathing protocol at frequency 0.25 Hz was applied to our subjects with the physiological ratio of 1:2 inspiration to expiration. Although such breathing results in breaths deeper and more rapid than spontaneous breathing, it is considered best to resemble normal breathing17.It is known that beat-to-beat patterns are strongly influenced by respirationUnder the baroreflex hypothesis of heart rate and blood pressure interactions, rises in SBP cause a deceleration of the heart rate, and falls in SBP result in an acceleration of the heart rate. This schema can be directly read from the MI’s of healthy people at rest, where slow, mid and fast dynamics of RR-increments and SBP are symmetrical to each other. However this picture is not as clear in the other groups considered. Let us explain the differences below.MI(q) estimates, we see that in healthy people at rest, the slow dynamics , which could be attributed to the tonic activity of the sympathetic nerves, is likely to rely on small accelerations and SBP rises, which are punctuated by greater decelerations and large falls, respectively. Therefore, we can hypothesize that the tonic sympathetic activity in vessels results in an increase in the blood pressure, which engages the baroreceptor reflex, activating the vagal system to slow down the heart rate.It is commonly believed that at rest, we should observe effects of the sympathetic tonic activity pacified by increased vagal activity. From q = 2 is close to the border between the mid-size and largest RR-increments. The presence of these large decelerations could be thought of as a manifestation of the strong parasympathetic activation caused by the driven (i.e. paced) expiration. Thus, the homeostatic state in vagal sensitive patients appears to be maintained by two opposing signals sent to the vagal nerves: to speed up the heart (sent from the vascular system), and to slow down the heart (sent from the respiratory system).Yet, the signals of vasovagal patients provide a different picture of the homeostatic regulation. The dynamical pattern of SBP increments is opposite or different to the regulation found in healthy people. Namely, there is a slight prevalence of small SBP falls over all small events. In the case of the NEG group, this is accompanied by a slight domination of small size decelerations. This could suggest a weak and potentially insufficient effect of tonic sympathetic activity to vessels that should activate the baroreflex driven intervention to accelerate the heart, hence to withdraw vagal activity. However, we observe the prevalence of accelerations only among mid-size events and not among the largest ones. The Porta index, RR and systolic blood pressure SBP change from beat to beat in the following way:δRR, δSBP stochastic variables centred at some non-zero values which describe slow dynamics; RR, ΔSBP stochastic variables centred at some non-zero values describing fast dynamics; δSBP < ΔSBP, while in the case of VVS patients, the relation seems to be opposite, i.e., 0 > δSBP > ΔSBP.Following the above observations, a very rough description of the underlying dynamics — ‘zero approximation’ can be suggested as follows. Let us assume that slow and fast dynamics correspond to distinct regulatory mechanisms coexisting together, which, however, are switched on-off in some specific manner. Then heart period MI(q) is the first index which so clearly distinguishes cardiovascular autonomic regulation of healthy people from vasovagal patients based on recordings at rest. MI identifies the opposite roles of the basic mechanisms maintaining the homeostasis.To our knowledge, The tilt provocation leads to a switch in the fast dynamics of SBP. Large rises in SBP are observed in all the groups in all time windows, which could be the effect of strong sympathetic stimulation. However, since we still observe an excess of occurrences of the largest heart decelerations, we might suppose that the heart rhythm remains under the strong influence of respiratory action. It is noticeable that only in healthy people are these rapid changes in SBP supported by slow dynamics, earlier attributed to tonic sympathetic activity, and that this support vanishes with time after tilting in healthy people, whilst in the case of vasovagal sensitive patients, it seems to increase. Therefore, we hypothesize that changes in the tonic sympathetic response, probably driven by adrenergic processes, could be slow or inefficient in the case of vasovagal patients. The effect is most pronounced in the early tilt window.31. The resistance is determined by the diameters of precapillary vessels, which are normally partially constricted. This state, called vascular tone, is maintained by smooth vascular muscle cells, which are located in the wall of the vessel. There are many vasoactive substances produced by the tissue cells around the resistance vessels. Vascular tone emerges as the net effect of vasoconstrictor and vasodilator influences acting on the vessel. The factors which determine the degree of smooth muscle activation are traditionally divided into the extrinsic: sympathetic nerves, circulating hormones, and the intrinsic: endothelial-derived factors, smooth muscle myogenic tone, locally produced hormones, and tissue metabolities1. Some of these factors promote vasocontriction , whereas others promote smooth muscle relaxation (nitric oxide derived from endothelium and tissue metabolites such as adenosine and hydrogen ion).Under normal physiological conditions, distribution of the blood is regulated by vascular resistance32, we can speculate that our observation reveals endothelium dysfunction.At rest, vascular tone is maintained locally. The extrinsic neurohumoral influence related to the baroreflex is low, and the intrinsic mechanisms of the blood vessels – myogenic tone and the tissue metabolism surrounding blood vessels – dominate. Our results suggest two different ways in which the vascular tone is preserved in healthy people and in vasovagal patients. At rest, a homeostatic state of SBP in healthy people is maintained by smaller size rises, which are balanced by falls of a larger size. In the case of vasovagal patients, we find the opposite result: small falls are balanced by larger rises. In analogy to heart period indices, we can consider the Porta index for SBP to be Under autonomic provocation, when the tilt test switches the autonomous nervous system regulation via stimulation of the baroreceptors, the main disparity from the resting state occurs in the properties of large rises in SBP. In all the groups studied and all the time windows, we observe a domination of these fast rises over falls. This might denote the strong activation of the mechanisms of the vessel contractions, namely strong sympathetic activity. Together with the prevalence of fast decelerations, which has been observed in all groups and time windows with the exception of the VVS2 group in T2, this suggests that the parasympathetic part of autonomic nervous system also remains activated.RR-interval and SBP dynamics. Our analysis performed in time windows allowed us only to discern such transients which persist for longer time intervals. Transients taking short time periods might be not discovered using the window-based method. Secondly, baroreflex entanglement of heart period and blood pressure, when represented and investigated through relationships, correspondence and symmetries between two univariable functions of 29. The sizes of the groups studied are modest, which implies that statistical significance was not always achieved. Finally, we used well-motivated thresholds for RR-increments and SBP-increments, which need to be included in considerations of the results.The MI approach has two sources of limitations. First of all syncope is a phenomenon which is characterized by transient properties in q changing from negative to positive values, exhaustively scan the distributions of RR-increments and SBP-increments for changes of specific size. The prevalences are attributed to and change systematically while moving with the q value. Thus, they provide a full overview of the non-linear properties of these indices and an additional interpretation of the Porta and Guzik indices. They can be considered as a generalisation of these specific indices by providing insight into the other parts of the q-spectral distributions.The proposed multistructure indices However, MI is a tool capable of assessing the entire multiscale size structure of the changes. Therefore, we suggest exploring the entire spectrum of the dynamics involved, revealing their non-linear dependence and irreversible character. Indeed, the methodology of the multistructure index is capable of contrasting properties of slow dynamics and fast dynamics, which could potentially be applicable to a wide range of problems where complex dynamical interactions are at play.MI has been proved to provide insightful measures of the cardiovascular interactions provoked by the HUTT test. Differences have been found in the organization of the homeostatic state between healthy people and vasovagal patients. Specifically, it has appeared that vasovagal syncope might be related to the delayed reaction of the slow SBP dynamics. These observations might be considered as precursory signs of vasovagal sensitivity, and hence of vasovagal syncope.