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Acute hepatic porphyrias (AHP) are a group of four different rare to ultra-rare, severely debilitating, and sometimes fatal diseases that significantly impact patients' lives: 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria (ADP), acute intermittent porphyria (AIP), hereditary coproporphyria (HCP), and variegate porphyria (VP). Based on literature estimates, a conservative estimate of the number of AHP patients in Belgium requiring treatment, defined as patients experiencing recurrent attacks and/or chronic debilitating symptoms, is likely limited to 11-34 patients. These patients face a considerable unmet need, as there is currently no pharmaceutical treatment available that effectively prevents attacks and has an impact on other chronic symptoms of the disease.A panel consisting of the two European Porphyria Network1 (EPNet) centers in Belgium (Center for inborn errors of metabolism of UZ Leuven and the 'Centre Belge des Porphyries' of Erasme Hospital and LHUB-ULB) participated in an advisory board on 24 January 2020. Representatives of the sponsoring pharmaceutical company, Alnylam Pharmaceuticals, organized and attended the meeting. The objective of the meeting was to obtain expert input on the state-of-the-art clinical practice of AHP in Belgium. Following this meeting, this expert consensus statement was drafted, in collaboration with and coordinated by the EPNet centers in Belgium. This statement provides an overview of the state-of-the art in AHP, by means of a concise overview of AHP pathophysiology, clinical manifestations, and burden of disease, (Belgian) epidemiology, treatments, and proposed organization of care. ispartof: ACTA CLINICA BELGICA vol:77 issue:4 pages:735-741 ispartof: location:England status: published

Background Acute hepatic porphyria (AHP) is a rare, debilitating disease characterized by potentially life-threatening attacks often resulting in chronic symptoms that negatively impact daily functioning and quality of life. Symptoms of AHP prevent many individuals from working and achieving lifetime work averages. The aim of this study was to apply a public economic framework to evaluate AHP in Belgium, taking into consideration a broad range of costs that are relevant to government in relation to social benefit payments and lifetime taxes paid. Methodology A public economic framework was developed exploring lifetime costs for government attributed to an individual with AHP and recurrent attacks in Belgium. Work-activity and lifetime direct taxes paid, indirect consumption taxes and requirements for public benefits were estimated based on established clinical pathways for AHP and compared to the general population (GP). The model includes AHP-related healthcare costs and non-AHP healthcare costs for the GP. Results Lifetime earnings are reduced in an individual with AHP by €347,802 per person (p.p.), translating to reduced lifetime taxes paid of €183,187 for an AHP individual compared to the GP. We estimate increased lifetime disability benefit support of €247,242 for an AHP individual compared to GP. Lifetime healthcare costs for a person with AHP were estimated to be €3,030,316 due to frequent hospitalisations associated with porphyria attacks compared to the GP. The lifetime costs for a person with 12 attacks per annum factoring in transfers, taxes and healthcare costs are estimated to be €3,460,745 p.p. Eliminating AHP attacks after 10 years of active disease, thus, enabling a person to return to work increases lifetime earnings by €224,575 p.p. Increased work activity in such individuals would generate an estimated €118,284 p.p. over their lifetime. The elimination of AHP attacks could also lead to reductions in disability payments of €179,184 p.p. and healthcare cost savings of €1,511,027 p.p. Conclusions Due to severe disability resulting from constant attacks, AHP patients with recurrent attacks incur significant public costs. Lifetime taxes paid are reduced as these attacks occur during peak earning and working years. In those patients, reducing AHP attacks can confer significant fiscal benefits for government, including reduced healthcare costs, reduced disability payments and improved tax revenue.

Background HIV patients face considerable acute and chronic healthcare needs and battling the HIV epidemic remains of the utmost importance. By focusing on health outcomes in relation to the cost of care, value-based healthcare (VBHC) proposes a strategy to optimize quality of care and cost-efficiency. Its implementation may provide an answer to the increasing pressure to optimize spending in healthcare while improving patient outcomes. This paper describes a pragmatic value-based healthcare framework for HIV care. Methods A value-based HIV healthcare framework was developed during a series of roundtable discussions bringing together 16 clinical stakeholder representatives from the Belgian HIV reference centers and 2 VBHC specialists. Each round of discussions was focused on a central question translating a concept or idea to the next level of practical implementation: 1) how can VBHC principles be translated into value-based HIV care drivers; 2) how can these value-based HIV care divers be translated into value-based care objectives and activities; and 3) how can value-based HIV care objectives and activities be translated into value-based care indicators. Value drivers were linked to concrete objectives and activities using a logical framework approach. Finally, specific, measurable, and acceptable structure, process and outcomes indicators were defined to complement the framework. Results Our framework identifies 4 core value areas where HIV care would benefit most from improvements: Prevention, improvement of the cascade of care, providing patient-centered HIV care and sustaining a state-of-the-art HIV disease management context. These 4 core value areas were translated into 12 actionable core value objectives. For each objective, example activities were proposed. Indicators are suggested for each level of the framework (outcome indicators for value areas and objectives, process indicators for suggested activities). Conclusions This framework approach outlines how to define a patient- and public health centered value-based HIV care paradigm. It proposes how to translate core value drivers to practical objectives and activities and suggests defining indicators that can be used to track and improve the framework’s implementation in practice.

Background Acute hepatic porphyria (AHP) is a rare, debilitating disease characterized by potentially life-threatening attacks often resulting in chronic symptoms that negatively impact daily functioning and quality of life. Symptoms of AHP prevent many individuals from working and achieving lifetime work averages. The aim of this study was to apply a public economic framework to evaluate AHP in Belgium, taking into consideration a broad range of costs that are relevant to government in relation to social benefit payments and lifetime taxes paid. Methodology A public economic framework was developed exploring lifetime costs for government attributed to an individual with AHP in Belgium. Work-activity and lifetime direct taxes paid, indirect consumption taxes and requirements for public benefits were estimated based on established clinical pathways for AHP and compared to the general population (GP). The model includes AHP-related healthcare costs and non-AHP healthcare costs for the GP. Results Lifetime earnings are reduced in an individual with AHP by €347,802 per person (p.p.), translating to reduced lifetime taxes paid of €183,187 for an AHP individual compared to the GP. We estimate increased lifetime disability benefit support of €247,242 for an AHP individual compared to GP. Lifetime healthcare costs for a person with AHP were estimated to be €3,030,316 due to frequent hospitalisations associated with porphyria attacks compared to the GP. The lifetime costs for a person with 12 attacks per annum factoring in transfers, taxes and healthcare costs are estimated to be €3,460,745 p.p. Eliminating AHP attacks after 10 years of active disease, thus, enabling a person to return to work increases lifetime earnings by €224,575. Increased work activity in this cohort would generate an estimated €118,284 p.p. over their lifetime. The elimination of AHP attacks could also lead to reductions in disability payments of €179,184 p.p. and healthcare cost savings of €1,511,027. Conclusions Due to severe disability resulting from constant attacks, AHP patients incur significant public costs. Lifetime taxes paid are reduced as these attacks occur during peak earning and working years. Reducing AHP attacks can confer significant fiscal benefits for government, including reduced healthcare costs, reduced disability payments and improved tax revenue.

Objectives This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample. Background Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. Methods Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] × 100), augmentation index ([Second/First systolic peak] × 100) and pulse pressure amplification ([Radial/aortic pulse pressure] × 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years. Results After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p Conclusions Arterial wave reflections represent a novel strong risk factor for CHF in the general population.

We recently introduced noninvasive methods to assess local pulse wave velocity (PWV) and wave intensity (ndI) in arteries based on measurements of flow velocity (U) and diameter (D). Although the methods were validated in an experimental setting, clinical application remains lacking. The aim of this study was therefore to investigate the effect of age and gender on PWV andndI in the carotid and femoral arteries of an existing population. We measured D and U in the carotid and femoral arteries of 1,774 healthy subjects aged 35-55 yr, a subgroup of the Asklepios population. With the use of the lnDU-loop method, we calculated local PWV, which was used to determine arterial distensibility (nDs). We then used the new algorithm to determine maximum forward and backward wave intensities (ndI+maxandndI−min, respectively) and the reflection index (nRI). On average, PWV was higher, andnDs was lower in the femoral than at the carotid arteries. At the carotid artery, PWV increased with age, butnDs,ndI+max, andndI−mindecreased;nRI did not change with age. At the femoral artery, PWV was higher, andnDs was lower in male, but all parameters did not change significantly with age in both women and men. We conclude that the carotid artery is more affected by the aging process than the femoral artery, even in healthy subjects. The new techniques provide mechanical and hemodynamic parameters, requiring only D and U measurements, both of which can be acquired using ultrasound equipment widely available today, hence their advantage for potential use in the clinical setting.

Background: The current standard for arterial stiffness assessment, aortic pulse wave velocity (aPWV), is measured at diastolic pressure. Arterial stiffness, however, is pressure dependent. At the carotid artery level, the degree of this dependency can be quantified as the difference (Delta PWV) between systolic and diastolic (cPWV(d)) carotid pulse wave velocity. Biomechanically, a greater Delta PWV implies greater increases in left ventricular afterload with physical activity. Therefore, we hypothesized, that Delta PWV is more strongly associated with left ventricular mass index (LVMI) than aPWV and cPWV(d). Methods: In 1776 healthy individuals from the Asklepios cohort (age 35-55 years), Delta PWV was obtained from combined carotid artery ultrasound and tonometry recordings. Multiple linear regression analysis was performed to investigate the associations of Delta PWV, cPWV(d) and aPWV with LVMI, adjusting for age, sex, mean blood pressure (MBP), central pulse pressure, and other possible confounders. Results: DPWV was 2.4 +/- 1.2 m/s (mean +/- SD), ranging from 0.8 m/s, indicating almost constant arterial stiffness over the cardiac cycle, to 4.4 m/s, reflecting substantial pressure dependency. Delta PWV was significantly associated with LVMI (beta of 2.46 g/m(1.7) per m/s, P < 0.001), even after full adjustment (beta of 0.56 g/m(1.7) per m/s, P = 0.03). cPWV(d) and aPWV had clear crude associations with LVMI (P < 0.001), but lost significance after adjustment (beta of -0.48 and -0.33 g/m(1.7) per m/s, with P = 0.11 and 0.2, respectively). Conclusion: The change in arterial stiffness over the cardiac cycle, rather than diastolic stiffness, is independently associated with LVMI in healthy middle-aged individuals. Therefore, the pressure dependency of arterial stiffness should be considered in cardiovascular risk assessment.

We thank the writers for providing well-founded, additional context to our manuscript[1].Our manuscript [2] focuses on the pharmaceutical cost and health impact of combined prevention only. Combine...

Proper non-invasive assessment of carotid artery pressure ideally uses waveforms recorded at two anatomical locations: the brachial and the carotid artery. Calibrated diameter distension waveforms could provide a more widely applicable alternative for local arterial pressure assessment than applanation tonometry. This approach might be of particular use at the brachial artery, where the feasibility of a reliable tonometric measurement has been questioned. The aim of this study was to evaluate an approach based on distension waveforms obtained at the brachial and carotid arteries. This approach will be compared to traditional pulse pressures obtained through tonometry at both the carotid and brachial arteries (used as a reference) and the more recently proposed approach of combining tonometric readings at the brachial artery with linearly or exponentially calibrated distension curves at the carotid artery. Local brachial and carotid diameter distension and tonometry waveforms were recorded in 148 subjects (119 women; aged 19-59 years). The morphology of the waveforms was compared by the form factor and the root-mean-squared error. The difference between the reference carotid PP and the PP obtained from brachial and carotid distension waveforms was smaller (0.9 (4.9) mmHg or 2.3%) than the difference between the reference carotid PP and the estimates obtained using a tonometric and a distension waveform (-4.8 (2.5) mmHg for the approach using brachial tonometry and linearly scaled carotid distension, and 2.7 (6.8) mmHg when using exponentially scaled carotid distension waves). We therefore recommend to stick to one technique on both the brachial and the carotid artery, either tonometry or distension, when assessing carotid blood pressure non-invasively.

Background Carotid–femoral pulse wave velocity can be determined using different distances – either direct carotid–femoral distance or subtracted [(sternal–femoral) − (carotid–sternal)] distance – resulting in pulse wave velocity differences of up to 30%. The present study aims to present and validate a population-based model for the conversion between distances. Method Three thousand one hundred and sixteen participants from the Asklepios study (n = 2510) and Hopital Europeen Georges Pompidou (n = 606) databases, in which all distance measurements were available, were randomly distributed in a model (n = 311) and validation (n = 2805) population. Model parameters for the conversion equations were selected and evaluated using multiple linear regression with stepwise selection of covariates (age, sex, weight, height, BMI and waist circumference). The proposed model was evaluated on the validation population. Results The difference between direct and subtracted distances was found to be partially dependent on body height, and its inclusion in the multivariate model improved model performance by over 20%. Other combinations of adjustments did not improve model prediction. Conversion equations derived in the model population were: Estimated Direct_distance = 0.45*Subtracted_distance + 0.21*height + 0.08 and Estimated Subtracted_distance = 1.04*Direct_distance − 0.11*height − 0.02, respectively. Applying these equations for estimation of direct and subtracted distances in the validation population yielded good correspondence to measured results (r2 = 0.73 and 0.57, respectively), with nonsignificant mean differences between estimated and measured values. Increasing the size of the model population did not significantly change the model validity. Conclusion In cases in which not all distance measurements are available for exact conversion, the presented equations can be used to convert between distance definitions.

Calibrated diameter distension waveforms could provide an alternative for local arterial pressure assessment more widely applicable than applanation tonometry. We compared linearly and exponentially calibrated carotid diameter waveforms to tonometry readings. Local carotid pressures measured by tonometry and diameter waveforms measured by ultrasound were obtained in 2026 subjects participating in the Asklepios study protocol. Diameter waveforms were calibrated using a linear and an exponential calibration scheme and compared to measured tonometry waveforms by examining the mean root-mean-squared error (RMSE), carotid systolic blood pressure (SBPcar) and augmentation index (AIx) of calibrated and measured pressures. Mean RMSE was 5.2(3.3) mmHg (mean(stdev)) for linear and 4.6(3.6) mmHg for exponential calibration. Linear calibration yielded an underestimation of SBPcar by 6.4(4.1) mmHg which was strongly correlated to values of brachial pulse pressure (PPbra) (R = 0.4, P < 0.05). Exponential calibration underestimated true SBPcar by 1.9(3.9) mmHg, independent of PPbra. AIx was overestimated by linear calibration by 1.9(10.1)%, the difference significantly increasing with increasing AIx (R = 0.25, P < 0.001) and by exponential calibration by 5.4(10.6)%, independently of the value of AIx. Properly calibrated diameter waveforms offer a viable alternative for local pressure estimation at the carotid artery. Compared to linear calibration, exponential calibration significantly improves the pressure estimation.

The relationship between aortic (carotid-femoral) pulse wave velocity and stiffness measures based on local diameter and pressure readings is not yet fully understood.We compared the relationship with age and gender of aortic pulse wave velocity to stiffness indices (compliance and distensibility coefficient) evaluated at the common carotid and femoral arteries in 2195 (1131 women) apparently healthy subjects, aged 35-55 years participating in the Asklepios study. Aortic pulse wave velocity was further compared with previously reported central arterial stiffness parameters on the same population. Subjects were divided into four age groups for analysis.Femoral arterial stiffness was higher in men than in women (P0.001) but did not change with age and no age-gender interaction was evident. Carotid arterial stiffness increased with age (P0.001) and showed a significant (P0.001) age-gender interaction, with carotid stiffness increasing more rapidly in women than in men, crossing over around the age of 45. Aortic pulse wave velocity did not differ between men and women, but did increase with age (P0.001). No age-gender interaction was evident.The relation with age and gender of local and central stiffness measures is not the same over the age range 35-55 in apparently healthy men and women. Depending on the central stiffness parameter used, age-gender effects evident at the carotid artery are or are not found centrally. Though the relevance of these differences requires further evaluation in a longitudinal study with outcome data, they need to be kept in mind when designing or interpreting results from arterial stiffness evaluation studies.

Background: Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic (AB) treatment. This study aimed to measure the overall prevalence of AAD (including mild to moderate diarrhea) in hospitalized AB treated patients, to investigate associated risk factors and to document AAD associated diagnostic investigations, contamination control and treatment. Methods: During 8 observation days (with time delay of 10-14 days between each observation day), all adult patients hospitalized at an internal medicine ward of 4 Belgian participating hospitals were screened for AB use. Patients receiving AB on the observation day were included in the study and screened for signs and symptoms of AAD using a period prevalence methodology. Clinical data were collected for all AB users and AAD related investigations and treatment were collected for the entire duration of AAD. Additionally, nurses noted daily the frequency of all extra care associated to the treatment of the diarrhea. Results: A total of 2543 hospitalized patients were screened of which 743 were treated with AB (29.2%). Included AB users had a mean age of 68 yr (range 16-99) and 52% were male. Penicillins were mostly used (63%) and 19% received more than one AB. AAD was observed in 9.6% of AB users including 4 with confirmed Clostridium difficile infection. AAD started between 1 and 16 days after AB start (median 5) and had a duration of 2 to 41 days (median 4). AAD was significantly associated with higher age and the use of double AB and proton pump inhibitors. AAD patients had extra laboratory investigations (79%), received extra pharmacological treatment (42%) and 10 of them were isolated (14%). AAD related extra nursing time amounted to 51 minutes per day for the treatment of diarrhea. Conclusions: In this observational study, with one third of hospitalized patients receiving AB, an AAD period prevalence of 9.6% in AB users was found. AAD caused extra investigations and treatment and an estimated extra nursing care of almost one hour per day. Preventive action are highly recommended to reduce the prevalence of AAD and associated health care costs.

Objective: Studies on changes in arterial stiffness and wave reflections during pregnancy are limited to cross-sectional studies. Our aim was to investigate maternal hemodynamic and cardiovascular adaptations at each trimester of pregnancy in a prospective longitudinal case-control study. Methods: Cardiovascular measurements were performed at 12, 20 and 35 weeks of gestation, and included peripheral (Omron M6) and central (Sphygmocor) blood pressures, wave reflection and arterial stiffness measures (Sphygmocor and Esaote AU5 Wall track system). Results: 109 healthy women with a normal pregnancy (mean age 29.3y, range 21–42) and 26 healthy non-pregnant control subjects (mean age 28.4y, range 21–40) were included. Except for peripheral and central systolic blood pressure, all cardiovascular parameters showed significant (p

Background: Arterial diastolic asymptotic pressure (P∞) is the pressure reached when the heart stops beating. Determination of the reservoir pressure (Pr) requires a value of P∞ which was previously assumed (1), calculated (2) and measured (3, 4) as 0, 35, 14, 24 mmHg respectively. The effects of varying P∞ on the determination of Pr is the primary objective of this study. Methods: Pr was calculated from the carotid pressure of 2003 subjects of the Asklepios study (a) using a free fitting algorithm for the determination of P∞ and (b) setting P∞ to the average of the experimental values (19 mmHg). Results: The reservoir pulse pressure (PPr) is higher using the free fitting method than setting P∞ (Fig1). PPr increases significantly with age and is higher in male than female in both cases. Conclusions: PPr is generally higher in male than female and its absolute value is dependant on the value of P∞. Higher values of PPr suggests deterioration of the arterial buffering function with age. Figure 1.Changes of PPr with age and gender using the free fitting algorithm (a) and 19mmHg (b).

Several large-scale studies have confirmed that intima-media thickness (IMT) values can be used to accurately identify cardiovascular risk. 1-5 With the advent of more accurate ultrasonographic measurement applications, there has been a growing interest in validated, clinically applicable tools for performing automated IMT measurements. This study aims to validate a new semi-automated IMT detection algorithm, supplied by GE Vingmed Ultrasound, by comparing it with IMT measurements performed manually at the common carotid artery.

Background: Recently, an expert group advised to measure carotid-femoral (cf) pulse wave velocity (PWV) on the right side of the body, and to use a sliding caliper when tape measure distance cannot be obtained in a straight line. The present study investigates the evidence for this advice by comparing the real travelled cf path lengths (RTPLs) at both body sides and comparing the straight distance (as can be obtained with a sliding caliper) with the tape measure distance. Methods: RTPLs were measured with MRI in 98 individuals (49 men, age 21-76 years). Path lengths from the aortic arch to the carotid (AA-CA) and femoral (AA-FA) sites were determined. RTPL was calculated as (AA-FA) - (AA-CA) and compared between both sides. RTPLs were compared with 80% of the direct cf distance using a tape measure and the straight cf distance obtained from MRI images. Results: RTPL was slightly longer [11mm (12), P < 0.001] at the right side. The 80%-rule overestimated RTPLs with 0.5% at the right and 2.7% at the left side. Straight MRI distance tended (P = 0.09) to perform slightly better than tape measure distance. Conclusion: The travelled cf path is slightly longer at the right than at the left body side and the straight MRI distance tends to perform better than tape measure distance. The present study supports the advice of the expert consensus group to measure cf-PWV at the right body side using a sliding caliper when tape measure distance cannot be obtained in a straight line.

Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

Carotid-femoral pulse wave velocity (PWV) is the gold standard method for determination of arterial stiffness. PWV is assessed by dividing travelled distance by travel time. Standardization and validation of the methodology for travelled distance measurement is of crucial importance. The aim of the current investigation was to standardize and validate the methodology for travelled distance measurement.Real travelled carotid-femoral path lengths were measured with MRI in 98 healthy men/women (50% men, age 21-76 years) and are used as reference distance. This reference distance was compared with 11 estimates of aortic path length from body surface distances commonly used in PWV measurement, nine of them based on tape measures and two based on body height. Determinants of the difference between reference distance and the best body surface distance were determined. Additionally, the influence of body contours was identified.The tape measure distance from carotid to femoral artery (CA-FA), multiplied by 0.8, yielded the best agreement with the reference aortic path length [difference 0.26 cm (SD 3.8), not statistically significant]. Thirty percent of the variation in difference between the reference distance and tape measure distance (CA-FA × 0.8) was explained by age. Adding BMI increased this number to 34%.The tape measure distance from CA-FA, multiplied by 0.8, corresponds best with the real travelled aortic path length. This distance is moderately (yet statistically significantly) influenced by age and minimally by BMI.

Background: The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method: For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results: When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion: The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor. http://dx.doi.org/10.1097/HJH.0b013e328346a3bc

Results: As expected, clinic blood pressure values and media to lumen ratio were higher in essential hypertensive patients than in normotensive controls. Fibronectin media content was significantly greater in essential hypertensive patients (7.41 2.28 %), compared with normotensive controls (5.62 0.40, P

Aims: Carotid-femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results: We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion: The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

The wave speed (c) and the arrival time of reflected wave (Trw) in the common left carotid artery and common left femoral artery have been evaluated in 70 healthy subjects, aged 35-55 years with a non-invasive method. Wave speed and the arrival time of reflected waves were determined with InDU-loop and non-invasive wave intensity analysis (ndl) techniques, respectively. Diameter (D) was measured with ultrasound echo wall tracking and velocity (U) was obtained by ultrasonography. A statistical analysis has been carried out in order to establish a potential relation of c and Trw with gender and age in the study population. Subjects have been divided in two classes of age, one from 35 to 45 years and the other from 45 to 55 years. Results show that c and Trw in the femoral artery are higher than those in carotid, in both men and women (P < 0.001). Also, the distance of the reflection (L) site from the point of measurement is higher in the femoral than in the carotid artery. We did not find statistically significant differences between c, age or gender in femoral artery. However, c in the carotid artery increases with age (P < 0.05), but did not change between men and women. In this paper InDU-loop has been used for the first time to determine c and Trw in carotid and femoral arteries in a large population of healthy subjects.

Background: Arterial stiffness is increasingly used as an early marker of atherosclerosis and for the individual's assessment of cardiovascular risk. Ultrasound wall tracking allows assessing the distensibility coefficient DC = (ΔD/D)/ΔP with D diastolic diameter, ΔD cyclic diameter change and ΔP the local pulse pressure. Although DC depends on intrinsic stiffness, it also depends on vessel geometry. In this study, we reconcile DC of the common carotid artery measured within the framework of the Asklepios population study. Methods: Diameter, intima-media thickness (IMT) and DC of the left common carotid artery were assessed in 2315 (1191women) apparently healthy subjects (age 35–56), using vascular ultrasound (Vivid 7, 12L probe) and wall tracking (media-adventitia transition) techniques. Evolution of DC and IMT/D with age was evaluated within the context of a theoretical framework linking DC, IMT/D and the Young elasticity modulus E [DC =1/(2.E.IMT/D)]. Results DC was higher in women than in men for age (35–40), while the inverse was true at age (51–56), suggesting a more rapid increase in stiffness in women. This evolution in DC is partly explained by arterial remodelling (increase in IMT/D) accompanied by an increase in intrinsic stiffness. While DC decreases by ≫30%, our data suggest an increase in intrinsic stiffness of about 25% over the studied age range. Conclusions: Clinically used measures of arterial stiffness are intrinsically dependent on arterial geometry. Direct measurements of stiffness are highly needed to avoid the ambiguity between an artery's kinematic behavior and its intrinsic mechanical properties.

Summary In this paper, we briefly revise some of the most widely applied methods to non-invasively assess pressure wave reflection (augmentation index) and arterial stiffness (pulse wave velocity; PWV) in clinical vascular research. It is clear that the pressure waveform alone provides insufficient information to accurately quantify the magnitude of pressure wave reflection or to even fully interpret its nature. A major difficulty arises from the identification of timing of return of the reflected pressure wave, the “fiducial” point, and incorrect assessment of this point has an effect on all of the derived parameters. From our studies, it also follows that the use of an approximated flow waveform has little or no added value to assess magnitude of wave reflection. As for PWV, carotid–femoral pulse wave velocity is currently considered as the gold standard method, although accurate assessment of travel distance remains ambiguous. New methods have also been suggested for the assessment of PWV, relying on the concept that the pressure wave is composed of one single forward wave and one single reflected wave, originating from a single reflection site. This simple conceptual scheme is no more than a paradigm for a complex physical reality of wave transmission and continuous reflections in a complex branching network of elastic vessels and the accuracy of these methods is very limited. As such, the benefit of the ease of use of these methods should be weighted against the desired accuracy and reliability.

Summary Measurement of pulse wave velocity is of increasing importance for assessment of arterial stiffness and risk evaluation. Different techniques are available, based either on pressure, distension or Doppler waveforms. Techniques not only differ by the algorithm used to identify specific part of the pulse signal, but also in the preferred way to measure distance between sites. The merits of each technique are described, and a brief overlook of the marketed devices to measure pulse wave velocity is given.

The relation between arterial function indices, such as pulse wave velocity and augmentation index with parameters derived from input impedance analysis, is still incompletely understood. Carotid pressure, central flow waveforms, and pulse wave velocity were noninvasively acquired in 2026 apparently healthy, middle-aged subjects (1052 women and 974 men) 35 to 55 years old at inclusion. Input and characteristic impedance, reflection coefficient, the ratio of backward-to-forward pressure amplitude (reflection magnitude), and augmentation index were derived. Pulse wave velocity increased by 15% (from 6.1 to 7.0 m/s) both in men and women. In qualitative terms, input impedance evolved from a pattern indicative of wave transmission and reflection to a pattern more compatible with a windkessel-like system. In women, a decrease in total arterial compliance led to an increased input impedance in the low frequency range, whereas few changes were observed in men. Characteristic impedance did not change with age in women and even decreased in men ( P P P

tThe linear time-varying elastance theory is frequently used to describe the change in ventricular stiffness during the cardiac cycle. The concept assumes that all isochrones (i.e., curves that connect pressure-volume data occurring at the same time) are linear and have a common volume intercept. Of specific interest is the steepest isochrone, the end-systolic pressure-volume relationship (ESPVR), of which the slope serves as an index for cardiac contractile function. Pressure-volume measurements, achieved with a combined pressure-conductance catheter in the left ventricle of 13 open-chest anesthetized mice, showed a marked curvilinearity of the isochrones. We therefore analyzed the shape of the isochrones by using six regression algorithms (two linear, two quadratic, and two logarithmic, each with a fixed or time-varying intercept) and discussed the consequences for the elastance concept. Our main observations were 1) the volume intercept varies considerably with time; 2) isochrones are equally well described by using quadratic or logarithmic regression; 3) linear regression with a fixed intercept shows poor correlation ( R2 < 0.75) during isovolumic relaxation and early filling; and 4) logarithmic regression is superior in estimating the fixed volume intercept of the ESPVR. In conclusion, the linear time-varying elastance fails to provide a sufficiently robust model to account for changes in pressure and volume during the cardiac cycle in the mouse ventricle. A new framework accounting for the nonlinear shape of the isochrones needs to be developed.

Keywords: Pulse-Wave Velocity ; Oscillometric Device ; Sphygmocor ; Stiffness ; Complior Reference EPFL-ARTICLE-171203doi:10.1097/HJH.0b013e328348f06dView record in Web of Science Record created on 2011-12-16, modified on 2017-05-10

Background: The average age of first childbirth is increasing in the United States, as well as the proportion of women who choose not to have children or have a smaller family size. Previous research identified lower parity in women with IBD compared to the general population due to disease-related pregnancy concerns. IBD management has changed over the past decade with the addition of biologic therapies, potentially altering IBD-related pregnancy concerns in women with IBD. We sought to explore disease-related pregnancy concerns and their effect on parity and future reproductive planning in a subset of women with IBD. Methods: Female reproductive age Crohn's and ulcerative colitis patients in an academic practice were identified by electronic database query, sent an opt-out letter, and then contacted for phone survey. Questions included demographics, medical and reproductive history, and plans for future pregnancy. Women were asked if IBD has affected their decision to become pregnant and, if so, a qualitative response on specific concerns was recorded. Qualitative data was coded and frequencies and proportions calculated. We analyzed quantitative data with Stata V11 (College Station, TX) and used Chi-square and Wilcoxon rank-sum tests, as appropriate. Results: 121 female participants (31% response rate) were predominately white (85%), had at least some college education, and a mean age of 34.2 years (SD 6.2). 60% had Crohn's, 30% had IBD-related surgery, 36% were on biologic therapy, and 30% on immunomodulators. 43% had at least one child, 58% desire a future pregnancy, and 54% reported IBD-related pregnancy concerns. Of the 70 women who desire a future pregnancy, the median parity was significantly higher in those with IBD-related concerns (0, range 0-3) compared to those without concerns (0, range 0-2) [Table 1]. IBD-related concerns did not affect the parity in women without a desire for future pregnancy [Table 1]. Women who desire a future pregnancy were more concerned about adverse pregnancy outcomes than those who do not and only four women (3.3%) identified IBD-related concerns that led to a smaller family size than desired [Table 2]. Conclusion: Reproductive planning is multi-faceted for every woman. These data suggest IBD-related concerns are less likely to affect a woman's planned family size than previously reported. The concern for adverse pregnancy outcomes is more common in women with IBD desirous of future pregnancy, suggesting a need for targeted counseling to moderate risk perception. Comparison of participant parity by future pregnancy desire and IBD-related pregnancy concerns