Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence.

BACKGROUND: Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited. METHODS: In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed. RESULTS: In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo. CONCLUSIONS: Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).

A new score for improving cardiovascular risk prediction and prevention.

BACKGROUND AND AIMS: The ultrasonographic detection of subclinical atherosclerosis (scATS) at carotid and femoral vascular sites using the atherosclerosis burden score (ABS) improves the risk stratification for atherosclerotic cardiovascular disease beyond traditional cardiovascular (CV) risk factors. However, its predictive value should be further enhanced. We hypothesize that combining the ABS and the Framingham risk score (FHRS) to create a new score called the FHRABS will improve CV risk prediction and prevention. We aim to investigate if incorporating the ABS into the FHRS improved CV risk prediction in a primary prevention setting. METHODS AND RESULTS: 1024 patients were included in this prospective observational cohort study. Carotid and femoral plaques were ultra-sonographic detected. Major incident cardiovascular events (MACEs) were collected. The receiver operating characteristic curve (ROC-AUC) and Youden's index (Ysi) were used to compare the incremental contributions of each marker to predict MACEs. After a median follow-up of 6.0 ± 3.3 years, 60 primary MACEs (5.8%) occurred. The ROC-AUC for MACEs prediction was significantly higher for the FHRABS (0.74, p < 0.024) and for the ABS (0.71, p < 0.013) compared to the FHRS alone (0.71, p < 0.46). Ysi or the FHRABS (42%, p < 0.001) and ABS (37%, p < 0.001) than for the FHRS (31%). Cox proportional-hazard models showed that the CV predictive performance of FHRS was significantly enhanced by the ABS (10.8 vs. 5.5, p < 0.001) and FHRABS (HR 23.30 vs. 5.50, p < 0.001). CONCLUSIONS: FHRABS is a useful score for improving CV risk stratification and detecting patients at high risk of future MACEs. FHRABS offers a simple-to-use, and radiation-free score with which to detect scATS in order to promote personalized CV prevention.

Habitual coffee and caffeinated beverages consumption is inversely associated with arterial stiffness and central and peripheral blood pressure.

The effects of chronic coffee consumption on the cardiovascular system are still under debate. Aortic stiffness, wave reflections, and central and peripheral blood pressure (BP) are milestone indicators of cardiovascular-risk. We sought to investigate the association between coffee and caffeine consumption, arterial stiffness, and central/peripheral BP. Aortic stiffness was evaluated via pulse wave velocity (PWV); wave reflections with the augmentation index (AIx);peripheral systolic BP (SBP), diastolic BP (DBP), and central BP (cSBP/cDBP) were non-invasively assessed. Coffee and caffeine consumption was ascertained using a questionnaire. A linear inverse relationship between coffee and caffeine consumption and arterial stiffness and central and peripheral BP was found.Light coffee and caffeine consumers showed ß-coefficients for PWV-0.15, SBP-3.61, DBP-2.48, cSBP-3.21, and cDBP-2.18 (all p values < 0.05).Present findings suggest that coffee and caffeine consumption is inversely associated with arterial stiffness and central and peripheral BP in a large population sample. Interventional prospective studies are needed to demonstrate the causal association.

[Subclinical atherosclerosis in hypercholesterolemia - Towards a personalized, shared decision-making cardiovascular prevention]. / Dépistage de l'athérosclérose dans l'hypercholestérolémie - Vers une prévention cardiovasculaire personnalisée et partagée.

Identification of subjects at increased cardiovascular risk (CV) using traditional risk calculators is established. Nevertheless, up to 50% of CV events occur in people classified as intermediate risk. Non-invasive atherosclerosis (ATS) assessment with carotid/femoral US and coronary artery calcium score, offers the opportunity of a personalized prevention. ATS detection could be useful in improving CV risk stratification, in optimizing individual therapeutic management and in promoting a shared decision-making process. Is this the era of a paradigm shift in CV-risk prediction? The fascinating question is still open, but the increasing number of evidences shed new insights for our everyday clinical practice. Here we strive to provide an updated scenario on the use of ATS imaging in the CV risk evaluation and therapeutic decision.

L'identification des sujets avec un risque cardiovasculaire (CV) élevé en utilisant les calculateurs de risque traditionnels est établie, cependant près de 50 % des événements CV surviennent chez des personnes à risque intermédiaire. Le dépistage de l'athérosclérose (ATS) par ultrason des artères carotides et fémorales et par le score calcique coronarien offre la possibilité d'une prévention personnalisée. La détection de l'ATS subclinique permettrait d'améliorer la stratification du risque CV, optimiser la prise en charge individuelle et la décision partagée. Est-ce l'ère d'un changement de la prédiction du risque CV ? La question est encore ouverte mais il y a des nouveautés concernant notre pratique clinique. Nous proposons un panorama actualisé du dépistage de l'ATS, son impact sur la stratification du risque CV et la décision thérapeutique.

[Screening for peripheral arterial disease : role of the primary care physician]. / Dépistage de l'artériopathie oblitérante des membres inférieurs : rôle du médecin de premier recours.

Peripheral arterial disease (PAD) is a widespread disease with high impact on global health. While general population screening is not currently indicated, the primary care physician has the critical role of identifying asymptomatic patients who are particularly at risk for PAD and could therefore benefit from screening. In addition, he or she must recognize the typical and atypical clinical presentations of patients with symptomatic PAD to ensure proper diagnosis and care. After an adequate medical history and clinical examination, the first diagnostic test is the « Ankle-Brachial Index ¼ (ABI) calculation. In case of pathologic ABI (≤ 0.9, or > 1.4), or in case of normal or borderline ABI with symptoms, the patient should be referred to a vascular medicine physician for diagnostic confirmation and management.

L'artériopathie oblitérante des membres inférieurs est une maladie très répandue ayant un impact remarquable sur la santé mondiale. Bien que le dépistage dans la population générale ne soit pas indiqué, le médecin de premier recours a le rôle essentiel d'identifier les patients asymptomatiques qui pourraient bénéficier du dépistage. En outre, il·elle doit reconnaître les présentations cliniques typiques et atypiques chez les patients symptomatiques, afin d'assurer le diagnostic. Après l'anamnèse et l'examen clinique, le premier test de dépistage est le calcul de l'index cheville-bras. En cas de valeurs pathologiques (≤ 0,9 ou > 1,4), normales ou « borderline ¼ en présence de symptômes, le patient doit être adressé à un angiologue pour confirmation du diagnostic et prise en charge.

[Vascular passport : a tool for secondary prevention among patients with peripheral artery disease]. / Passeport vasculaire : un outil pour la prévention secondaire des patients avec maladie artérielle périphérique.

Peripheral arterial disease (PAD) is a major health problem in Switzerland, as myocardial infarction or stroke, all three sharing common cardiovascular (CV) risk factors and similar pathophysiological mechanisms (atherosclerosis). Unfortunately, PAD is still often overlooked, despite being fraught with significant morbidity/mortality and increasing the patient's overall CV risk. It is therefore essential to improve secondary prevention in order to decrease this burden and the overall CV risk of the patient. We will review the treatment targets for CV risk factors as secondary prevention in patients with PAD and see how the use of a vascular passport may improve management.

La maladie artérielle périphérique (MAP) est une problématique de santé majeure en Suisse, au même titre que l'infarctus du myocarde ou l'AVC, tous les trois partageant des facteurs de risque cardiovasculaire (FRCV) communs et des mécanismes physiopathologiques similaires (athérosclérose). Malheureusement, l'importance de la MAP est encore souvent sous-estimée, alors qu'elle est grevée d'une morbidité et d'une mortalité importantes et augmente le risque cardiovasculaire (CV) global du patient. Il est capital d'améliorer la prévention secondaire afin de diminuer ce fardeau et le risque CV global du patient. Nous allons passer en revue les cibles de traitement des FRCV en prévention secondaire chez les patients avec MAP et voir comment l'utilisation d'un passeport vasculaire permet d'améliorer la prise en charge.

Peer-pressure and overuse: The effect of a multimodal approach on variation in benzodiazepine prescriptions in a network of public hospitals.

BACKGROUND: The epidemic phenomenon leading to a progressive increase in benzodiazepine prescriptions represents a challenge for healthcare systems. In the hospital setting, indicators of prescription variation and potential of overuse are lacking and are rarely monitored. Inter-hospital monitoring/benchmarking, via peer-pressure, can foster the motivation to change. The aim of this investigation was to analyse whether, the reduction in new benzodiazepine prescriptions obtained thanks to a Choosing Wisely campaign, also contributed to reducing inter-hospital variation. METHODS: Secondary analysis of a multicentre longitudinal intervention in a network of five teaching hospitals in Switzerland. We set out to explore the effect, on inter-hospital benzodiazepine prescription variation, of a continuous monitoring/benchmarking strategy, which was proven effective in reducing the intra-hospital prescription rate. The variance was used to assess inter-hospital variation. To investigate the impact of the intervention a segmented regression analysis of interrupted time series was performed. RESULTS: A total of 36 299 admissions over 42 months were analysed (1 July 2014 to 31 December 2017). Before the intervention a significant constant upward trend in inter-hospital variability was found (+0.901; SE 0.441; P < .05). After the intervention, the variance trend line significantly changed, decreasing by -0.257 (SE 0.005: P < .001) and producing by December 2017, a 27% absolute reduction. CONCLUSIONS: Thanks to a multimodal approach based on monitoring-benchmarking, a significant reduction in inter-hospital benzodiazepine prescription variation was obtained. Aligning to peer strategy is a spontaneous consequence of open benchmarking that can be used to convert a variation-based suspicion of overuse, into an occasion to actively review prescription habits.

Ionized and total serum magnesium in hemodialysis: predictors and variability. A longitudinal cross-sectional study.

BACKGROUND: Ionized Magnesium (ion-Mg) represents the active biological fraction of the serum magnesium content. The assessment of total serum Mg (tot-Mg) might not accurately identify patients with hypo-or hyper-magnesaemie. In hemodialysis, serum tot-Mg levels in the upper part of the distribution, have been associated with reduced mortality and fewer vascular calcifications; thus, resulting in the tendency to increase the Mg concentration in the dialysate, traditionally set at 0.5 mmol/L. METHODS: Single-center study in chronic hemodialysis patients, designed in two phases, cross-sectional and longitudinal, aimed to investigate: (1) the sensitivity for pathological values of ion-Mg compared to tot-Mg (2) the predictors of ion-Mg developing ad hoc equations; (3) the inter- and intra-individual variabilities of ion-Mg; and (4) the risk factors for hypermagnesemia. Tot-Mg, ion-Mg, and covariates of 42 hemodialysis sessions, in 42 patients during the cross-sectional phase and of 270 sessions in 27 patients in the longitudinal one were analysed. RESULTS: Ion-Mg significantly correlates with tot-Mg: ß = 0.52; r = 0.88, p < 0.001. Multiple linear regressions in normo- and hypo-albuminemic patients gave the following results: ion-Mg = tot-Mg/2-K+/50 + Ca2+/5-HCO3-/100 and ion-Mg = tot-Mg/2 + albumin/100. Ion-Mg showed a high temporal variability in the longitudinal phase (between months p < 0.001; winter vs. summer, p < 0.027). A high intra-individual variability was also found: coefficient of variation 0.116. Comparing patients with high and low intra-individual variability, we found: age 67 vs. 77 years; p < 0.001; urea 26.3 ± 0.5 vs. 21.2 ± 0.4 mmol/L, p < 0.001; nPCR 0.92 ± 0.1 vs. 0.77 ± 0.1 g/kg day, p < 0.001; PTH 46.3 ± 4 vs. 28.5 ± 3 pmol/L, p < 0.001. CONCLUSIONS: Ion-Mg can be useful in unmasking unrecognized hyper- and hypo-magnesemic and false hyper-magnesemic patients. Ion-Mg is characterized by high intra- and inter-individual variabilities particularly in younger women and those with better nutrition. Patients with greater variability could potentially be at risk if exposed to higher concentrations of magnesium in the dialysate. An interventional study, with controlled increase of magnesium concentrations in the dialysate has been planned.

Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. METHODS: The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. DISCUSSION: The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.

A multi-level strategy for a long lasting reduction in unnecessary laboratory testing: A multicenter before and after study in a teaching hospital network.

BACKGROUND: Reducing unnecessary laboratory blood testing in the hospital setting represents a challenge to improve the adequacy of healthcare and a tricky task for teaching hospitals. Our hospital network actively participates in the Choosing Wisely Campaign and is engaged in avoiding unnecessary low value interventions and investigations. We aimed to study whether a multi-level approach combining educational and web-system based interventions, could be effective in reducing laboratory testing and related costs. METHODS: Multicenter, proof of concept, prospective, observational, before and after study, in a network of public hospitals in Switzerland. All patients admitted between 1 January 2015 and 31 December 2017 were analyzed. A multi-level strategy based on online continuous monitor benchmarking and educational support was applied in the internal medicine services. The primary outcome was a significant reduction in the number of laboratory tests per patient and per day during the hospital stay. Secondary outcomes were reduction in the blood sample volume taken per patient and per day in laboratory costs. RESULTS: Over the 36 months of the study, 33 309 admissions were analyzed. A significant reduction of laboratory tests per patient and per day of hospitalisation was found:-11%, P-value<0.001; -6%, P-value <0.001. The mean monthly blood volume, per patient and per day of hospital stay and laboratory costs per patient was also significantly reduced: -7%, P-value<0.05; -3%, P-value<0.01, and -17%, P-value<0.01, respectively. CONCLUSIONS: The obtained reduction in the number of laboratory tests, blood volume withdrawn and related costs, support the idea that an open web-based system, involving all health care providers, coupled with educational interventions, can be helpful in generating awareness of prescriber habits and to catalyze changes in their behaviour. The peer pressure related to the unmasked benchmarking process did probably play a determinant role.

[Benzodiazepines in elderly patients : the dark side of a magic pill]. / Benzodiazépines chez les patients âgés : le côté sombre d'une pilule magique.

Clinical studies show that prescription of benzodiazepines increases with age, and well outside of recognized indications. It often is inappropriate and abusive. Its consequences can be very serious and considerably increase patients' morbidity and mortality. Strategies exist to stop these medications through a multidisciplinary approach. Widespread campaigns are necessary to correct what has become a significant public health problem.

Les études cliniques montrent que la prescription de benzodiazépines augmente avec l'âge et se fait en dehors des indications reconnues. Elle est souvent inappropriée et abusive. Ses conséquences peuvent être très sérieuses et augmentent considérablement la morbidité et la mortalité des patients. Des stratégies de prise en charge multidisciplinaire existent qui permettent d'interrompre ces traitements. D'importantes campagnes de sensibilisation sont nécessaires pour corriger ce qui est devenu un réel problème de santé publique.

Circadian Urinary Excretion of Water, and Not Salt, Is Affected by the White Coat Effect.

Hypertension is an important morbidity factor. The prognostic consequences of the white-coat effect have been studied extensively. The repercussion on the circadian rhythm of urinary water and salt excretion in the same subgroup remain, conversely, among the open topics. Postulating an impaired diurnal sodium and volume excretion we decided to investigate both, in subjects with or without a white-coat effect, in the general population. A sample of 1023 subjects, has been considered. We collected 24-h urine samples, divided in day and night, and we measured the blood pressure with an Ambulatory Blood Pressure Monitoring (ABPM). ABPM values were then compared with physician collected in-office values to assign subjects to the group with or without the white-coat effect. Concerning the circadian pattern of urinary sodium excretion, we found no significant differences between the groups. There was instead in the white-coat effect group a higher night/day ratio of urinary water excretion. The white-coat effect, has been considered a potential hypertension precursor, and its consequent handling could be prospectively relevant in hypertension prevention. The absence of repercussions on the urinary circadian sodium excretion pattern and on the potentially related risk factors in subjects with a white coat effect is reassuring. The clinical significance of the impact on the night/day ratio of water excretion needs to be further investigated.

Association between Alcohol Intake and Arterial Stiffness in Healthy Adults: A Systematic Review.

BACKGROUND: Arterial stiffness as assessed by Pulse Wave Velocity (PWV) represents an independent predictor of cardiovascular disease. Several dietary compounds and lifestyle factors could influence arterial stiffness. The debate on the significance of the correlation between alcohol consumption and arterial stiffness is still open, given that the relationship is complex and potentially affected by several factors such as alcohol type, consumption levels, gender and age differences. OBJECTIVE: This systematic literature review aims to examine the evidence supporting an association between alcohol use and PWV, in electronic databases including PubMed/MEDLINE and the Cochrane Library, from January 2010 to November 2020. Screening and full-text reviews were performed by three investigators and data extraction by two. Considering the significant heterogeneity of data only a qualitative analysis (systematic review) was performed. RESULTS: A total of 13 studies met the inclusion criteria. Alcohol consumption was independently associated with arterial stiffness in a J-shaped way in most of the studies included. A benefit of alcohol consumption on arterial stiffness was found in four experimental studies, whilst an unfavorable increasing linear association was found in four others. Associations were confirmed with both oscillometric and tonometric PWV assessment methods. In some studies, a gender and age correlation was found with a more pronounced association in older males. In all studies elevated levels of alcohol consumption were associated with a worsening of arterial stiffness. CONCLUSIONS: Despite the variable findings across studies, the current review provides preliminary evidence that light-to-moderate alcohol consumption is associated with arterial stiffness values lower than expected, and evidence that high doses accelerate arterial ageing. These findings could be useful for clinicians who provide recommendations for patients at cardiovascular (CV) risk. Nevertheless, given the heterogeneity of study designs, interventions, measurement methods and statistical evaluations, the protective role of moderate alcohol consumption on arterial stiffness is likely but not certain, warranting additional trials and evidence.

Does Ionized Magnesium Offer a Different Perspective Exploring the Association between Magnesemia and Targeted Cardiovascular Risk Factors?

Evidence of the association of magnesium (Mg) with arterial stiffness has so far been conflicting. The interplay between hypertension and elevated body mass index (BMI), with hypomagnesemia, instead, has been described in the literature in a more consistent way. Our study aims at revisiting the correlations between blood Mg levels and hemodynamic and body composition parameters in the general population, exploring the sensitivity profile of ionized Mg (Ion-Mg) compared to total Mg (Tot-Mg). We collected data from 755 subjects randomly chosen from a Swiss population previously described and stratified our sample into four equivalent classes according to ionized (whole blood) and total (serum) magnesium. After correcting for age, statistically significant differences emerged between: (i) Tot-Mg ≤ 0.70 and 0.81 ≤ Tot-Mg ≤ 0.90 for cf-PWV (p = 0.039); (ii) Tot-Mg ≤ 0.70 and Tot-Mg ≥ 0.91 for o-PWV (p = 0.046). We also found a statistically significant difference among groups of Ion-Mg values for the 24 h extremes of systolic blood pressure (p = 0.048) and among groups of Tot-Mg for BMI (p = 0.050). Females showed significantly lower levels of total magnesium (p = 0.035) and ionized magnesium (p < 0.001) than males. The overall agreement between magnesium analysis methods was 64% (95%CI: 60.8−67.7%). Our results confirm that Ion-Mg compared with Tot-Mg offers a different profile in detecting both correlations with hemodynamic and body composition parameters and dysmagnesemias. Lower levels of magnesium were associated with worse arterial aging parameters, larger 24 h blood pressure excursions, and higher BMI. Ion-Mg was superior in detecting the correlation with blood pressure only. Considering Ion-Mg as a more specific marker of the magnesium status, and the partially contradictory results of our explorative cross-sectional study, to avoid confounding factors and misinterpretations, ionized magnesium should be used as reference in future studies.

Comparing oscillometric and tonometric methods to assess pulse wave velocity: a population-based study.

BACKGROUND: Oscillometric pulse wave velocity (o-PWV) represents an attractive, non invasive and non operator-dependent method to estimate arterial stiffness. Tonometric carotid-femoral measurements (cf-PWV),are considered the gold-standard for non-invasive aortic stiffness assessment. To date, no studies in the general population comparing the two methods have been performed. METHODS AND RESULTS: 1162 subjects were analysed. O-PWV and cf-PWV showed a mean difference of -0.31 m/sec(p ≤ 0.001). No significant differences between cf-PWV and o-PWVs were observed in patients without cardiovascular risk factors. The Bland and Altman analysis showed a moderate agreement between 24 h-o-PWV and cf-PWV (mean difference -0.99, LoA 4.23 to -6.22m/s). O-PWVs underestimate and overestimate arterial stiffness under and over 50 years respectively(p ≤ 0.001). Systolic blood pressure (SBP) and age differently impact cf-PWV and in office o-PWV variability (r2 0.35 and 0.88 respectively). In younger subjects a strong relationship between o-PWV and SBP reducing as age increases was found. Analysing the impact of age, an opposite trend was noticed. CONCLUSIONS: Oscillometric PWV estimates provide reliable values in the general population. An o-PWV tendency to underestimate arterial stiffness in younger subjects and in subjects with diseases known to increase arterial stiffness and to overestimate it with increasing age was found, even if scarcely relevant in clinical perspective. Overall the present findings underline an acceptable and satisfactory agreement between oscillometric and tonometric methods for the PWV assessment. KEY MESSAGES Oscillometric and tonometric PWV estimates showed a good and satisfactory agreement in the general population, above all in subjects without cardiovascular risk factors or a documented vascular damage. In comparison with tonometric values, oscillometric PWV estimates showed, however, the tendency to underestimate arterial stiffness in younger subjects and to overestimate it with increasing age, while diverging when diseases known to increase arterial stiffness are present. The magnitude of differences in PWV estimates between tonometric and oscillometric methods found in the general population appears most likely not to be significant in everyday clinical practice.

Phase angle is associated with length of hospital stay, readmissions, mortality, and falls in patients hospitalized in internal-medicine wards: A retrospective cohort study.

OBJECTIVES: The aim of this study was to investigate the predictive value of bioimpedance phase angle (PA) on selected clinical outcomes in patients hospitalized in internal-medicine wards. METHODS: This was a retrospective observational study of 168 patients admitted to the internalmedicine service (52.9% women, 47.1% men), with a mean (± SD) age of 73.9 ± 15.9 y. Anthropometric examination, laboratory tests, and bioelectrical impedance analysis were performed. Bioimpedance-derived PA was the study's parameter. Length of hospital stay, prospective all-cause hospital readmission, mortality, and falls were the clinical endpoints. RESULTS: Across the four PA quartile groups, age was incrementally higher (P ≤ 0.001). Multivariate linear regression models showed that PA quartile 1 was significantly associated with length of hospital stay (ß, SE) in both crude and adjusted models-respectively, ß (SE) = 6.199 (1.625), P ≤ 0.001, and ß = 2.193 (1.355), P = 0.033. Over a 9-mo follow-up period, the hazard ratios for readmission, in-hospital falls, and mortality were associated with the lowest phase angle (PA quartile 1 versus quartiles 2-4)-respectively, 2.07 (95% confidence interval [CI], 1.28-3.35), 2.36 (95% CI, 1.05-5.33), and 2.85 (95% CI, 1.01-7.39). Associations between narrow PA and outcomes continued to be significant after adjustments for various confounders. CONCLUSIONS: In internal-medicine wards, bioimpedance-derived PA emerged as a predictor of length of hospital stay, hospital readmission, falls, and mortality. The present findings suggest that in the hospital setting, PA assessment could be useful in identifying patients at higher risk who need specific nutritional support.

Arterial Stiffness and Central Hemodynamics are Associated with Low Diurnal Urinary Sodium Excretion.

BACKGROUND: Excessive salt intake is an important determinant of cardiovascular (CV) health, impacting arterial stiffness and central blood pressure. However, sodium exhibits several patterns of excretion in urine during day- and night-time, which could differently affect CV risk. Here, we sought to explore the relationship between the day:night urinary sodium excretion ratio and arterial stiffness and central hemodynamics in the general population. METHODS: Cross-sectional analysis in 1062 subjects. Arterial stiffness (pulse-wave velocity, PWV), central blood pressure (central systolic blood pressure, cSBP; central diastolic blood pressure, cDBP), and other hemodynamic parameters were noninvasively assessed. Day- and night-time urinary sodium were separately detected. Analyses were performed according to the day:night urinary sodium excretion ratio tertiles (T1-T3). RESULTS: Low day-time excretors (T1) showed significantly higher values of arterial stiffness when compared with high day-time excretors (T3) (cf-PWV 7.6 ± 1.9 vs 6.9 ± 1.5 m/sec; p ≤ 0.001), and higher central BP parameters (cSBP: 111.6 ± 12.1 vs 109.0 ± 11.1 mmHg, p ≤ 0.001; cDBP, 76.9 ± 9.2 vs 75.1 ± 9.3 mmHg, p ≤ 0.001). In multivariate linear-regression models (ß, CI), the day:night ratio of sodium excretion was significantly associated with arterial stiffness (cf-PWV -0.386, -0.559, -0.213, p ≤ 0.001) and with central hemodynamic parameters (cSBP -1.655, -2.800, -0.510; p ≤ 0.001; cDBP -1.319, -2.218, -0.420, p ≤ 0.001). Associations persisted after controlling for multiple confounding factors. In logistic-regression models, the risk of increased arterial stiffness was significantly reduced as the day:night ratio of urinary sodium excretion increased (OR 0.40, 95% CI 0.25-0.65, p ≤ 0.001). CONCLUSION: The individual, intra-daily pattern of urinary sodium excretion, characterised by low daytime excretion, is associated with increased arterial stiffness and central blood pressure. Further studies are advocated to clarify the clinical utility of assessing the daily pattern of sodium excretion.

Impaired Daytime Urinary Sodium Excretion Impacts Nighttime Blood Pressure and Nocturnal Dipping at Older Ages in the General Population.

The circadian rhythm of urinary sodium excretion is related to the diurnal blood pressure regulation (BP) and the nocturnal dipping pattern. The renal sodium excretion expressed as daytime/nighttime ratio impacts BP, but a limited number of studies have investigated this topic to date. In this cross-sectional study, we aimed to investigate the impact of different daily patterns of sodium excretion (comparing low with high ratios) on BP and nocturnal dipping and to explore the relationship with age. Twenty-four-hour ambulatory BP monitoring and daytime and nighttime urinary sodium collections were used to assess 1062 subjects in Switzerland. Analyses were performed according to the day/night urinary sodium excretion ratio quartiles (Q1-Q4) and by age group (≤50 and ≥50 years). Subjects in Q1 can be considered low excretors of sodium during the daytime since the rate of sodium excretion during the daytime was 40% lower than that of subjects in Q4. Quartiles of the day/night urinary sodium excretion ratio showed that subjects in Q1 were 7 years older and had respectively 6 and 5 mmHg higher nighttime systolic and diastolic BP and a higher nocturnal dipping compared with subjects in Q4 (p-value ≤0.001). Associations found were significant only for subjects older than 50 years (all p < 0.05). The present results suggest that a decreased capacity to excrete sodium during daytime is more prevalent as age increases and that it impacts nighttime blood pressure and nocturnal dipping in older subjects.

Consequences of Supraphysiological Dialysate Magnesium on Arterial Stiffness, Hemodynamic Profile, and Endothelial Function in Hemodialysis: A Randomized Crossover Study Followed by a Non-Controlled Follow-Up Phase.

INTRODUCTION: Increasing dialysate magnesium (D-Mg2+) appears to be an intriguing strategy to obtain cardiovascular benefits in subjects with end-stage kidney disease (ESKD) on hemodialysis. To date, however, hemodialysis guidelines do not suggest to increase D-Mg2+ routinely set at 0.50 mmol/L. METHODS: A randomized 4-week crossover study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a 6-month follow-up. Data were analyzed by linear mixed models for repeated measures. RESULTS: Data of 39 patients were analyzed. Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by - 0.91 m/s (95% confidence interval - 1.52 to - 0.29; p = 0.01) and - 9.61 mmHg (- 18.89 to - 0.33, p = 0.04), respectively. A significant reduction in systolic blood pressure of - 12.96 mmHg (- 24.71 to - 1.22, p = 0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up phase the higher D-Mg2+ significantly increased ionized and total serum Mg (respectively from 0.54 to 0.64 and from 0.84 to 1.07 mmol/L; mean percentage change from baseline to follow-up + 21% and + 27%; p ≤ 0.001), while parathormone (PTH) decreased significantly (from 36.6 to 34.4 pmol/L; % change - 11%, p = 0.03). CONCLUSIONS: Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of 0.75 mmol/L D-Mg2+ on major clinical outcomes. TRIAL REGISTRATION: The study was retrospectively registered on the ISRCTN registry (ISRCTN 74139255) on 18 June 2020.

Nutritional Risk Screening and Body Composition in COVID-19 Patients Hospitalized in an Internal Medicine Ward.

BACKGROUND: Malnutrition in patients hospitalized in internal medicine wards is highly prevalent and represents a prognostic factor of worse outcomes. Previous evidence suggested the prognostic role of the nutritional status in patients affected by the coronavirus disease 2019 (COVID-19). We aim to investigate the nutritional risk in patients with COVID-19 hospitalized in an internal medicine ward and their clinical outcomes using the Nutritional Risk Screening 2002 (NRS-2002) and parameters derived from bioelectrical impedance analysis (BIA). METHODS: Retrospective analysis of patients with COVID-19 aimed at exploring: 1) the prevalence of nutritional risk with NRS-2002 and BIA; 2) the relationship between NRS-2002, BIA parameters and selected outcomes: length of hospital stay (LOS); death and need of intensive care unit (ICU); prolonged LOS; and loss of appetite. RESULTS: Data of 90 patients were analyzed. Patients at nutritional risk were 92% with NRS-2002, with BIA-derived parameters: 88% by phase angle; 86% by body cell mass; 84% by fat-free mass and 84% by fat mass (p-value ≤0.001). In ROC analysis, NRS had the maximum sensitivity in predicting the risk of death and need of ICU and a prolonged hospitalization showing moderate-low specificity; phase angle showed a good predictive power in terms of AUC. NRS-2002 was significantly associated with LOS (ß 12.62, SE 5.79). In a multivariate analysis, blood glucose level and the early warning score are independent predictors of death and need of ICU (OR 2.79, p ≤0.001; 1.59, p-0.029, respectively). CONCLUSION: Present findings confirm the clinical utility of NRS-2002 to assess nutritional risk in patients with COVID-19 at hospital admission and in predicting LOS, and that bioimpedance does not seem to add further predictive value. An early detection of nutritional risk has to be systematically included in the management of COVID-19 patients hospitalized in internal medicine wards.