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Objective: The aim of the study was to examine the relationship between AASI and age in a cohort of stage I hypertensives < 50 years of age and to investigate its predictive capacity for future established hypertension. Methods: We studied 1157 subjects from the HARVEST study (mean follow-up 5.9 years). AASI and 24-h pulse pressure (PP) were calculated from 24-h ambulatory recordings. The predictive value of AASI for incident hypertension was evaluated with Cox regression analysis adjusting for age, sex, mean 24-h blood pressure (BP). Results: Baseline office BP was 145.5±10.4/93.6±5.6 mmHg, 24-h PP was 49.6±11.2 mmHg, AASI was 0.56±0.2. AASI was correlated with 24-h PP (r=0.41, p

Objective: To determine the accuracy of the KOROT P3 Accurate (previously InBody BPBIO480KV) monitor, an automated auscultatory blood pressure (BP) measuring device developed for professional use, in people with extra-large arms according to the ISO81060-2 2018 protocol., Methods: The KOROT P3 Accurate was tested in 37 subjects with upper-arm circumference ranging from >42 to 53 cm using a mercury sphygmomanometer coupled to a 20 × 40 cm tronco-conical cuff as the reference standard., Results: The mean BP difference between the device and the observers' reference measurements was 1.2 ± 2.0 mmHg for systolic BP and 1.0 ± 2.0 mmHg for diastolic BP. These data were in agreement with criterion 1 of the protocol standard requirements (≤5 ± 8 mmHg). Also criterion 2 was satisfied being the standard deviations ± 1.7 mmHg for systolic BP and ± 1.6 for diastolic BP, well below the maximum values required by the protocol (±6.84/6.87 mmHg). Scatterplots of device-reference systolic and diastolic BP differences showed similar accuracy across the range of participants' BP, arm circumference and upper-arm slant angle., Conclusions: These data show that the KOROT P3 Accurate monitor satisfied the ISO 81060-2:2018 standard requirements in a special population of people with extra-large arms ranging from >42 to 53 cm., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Context: Insulin resistance, glucose alterations, arterial hypertension (HTN), and the renin-angiotensin-aldosterone system (RAAS) are related in adult obesity. This crosstalk is still unexplored in childhood., Objective: Characterize the relationships of fasting and postload glucose and insulin levels with new American Academy of Pediatrics classification of HTN and RAAS in pediatric obesity., Methods: This was a retrospective observational study; 799 pediatric outpatients (11.4 ± 3.1 years) at a tertiary center who were overweight or obese and not yet on diet were included. The main outcome measures were mean and correlations among parameters of a complete clinical and metabolic screening (body mass index, blood pressure, and glucose and insulin levels during an oral glucose tolerance test, and renin and aldosterone levels and their ratio)., Results: 774 subjects had all the parameters, of whom 87.6% had HTN (5% elevated blood pressure, 29.2% stage I HTN, and 53.4% stage II HTN). Eighty subjects had 1 or more glucose alterations, and more frequently presented HTN. Blood pressure levels were higher in subjects with glucose alterations than in those with normal glucose levels. Fasting and stimulated glucose and insulin levels were directly related to the HTN stages, and insulin sensitivity was lower in HTN than in normal blood pressure. Aldosterone, renin, and aldosterone-renin ratio (ARR) were similar in sexes, whereas aldosterone was higher in prepubertal individuals. Subjects with impaired glucose tolerance (IGT) had higher renin and lower ARR. Renin was positively correlated with postload glucose, and ARR was negatively correlated with the Homeostatic Model Assessment for Insulin Resistance index., Conclusion: A close relationship exists among insulin resistance, glucose alterations, HTN, and renin in childhood obesity. Specific categories of risk could provide indicators for strict clinical surveillance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Aim: To evaluate the association of alcohol and smoking combined with cardiovascular and renal events and investigate whether moderate and heavy alcohol consumption have a different impact on this association., Methods: The study was conducted in 1208 young-to-middle-age stage 1 hypertensive patients. Subjects were classified into three categories of cigarette smoking and alcohol use, and the risk of adverse outcomes was assessed over a 17.4-year follow-up., Results: In multivariable Cox models, smoking showed a different prognostic impact on alcohol drinkers and abstainers. In the former, an increase in the risk of cardiovascular and renal events was observed compared to nonsmokers (hazard ratio, 2.6, 95% CI, 1.5-4.3, p < 0.001), whereas in the latter, the risk did not achieve the level of statistical significance ( p = 0.27) with a significant interaction between smoking and alcohol use ( p < 0.001). Among the heavy smokers who also drank alcoholic beverages, the hazard ratio from the fully adjusted model was 4.3 (95% CI, 2.3-8.0, p < 0.0001). In the subjects with moderate alcohol consumption, the risk of smoking and alcohol combined was similar to that found in the whole population (hazard ratio, 2.7; 95% CI, 1.5-3.9, p < 0.001). Among the subjects with heavy alcohol consumption, the hazard ratio was 3.4 (95% CI, 1.3-8.6, p = 0.011)., Conclusion: These findings indicate that the detrimental cardiovascular effects of smoking can be worsened by concomitant alcohol use. This synergistic effect occurs not only for heavy alcohol consumption but also for moderate use. Smokers should be aware of the increased risk associated with concomitant alcohol consumption.

To determine the accuracy of the Hingmed DBP-01P monitor for clinical automatic blood pressure (BP) measurement according to the International Organization for Standardization (ISO) 81060-2 2018 protocol. The DBP-01P was tested in 85 subjects from the general population (mean age, 69.9 years; 43 men) using a wide-range cuff for arm circumferences from 17 to 42 cm. The mean device-observer difference was 1.32 ± 3.18 mmHg for SBP and 0.78 ± 3.15 mmHg for DBP. These data were in agreement with criterion 1 of the protocol standard requirements (≤5 ± 8 mmHg). Also, criterion 2 was satisfied with the SDs of the 85 participants being well below the maximum values required by the protocol (6.80 and 6.89 mmHg for SBP and DBP pressure, respectively). These data show that the Hingmed BP monitor DBP-01P satisfied the ISO 81060-2:2018 standard requirements for a general population across a wide range of arm sizes using a single wide-range cuff., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Recommendations about the dimensions of the reference cuff for device validations in people with arm size >42 cm are still unavailable. The aim of this study was to identify the criteria for an appropriate reference cuff for validation studies in people with upper arm circumference between 43 and 50 cm., Methods: In 20 adults with upper arm circumference between 43 and 50 cm (X-large group), 34 subjects with arm circumference between 37 and 42 cm and 78 subjects with arm circumference <37 cm cylindrical and tronco-conical cuffs were compared. In all participants, the pressure transmitted to the arm under the two cuffs was measured using a paper-thin pressure sensor., Results: In the X-large group, all participants had an arm slant angle <86.0°. In this group, the difference between the pressure detected on the arm surface with the sensor using the cylindrical versus the tronco-conical cuff (13.5 mmHg) was larger than in the group with an arm circumference of 37-to 42 cm and the group with a circumference <37 cm (3.7 and 0.6 mmHg, respectively, P  < 0.001 versus both). In the whole sample, the between-cuff pressure difference was proportional to the conical shape of the arm ( P  < 0.001)., Conclusions: These data suggest that in people with arm size between 43 and 50 cm the reference cuff for validation studies should have a conical shape with an 84-85° slant angle. To comply with current guidelines, an 18.5 × 37.0 cm bladder should be used which would allow proper cuffing in the large majority of subjects., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

(1) Aim. The aim of the study was to investigate the reproducibility of white-coat hypertension (WCH) and its predictive capacity for hypertension needing antihypertensive treatment (HT) in young to middle-age subjects. (2) Methods. We investigated 1096 subjects from the HARVEST. Office and 24 h blood pressures (BP) were measured at baseline and after 3 months. The reproducibility of WCH was evaluated with kappa statistics. The predictive capacity of WCH was tested in multivariate Cox models (N = 1050). (3) Results. Baseline WCH was confirmed at 3-month assessment in 33.3% of participants. Reproducibility was fair (0.27, 95%CI 0.20-0.37) for WCH, poor (0.14, 95%CI 0.09-0.19) for office hypertension, and moderate (0.47, 95%CI 0.41-0.53) for ambulatory hypertension. WCH assessed either at baseline or after 3 months (unstable WCH) was not a significant predictor of HT during 17.4 years of follow-up. However, participants who had WCH both at baseline and after 3 months (stable WCH) had an increased risk of HT compared to the normotensives (Hazard ratio, 1.50, 95%CI 1.06-2.1). (4) Conclusions. These results show that WCH has limited reproducibility. WCH diagnosed with two BP assessments but not with one showed an increased risk of future HT. Our data indicate that WCH should be identified with two sets of office and ambulatory BP measurements.

Background: Published evidence has shown that troncoconical cuffs improve blood pressure measurement accuracy in subjects with obesity. However, the exact shape of these cuffs according to arm size is unknown. The aim of the present study was to investigate the anthropometric characteristics of the arm in a large population in order to identify the appropriate shape of the cuff for each arm., Methods: The anthropometric characteristics were assessed in 729 adults with middle arm circumference ranging from 16 to 55 cm. Subjects were divided into classes of arm size and the upper-arm slant angle of the truncated cone was calculated., Results: In the whole sample, the conical shape of the arm progressively increased with increasing arm circumference (r = 0.61, P < 0.0001). Independent predictors of the conical shape were arm circumference (P < 0.0001) and length (negative relationship, P < 0.0001), and female sex (P = 0.048). Women had a slightly more pronounced conical shape of the arm (P = 0.007) than men. However, the decrease in the slant angle across the arm-size classes showed a similar trend in men and women, and in a 2-way analysis of variance there was no interactive effect between arm size and sex on the conical shape of the arm (P = 0.11). On the basis of the slant angle calculated in each arm-size class, we provide dimensions for bladders that would appropriately fit the arm within a given circumference range., Conclusions: To properly fit the upper arm in patients with obesity cuffs should have a troncoconical shape. This study provides reference data according to arm size., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Whether oscillometric devices provide accurate measurements of heart rate (HR) is not known. Our aim was to determine the accuracy of an oscillometric device for the measurement of HR during rest and exercise., Methods: The Microlife WatchBP O3, a monitor previously validated for blood pressure measurement, was tested in 36 individuals from the general population (mean age, 72.9 years; 18 men). HR was measured at rest and during stress testing on a cycle ergometer in order to increase HR by 15% or more. HR was computed from the oscillometric waves recorded during the deflation phase of the blood pressure measurement and was compared with HR measured by pulse palpation by two observers., Results: At rest, the mean device-observer HR difference was 0.9 ± 2.1 bpm. During exercise, the average HR increase was 20.3% and the mean device-observer difference was 0.6 ± 2.6 bpm. The device-observer HR differences were all included within ±6 bpm both at rest and during exercise. Kappa statistics showed a very good agreement between device and observers both at rest (kappa scores, 0.82-0.88) and during exercise (kappa scores, 0.81 and 0.86). The device-observer HR differences were unrelated to the level of HR or to pulse pressure., Conclusion: The present study shows that the oscillometric technique is able to provide reliable HR measurements during rest and mild exercise. Whether evaluation of HR performance should be included during validation testing of automatic monitors should be established by regulatory bodies., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The detection and quantification of immunoglobulin free light chains in serum and urine is recommended for the diagnosis and monitoring of monoclonal gammopathies according to the guidelines of the International Myeloma Working Group (IMWG). Several tests are currently available in the clinical laboratory to detect and quantify free light chains but although quality, efficiency, and effectiveness have been improved, the results are still variable and poorly harmonized and standardized. The present review article wants to analyze these aspects, with a keen eye on techniques, such as mass spectrometry, that could replace in the practical clinical laboratory the current methods including Bence-Jones protein assay and free light chain immunoassays., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to determine the accuracy of the oscillometric blood pressure measurement technology of the Novacor Diasys 3 (model number DIS-0001-00) blood pressure monitor, intended for ambulatory blood pressure measurement, when used with the recommended Standard (ACC-0213-00), Large (ACC-0214-00) and Paediatric (ACC-0215-00) cuffs., Methods: The Novacor Diasys 3 (model number DIS-0001-00) was evaluated according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard, including an additional cardiac-stress study, a requirement for ambulatory blood pressure measurement devices. It was also validated according to the requirements of the European Society of Hypertension International Protocol revision 2010. The protocol requirements for all thee studies were followed precisely., Results: The Novacor Diasys 3 (model number DIS-0001-00) fulfilled all of the requirements for a pass in each of the three studies. In the primary AAMI/ANSI/ISO 81060-2:2013 study, the Criterion 1 errors were +3.9 mmHg ± 2.9 mmHg for SBP and +3.4 ± 2.5 mmHg for DBP., Conclusion: The Novacor Diasys 3 (model number DIS-0001-00), when used with the recommended cuffs, can be recommended for ambulatory blood pressure measurement in the adult population., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Oxysterols are products of enzymatic and/or chemical cholesterol oxidation. While some of the former possess broad antiviral activities, the latter mostly originate from the deterioration of the nutritional value of foodstuff after exposure to heat, light, radiation and oxygen, raising questions about their potential health risks. We evaluated the presence of selected oxysterols in bovine colostrum and monitored the evolution of their cholesterol ratio throughout an entire industrial-scale milk production chain and after industrially employed storage procedures of milk powders. We report here for the first time the presence of high levels of the enzymatic oxysterol 27-hydroxycholesterol (27OHC) in concentrations of antiviral interest in bovine colostrum (87.04 ng mL -1 ) that decreased during the first postpartum days (56.35 ng mL -1 ). Of note, this oxysterol is also observed in milk and milk products and is not negatively affected by industrial processing or storage. We further highlight an exponential increase of the non-enzymatic oxysterols 7β-hydroxycholesterol (7βOHC) and 7-ketocholesterol (7KC) in both whole (WMPs) and skimmed milk powders (SMPs) during prolonged storage, confirming their role as reliable biomarkers of cholesterol oxidation over time: after 12 months, 7βOHC reached in both SMPs and WMPs amounts that have been found to be potentially toxic in vitro (265.46 ng g -1 and 569.83 ng g -1 , respectively). Interestingly, industrial processes appeared to affect the generation of 7βOHC and 7KC differently, depending on the presence of fat in the product: while their ratios increased significantly after skimming and processing of skimmed milk and milk products, this was not observed after processing whole milk and milk cream.

Objective: The objective of this study was to determine the accuracy of the auscultatory and oscillometric blood pressure (BP) measurement technologies of the Novacor Diasys 3 Plus (model number DIP-0001-00) BP monitor, intended for ambulatory BP measurement when used with the recommended Standard Plus (ACC-0210-00), Large Plus (ACC-0211-00) and Paediatric Plus (ACC-0212-00) cuffs., Methods: The auscultatory measurement technology Novacor Diasys 3 Plus (model number DIP-0001-00) was evaluated according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard, including an additional cardiac-stress study, a requirement for ambulatory BP measurement devices. It was also validated according to the requirements of the European Society of Hypertension International Protocol revision 2010. The oscillometric measurement technology was compared to that of the Novacor Diasys 3 (model number DIS-0001-00) according to the equivalence requirements of MEDDEV 2.7/1 rev 4. The protocol requirements for all three studies and the equivalence were followed precisely., Results: The Novacor Diasys 3 Plus (model number DIP-0001-00) fulfilled all of the requirements for a pass in each of the three studies of the auscultatory measurement technology. In the primary AAMI/ANSI/ISO 81060-2:2013 study, the criterion 1 errors were + 3.6 ± 2.7 mmHg for SBP and + 3.0 ± 2.7 mmHg for DBP. It was also proven to be equivalent to the Novacor Diasys 3 (model number DIS-0001-00) with respect to the oscillometric measurement technology CONCLUSION: The Novacor Diasys 3 Plus (model number DIP-0001-00), when used with the recommended cuffs, can be recommended for ambulatory BP measurement in the adult population.

Background: Whether blood pressure variability (BPV) measured with ambulatory monitoring (short-term BPV) or computed from office visits (long-term BPV) are related to each other and carry similar prognostic information is not well known. We investigated the independent determinants of short-term and long-term BPVs and their predictive capacity for the development of major adverse cardiovascular and renal events (MACEs) in a cohort of young hypertensive participants., Methods: Long-term BPV was calculated as visit-to-visit SD and average real variability from office blood pressure (BP) measured during 7 visits, within 1 year. Short-term BPV was calculated as weighted 24-hour SD and coefficient of variation. Hazard ratios (HRs) for risk of MACE were computed from multivariable Cox regressions., Results: 1,167 participants were examined; mean age was 33.1 ± 8.5 years. Variables independently associated with 24-hour systolic SD were 24-hour systolic BP, low physical activity, smoking, baseline office pulse pressure, systolic BP dipping, and diastolic white coat effect, while those associated with long-term BPV were mean systolic BP, age, female gender, and baseline office heart rate. During a median follow-up of 17.4 years 75 MACEs occurred. In Cox analysis only short-term BPV resulted a significant predictor of MACE (HR, 1.31 (1.07-1.59); P = 0.0086), while no index of long-term BPV was independently associated with outcome., Conclusions: In young hypertensive subjects only short-term BPV resulted a significant predictor of MACE on top of traditional ambulatory BP monitoring parameters. Whether reduction of short-term BPV with therapy may reduce the cardiovascular risk independently from the effects on 24-hour BP is a matter for future research., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of the study was to determine the accuracy of the Microlife WatchBP O3 monitor for ambulatory blood pressure (BP) measurement according to the new ISO81060-2 2018 protocol., Methods: The WatchBP O3 was first tested in 97 subjects from the general population (mean age, 71.3 years; 48 men) using four cuffs of different sizes. In a second study, 36 subjects (mean age, 72.9 years; 18 men) underwent stress testing on a cycle ergometer in order to increase their heart rate by 15% or more., Results: In the general population, the mean device-observer difference was 1.3 ± 3.2 mmHg for systolic BP and was 0.7 ± 3.2 mmHg for diastolic BP. These data were in agreement with criterion 1 of the protocol standard requirements (≤5 ± 8 mmHg). Also, criterion 2 was satisfied being the SDs of the 97 participants well below the maximum values required by the protocol (6.82 and 6.90 mmHg, respectively). During the ambulatory monitoring study, the average heart rate increase was 20.3% (range 15.4-28.9%). The mean device-observer difference was 1.5 ± 2.8 mmHg for systolic BP and was 1.7 ± 2.6 mmHg for diastolic BP. Also, these data were in agreement with criterion 1 of the protocol., Conclusions: These data show that the Microlife WatchBP O3 monitor satisfied the ISO 81060-2:2018 standard requirements for a general population across a wide range of arm sizes and that also the protocol criteria for validation of devices intended for ambulatory BP monitoring were fulfilled.

Purpose: Previous data suggest that tronco-conical cuffs should be used for accurate blood pressure (BP) measurement in the obese. However, not only arm size but also its shape may affect the accuracy of BP measurement when a cylindrical cuff is used. Methods: In 197 subjects with arm circumference >32 cm, and 157 subjects with arm circumference ≤ 32 cm, the upper-arm was considered as formed from two truncated cones and the frustum slant angles of the proximal (upper angle) and distal (middle angle) truncated cones were measured. Five cylindrical and five tronco-conical cuffs of appropriate size in relation to arm circumference were used. Results: In the group with large arm, the upper slant angle was greater than the middle angle (86.5 ± 1.7° versus 84.7 ± 2.3°), whereas in the group with normal arm the two angles were similar. In the former group, the cylindrical cuff overestimated BP by 2.5 ± 5.4/1.7 ± 4.7 mmHg, whereas in the latter negligible between-cuff BP discrepancies were found. In the whole sample, BP discrepancies between the cylindrical and the tronco-conical cuffs correlated with both arm size and shape, considered as the difference between the upper and middle slant angles (all p  < 0.0001). Among the participants with large arm, the between-cuff BP discrepancies increased progressively with increasing upper-middle angle difference (3.75 ± 0.38/2.78 ± 0.32 mmHg for the top tertile, p  < 0.001/<0.001). Conclusions: These data indicate that in people with large upper arms, the tronco-conical shape of the arm is more pronounced on the lower than the upper half, a feature that amplifies the BP measurement error when cylindrical cuffs are used.

Introduction: Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction., Methods: High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI., Results: Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI., Conclusions: Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Trichophyton rubrum and Trichophyton mentagrophytes spp. are two of the most frequently isolated dermatophytes causing dermatophytosis worldwide. Since the incidence of resistance to antifungal agents is increasing, antifungal susceptibility tests are needed to successfully treat dermatophytoses. Most of the methods currently available are complicated, time-consuming and lack of reference procedures. The aim of this work was to establish a simple protocol to test the susceptibility of dermatophytes isolated from clinical samples against five antifungal drugs using E-test and disk diffusion methods. We used the E-test on non-supplemented Mueller-Hinton agar plates to determine the minimum inhibitory concentrations (MICs) of fluconazole, itraconazole, voriconazole and amphotericin B, and disk diffusion method to determine the interpretive MIC of terbinafine. Fifty dermatophytes-10 T. rubrum and 40 T. mentagrophytes spp.-were assessed after only 96 h of colony growth. Terbinafine was the most active antifungal agent with an inhibition diameter greater than 70 mm (sensitivity > 20 mm), followed by voriconazole, itraconazole and amphotericin B with MICs ranging from 0.032 to 0.38 µg/mL, from 0.006 to 0.125 µg/mL and from 0.5 to 1.5 µg/mL, respectively. All isolates were resistant to fluconazole. Collectively, the less laborious E-test and disk diffusion method were shown to be suitable and reliable to determine antifungal sensitivity of dermatophytes. This simple standard protocol could be employed in the routine of clinical laboratories.

Objective: The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension., Methods: We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ± 8.5 years, untreated at baseline examination. Participants were divided into two categories with low (<12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models., Results: During 15.4 ± 7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P < 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included., Conclusion: Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

The objective of this study was to determine the accuracy of the Hingmed WBP-02A device for ambulatory blood pressure (BP) monitoring according to the International Protocol of the European Society of Hypertension (ESH-IP). Device evaluation was carried out in 33 patients. The mean age was 69.8±13.8 years, the mean systolic BP was 137.6±27.0 mmHg (range: 96-172), the mean diastolic BP was 86.7±20.1 mmHg (range: 48-124) and the mean arm circumference was 30.1±6.2 cm (range: 20-43). The protocol requirements were followed precisely. Four different cuffs, small, standard, large, and extra-large were used. The device comfortably passed all ESH-IP requirements, as 84 out of 99 device-observer systolic BP differences and 97 of 99 diastolic BP differences were within ±5 mmHg thereby fulfilling the standards of the protocol. Device-observer BP differences were unrelated to arm circumference. These data show that the Hingmed WBP-02A device for ambulatory BP monitoring met the requirements for validation by the ESH-IP and can be recommended for clinical use in the adult population.

Background: The use of phase contrast in urinalysis has been highly recommended. A new system, sediMAX conTRUST PRO, is now available providing simultaneous automated phase contrast and bright field microscopy. This study aimed to evaluate both analytical and diagnostic performance of this new analyzer., Methods: Results from 504 samples evaluated with the sediMAX conTRUST PRO were compared to those obtained from the same samples by manual microscopy (MM). Analytical and diagnostic performance were assessed according to established guidelines., Results: The concentration of red blood cells (RBCs)and white blood cells (WBCs) at which the LoQ satisfied a CV< 25% was 12 particles per μL (p/μL) and 8 p/μL, respectively. Within one grade of agreement concordance was quite high, 97.8% for RBCs and 98.0% for WBCs, and above 90% for all other particles. Overall, diagnostic sensitivity and specificity were good (>80%) for the particles considered, although lower sensitivities, 70.6% and 61.8%, were respectively found for hyaline and pathological casts., Conclusions: The sediMAX conTRUST PRO provides very good performance in terms of RBC and WBC recognition and enumeration, and quite good performance for all other particles. Hyaline cast and pathological cast identification is fine and comparable to other automated systems, but could use further improvement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Rectangular (cylindrical) cuffs and bladders are currently used for blood pressure (BP) measurement at the upper arm. However, large arms have a troncoconical shape, which make cylindrical cuffs potentially unsuitable. Aim of this study was to investigate the effect of the shape of the cuff on BP measurement in very obese participants., Methods: In 33 participants with upper arm mid-circumference at least 42 cm and 33 participants of control, cylindrical and troncoconical cuffs of appropriate size were compared. In addition, in the obese participants, the pressure transmitted to the arm under the cuffs was measured at five cuff pressure levels using a paper-thin pressure sensor., Results: In all obese participants, the upper arm shape was troncoconical (mean ± SD slant angle, 84.1 ± 1.4°). In this group, SBP and DBP differences between the troncoconical and the cylindrical cuff were -5.3 ± 4.0 and -3.0 ± 4.3 mmHg, respectively (P < 0.001/=0.01 versus controls). In the obese participants of the top BP quintile, the between-cuff SBP difference was -9.1 ± 5.1 mmHg. Arm slant angle was an independent predictor of the between-cuff SBP discrepancy (P = 0.003). When the cylindrical cuff was used, measurement with the pressure sensor showed a marked disagreement between the pressure in the cuff and the pressure transmitted to the arm (mean difference, -10.2 ± 5.2 mmHg) a difference, which increased with increasing level of the pressure pumped in the cuff., Conclusion: In very obese people, cylindrical cuffs overestimate BP chiefly in people with high SBP and thus only troncoconical cuffs should be used.

Objective: The clinical significance of isolated systolic hypertension (ISH) in youth is controversial. One main confounding factor is the strong white-coat effect often observed in ISH patients. The aim of this study was to investigate the risk of hypertension needing pharmacological treatment in ISH identified with ambulatory 24-h blood pressure (24-h BP)., Methods: We examined 1206, 18-45-year-old participants from the Hypertension and Ambulatory Recording VEnetia STudy. Based on 24-h BP, 269 participants were normotensive, 209 had ISH, 277 had isolated diastolic hypertension, and 451 had systolic-diastolic hypertension. The predictive role of ISH for incident hypertension was evaluated in Cox survival analyses, adjusting for risk factors and confounders., Results: ISH participants were more frequently young men active in sports, with lower heart rate and cholesterol. During a 6.9-year follow-up, 61.1% of participants developed hypertension. ISH participants had a nonsignificant increase in risk of hypertension compared with normotensive (reference group). In contrast, participants with diastolic hypertension (1.44; 1.13-1.85) or systolic-diastolic hypertension (2.04; 1.59-2.64) had a significant increase in risk. When the ISH participants were divided according to whether 24-h mean BP was normal (<97 mmHg) or high, ISH patients with normal mean BP had no increase in risk (1.01; 0.73-1.40), whereas those with high mean BP had a significant increase in risk (1.70; 1.16-2.49)., Conclusion: These data obtained with ambulatory BP monitoring show that in ISH people younger than 45 years, only mean BP is a predictor of future hypertension needing treatment, whereas the ISH status per se does not necessarily imply an increase in risk.

Background: There are a limited number of studies investigating the type of serum proteins capable of differentiating intraductal papillary mucinous neoplasms from benign or malignant diseases of the pancreas., Aims: To select proteins able to differentiate intraductal papillary mucinous neoplasms from benign and malignant pancreatic disease using semiquantitative proteomics., Methods: Serum samples were obtained from 74 patients (19 with type II intraductal papillary mucinous neoplasms, 8 with type I/III intraductal papillary mucinous neoplasms, 24 with chronic pancreatitis, 23 with pancreatic ductal adenocarcinomas) and 21 healthy subjects. Small proteins and peptides were assayed by matrix-assisted laser desorption/ionization for the detection of differentially abundant species possibly related to tumor onset. Serum pancreatic amylase, lipase, carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) were also assayed., Results: Twenty-six of 84 peaks detected were dysregulated (7 more abundant and 19 less abundant in the type II intraductal papillary mucinous neoplasms, p < 0.05). Of the differentially abundant peaks, 17 were commonly dysregulated (3 peaks more abundant and 13 less abundant in type II intraductal papillary mucinous neoplasms, and one at  m/z = 9961 at variance), indicating a protein fingerprint shared by types I/III and type II intraductal papillary mucinous neoplasms and pancreatic ductal adenocarcinomas., Conclusions: These results suggest that our approach can be used to differentiate type II intraductal papillary mucinous neoplasms from type I/III neoplasms, and type II intraductal papillary mucinous neoplasms from pancreatic ductal adenocarcinomas.

The aim of this study was to determine the accuracy of the WatchBP Office ABI monitor for office blood pressure measurement over a wide range of arm circumferences using the ANSI/AAMI/ISO 81060-2:2013 protocol. The device accuracy was tested in 88 participants whose mean±SD age was 54.5±17.6 years, whose arm circumference was 30.6±8.3 cm (range: 15-46 cm), and whose entry blood pressure (BP) was 138.3±23.4 mmHg for systolic and 83.7±14.6 mmHg for diastolic BP. Four cuffs (small, standard, large, and extra-large) suitable for arm circumferences ranging from 14.0 to 52.0 cm were used. The mean device-observer difference in the 264 separate BP data pairs was 0.7±3.8 mmHg for systolic BP and was 0.0±3.7 mmHg for diastolic BP. These data were in agreement with criterion 1 of the ANSI/AAMI/ISO 81060-2:2013 standard requirements (≤5±8 mmHg). Moreover, criterion 2 was satisfied, the mean±SD device-observer difference of the 88 participants being 0.7±3.1 and 0.0±3.2 mmHg, respectively, for systolic and diastolic BP. Good agreement between observer and device was present across the whole range of arm circumferences. These data show that the Microlife WatchBP Office ABI monitor satisfied the ANSI/AAMI/ISO 81060-2:2013 standard requirements across a wide range of arm sizes.

Purpose: Several studies have shown that the augmentation index (AIx) is negatively correlated with heart rate (HR). This led some authors to claim that the use of HR-lowering drugs may be detrimental in hypertension. The aim of this study was to assess the longitudinal and cross-sectional relationships of HR with AIx and central blood pressure (BP) in 346 subjects from the HARVEST (mean age 30.7 ± 8.5 years)., Methods: At baseline, HR was measured with 24-h ambulatory recording. Central hemodynamics were evaluated with Specaway DAT system after a median of 8.0 years from baseline. In multivariate linear regression analyses, AIx and central systolic BP were used as dependent variables and night-time HR or office HR as predictors adjusting for several risk factors and confounders., Results: In fully adjusted models, baseline night-time HR was a significant positive predictor of AIx (p < 0.001) and central BP (p = 0.014) measured 8 years later. Adjusted office HR measured at the time of arterial distensibility assessment was inversely correlated with AIx (p = 0.001) a relationship which was attenuated after physical activity (p = 0.004) and left ventricular ejection time (p = 0.015) were taken into account. In addition, office HR was inversely correlated with central BP (p = 0.039) a relationship which was no longer significant after physical activity and ejection time were accounted for., Conclusions: These data show that HR measured during sleep is longitudinally associated with AIx and central BP. Thus, low HR in the long term may have beneficial effects on central hemodynamics and the wall properties of the large arteries in hypertension.

Collagen VI is an extracellular matrix (ECM) protein playing a key role in skeletal muscles and whose deficiency leads to connective tissue diseases in humans and in animal models. However, most studies have been focused on skeletal muscle features. We performed an extensive proteomic profiling in two skeletal muscles (diaphragm and gastrocnemius) of wild-type and collagen VI null ( Col6a1 -/- ) mice at different ages, from 6- (adult) to 12- (aged) month-old to 24 (old) month-old. While in wild-type animals the number of proteins and the level of modification occurring during aging were comparable in the two analyzed muscles, Col6a1 -/- mice displayed a number of muscle-type specific variations. In particular, gastrocnemius displayed a limited number of dysregulated proteins in adult mice, while in aged muscles the modifications were more pronounced in terms of number and level. In diaphragm, the differences displayed by 6-month-old Col6a1 -/- mice were more pronounced compared to wild-type mice and persisted at 12 months of age. In adult Col6a1 -/- mice, the major variations were found in the enzymes belonging to the glycolytic pathway and the tricarboxylic acid (TCA) cycle, as well as in autophagy-related proteins. When compared to wild-type animals Col6a1 -/- mice displayed a general metabolic rewiring which was particularly prominent the diaphragm at 6 months of age. Comparison of the proteomic features and the molecular analysis of metabolic and autophagic pathways in adult and aged Col6a1 -/- diaphragm indicated that the effects of aging, culminating in lipotoxicity and autophagic impairment, were already present at 6 months of age. Conversely, the effects of aging in Col6a1 -/- gastrocnemius were similar but delayed becoming apparent at 12 months of age. A similar metabolic rewiring and autophagic impairment was found in the diaphragm of 24-month-old wild-type mice, confirming that fatty acid synthase (FASN) increment and decreased microtubule-associated proteins 1A/1B light chain 3B (LC3B) lipidation are hallmarks of the aging process. Altogether these data indicate that the diaphragm of Col6a1 -/- animal model can be considered as a model of early skeletal muscle aging.

Obesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D deficiency and pathological levels of triglycerides, high-density lipoprotein cholesterol and high total cholesterol levels. The serum protein profiles of 64 vitamin D deficient (serum 25(OH)D < 50nmol/L) individuals with metabolic syndrome and with (n = 31; BMI ≥ 30) or without (n = 33; BMI < 30) obesity were analyzed by a quantitative label-free mass spectrometry approach (MALDI-profiling), combined with different serum immunodepletion strategies (Human7 and Human14 immuno-chromatographies), to analyze the intermediate- and low-abundant protein components. The analysis of intermediate-abundant proteins (Human7) in obese vs. non-obese subjects identified 14 changed peaks (p < 0.05) in the m/z range 1500-35000. Furthermore, the Human14 depletion provided new profiles related to obesity (121 changed peaks). Among changed peaks, 11 were identified in the m/z range 1500-4000 Da by high-resolution tandem mass spectrometry, belonging to apolipoprotein CIII, apolipoprotein B100, alpha-1-antichymotrypsin and complement C3. Data herein show that distinct protein profiles identify specific peptides belonging to lipid metabolism and inflammation processes that are associated with obesity and vitamin D deficiency.

The aim of this study was to define the accuracy of UM-211, an automated oscillometric device for office use coupled to several cuffs for different arm sizes, according to the International Protocol of the European Society of Hypertension. The validation was performed in 33 individuals. Their mean age was 59.6±12.9 years, systolic blood pressure (BP) was 144.3±21.5 mmHg (range: 96-184 mmHg), diastolic BP was 86.8±18.5 mmHg (range: 48-124 mmHg), and arm circumference was 30.2±4.3 cm (range: 23-39 cm). Four sequential readings were taken by observers 1 and 2 using a double-headed stethoscope and a mercury sphygmomanometer, whereas three BP readings were taken by the supervisor using the test instrument. The differences between the readings provided by the device and the mean observer measurements were calculated. Therefore, each device measurement was compared with the previous and the next mean observer measurement. The validation results fulfilled all the 2010 European Society of Hypertension revision Protocol criteria for the general population and passed all validation grades. On average, the device overestimated systolic BP by 1.7±2.4 mmHg and diastolic BP by 1.7±2.5 mmHg. These data show that the UM-211 device coupled to several cuffs for different ranges of arm circumference met the requirements for validation according to the International Protocol and can be recommended for clinical use in the adult population. However, these results mainly apply to the use of the 22-32 and the 31-45 cm cuffs.

In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile α subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O 2 delivery by tuning its metabolism. The present study provides a comprehensive overview of skeletal muscle metabolic adaptation to hypoxia in mice and in human subjects exposed for 7/9 and 19 days to high altitude levels. The investigation was carried out combining proteomics, qRT-PCR mRNA transcripts analysis, and enzyme activities assessment in rodents, and protein detection by antigen antibody reactions in humans and rodents. Results indicate that the skeletal muscle react to a decreased O 2 delivery by rewiring the TCA cycle. The first TCA rewiring occurs in mice in 2-day hypoxia and is mediated by cytosolic malate whereas in 10-day hypoxia the rewiring is mediated by Idh1 and Fasn, supported by glutamine and HIF-2α increments. The combination of these specific anaplerotic steps can support energy demand despite HIFs degradation. These results were confirmed in human subjects, demonstrating that the TCA double rewiring represents an essential factor for the maintenance of muscle homeostasis during adaptation to hypoxia.

Purpose: An interactive effect of tobacco and alcohol use has been described for cancer. The aim of this study was to investigate the joint effect of smoking and alcohol intake on major adverse cardiovascular and renal events (MACE) in young subjects screened for stage 1 hypertension., Methods: A total of 1204 untreated patients aged from 18 to 45 years (mean 33.1) were included in this prospective cohort study. Subjects were classified into 4 categories of cigarette smoking and 3 classes of alcohol use. Main outcome variable was risk for MACE., Results: During a 12.6-year follow-up, there were 74 fatal and nonfatal MACE. In multivariable Cox models, current smoking and alcohol drinking were associated with risk of MACE. In a multivariable model also including follow-up changes in blood pressure and body weight, hazard ratio (HR) was 1.48 (95% confidence interval [CI], 1.20-1.83) for smoking and was 1.82 (95% CI, 1.05-3.15) for alcohol use. In addition, an interactive effect was found between smoking and alcohol on risk of MACE (P <.001). Among the 142 smokers who also drank alcoholic beverages, the risk of MACE (HR 4.02; 95% CI, 1.98-8.15) was more than doubled compared with the 112 smokers who abstained from drinking (HR 1.64; 95% CI, 0.63-4.27). In the group of heavy smokers who also were alcohol drinkers (n = 51), the risk of MACE was even quadrupled (HR 7.79; 95% CI, 4.22-14.37)., Conclusion: Alcohol use potentiates the deleterious cardiovascular effects of heavy smoking in stage 1 hypertensive subjects younger than 45 years. These results call for prompt intervention addressed to improve unhealthy behaviors in these subjects., (Copyright © 2017 Elsevier Inc. All rights reserved.)