Simultaneous measurement of four-limb blood pressures can improve the accuracy of cardiovascular disease diagnosis. This study aims to investigate the association of simultaneously measured four-limb blood pressures with cardiovascular function as the non-invasive diagnostic method of cardiovascular disease in primary care.229 subjects  were enrolled. Four-limb blood pressure measurements were simultaneously performed using a blood pressure and pulse monitor device in the supine position. Cardiac functional parameters were also measured by using a cardiac hemodynamic detector in the same position. Data were statistically analyzed with SPSS15.0.The mean age of the 229 subjects was 60.56 ± 8.68 years. Cardiovascular functional parameters decreased with age and body mass index (BMI), only the total peripheral resistance (TPR) was in contrast. Age, BMI, left ankle diastolic pressure (LADP), high arm mean arterial pressure (HARMAP), left arm diastolic pressure (LARDP) and right ankle diastolic pressure (RADP) were significantly correlated with cardiovascular functional parameters. Cardiovascular functional parameters have significant differences with inter-arm difference in systolic blood pressure (SBP) between ≥10 and <10 mmHg, inter-ankle difference in SBP between ≥15 and ≥20 mmHg, inter-ankle difference in SBP between ≥15 and <10 mmHg and right ankle brachial index (RABI) between ≤0.9 and ≥1.0. After excluding 99 hypertensive patients, a part of cardiovascular functional parameters has still significant differences with inter-arm difference in SBP between ≥10 and ≥15 mmHg and RABI between ≤0.9 and ≥1.0.Age, BMI, LADP, HARMAP, LARDP and RADP were the determinants of cardiovascular functional parameters. In addition, a part of cardiovascular functional parameter is associated with inter-arm difference in SBP ≥10 mmHg, inter-ankle difference in SBP ≥15 mmHg and RABI ≤0.9, while these differences still existed after excluding 99 hypertensive patients. Hence, simultaneous measurement of four-limb blood pressures has become feasible and useful approach to the non-invasive diagnostic method of cardiovascular disease in primary care. Accurate measurement of blood pressure and scientific evaluation are the precondition for the early detection of cardiovascular disease. The studies found that four-limb blood pressure simultaneous measurement can improve the accuracy of blood pressure for cardiovascular disease diagnosis –3. ThereA blood pressure difference between arms has been associated with subclavian stenosis, peripheral artery disease, cardiovascular mortality and all-cause mortality , 8–11, mAccordingly, this study aims to investigate the association of simultaneously measured four-limb blood pressures with cardiovascular function as the current non-invasive diagnostic method of cardiovascular disease in primary care.This study was approved by the Ethics Committee of Hospital in Beijing University of Technology, and College of Life Science and Bioengineering in Beijing University of Technology. All subjects gave written informed consent. From September 2015 to January 2016, staffs of Beijing University of Technology took part in comprehensive examinations of cardiovascular disease and its risk evaluation. Subjects with limb disability, hemiplegia, congenital heart disease, heart failure, and the history of artery intervention were excluded. Finally, 229 subjects  were enrolled in this study.Four-limb blood pressure was measured in an air-conditioned room at a temperature of 22–23 °C by using the VS-1500 blood pressure and pulse monitor device . Trained technicians placed the blood pressure cuffs on both arms and both ankles and performed the measurements, after each subject had bared four limbs and taken 10-min rest in supine position. The device simultaneously and automatically measured the supine blood pressure of four limbs, and automatically calculated the ankle-brachial index (ABI) [ABI include right ankle-brachial index (RABI) and left ankle-brachial index (LABI)], and then stored the measurement data in a database.Based on the systolic and diastolic blood pressure, we calculated the inter-arm and inter-ankle blood pressure differences as the absolute value of the difference between the right and left arm blood pressure and between the right and left ankle blood pressure, respectively. Pulse pressure (PP) was the absolute value of difference between systolic and diastolic blood pressure. Pulse pressure index (PPI) was calculated as the ratio of PP divided by systolic blood pressure. Mean arterial pressure (MAP) was two-thirds diastolic pressure plus one-third systolic pressure.Cardiac functional parameters were also measured by using a cardiac hemodynamic detector device  in the supine position and in the same air-conditioned room after obtaining four limbs blood pressure. Before cardiovascular function measurement, each subject had bared abdomen and neck, stuck to electrode slices and taken 10-min rest in supine position. Trained technicians placed the red/black electrode holders on abdomen and neck, placed one yellow electrode holder on the fifth rib left anterior axillary line, respectively. The specific measurement positions were shown in Fig. Cardiac pump function parameters include cardiac output per minute (CO), stroke volume (SV), cardiac index (CI), stroke volume index (SVI) and ejection fraction (EF). Cardiac systolic function parameters have function index of left ventricular (LFVI), index of contractility (IC) and heather index (HI). Cardiac diastolic function parameters have end diastolic volume (EDV) and left ventricular end diastolic pressure (LVEDP). Cardiac efficiency function parameters have stroke work (SW), cardiac work (CW), stroke work index (SWI) and cardiac work index (CWI). Vascular elasticity function parameters have aortic compliance (AC) and total peripheral resistance (TPR).In addition, the observer also administered a standardized questionnaire to collect information of subjects on age, sex, height, weight, medical history, lifestyle, use of medications, drinking and smoking history. The body mass index (BMI) was calculated as the ratio of weight in kilograms divided by the square of height in meters.Data were stored in Excel 2013 and statistically analyzed with SPSS15.0. Data were expressed as percentages and mean ± SD. The differences of inter-arm and inter-ankle were divide into five groups , and ABI were divide into three groups . The differences between groups were checked by the analysis of variance for continuous variables or by Chi square test for categorical variables. Pearson correlation analysis was used to determine the correlation degree between cardiac functional parameters and four-limb blood pressure. Multiple linear regression analysis was used to determine the relationship between cardiac functional parameters and four-limb blood pressure. A difference was considered significant if the P value was less than 0.05.The mean age of the 229 subjects was 60.56 ± 8.68 years, 9 subjects were younger than 45 years, 31 subjects between 45 and 54 years, 136 subjects between 55 and 64 years, 39 subjects between 65 and 74 years, and 14 subjects were aged 75 years or older. Table Pearson correlation analysis presents the correlation degree between four-limb blood pressures and cardiovascular functional parameters as shown in Table Multiple linear regression stepwise analysis presents the determinants of cardiovascular functional parameter as shown in Table In additional, variance analysis was performed to check the difference among the cardiovascular functional parameters, four-limb blood pressure differences  and ABI . The distribution of four-limb blood pressure differences as shown in Fig. Since cardiovascular function has been associated with hypertension, we also performed a subgroup analysis after excluding 99 hypertension patients. After Pearson correlation analysis in subgroup, we found that a part of blood pressure parameters correlation with cardiovascular functional parameters disappeared, and the correlation coefficient reduced. In addition, after analysis of variance in subgroup, we also found that cardiovascular functional parameters  have significant differences (P < 0.05) with inter-arm difference in systolic blood pressure between ≥10 and ≥15 mmHg, and cardiovascular functional parameters  have significant differences (P < 0.05) with RABI between ≤0.9 and ≥1.0.In this cross-sectional study, by using a simultaneous measurement technique, the association between four-limb blood pressure and cardiovascular function and related risk factors was evaluated. Cardiovascular functional parameters illustrated the cardiac pump function, cardiac systolic, cardiac diastolic, cardiac efficiency and vascular elasticity. Thus, this study has more systematicness and pertinence than previous studies. This study suggested that cardiovascular functional parameters  have all a significant difference with HARDP, HARMAP, HASP, HADP, LARDP, RADP, LASP, and LADP, while there was a negative correlation between them except TPR. Meanwhile, the determinants of cardiac functional parameter were age, BMI, LADP, HARMAP LARDP, HARPPI ADBPD, RARSP, RADP and LARSP, while the TPR was positively correlated with age, BMI, LADP and HARMAP.Previous studies demonstrated that population aging has become the uncontrolled risk factor of cardiovascular disease –18. It iPrevious studies have reported that inter-arm or inter-ankle blood pressure difference predicted cardiovascular mortality –13, 15. A clinical device, the VS-1500 blood pressure and pulse monitor device , has been developed to automatically and simultaneously measure blood pressure in four limbs, and the measurement can be easily obtained. The similar device was reported by previous studies, for example, VP-1000 ABI—form device  and VP-1000 device  were used to automatically and simultaneously measure four limbs’ blood pressures. The validation in measurement technology of device  might be prone for measurement errors, especially in multinomial detection of cardiac function parameters rather than single detection. Although it could not give very precise measurements for the clinical value of cardiac function parameters, it can provide objective evaluation of health in the early stage of cardiovascular diseases. Thus, these devices can be applied for the epidemiological evaluation between four limbs’ blood pressures and cardiac function parameters.In this study, by using a simultaneous and noninvasive measurement technique, we measured four limbs blood pressures. But this technique was not a popular one to measure blood pressure in daily clinical practice. Hence, although four limbs blood pressure with simultaneous measurement could improve the predictive value for cardiovascular disease, our results might be changed if daily clinical measurement was used. In addition, the subjects were mainly from retired people, whose health care consciousness is better than the serving officer. The factors of smoking, drinking, salting and movement have no significant difference in this study subjects. Hence, the clinical utility of this study may be limited in community people.LADP, HARMAP, LARDP, and RADP were all significantly correlated with cardiovascular functional parameter. Age and body mass index are all the major risk factors for cardiovascular function parameters. In addition, a part of cardiovascular functional parameter is associated with inter-arm difference in systolic blood ≥10 mmHg, inter-ankle difference in systolic blood pressure ≥15 mmHg and RABI ≤0.9, while these differences still exist after excluding 99 hypertension patients. Hence, simultaneous measurement of four-limb blood pressures has become feasible and useful approach to the current non-invasive method of cardiovascular disease in primary care.


All patients with hypertension are at increased risk for vascular events and hypertension is widely regarded as one of the most important risk factors for cardiovascular disease.2The role of the renin–angiotensin– aldosterone system (RAAS), even in the early stages of the cardiovascular continuum, is well-established, with positive results being obtained in clinical trials of cardiovascular event reduction using specific RAAS blockers.In hypertension management, tolerability is key to patient compliance and the long-term reduction of cardiovascular events. ARBs with placebo-like tolerability and efficacy in reducing cardiovascular and cerebrovascular events should be favoured in guidelines.3ARBs reduce blood pressure at least to the same extent as ACE inhibitors and more so in some cases. For example, the largest study undertaken to compare an ARB with an ACE inhibitor, the 1 600-patient Prospective Randomized Investigation of the Safety and efficacy of Micardis versus ramipril using Ambulatory blood pressure monitoring (PRISMA) study found greater blood pressure reductions from telmisartan than ramipril.4There is significant evidence of within-class differences among ARBs with respect to their plasma half-lives, lipophilicity and receptor-binding affinity. Drugs in the ARB class also differ in their antihypertensive efficacy.There is also increasing evidence that, as with ACE inhibitors, ARBs confer benefits beyond their blood pressurelowering effects by reducing morbidity and mortality in cardiovascular, renal and cerebrovascular outcomes through renin–angiotensin system (RAS) blockade.6Telmisartan is the only ARB that has demonstrated therapeutic equivalence to the ACE inhibitor ramipril in hypertensive patients at increased vascular risk. The patient population in this study (ONTARGET) is of particular interest as it is representative of the majority of hypertensive patients seen in everyday clinical practice.The findings from this study showed that telmisartan 80 mg per day was as efficacious as the proven dosage of ramipril (10 mg/day) in reducing risk of cardiovascular death, myocardial infarction, stroke and hospitalisation for heart failure in a broad cross section of highrisk cardiovascular patients. It achieved these results with far fewer side effects, resulting in significantly fewer patients discontinuing therapy.7In clinical practice, ARBs are linked to greater patient adherence and to better blood pressure control. For this reason, first-line ARBs can offer improved efficacy, greater compliance and reduced healthcare utilisation, which offset higher acquisition costs.Importantly, all ACE-intolerant patients who are at risk of diabetes, myocardiaI infarction, stroke or peripheral arterial disease should be switched to the ARB with proven benefit.


Acute Compartment Syndrome is a limb-threatening emergency and it occurs most commonly after fractures. The aim of our study is to find out the effectiveness of serial measurement of differential pressure in closed tibial diaphyseal fractures, in diagnosing acute compartment syndrome, using Whiteside’s technique. A total of 52 cases in the age group of 15 to 55 years admitted with closed fractures were studied for serial compartment pressure as well as serial differential pressure. Eight patients had persistent compartment pressure > 40mmHg, out of which only two patients had persistent differential pressure < 30mmHg and these two patients underwent fasciotomy. Thus, by measuring the compartment pressure serially and calculating differential pressure serially, acute compartment syndrome can be diagnosed or ruled out with higher precision, so that unnecessary fasciotomies can be avoided. The reported incidence of ACS following tibial fracture varies from 2.7 to 11%4. Along with providing an improved patient outcome, an early diagnosis is associated with decreased indemnity risk forlegal claims6. Symptoms and signs of a compartment syndrome may be ambiguous, that, definite diagnosis cannot be made on clinical grounds alone10. Even though various techniques including saline infusion technique, slit catheter, wick catheter, Stryker STIC  catheter and near infrared spectroscopy can be used to identify compartment pressure, we have measured Intra Compartmental Pressure (ICP) with Whiteside’s technique and formulated an easy and reliable protocol to diagnose ACS accurately. Among the above mentioned techniques, slit catheter and wick catheter techniques are inaccurate and out of vogue. Stryker STIC catheter, although accurate is very expensive and not available in all emergency departments. Near infrared spectroscopy is expensive and effectiveness has not been extensively studied.The average annual incidence of Acute Compartment Syndrome (ACS) is 3.1 per 1,00,000 populationAmong the etiological factors, tibial diaphyseal fractures are the most common contributing cause for ACS. The aim of our study was to find out the effectiveness of serial measurement of differential pressure in closed tibial diaphyseal fractures, in diagnosing ACS, using Whiteside’s technique.This descriptive prospective study has been done involving 52 patients with closed tibial diaphyseal fracture in the age group of 15 to 55 years  from December 2013 to May 2014 and follow up thereafter. The sample consisted of patients who presented to our emergency department consecutively with closed tibial diaphyseal fractures. Written consent was obtained from the patients for ethical clearance. Patients with compound fractures, multiple fractures, head injury, age < 15 years and > 55 years and known preexisting hypertension were excluded from the study.Patient received in the emergency department were immediately subjected to head to foot survey and hemodynamic stabilization was done. Fractured limb was examined clinically for pain on passive stretching, tense compartment, pallor, paraesthesia, paralysis and pulselessness and the findings were recorded. Leg circumference was measured and compared with normal side. Eight patients who presented with tight cast underwent complete removal of cast. In all patients with ICP >40mmHg, limb elevation was avoided. Fracture was managed appropriately according to the need of the patient.We performed Whiteside’s technique of ICP measurement in the anterior compartment of leg within 5cm from the fracture site. Blood pressure was recorded in the upper limb simultaneously. Whiteside’s apparatus  was consThere were 36 males and 16 females in our study. Mean of presentation’s time after injury was 3 hours . Mean ofTwo patients who had ΔP < 30mmHg on serial monitoring underwent fasciotomy. The eight patients in whom tight cast was removed subsequently showed ΔP >30mmHg on serial monitoring. The follow up of all patients (except those who underwent fasciotomy) was uneventful at the end of six months.12. Badhe et alreported four cases of ACS in which any form of pain was absent, with diagnosis confirmed on subsequent fasciotomy13.Although clinical signs; like pain on passive stretch, pallor, tense compartment, help in diagnosing ACS, they may be absent in some cases, indicating poor sensitivity. The clinical findings of pain, pulselessness etc for diagnosing ACS was low at 13% to 19% and specificity was 97%, meaning all the clinical signs are better at excluding than confirming a diagnosis14. It is now recognized that a patient’s tolerance to the ICP is dependent on perfusion or the systemic blood pressure19. There is now experimental and clinical work suggesting a ΔP of less than or equal to 30mmHg should be considered diagnostic 2,15,20-22. The use of a differential pressure of <30 mmHg as a threshold for fasciotomy lead to no missed cases of ACS, no unnecessary fasciotomies and no complications in any patients15. In our study, 75% of patients who had ICP > 40mmHg did not undergo fasciotomy, since serial ΔP monitoring was instituted in these patients.The normal ICP of healthy muscle is 10mmHg25.Studies have demonstrated that the duration of pressure elevation is fully as important in the production of neuromuscular deficits as is the magnitude of pressure elevation. Pressures that are benign for a few hours may be detrimental if allowed to persist for longer periods. Thus, serial monitoring of tissue pressure provides clinically useful information as to the trend of ICP26, hence the early diagnosis becomes important. In the leg, the anterior compartment is routinely used for pressure monitoring, as it is the most frequently affected and accessible27. Our study, as well as literature, supports the fact that any limb showing signs of a compartment syndrome is freed from circumferential dressings and is placed at the level of the heart to ensure that local blood pressure is not compromised by elevation of the extremity29.Muscles tolerate 4 hours of ischemia well, but by 6 hours the result is uncertain, after 8 hours, the damage is irreversible 30. Among these, Whiteside’s technique is inexpensive, easily available and easy to assemble.The Stryker STIC catheter is a device specifically designed to measure ICP. Because it is expensive, not all medical facilities may have access to this device. Alternative ICP measurement methods to the Stryker device include the IV pump method and the Whiteside’s techniqueThe use of differential pressure as a parameter particularly when measured serially helps in accurate decision making in either performing or avoiding fasciotomies. Being an easier parameter to measure, this method seems to be far better in making decision than methods based on ICP measurement alone. Whiteside’s technique which is more or less nearer to accuracy when compared to Stryker STIC catheter, and at the same time is cheap and easily available, will help more institutions to diagnose and treat ACS effectively. It also protects the treating team against litigations in the court of law.


Blood pressure is the most important, modifiable risk factor for cardiovascular diseases. Lifestyle factors and also workload are the main, potential risk factors for the development of hypertension. This study focused on the early detection of unknown hypertension by screening employees in the hotel and restaurant industry (HRI). 148 HRI employees without hypertension  self-measured their blood pressure during rest and for 24 hours of a normal workday. Individuals with a resting blood pressure ≥ 135/85 mmHg were classified as hypertensive. A further analysis investigated whether the currently applicable thresholds for hypertension during work, leisure, and sleep were exceeded on a working day. At rest, 36% of the study participants suffered from hypertension, which increased to 70% under workload and 46% during leisure time and dropped to 8% during sleep. Normal nocturnal dipping (10–20%) occurred only in 18% of cases; 78% were extreme dippers (>20%). Occupational hypertension screening is a suitable component of preventive healthcare. Resting blood pressure measurement alone is insufficient for the early detection of risk individuals and should be supplemented by 24-hour ambulatory blood pressure monitoring under working conditions. The impact of workload on blood pressure needs to be given more attention in the guidelines. Hypertension presents the most significant health risk worldwide . Its preIn addition to genetic, social, and lifestyle-related factors , 4, workOffice blood pressure measured by physician results in increased blood pressure values in approximately 20% of the general population (white-coat effect), something which does not occur however in self-monitored home blood pressure measurement (home BPM) or in an ambulatory 24-hour blood pressure monitoring (a 24-hour ABPM) , 10. ConThus, office blood pressure is only partially suitable as a diagnostic procedure. For reliable blood pressure measurements, international consensus recommends measuring out-of-office blood pressure such as home BPM or a 24-hour ABPM under normal day-to-day conditions , 15.In comparison to office blood pressure, home BPM and a 24-hour ABPM are also better predictors of hypertensive organ damage and cardiovascular risk –19. To iIn the present study, the blood pressure (BP) of employees in the hotel and restaurant industry was monitored under resting conditions at home and under work and recovery conditions. This branch is known for shift work, long working hours, and work under time pressure .Within the framework of an occupational screening, home BPM was used as a diagnostic procedure to identify undiagnosed hypertension. The subsequent 24-hour ABPM followed with the question of whether a classification into normotensive and hypertensive persons based on the home BP changes under work and recovery conditions. Then, an analysis was carried out to determine whether work and recovery are predictors of hypertension.The participants in the study were 160 employees in the hotel and restaurant industry (HRI). They came from 11 hotels of the upmarket class in Berlin and the surrounding area. The data were collected within an occupational screening programme from October 2014 to February 2016. The participants took part voluntarily (participation rate: 75%).n = 12) were excluded from the statistical analysis; that is, 148 restaurant and hotel employees were included in the analyses (45% men). Among the participants were 49% with standard secondary school education, 45% with high school level, and only one employee with lower secondary school education. The participants were between 18 and 63 years old (Ø 34 ± 9 years); 49% worked in shifts ) and 51% in day work .Persons with known hypertension and persons already being treated with medication (p = .003). The median employment duration was seven years.On average, the employees worked 42 ± 8 hours per week, whereby men worked four hours longer than women , restaurant and hotel specialists (16%), administration and management staff (33%) as well as room service and housekeeping (9%), reception staff (13%), and other service personnel. The detailed description of the sample is shown in The occupational health screening programme with its focus on hypertension diagnosis consisted of three parts: a questionnaire, a self-monitored home BPM, and a 24-hour ABPM.A modified version of the shift worker questionnaire for employees of the hotel and restaurant industry  was usedThe home BPM served to record resting BP and to determine hypertension . It tookWORK: time between beginning and end of work with recovery periods LEISURE: time between end of work and going to bed (including sleep periods on day between end of work and before going to bed)AWAKE: time after getting up until going to bed (=WORK + LEISURE)SLEEP: time between going to bed and getting up the following morning.The 24-hour ABPM ensued under work and recovery conditions. It was performed using the fully automatic measuring device TM-2430 . Three cuff sizes were used for the measurements, which were selected in accordance with the size of each participant's upper arm . The mea Parallel to these 24-hour ABPM, the participants completed a diary at intervals of 30 minutes. In this, they noted their activities and body positions. This enabled the retrospective allocation of the BP values to the activities and the start of the time periods, as well as the subsequent estimation of workloads.The mean values and standard deviations (SD) were then calculated for SBP and DBP, and the differences between the BP levels in the three time periods  were determined. The mean BP values of each time period and the differences of the values were used for the statistical analyses.According to the guidelines of the European Society of Hypertension , the hypp < .05 was considered statistically significant and supplemented by effect sizes. The interpretation of the effect sizes is based on the Cohen conventions [2-Test was used to test the difference in categorical variables. Correlations between the measurements of home BPM and 24-hour ABPM were analysed with partial correlations (control variables: sex and body mass index). In order to determine the effect of the independent variables on the hypertension diagnosis, covariance analyses were carried out controlled by sex and body mass index. To determine the predictors of undiagnosed hypertension, a binary logistic regression model was calculated in which lifestyle factors and control variables were taken into account in addition to the time periods of the 24-hour ABPM.The statistical data analysis was performed using the “Statistical Package for Social Science” programme (SPSS 23.0) for Windows . The error probability value of ventions . The comThis study was conducted in conformance with the guidelines of the World Medical Association (WMA) Declaration of Helsinki and the ethical principles of medical research involving human subjects amended by the 9th WMA General Assembly, Soul, Republic of Korea, October 2008. The study was approved by the Ethics Committee of the Technische Universität Dresden (EK 250397) and written informed consent was obtained from all participants included in this study.In the self-monitored home BPM, approximately one-third (36%) of the 148 participants showed elevated BP . Other significant differences were found only for sex (p = .001) and professional spectrum (p = .041).Subsequently, participants were classified as normotensives and hypertensives and were studied comparatively . For thep = .194). The professional spectrum was distributed significantly differently between both groups . Employees with primarily a physical workload (kitchen and room service staff) showed more frequent hypertension (48%) than employees with primarily mental workload (23%) or “mixed” workload (29%). Within the workload groups, it became clear that almost one-third of the employees in administration and management fields (30%) and almost one-quarter of the kitchen staff (24%) had untreated hypertension (p = .099).Approximately half of the participants were employed in shift work   apart from the SLEEP period (Ø BP: 119/68 mmHg). Most noticeable however is the presence of hypertensive mean values in normotensive participants in the WORK period . For sex, the results showed no significant effect on BP during the working day. The BMI only had an influence on SBP .Due to the influence of sex and body mass index, the expected BP differences between normotensive and hypertensive participants were confirmed for all time periods of the 24-hour ABPM ( effect) . On averp = .371; DBP: p = .230; SLEEP: SBP: p = .312; DBP: p = .281) (The normotensive and hypertensive participants did not differ in cardiovascular recovery after WORK (LEISURE: SBP:  = .281) . The drop = .920) and body mass index (p = .070) have no influence on the recovery processes. The standard deviations for the BP recovery values however indicate that there were very different physical activities in the WORK and LEISURE periods, respectively, very different individual recreational activities.Contrary to our expectations, for hypertensives, the results show a trend towards a more favourable cardiovascular recovery (largest BP difference between WORK and LEISURE). Sex  of them. For the AWAKE and for the 24-hour TOTAL period, one-third of the employees had normal values .It is important to note that even half of normotensive employees had hypertensive BP during WORK (56%) and more than one-third had it in the LEISURE period . A smallBased on the hypertension criteria of the European Society of Hypertension , the hypr = .36–.52; HT: r = .27–.50) and the DBP  in both groups; this means that only a maximum of 35% of the variance between both BP values was declared.There were only slight to medium correlations between the values of home BP and 24-hour ABPM for both the SBP  were performed to determine whether the work and recovery periods are predictors which can explain the unknown diagnosis of hypertension and how it is effected by health-related behaviour . In addition, sociodemographic variables  were included in the analyses. Whether there are predictors among these variables has not been found in the literature reviewed here to date.Moreover, the sociodemographic variables, the variables of health-related behaviour, and the diagnoses for the periods of the 24-hour ABPM were individually subjected to the binary logistic regression analysis. In the second analysis step, a whole model was created which contained all the variables significant in the first step .In the first step, a significant influence on hypertension diagnosis by home BPM was found only for sex and body mass index; this explains 23% of the variance. The best result was achieved simultaneously including the interpreted BP values from WORK, LEISURE, and SLEEP, which allowed explaining 44% of the variance in hypertension diagnosis.In the whole model, it was shown that only sex and the diagnoses in the time periods LEISURE and SLEEP had a significant influence on the diagnosis by home BPM and could explain a total of 52% of the variance.Using this predictor model, 82% of the employees from the sample were classified with the correct diagnosis. 83% of the normotensives were predicted correctly; however, 17% were classified as hypertensive. 79% of the hypertensives were predicted correctly and 21% as normotensive .Men had a 3.6-fold higher risk of hypertension than women. As opposed to normotensives, hypertensives showed a 6.3-fold higher risk of hypertension in LEISURE period and a 5.3-fold higher risk in SLEEP period.Elevated blood pressure values in the workplace and their health significance have so far been underestimated. Correspondingly, a screening programme was used to diagnose hypertension in employees in the restaurant and hotel industry. The blood pressure status of these employees was analysed under resting conditions (home BPM) as well as working and recovery conditions (24-hour ABPM).p = .001) and workload (p = .041). Accordingly, the employees with primarily physical workload showed more frequent hypertensive blood pressure values (48%) than those with primarily mental (23%) or mixed workload (29%).In the self-monitored home BPM, an unexpectedly high number of the participants (36%) were identified as unknown hypertensives (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg). This diagnosis was influenced by gender . During the recovery period after work, the BP behaviour did not differ significantly between both groups. During the LEISURE period, BP dropped only from 3 to 6 mmHg on average  occurred in only 18% of the participants, whereby in 78% of them the nocturnal decline in BP was more than 20%. This phenomenon is called “extreme dipping” and is linked to a higher risk of cardiovascular diseases in patients with untreated hypertension . IndepenIn comparison with the home BPM (36% hypertensives), the number of hypertensives rose to 70% under working conditions, to 54% during LEISURE time, and to 62% based on the TOTAL 24-hour period.Over half (56%) of those who had normal BP values in home BPM were classified as hypertensive under working conditions. At LEISURE, this accounted for 35% and even during the SLEEP period it was still 8%. Contrarily, normal BP was measured in only 6% and 11%, respectively, of the hypertensives under working and leisure conditions, but in the SLEEP period, it accounted for half of the hypertensives. This indicates that only measuring resting BP is insufficient to detect all vulnerable persons.Pieper et al.  had alreIn relation to maintain current BP thresholds, even under working conditions, there is also still uncertainty in the international guidelines. The fact that the same threshold for BP under resting conditions is used as for average daytime BP in the 24-hour ABMP should be reviewed in future studies.This study also analysed the participants' lifestyle as a risk factor in hypertension development. An influence of health-related behaviour on BP could not be demonstrated although there were significantly more overweight (38%) and obese employees (24%) among the hypertensives than among the normotensives . The number of smokers (41%) and physically active persons (43%) was the same for both groups.In a separate analysis of health-related behaviour variables in combination with the sociodemographic data, body mass index emerged in addition to sex as a predictor of hypertension by home BPM (variance explanation: 23%). This indicates that high BP was present primarily in overweight and obese men. This correlation is known from epidemiological studies. The men in this sample showed a 3.6-fold higher risk of hypertension than the women. Moreover, the risk of the overweight and obese employees, respectively, was 3.6 times higher compared to those of normal weight. Critical for a reliable diagnosis was the BP level, in addition to sex, in the LEISURE and SLEEP period. 52% of the resulting variance could be explained by the predictor model and 82% of all cases were correctly diagnosed.It was assumed that BP during work in particular is suitable to correctly predict the diagnosis. The accuracy of the prediction was however influenced by the fact that more than half of those analysed (56%), who measured normal BP during home BPM, showed hypertension under workload. The results of the regression analyses support the assumption that the internationally accepted daytime average for 24-hour ABMP “might be regarded as too conservative by some” .From a methodological perspective, the rest blood pressure values from the home BPM indicate high objectivity and validity. They are based on a total of 24 measurement values and the data collection is in line with the guidelines of the European Society of Hypertension . The strA limitation of the study was the cross-sectional design, which was only able to describe correlations but unable to prove causality. The results can however be used to generate hypotheses in future studies on the tendency of correlations and differences.The generalisability of the study was limited by the convenience sampling of 148 participants; that is, selection effects cannot be excluded. The limitation of representativeness may have been caused by the fact that this sample was a regional one . Nonetheless, the sample was representative of all German staff in the hotel and restaurant industry with regard to age and sex.Regardless of these limitations, an occupational screening programme can make an important contribution to preventive healthcare. Various studies have shown that particularly young, male employees with subjectively good health and seldom contact to a physician are not often diagnosed as hypertensive and thus remain untreated , 35. YouThe present data indicate occupational screening with home BPM to be an alternative path to detect undiagnosed hypertensive persons. Home BPM should however be complemented by a 24-hour ABPM as a number of presumed normotensive individuals do develop hypertension under daily workload. It is thus crucial to give a critical account of current guidelines which recommend the same blood pressure thresholds for both home BP at rest and the average daytime BP under daily conditions.


N = 27) during each LBNP stage, from which heart rate , systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP) showed a significantly (p < 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR). In response to moderate category hemorrhage (−30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR→SBP (p = 0.76), RR→MAP (p = 0.60), and SBP→RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression.Early detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to −40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate  is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years,  Hemorrhage, a physiological condition resulting in central hypovolemia; owing to loss of blood from the circulation which leads to inadequate tissue perfusion , the interventional strategies have limited effect  toward maintenance of arterial blood pressure homeostasis  pre-syncopal symptoms, (2) sudden drop in blood pressure and/or heart rate (3) any discomfort, or (4) upon request.The experimentation was conducted in the Aerospace Physiology Laboratory in the Department of Biomedical Physiology and Kinesiology, Simon Fraser University (SFU), Canada. A participant in the age range of 18–40 years and without a history of cardiovascular disease was eligible to participate in the study. The experimental protocol was approved to be of minimal risk and complied with the rules and regulations set forth by the research ethics board of SFU. Written informed consent for participation was obtained from each participant prior to any experimentation. A registered nurse was present during experimentation for the safety of participants.Simultaneous electrocardiogram (ECG) and blood pressure were acquired from 27 young, healthy participants  who underwent graded LBNP. The ECG signal was acquired in a lead II configuration using LifePak8  and the blood pressure signal was acquired using a finger photoplethysmograph cuff  applied on the mid phalanx of the middle finger (left hand). Five minutes of data were acquired during rest i.e., baseline and each LBNP stages using an NI 9205 analog input module  at a sampling rate of 1,000 Hz.Y → X = ρ, similarly, the causal information flowing from X to Y is represented as CCM proposed by Sugihara et al. is a non-linear approach of studying cause and effect relationship based on the state space reconstruction of a time series  and Y (using X manifold), respectively, and ρ is the Pearson correlation coefficient signifying the strength of coupling. Further details of the methodology to infer a causal relationship between two time series is presented in the supplementary material of Sugihara et al.  was determined according to the false nearest neighbor algorithm in MATLAB using CRP toolbox  converged was considered as a degree of directional information flow from one variable to another. The significance of correlation was set at α = 0.05. The MATLAB  implementation of CCM algorithm demonstrated in an application with non-linear signals in the study conducted by Krakovská et al.  were obtained using Beatscope software . The mean arterial pressure (MAP) was obtained from the systolic and DBP as; á et al.  was conspost-hoc analysis using the Tukey-HSD method. All tests for significance were conducted using a statistical toolbox of MATLAB . The test result at α = 0.05 was considered as significant. All tabular results are presented as mean ± SD while all graphical results are presented as mean ± SE unless mentioned otherwise.The group mean of RR, SBP, DBP, MAP, pulse pressure (PP = SBP-DBP), the non-baroreflex i.e., feedforward (RR→SBP and RR→MAP), and the baroreflex i.e., feedback (SBP→RR and MAP→RR) causality values for the last 3 min of each LBNP stage was obtained. Test for normality of the data was conducted using the Shapiro-Wilk test at α = 0.05. A one-way test of ANOVA  or Wilcoxon rank sum test  was conducted to test the significance of the difference. The group mean of baroreflex causality (SBP→RR and MAP→RR) was compared with the group mean of non-baroreflex causality (RR→SBP and RR→MAP) under baseline using one-way ANOVA. A multiple comparison test, to account for the significance of the difference in the cardiovascular parameters and the SBP↔RR and MAP↔RR causality, inflicted by different LBNP stages, was conducted using one-way ANOVA followed by p > 0.05). The behavior of cardiovascular parameters with progressive LBNP is summarized in Figure post-hoc analysis using the Tukey-HSD method, the resulting p-value of the comparison is summarized in Table p = 0.001) at −40 mmHg, and RR interval at −30 mmHg (p = 0.001), and −40 mmHg (p < 0.001) was observed compared to the resting stage. Additionally, a significant difference was observed between −20 and −40 mmHg LBNP in PP (p = 0.02) and RR interval (p < 0.001), Figure p = 0.50), DBP (p = 0.79), and MAP (p = 0.99), Figure The cardiovascular parameters , as well as the non-baroreflex and the baroreflex causal events, passed the test of normality (p = 0.76) and RR→MAP (p = 0.60) causality did not change  and MAP→RR (p = 0.01) successfully differentiated −40 mmHg LBNP from −20 mmHg LBNP. Table The compensatory behavior, responsible for maintaining blood pressure equilibrium via SBP↔RR and MAP↔RR interaction was quantified in response to progressing LBNP. This behavior is summarized in Figure e Figure . The SBPp < 0.05) with the LBNP stages. Also, the group mean of SBP, DBP, and RR→SBP was significantly (p < 0.05) correlated with LBNP stages while the group mean of MAP (p = 0.26) and RR→MAP (p = 0.14) showed no relation with the LBNP stages.Figure The major finding of the current research was the feasibility of the causal heart rate and blood pressure interaction toward differentiating the onset of moderate intensity of simulated hemorrhage from the resting stage. A significant elevation was observed in the strength of baroreflex arm (MAP→RR) of the heart rate blood pressure interaction in response to the LBNP induced redistribution of central blood volume to the lower peripheral parts. This elevation was evident as early as −30 mmHg of LBNP. On the contrary, the conventional indicators of blood loss i.e., blood pressure  failed to differentiate −30 mmHg LBNP intensity from the resting stage, thus, highlighting the potential of compensatory baroreflex arm of the heart rate and blood pressure interaction toward early detection of progressing blood loss.p = 0.10) failed to show a significant change in its dynamics compared to resting stage until the tail end of moderate category hemorrhage (−40 mmHg), which raises concern regarding its potential to provide an early trace of central blood loss.Early detection of hemorrhage progression has eluded the research and clinical communities for years. Stroke volume is shown to be an early indicator of mild hypovolemia or blood loss  correlated with LBNP stages, however, neither of them showed a significant change in their dynamics with the application of LBNP simulating moderate category hemorrhage  as early as −30 mmHg compared to resting baseline  during the resting stage compared to the baroreflex arm (SBP→RR and MAP→RR), Figure To impede progressing hemorrhage, it is central to quantify the compensatory mechanisms regulating arterial blood pressure. To this end, the current research investigated the sensitivity of causal heart rate and blood pressure interaction for monitoring simulated central hypovolemia. Furthermore, owing to the robustness of the non-linear methodology, we successfully highlighted the contribution of the non-baroreflex (RR→SBP and RR→MAP) and the baroreflex (SBP→RR and MAP→RR) mechanisms responsible for blood pressure regulation under a variable degree of LBNP induced physiological stressor Figure . The dirp = 0.07) causality but significant elevation in the causal drive from MAP→RR (p = 0.004) while no change was observed in the strength of reverse drive, which is a representative of heart rate mediated blood pressure changes i.e., RR→SBP (p = 0.76) and RR→MAP (p = 0.60). This observation indicated that under resting condition blood pressure is primarily maintained through blood pressure changes mediated by heart rate, contrarily, under physiologically perturbed cardiovascular system due to a decline in venous return, the baroreflex mediated heart rate control acts as a compensatory mechanism leading to arterial blood pressure homeostasis. Thus, the two blood pressure regulatory mechanisms interact in closed loop at any given time in order to maintain blood pressure homeostasis. Furthermore, the baroreflex causality (SBP→RR and MAP→RR) was able to differentiate −40 mmHg from −20 mmHg, therefore highlighting its capability to track and differentiate varying intensity of hemorrhage  was observed, representing activation of baroreflex mediated control of heart rate toward maintenance of arterial blood pressure homeostasis. Progression of central hypovolemia to moderate intensity (−30 mmHg) was accompanied by no significant elevation in the SBP→RR  + CVP  in response to LBNP. As such, we found MAP to be a more sensitive marker of baroreflex mediated heart rate control in response to moderate category (−30 mmHg) LBNP compared to SBP Figure . The MAPThe behavior of non-linear causal heart rate and blood pressure interaction in response to simulated hemorrhage via LBNP is not extensively explored in the literature. The references that exist regarding such behavior have been outlined under orthostatic challenge induced via head-up tilt and stand test, which have considered SPB as a marker of arterial blood pressure. The LBNP is hypothesized to exert orthostatic challenge on the human body analogous to head-up tilt  while the gravity induced orthostatic stress  increases the blood volume in the splanchnic bed  from resting baseline.p = 0.004) increase in the baroreflex arm (MAP→RR) of the interaction was observed in response to early phase of moderate category hemorrhage  in response to LBNP stages. Accordingly, the outcome of the analysis highlights the sensitivity of the baroreflex mediated heart rate control (MAP→RR) toward monitoring progression of central hypovolemia, ascertained by its significant increase in the strength as early as the onset of moderate category hemorrhage (−30 mmHg LBNP).In 22 out of 27 participants, there was an increase in the baroreflex causality (MAP→RR), in 2 participants the causality decreased at −30 mmHg, while in three participants the causality did not change  In the case of hemorrhage simulated by LBNP, blood volume is not lost from the circulatory system compared to actual hemorrhage but sequestered in the lower periphery of the body, which reduces venous return and therefore, preload. Since the blood is not lost from the circulatory system, inter-subject variability is expected, due to variable tolerance level of individual participants  The degree of blood pooling achieved as a consequence of LBNP was unknown. To accurately quantify the redistribution of blood volume to the peripheral regions, future work could utilize near-infrared spectroscopy (NIRS) in the experimental protocol, analogous to Blaber et al. . The invp > 0.05) change in response to the LBNP. On the contrary, the baroreflex causality increased with the progression of LBNP and can be differentiated from rest at the onset of a moderate level of simulated hemorrhage (−30 mmHg LBNP).The current work studied the compensatory behavior responsible for blood pressure regulation with the progressing LBNP, of which the findings showcase the potential of causal heart rate and blood pressure interaction toward differentiating the severity of simulated hemorrhage. We demonstrated that non-baroreflex causality dominates during resting stage followed by no significant . Therefore, the compensatory mechanisms shall also be considered in addition to the traditional non-invasive markers of central blood loss  to gain early and reliable insights regarding the progression of hemorrhage for effective surgical triage.AV and KT conceived research. AB and KT designed experiment. AB and KT performed data acquisition. DX and KT pre-processed data. AV analyzed data, performed statistical analysis, created figures and tables, and drafted the manuscript. AV, DX, AG, AC, NG, AB, and KT, interpreted results. All authors read, edited, and approved the final manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


As diabetes evolves, the controlled breathing peak loses power and shifts to smaller frequencies, indicating that heart rate modulation is slower in diabetic patients than in controls. In contrast to the traditional parameters LF, HF and LF/HF, which do not show significant differences between the three populations in neither of the clinical tests, the new parameters rf and β, distinguish between control and diabetic subjects in the case of controlled breathing. Sympathetic activity that is driven by the baroreceptor reflex associated with the 0.1 Hz breathing modulations is affected in DM patients. Diabetes produces not only a rigid heartbeat with less autonomic induced variability (rf diminishes), but also alters the coupling between breathing and heart rate (reduced β), due to a progressive decline of vagal and sympathetic activity.Healthy subjects under rhythmic breathing have heart interbeat intervals with a respiratory band in the frequency domain that can be an index of vagal activity. Diabetes Mellitus Type II (DM) affects the autonomic nervous system of patients, thus it can be expected changes on the vagal activity. Here, the influence of DM on the breathing modulation of the heart rate is evaluated by analyzing in the frequency domain heart interbeat interval (IBI) records obtained from 30 recently diagnosed, 15 long standing DM patients, and 30 control subjects during standardized clinical tests of controlled breathing at 0.1 Hz, supine rest and standing upright. Fourier spectral analysis of IBI records quantifies heart rate variability in different regions: low-frequencies , high-frequencies , and a controlled breathing peak . Two new parameters are introduced: the frequency radius r The autonomic nervous system modulates the cardiac cycle through central (e.g. vasomotor and respiratory centers) and peripheral  oscillators that manifest as short and long-term oscillations in the heart rate. Parasympathetic modulation decreases the heart rate and cardiac contractility, whereas activity of the sympathetic branch opposes these effects and regulates peripheral vasoconstriction . Loss off), revealing the cyclic components responsible for variability in the recording period [f<0.04 Hz), a low frequency region , and a high frequency region  [A common measure of HRV is the power spectral density (PSD) of the signal, which reflects how the variance of the IBI time series is distributed as a function of frequency (g period . PSD is <0.4 Hz) –12. VLF <0.4 Hz) ; therefo<0.4 Hz) –12 while<0.4 Hz)  or as a <0.4 Hz) , 13, 14.<0.4 Hz) , 11–14. <0.4 Hz)  or heart<0.4 Hz) –18.Analysis of short-term and/or long-term HRV has been used in the past to study DM , 19–26. In the frequency domain, the PSD of HRV of healthy subjects exhibits a respiratory band that is thought to be mediated by fluctuations of vagal-cardiac nerve traffic, so it can be an index of vagal activity . RespiraThe objective of the present research is to evaluate the influence of a disease such as DM on the cardiovascular response using non-invasive short-term (5-min) IBI records. These measures can be easily obtained during routine clinical examination. We investigate how cardiac dynamics is affected by DM using a frequency-domain analysis of IBI records taken during the standard cardiovascular reflex tests established by the American Diabetes Association (ADA) , 31: hea® device of Finapres Medical Systems, The Netherlands [® is a portable ambulatory blood pressure monitoring tool that records multiple hemodynamic parameters, including blood pressure , heart rate and interbeat interval. It consists of a lightweight main unit worn by the subject on a waist belt and a frontend unit worn on the wrist connected to a finger cuff to perform the measurement. The device continually records the pressure waveform at the finger and automatically reconstructs the brachial artery pressure waveform, which allows to derive the other hemodynamic parameters. Time is recorded with 1 ms precision while blood pressure values are recorded with 1 mmHg precision. Previous studied comparing the Portapres® to direct invasive intra-aortic measurements have shown that pressure and pulse can be determined reliably within the Association for the Advancement of Medical Instrumentation (AAMI) requirements [The present study is based on non-invasive short-term measurements of blood pressure taken at each heartbeat using a Portapresherlands , 26, 32.irements .The study population was composed by 75 subjects clinically classified in 3 distinct groups as follows:2 (25±3 kg/m2). Subjects were accepted as controls if they were healthy, did not smoke, had no cardiac diseases, were not hypertensive, had blood pressure levels of 120/80 mmHg or less, and did not take anticholinergic or adrenergic medication.30 control subjects, 13 males, 17 females, 21 to 50 years of age (with a mean and standard deviation of 39±12 yr) with body mass index (BMI) from 19.1 to 28.5 kg/m2 (27±2 kg/m2). They were part of a cohort of patients with metabolic syndrome who underwent yearly an oral glucose tolerance test (GTT) of 75 g for two hours, and were declared diabetic when the GTT exceeded 200 mgs/dl. In their previous medical examination, they were considered to have metabolic syndrome but did not take medications.30 patients with recently diagnosed DM type II, 14 males, 16 females, 38 to 48 years of age (41±5 yr) with BMI from 25.8 to 29.4 kg/m2 (27±6 kg/m2). DM patients underwent a medical diagnosis by an expert, had blood glucose levels larger than 200 mg/dL at two hours in a glucose tolerance test, in agreement with the recommendations of the “Asociación Mexicana de Diabetes” and the 2011 “American Diabetes Association” [15 patients with long standing DM type II diagnosed 15±9 years ago, 5 males, 10 females, 20 to 76 years of age (53±18 yr) with BMI from 18.1 to 36.8 kg/mciation” .Control subjects and DM patients abstained from caffeine, beta-blockers, anticholinergics, antihistamines, opioids and adrenergic medicaments during the 48 hours previous to the examination. Previous to the cardiovascular monitoring, all subject underwent a 12-lead ECG study to exclude patients with arrhythmia.All subjects provided written informed consent, underwent a physical examination and had their medical history screened. The Ethics’ Committee of Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” from México approved the protocol for data recording.The hemodynamic parameters of all patients were recorded during three standardized clinical tests recommended by ADA : supine ® were visually inspected for artifacts, ectopic beats or abnormal intervals. No ectopic beats  or obvious artifacts were found in the data. Also, no initial transient effects could by identified in the signals, indicating that the 1min adaptation interval between change in posture was sufficient.All IBI records obtained with the Portapres® 9.1, 64 bits, an equally-spaced time series (with a sampling rate of one second) was generated from the irregularly sampled IBI data using a cubic spline interpolation. The equally-spaced time series differed only slightly from the original signal, but interpolation was performed to ensure the applicability of spectral methods based on the Fourier transform , which might not be present during the supine rest and/or the standing upright tests.f, defined asf corresponds simply to the distance from the point  to the origin. We will demonstrate that this parameter gives a statistical significant separation of control and diabetic subjects.Traditionally, LF and HF spectral indices are considerably reduced as diabetes evolves . We founz,1.0) for a normal distribution was used to compare the study groups and to test the correlations related to the evolution DM. Student’s t test was used to compare the statistical measures of the IBI records from control subjects, recently diagnosed, and long-standing DM patients. A value of p<0.05 was considered to be statistically significant. Graphs and calculations of statistical parameters were realized in OriginPro® 9.1, 64 bits, and were double checked with an independent Python® program.The parametric Kolmogorov-Smirnov test , but gradually shifts towards lower frequencies as diabetes evolves, as observed also in Ref. [ in Ref. . Similarf and β, both exhibit a statistically significant progressive decrease as the disease evolves (with p<0.05). The values of these two parameters thus characterize each of the test groups, specially permitting to distinguish between the control and advanced evolution test groups. This is further accentuated when they are used in combination. This is visually evident in f and β for all subjects in two-dimensional space. Most of the individuals in each test group are clustered in distinct regions of the space, with long-evolution DM subjects clustered much closer to the origin than control subjects.The traditional “HF/LF” ratio was not significantly altered in our tests: all three control groups exhibited values that are within the measurement errors of each other. On the other hand, our new parameters, rRecently, a meta-review was published that shows a gender difference in heart rate variability, in particular, women have a statistically significant lower total spectral power than men . HoweverControl and recently diagnosed DM groups have the same average age around 40 years). But the long-standing DM group has an age bias mainly because of the very strict inclusion and exclusion criteria that were applied, making it difficult to find elderly subjects that fulfill all the necessary requirements to be considered as control, and also because of the definition of the “long-standing” DM group (having being diagnosed at least 5 years prior to the study) which makes it harder to find young subjects for this group. From the few studies of short-term heart rate variability available, there is evidence that the scaling and nonlinear properties of the heart rate variability remain on average unchanged with respect to age  years. B, 42 haveWe found no statistically significant differences between control subjects and diabetic patients for the supine rest and standing upright tests for none of the statistical parameters discussed above (student’s t test gives p>0.1); we thus focused our analysis in the results of the controlled breathing test. For this test, the traditional LF, HF and LF/HF measures are similar for all subjects.f parameter, designed to quantify the loss of power across the spectrum in a nonlinear fashion, spectral analysis of the respiration peak under the controlled breathing test offers a new statistically significant distinction between healthy and diabetic subjects (with p<0.05), as is visually evident in the scatter plot of The most striking difference we found in the Fourier spectra of the test subjects lies in the presence and strength of the cardiorespiratory coupling seen during the test. For the control subjects, a strong peak associated with the controlled breathing is present at the breathing frequency . This peak gradually loses power as DM evolves over time, as can be appreciated by comparing the RP of recently diagnosed and long-standing DM II patients see . As diabf parameter diminishes, reflecting a reduction of the modulation capacity of the autonomous nervous system. Our analysis suggests that diabetes not only produces a more rigid heart rate with less variance, but, more importantly, also alters the coupling between breathing and the heart rate. These findings can be explained by a progressive decrease of vagal activity in the heart and possibly also by a gradual decrease of sympathetic activity given that the breathing frequency oscillation coincides with the baroreceptor activity. The new parameters rf and the β are simple to evaluate and, in contrast to the traditional parameters , allow to distinguish between control subjects, recently diagnosed and long-standing diabetic patients so they can be helpful for clinical diagnosis.Breathing modulations at 0.1 Hz have been associated with an oscillation of the baroreceptor reflex. From the displacement of the RP peak in the diabetic patients, we deduce that the sympathetic activity that is driven by the baroreceptor may also be affected in DM patients. As diabetes evolves over time, the β parameter obtained during the controlled breathing test decreases, indicating a loss of the breathing modulation of the heart rate, and the rThe results of this study indicate that the coupling of the respiratory and cardiac systems is significantly altered in diabetic patients, as shown mainly by the loss of the respiration peak in the power spectrum of IBI time series, and also by a reduction of the power of both the high-frequency  and low-frequency  regions of the IBI spectrum. Given that a reduction in heart rate variability indices has been linked to increased all-cause and cardiac mortality, it is tempting to suggest that patients with diabetes who have a low HRV are at an increased risk of mortality.


To evaluate the possible changes in tidal volume, minute volume andrespiratory rate caused by the use of a heat and moisture exchanger inpatients receiving pressure support mechanical ventilation and to quantifythe variation in pressure support required to compensate for the effectcaused by the heat and moisture exchanger.t test, andincremental values were expressed as percentages of increase required.Patients under invasive mechanical ventilation in pressure support mode wereevaluated using heated humidifiers and heat and moisture exchangers. If thevolume found using the heat and moisture exchangers was lower than thatfound with the heated humidifier, an increase in pressure support wasinitiated during the use of the heat and moisture exchanger until a pressuresupport value was obtained that enabled the patient to generate a valueclose to the initial tidal volume obtained with the heated humidifier. Theanalysis was performed by means of the paired A total of 26 patients were evaluated. The use of heat and moistureexchangers increased the respiratory rate and reduced the tidal and minutevolumes compared with the use of the heated humidifier. Patients required a38.13% increase in pressure support to maintain previous volumes when usingthe heat and moisture exchanger.The heat and moisture exchanger changed the tidal and minute volumes andrespiratory rate parameters. Pressure support was increased to compensatefor these changes. This heating and moisture deficit has been recognized asdamaging to the tracheobronchial mucosa and may lead to undesirable clinicalrepercussions.,5-7During breathing, inspired air is heated and humidified as it passes through theoral, nasal and pharyngeal cavities. When a patient receives ventilatory supportthrough an endotracheal tube, these physiological mechanisms aresuppressed, Thehumidification and heating tasks can be performed either actively, by means ofheated humidifiers (HHs), or passively, by means of heat and moisture exchangers(HMEs).The conditioning of inspired gases is essential to promote adequate heating andhumidification.-14 condensation of water vapor in the ventilation circuit andreservoir, potential for bacterial contamination,,15,16 need for a powersupply and need for aconstant water supply.,17,18Heated humidifiers are widely used because they promote adequate heating andhumidification, but they have some drawbacks, such as cost,-14,19 ease ofuse, microbiologicalfilter-21 and no requirement for a power source. These devices are placed betweenthe endotracheal tube and the Y-connector of the patient's ventilatorcircuit,23-25 andessentially retain moisture and heat during expiration and then release them intothe inspired dry air, thereby returning heat and moisture to the patient'sairways.,10,26-29The use of HMEs has recently increased in an effort to reduce water loss andcondensation in the ventilatory circuit. The HME also offers other advantages, suchas low cost,We must be careful when using an HME, as it can add an excessive resistive load incritical and debilitated patients, especially when high flow is associated withprolonged use. The additional respiratory load imposed by an HME may be substantialfor these patients, causing respiratory muscle fatigue and consequent ventilatoryfailure, or it may affect weaning.,30-34 increased respiratory work,,32,35-38 and hypercapniadue to the increase in dead space.,35,39-43Heat and moisture exchangers may cause clinical problems that contraindicate theiruse. Complications associated with their use include increasedresistance, Heat and moisture exchangers witha large dead space may have a negative effect on the respiratory function ofspontaneously breathing patients due to the increased respiratory work required andmay lead to carbon dioxide (CO2) retention in paralyzedpatients.The determinants of resistive pressure in mechanically ventilated patients includenot only patient airway resistance and inspiratory flow but also the resistance ofparts of the ventilator, the endotracheal tube and the HME.,39 thus affecting the weaningprocess. These adverse effects of the addition of HME-related dead space may be evenmore pronounced in patients who already have low tidal volume (TV) and/or highpartial carbon dioxide pressure (PaCO2).The direct clinical effects of these drawbacks can be seen, for example, duringmechanical ventilator weaning, when, if the addition of dead space changes thealveolar ventilation, the efficiency of spontaneous ventilation may beimpaired,Changes caused to minute volume should be taken into account in the case of weaningdifficulty when an HME is used on patients in spontaneous ventilation, and careshould be taken, as we often have to increase the ventilatory parameters tocompensate for the presence of an HME. These increases in pressure and volume raisethe risk of barotrauma and volutrauma in patients who have more severe changes inrespiratory mechanics.We have not identified any studies that quantify the increase in pressure supportneeded to minimize the adverse effects of HMEs. Therefore, we aim to evaluate thepossible changes in TV, minute volume and respiratory rate caused by the use of HMEsin patients submitted to mechanical ventilation in pressure support mode and toevaluate the variation in pressure support required to compensate for the effectcaused by the HME's dead space.Hospital Geral de Carapicuíbain the state of São Paulo. A total of 26 patients, of both genders, wereevaluated. Patients submitted to invasive mechanical ventilation via an endotrachealcannula or tracheostomy were included who were ventilated under pressure supportventilatory mode and who had hemodynamic stability. Exclusion criteria were presenceof psychomotor agitation of any origin; use of sedatives; need for positiveend-expiratory pressure (PEEP) greater than or equal to 15cmH2O;hydroelectrolytic or metabolic changes that might interfere with the patient'srespiratory rhythm; pathological respiratory rhythms; bronchopleural fistula and bronchial hyperreactivity. Minutevolume, TV and respiratory rate were measured in two situations: in the first, thepatients received gas humidification and heating by HH; in the second, they receivedit by HME - always with the use of the intermediary that accompanies thesedevices.This field-based prospective, self-controlled, quantitative analysis was approved bythe Research Ethics Committee  and was conducted in the adultintensive care unit (ICU) of The measurements were performed after 30 minutes of physiotherapeutic treatment,which occurred daily in the ICU and consisted of bronchial hygiene maneuvers,aspiration and positioning in dorsal decubitus elevated to 45°, mainly to avoid theeffect of the presence of secretions on the values found during data collection.Before measuring the desired data, all ventilatory parameters were recorded, witheach of the humidification and heating systems used, in addition to blood gases,heart rate, blood pressure and oxygen saturation.2O/L and was recommended for TVs greaterthan 150mL. The HH was connected and installed before the patient's inspiratorybranch, and the intermediary used was positioned between the endotracheal cannulaand the Y of the ventilatory circuit. The HME was positioned between the Y of theventilatory circuit and the endotracheal cannula, and, as accompanied by theintermediary, the latter was positioned between the HME and the endotrachealcannula.The protocol consisted initially of the use of an HH followed by the use of an HME with trachea (15cm intermediary) in the same patient. TheHME used at the time of the measurements was new, weighing 30g, with a dead space of45mL and a resistance of 2.5cmHAt every change of humidification device, 5 minutes were allowed to pass beforemeasurements were taken. The TV and minute volume measurements were taken using aventilometer  on the exhalation valve for 1 minute, whenthe respiratory rate was also verified. The patient was excluded from the study ifthe ventilator presented bias flow with flow sensitivity that did not allow itsdeactivation.2O with the use ofthe HME until a pressure support value was found that would allow the patient togenerate a TV value with a difference of less than 10% of the initial value foundwith the HH. Respiratory compensations (such as increased respiratory rate) shown bythe patient were also observed. At this stage, with each increase of1cmH2O in pressure support, 5 minutes were allowed to pass beforemeasurements were taken.After the first measurement using the HH, the values were annotated and later servedas a parameter for continuity of the study measurements. If the TV found using theHME was lower than the HH finding, the other part of the study was started, whichentailed increasing the pressure support by 1 in 1cmHAt the end of data collection, the patients were returned to the device forconditioning of inspired gases and to ventilatory parameters that were being usedprior to the study.t test. The SigmaStat 11.0 statistical package for Windowswas used, and a p value of < 0.05 was adopted for statisticalsignificance.The mechanical ventilation time data are expressed as medians and interquartileranges, and the other numeric data are expressed as means and standard errors.Data were tested for normality using the Shapiro-Wilk test. The comparisonsbetween groups using an HH and an HME in the minute volume, TV, respiratory rateand pressure support evaluations were performed using the pairedTwenty-six patients in the general ICU of a large hospital in São Paulo wereselected. The patients' clinical characteristics are shown in 2O) when compared with the HH device (11.8 ±0.7cmH2O) to maintain the baseline TV. An increase of 4.5 ±0.7cmH2O of pressure support was required - approximately 38.13% ofthe baseline value (p < 0.001).In mechanically ventilated patients, the humidification device used is occasionallyignored when determining respiratory system mechanics, which can lead to unnecessarytreatment and can be responsible for slowing the transition to spontaneousbreathing. We evaluated changes to the TV, minute volume and respiratory rate ofpatients with artificial airways, ventilated in pressure support mode and receivinghumidification and heating by HMEs. Our goals were to know whether the HME affectedthe TV, minute volume and respiratory rate measurements when inserted between theendotracheal tube and the mechanical ventilator circuit and to establish by how muchwould we need to increase the pressure support to reach the initial values of theseparameters. Thus, we needed to ascertain the values without the use of the HME. Toaccomplish this goal without leaving the patient with no humidification and heatingsystem, the initial measurement was taken with the HH as the baseline. Our studyshowed that when using HMEs in these patients, an increase of 38.13% from thebaseline pressure support was required.In an earlier study, an analog respiratory system was constructed using a mechanicalmodel to simulate normal- and high-demand situations. Three different levels ofinspiratory effort were simulated to calculate the resistance imposed by the HME.The measurements were obtained with dry and saturated HMEs. Resistance increasedwith HME saturation but showed little increase in response to increasedflow. found the HME to be the preferred humidification option,as it reduced pulmonary complications and improved patient collaboration.In a systematic review to identify the best humidification system for spontaneouslybreathing tracheostomized patients, Wong et al. recentlyconducted a study in which they evaluated the vital capacity and maximum inspiratorypressure of 20 healthy young adults in two situations: with and without an HMEcoupled to a ventilometer or pressure manometer. The use of the HME did not modifyeither pulmonary volumes or respiratory muscle strength and could be used safelywith these devices to reduce the occurrence of pulmonary infection.Lucato et al. using the HME,nor any changes in lung volume and muscle strength, other studies have shown that resistance to gasflow during use of the HME increased with increasing material density,20 and may also increase with increasing flow,47 and duration of use.,34,48,49 This increase in resistance in the ventilatory circuit maylead to an incorrect evaluation of respiratory system mechanics, inappropriatetreatment (bronchodilators) or difficulty in mechanical ventilationweaning, in additionto increasing the patient's breathing effort.,31,50Although we did not find a significant increase in resistance in our previousstudies,21,43 Whenpatients were able to increase their respiratory rate and TV, arterialCO2 remained constant. When a patient was unable to increase theirminute volume due to either respiratory muscle weakness or fatigue or paralysis, theCO2 concentration increased.,33,35,43The use of an HME causes an increase in dead space of an amount equal to its internalvolume. The patient should increase their respiratory rate, TV or both to maintainnormal alveolar ventilation in the presence of increased dead space related to theuse of the HME. subjected 31neurocritical patients to ventilation, providing two forms of humidification (HMEand HH) in a random manner. TV, peak inspiratory and expiratory flow, staticcompliance and respiratory system dynamics and resistance were evaluated. The HMEpromoted reductions in TV, peak inspiratory and expiratory flow and dynamiccompliance, in addition to increased respiratory system resistance.In the current study, 26 patients were evaluated in regard to changes in TV, minutevolume and respiratory rate using an HH and an HME. There was a decrease in TV inpatients when using the HME compared with the HH. Corroborating our study, Siqueiraet al. evaluated theeffects of the HME and the HH on respiratory rate, minute volume, carbon dioxideconcentration (ETCO2), oxygen saturation, airway occlusion pressure(P0.1) and perception of comfort during non-invasive mechanical ventilation (NIMV),they found no differences between the HH and the HME in any of the parametersstudied. The increase in respiratory rate of the patients in our study was notenough to maintain minute volume, which decreased due to the significant reductionin TV.In our study, an increase in respiratory rate and a decrease in minute volumes wereobserved in patients using the HME device compared with using the HH. However, whenBoyer et al. alsousing NIMV, concluded that during NIMV, increased dead space may adversely affectventilatory function and gas exchange. The use of the HME may lead to a significantincrease in PaCO2, despite a significant increase in minute volume. Inthis study, respiratory effort was not measured, but P0.1 increased significantlywhen the HME was added into the ventilatory circuit, suggesting that the device mayalter the efficiency of NIMV in some patients, especially in the very debilitated.An increase in minute volume resulting from the additional dead space and anincrease in P0.1 can lead to an overload of the respiratory muscles. Considering theaforementioned studies, the increased respiratory rate of patients in the presentstudy was not sufficient to maintain minute volume because there was a decrease inTV, likely due to a response to the increased resistance imposed by the device.Jaber et al.'s study, also observedthat in patients with chronic respiratory failure, the airway humidification typemay negatively affect mechanical ventilation efficacy. They evaluated theperformance of the HH and the HME in regard to diaphragmatic muscle activity,respiratory pattern, gas exchange and respiratory comfort during mechanicalventilation weaning using pressure support ventilation. Their results revealed thatthe HME significantly increased all respiratory effort variables  and also produced anincrease in PaCO2, which was insufficiently compensated for by theincrease in minute volume. These effects were counterbalanced by an increase inpressure support level, corroborating our study, which demonstrated that increasedpressure support was needed when using an HME device (16.3 ±1.2cmH2O) compared to HH (11.8 ± 0.7cmH2O) tomaintain baseline TV. Therefore, there was a need for an increase of 4.5 ±0.7cmH2O in pressure support, which corresponds to approximately38.13% of the baseline value.Girault et al.The direct clinical impact of the use of the HME can be seen during mechanicalventilator weaning. If the addition of dead space changes alveolar ventilation, theefficiency of spontaneous ventilation may be impaired, thus affecting the weaningprocess.It is important to take into account not only the endotracheal tube and themechanical ventilator but also the additional workload imposed by an HME when thepatient is in the weaning process. noted that the performance of a hydrophobic HME depends onthe ambient temperature because a high ambient temperature reduces the thermalgradient between the two sides of the HME. In this regard, Thomachot etal. evaluated tensedated patients who were ventilated for three consecutive 24-hour periods with aheated humidifier, a hydrophobic HME and a hygroscopic HME and showed that trachealtemperature measurements revealed no differences in ambient air temperature. Theincreased resistance in this regard appears to be related to high temperaturesraising the moisture and occlusion of a device in prolonged use. In view of thislikelihood and despite this limitation, we emphasize that all patients wereevaluated in the same period with the use of the two devices and at the same roomtemperature. We also emphasize that the device used was new at the time of theevaluation to avoid the effects of HME occlusion or saturation.The non-evaluation of the temperature gradient between the ambient and tracheal airof the evaluated patients is a limitation of the present study, as this gradientcould have changed the humidification and heating performance of the HME, or evenrespiratory system resistance. Roustan et al.2 could take place.,56 It should be borne in mind that the patient is taken froma condition of pressure and volumetric equilibrium to a transitional condition, andwe do not know the time necessary for the new equilibrium to be established.Therefore, it is possible that 5 minutes of evaluation is not sufficient time tostabilize the ventilatory adjustments required in this type of situation.Another limitation of our study was that we adopted the protocol, used in otherstudies, of waiting 5 minutes before taking measurements so that sensory adaptationof the respiratory center to oxygen and COThe use of an heat and moisture exchanger changed the tidal volume, minute volume andrespiratory rate parameters. Increased pressure support was required to compensatefor these changes.