Reference values for plasma and urine trace elements in a Swiss population-based cohort.

OBJECTIVES: Trace elements (TEs) are ubiquitous. TE concentrations vary among individuals and countries, depending on factors such as living area, workplaces and diet. Deficit or excessive TEs concentrations have consequences on the proper functioning of human organism so their biomonitoring is important. The aim of this project was to provide reference values for TEs concentrations in the Swiss population. METHODS: The 1,078 participants to the SKiPOGH cohort included in this study were aged 18-90 years. Their 24-h urine and/or plasma samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine 24 TEs concentrations: Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, I, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Se, Sn, Tl, V and Zn. Statistical tests were performed to evaluate the influence of covariates (sex, age, BMI, smoking) on these results. Reference intervals for the Swiss adult population were also defined. RESULTS: TEs concentrations were obtained for respectively 994 and 903 persons in plasma and urine matrices. It was possible to define percentiles of interest (P50 and P95) for almost all the TEs. Differences in TEs distribution between men and women were noticed in both matrices; age was also a cofactor. CONCLUSIONS: This first Swiss biomonitoring of a large TEs-panel offers reference values in plasma and in urine for the Swiss population. The results obtained in this study were generally in line with clinical recommendations and comparable to levels reported in other population-based surveys.

Self-reported caffeine consumption miss-matched consumption measured by plasma levels of caffeine and its metabolites: results from two population-based studies.

IMPORTANCE AND OBJECTIVE: Self-reported caffeine consumption has been widely used in research while it may be subject to bias. We sought to investigate the associations between self-reported caffeine consumption and plasma levels of caffeine and its two main metabolites (paraxanthine and theophylline) in the community. METHODS: Data from two population-based studies (SKIPOGH1 and 2 (N = 1246) and CoLaus|PsyCoLaus (N = 4461)) conducted in Switzerland were used. Self-reported caffeine consumption was assessed using questionnaires. Plasma levels of caffeine and its metabolites were quantified by ultra-high performance liquid chromatography coupled to a tandem quadrupole mass spectrometer. RESULTS: In both studies, mean log plasma levels of caffeine and its two metabolites were over 6.48 (plasma levels = 652 ng/ml) when no caffeine consumption was reported. Subsequently, nonlinear associations between log plasma levels and self-reported caffeine consumption were observed in SKIPOGH, with a change of the slope at 3-5 cups of espresso per day in SKIPOGH1 but not SKIPOGH2. In CoLaus|PsyCoLaus, increased daily consumption of caffeinated beverages was associated with increased log plasma levels with a change of the slope at 3 cups. In both studies, declared caffeine consumption higher than 3-5 cups per day was not associated with higher plasma levels of caffeine and its metabolites. CONCLUSION: Self-reports of no or low caffeine consumption and consumption of more than 3-5 cups of coffee should be interpreted with caution, with possible under- or over-estimation. Quantifying plasma levels of caffeine and its metabolites may contribute to a better estimation of caffeine intake.

[Hypertension: what's new in 2023]. / Hypertension artérielle : ce qui a changé en 2023.

Highlights for 2023 include the confirmation of hypertension as a cardiovascular risk factor and the standard procedure for measuring blood pressure. Transdermal oestrogens do not appear to be associated with an increased risk of hypertension unlike oestrogen given orally. The usefulness of blood pressure measured in hospital in elderly patients and the risks of intensive treatment are reviewed. A new study suggests that we are not all equal when it comes to recommended treatments. Finally, RNA interference technology has enabled the synthesis of a new antihypertensive treatment administered every 6 months that inhibits the production of hepatic angiotensinogen with a good effect on blood pressure.

Le survol de l'année 2023 met l'accent sur l'hypertension artérielle (HTA) comme facteur de risque cardiovasculaire et sur les conditions de mesure de la pression artérielle. Du côté hormonal, les œstrogènes en application transdermique ne semblent pas être associés à un risque augmenté d'HTA, contrairement à ceux administrés par voie orale. L'utilité de la pression artérielle mesurée en milieu hospitalier chez des patients âgés et les risques de son traitement intensif sont également discutés. Une nouvelle étude suggère que nous ne sommes pas tous égaux face aux traitements recommandés. Enfin, la technologie des ARN interférents a permis la synthèse d'un nouveau traitement antihypertenseur administré aux 6 mois inhibant la production d'angiotensinogène hépatique avec un bon effet sur la pression artérielle.

Multitargeted Internal Calibration for the Quantification of Chronic Kidney Disease-Related Endogenous Metabolites Using Liquid Chromatography-Mass Spectrometry.

Accurate quantitative analysis in liquid chromatography-mass spectrometry (LC-MS) benefits from calibration curves generated in the same matrix as the study sample. In the case of endogenous compound quantification, as no blank matrix exists, the multitargeted internal calibration (MTIC) is an attractive and straightforward approach to avoid the need for extensive matrix similarity evaluation. Its principle is to take advantage of stable isotope labeled (SIL) standards as internal calibrants to simultaneously quantify authentic analytes using a within sample calibration. An MTIC workflow was developed for the simultaneous quantification of metabolites related to chronic kidney disease (CKD) using a volumetric microsampling device to collect 20 µL of serum or plasma, followed by a single-step extraction with acetonitrile/water and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Since a single concentration of internal calibrant is necessary to calculate the study sample concentration, the instrument response function was investigated to determine the best SIL concentration. After validation, the trueness of 16 endogenous analytes in authentic human serum ranged from 72.2 to 116.0%, the repeatability from 1.9 to 11.3%, and the intermediate precision ranged overall from 2.1 to 15.4%. The proposed approach was applied to plasma samples collected from healthy control participants and two patient groups diagnosed with CKD. Results confirmed substantial concentration differences between groups for several analytes, including indoxyl sulfate and cortisone, as well as metabolite enrichment in the kynurenine and indole pathways. Multitargeted methodologies represent a major step toward rapid and straightforward LC-MS/MS absolute quantification of endogenous biomarkers, which could change the paradigm of MS use in clinical laboratories.

The urine-to-plasma urea concentration ratio is associated with eGFR and eGFR decline over time in a population cohort.

BACKGROUND: Evaluation of renal function and of factors associated with its decline are important public health issues. Besides markers of glomerular function [e.g. glomerular filtration rate (GFR)], those of tubular functions are rarely evaluated. Urea, the most abundant urinary solute, is markedly concentrated in urine when compared with plasma. We explored the urine-to-plasma ratio of urea concentrations (U/P urea ratio) as a marker of tubular functions. METHODS: We evaluated the relationship of the U/P urea ratio with eGFR at baseline in 1043 participants (48 ± 17 years) from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) population-based cohort, using mixed regression. In 898 participants, we assessed the relation between U/P urea ratio and renal function decline between two study waves 3 years apart. We studied U/P ratios for osmolarity, Na, K and uric acid for comparison. RESULTS: In a transversal study at baseline, estimated GFR (eGFR) was positively associated with U/P-urea ratio [ßscaled = 0.08, 95% CI (0.04; 0.13)] but not with the U/P ratio of osmolarity. Considering separately participants with renal function >90 or ≤90 mL/min × 1.73 m2, this association was observed only in those with reduced renal function. In the longitudinal study, eGFR declined at a mean rate of 1.2 mL/min per year. A significant association was observed between baseline U/P urea ratio and eGFR decline [ßscaled = 0.08, 95% CI (0.01; 0.15)]. A lower baseline U/P urea ratio was associated with a greater eGFR decline. CONCLUSION: This study provides evidence that the U/P urea ratio is an early marker of kidney function decline in the general adult population. Urea is easy to measure with well-standardized techniques and at low cost. Thus, the U/P urea ratio could become an easily available tubular marker for evaluating renal function decline.

Variability of 24-Hour Sodium Urinary Excretion in Young Healthy Males Based on Consecutive Urine Collections: Impact on Categorization of Salt Intake.

OBJECTIVE: Several nonconsecutive 24-h urinary collections are considered the gold standard for estimating dietary salt intake. As those samples are logistically demanding, we aimed to describe the variability of 24-h sodium urinary excretion over consecutive days and report its adequacy with sodium intake. METHODS: We enrolled 16 healthy male volunteers in a prospective controlled study. All participants randomly received a low salt diet (LSD) (3 g/day of NaCl), a normal salt diet (NSD) (6 g/day of NaCl), and a high salt diet (HSD) (15 g/day of NaCl) for 7 days in a crossover design without wash-out period. RESULTS: On day 6, median sodium urinary excretion was 258 (216-338), 10 (8-18), and 87 (69-121) mmol/day for HSD, LSD, and NSD, respectively (P < .001). When considering days 4-6, sodium urinary excretion was in steady state as models with and without interaction term "diet type X sample day" were not significantly different (P = .163). On day 6, area under the curve (AUC) of receiver operating characteristic for urinary sodium excretion to detect HSD was 1.0 (1.0-1.0) and a cut-point of 175 mmol/day was 100% sensitive and specific to detect HSD. On day 6, receiver operating characteristic AUC to detect LSD was 0.993 (0.978-1.0) and a cut-point of 53 mmol/day was 96.4% sensitive and 100% specific to detect LSD. CONCLUSION: A steady state of sodium balance, where sodium intake is proportional to its excretion, is reached within a few days under a constant diet in the real-life setting. Categorization of salt consumption into low (3 g/day), normal (6 g/day), or high (15 g/day) based on a single 24-h urine collection is nearly perfect. Based on these results, repeated nonconsecutive urine collection might prove unnecessary to estimate sodium intake in daily clinical practice provided that diet is rather constant over time.

[HTA and PTSD: mechanisms and clinical implications]. / HTA et PTSD : mécanismes et implications pratiques.

The causes of arterial hypertension are numerous, but the environment can be a contributing factor. Stress is one of these environmental factors that is difficult to assess. We focus on Post-Traumatic Stress Disorder (PTSD), which is often under-diagnosed and under-recognised in diagnostic and therapeutic strategies. We specifically look at the psychosomatic implications of stress, which put patients with PTSD at a higher risk of developing HTA, and we suggest some therapeutic approaches. Early screening and diagnosis are essential to reduce this major cardiovascular risk factor.

Les causes d'hypertension artérielle (HTA) sont multiples mais l'environnement peut être un facteur favorisant. Le stress fait partie des facteurs environnementaux difficiles à évaluer. Nous nous intéressons plus particulièrement au syndrome de stress post-traumatique (PTSD), souvent sous-diagnostiqué et peu pris en compte dans les stratégies diagnostiques et thérapeutiques. Nous nous intéressons notamment aux implications psychosomatiques engendrées par le stress mettant les personnes atteintes de PTSD plus à risque de développer une HTA et proposons des orientations thérapeutiques. Les enjeux d'un dépistage et d'un diagnostic précoces sont essentiels pour réduire ce facteur de risque cardiovasculaire majeur.

[Hypertension: what's new in 2022]. / Hypertension artérielle : ce qui a changé en 2022.

Our article summarizing the most important studies of the past year emphasizes the difficulty of controlling blood pressure (BP) in hypertensive patients. In addition, it discusses factors such as temperature and sodium that may influence BP, proposes new targets in pregnant hypertensive patients, and challenges the usefulness of taking an antihypertensive drug nightly. Finally, a strategy targeting endothelin blockade in resistant hypertension is presented.

Notre article résumant les études marquantes de l'année écoulée met l'accent sur la difficulté à contrôler la pression artérielle (PA) chez les hypertendus. De plus, il aborde certains facteurs comme la température et le sodium pouvant influencer la PA, les cibles chez les patientes hypertendues enceintes et l'utilité d'une prise vespérale d'un antihypertenseur. Finalement, une stratégie visant le blocage de l'endothéline est présentée dans l'hypertension résistante.

[Solitary kidney: a risk factor for hypertension]. / Rein unique : un facteur de risque pour une hypertension artérielle ?

In patients with solitary kidney, either congenital or acquired, compensatory mechanisms come into play to maintain renal function, such as glomerular hyperfiltration and hypertrophy and renin-angiotensin-aldosterone system activation. In the long term, these mechanisms lead to arterial hypertension and then chronic kidney disease. The risk of arterial hypertension is greater in cases of congenital single kidney or of nephrectomy in childhood than in adulthood. Having a single kidney increases the risk of gestational hypertension and pre-eclampsia. Antihypertensive treatment is based on Angiotensin-converting enzyme inhibitors and sartans for their anti-proteinuric effect but otherwise does not differ from that of the general population.

Chez les patients avec un rein unique, qu'il soit d'origine congénitale ou acquise, des mécanismes compensatoires se mettent en place pour le maintien de la fonction rénale, comme une hyperfiltration et hypertrophie glomérulaires et une activation du système rénine-angiotensine-aldostérone. À terme, ces mécanismes mènent à une hypertension artérielle (HTA), puis à une insuffisance rénale chronique (IRC). Le risque d'HTA est plus important en cas de rein unique congénital ou de néphrectomie dans l'enfance qu'à l'âge adulte. Avoir un rein unique augmente les risques d'HTA gestationnelle et de prééclampsie. Le traitement antihypertenseur se base sur les inhibiteurs de l'enzyme de conversion (IEC) et les sartans pour leur effet antiprotéinurique, mais ne diffère pas sinon de celui de la population générale.

Changes of lipoprotein(a) levels with endogenous steroid hormones.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). METHODS: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. RESULTS: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value<2⋅10-16 ). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. CONCLUSIONS: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

Outcomes of incident patients treated with incremental haemodialysis as compared with standard haemodialysis and peritoneal dialysis.

BACKGROUND: Residual kidney function is considered better preserved with incremental haemodialysis (I-HD) or peritoneal dialysis (PD) as compared with conventional thrice-weekly HD (TW-HD) and is associated with improved survival. We aimed to describe outcomes of patients initiating dialysis with I-HD, TW-HD or PD. METHODS: We conducted a retrospective analysis of a prospectively assembled cohort in a single university centre including all adults initiating dialysis from January 2013 to December 2020. Primary and secondary endpoints were overall survival and hospitalization days at 1 year, respectively. RESULTS: We included 313 patients with 234 starting on HD (166 TW-HD and 68 I-HD) and 79 on PD. At the end of the study, 10 were still on I-HD while 45 transitioned to TW-HD after a mean duration of 9.8 ± 9.1 months. Patients who stayed on I-HD were less frequently diabetics (P = .007). Mean follow-up was 33.1 ± 30.8 months during which 124 (39.6%) patients died. Compared with patients on TW-HD, those on I-HD had improved survival (hazard ratio 0.49, 95% confidence interval 0.26-0.93, P = .029), while those on PD had similar survival. Initial kidney replacement therapy modality was not significantly associated with hospitalization days at 1 year. CONCLUSIONS: I-HD is suitable for selected patients starting dialysis and can be maintained for a significant amount of time before transition to TW-HD, with diabetes being a risk factor. Although hospitalization days at 1 year are similar, initiation with I-HD is associated with improved survival as compared with TW-HD or PD. Results of randomized controlled trials are awaited prior to large-scale implementation of I-HD programmes.

Dietary sodium intake does not alter renal potassium handling and blood pressure in healthy young males.

BACKGROUND: The effects of sodium (Na+) intakes on renal handling of potassium (K+) are insufficiently studied. METHODS: We assessed the effect of Na+ on renal K+ handling in 16 healthy males assigned to three 7-day periods on low salt diet [LSD, 3 g sodium chloride (NaCl)/day], normal salt diet (NSD, 6 g NaCl/day) and high salt diet (HSD, 15 g NaCl/day), with constant K+ intake. Contributions of distal NaCl co-transporter and epithelial Na+ channel in the collecting system on K+ and Na+ handling were assessed at steady state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively. RESULTS: Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 mL/min under LSD to 187.00 ± 49.10 under HSD (P = 0.005). The 24-h K+ excretion remained stable on all Na+ intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD; and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h) and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all three diets. CONCLUSIONS: Neither spontaneous nor diuretic-induced K+ excretion was influenced by Na+ intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal Na+ handling was dependent on dietary Na+ intake.

PhenoExplorer: An Interactive Web-based Platform for Exploring (Epi)Genome-Wide Associations Using a Swiss Population-based Study.

The recent advent of high-throughput sequencing technologies has allowed exploring the contribution of thousands of genomic, epigenomic, transcriptomic, or proteomic variants to complex phenotypic traits. Here, we sought to conduct large-scale (Epi)Genome-Wide Association Studies (GWAS/EWAS) to investigate the associations between genomic (Single Nucleotide Polymorphism; SNP) and epigenomic (Cytosine-Phospho-Guanine; CpG) markers, with multiple phenotypic traits in a population-based context. We used data from SKIPOGH, a family- and population-based cohort conducted in the cities of Lausanne, Geneva, and Bern (N=1100). We used 7,577,572 SNPs, 420,444 CpGs, and 825 phenotypes, including anthropometric, clinical, blood, urine, metabolite, and metal measures. GWAS analyses assessed the associations between SNPs and metabolites and metals (N=279), using regression models adjusted for age, sex, recruitment center, and familial structure, whereas EWAS analyses explored the relations between CpGs and 825 phenotypes, additionally adjusting for the seasonality of blood sampling and technical nuisance. Following the implementation of GWAS and EWAS analyses, we developed a web-based platform, PhenoExplorer, aimed at providing an open access to the obtained results. Of the 279 phenotypes included in GWAS, 103 displayed significant associations with 2804 SNPs (2091 unique SNPs) at Bonferroni threshold, whereas 109 of the 825 phenotypes included in EWAS analyses were associated with 4893 CpGs (2578 unique CpGs). All of the obtained GWAS and EWAS results were eventually made available using the in-house built web-based PhenoExplorer platform, with the purpose of providing an open-access to the tested associations. In conclusion, we provide a comprehensive outline of GWAS and EWAS associations performed in a Swiss population-based study. Further, we set up a web-based PhenoExplorer platform with the purpose of contributing to the overall understanding of the role of molecular variants in regulating complex phenotypes.

[Age-related decline in renal function Physiological aging or chronic kidney disease ?] / Déclin de la fonction rénale liée à l'âge - Sénescence physiologique ou insuffisance rénale chronique ?

Kidneys undergo structural as well as functional aging. Imaging and microscopic exams show alterations that manifest as a decline in glo merular filtration rate (GFR) over time. As a GFR < 60 ml/min/1,73m2 during more than three months is sufficient to diagnose chronic kidney disease (CKD), a large proportion of elderly fall into this category. However, morphological, clinical and epidemiological data show that the decline in GFR with age is not per se associated with adverse consequences. An age-adapted definition of CKD would allow managing patients on an individual prognostic basis rather than on an arbitrary biological construct.

Les reins subissent un processus de vieillissement entraînant des répercussions de structure et de fonction. Les examens d'imagerie et de microscopie mettent ainsi en évidence des altérations qui sont reflétées par une diminution du débit de filtration glomérulaire (DFG) avec le temps. La présence d'un DFG < 60 ml/min/1,73 m2 durant plus de trois mois étant suffisant pour poser le diagnostic d'insuffisance rénale chronique (IRC), une proportion importante de personnes âgées entre dans cette catégorie. Les données morphologiques, cliniques et épidémiologiques montrent toutefois que le déclin physiologique du DFG avec l'âge n'est pas en soi associé à des conséquences néfastes. Une définition de l'IRC tenant compte de l'âge permettrait une prise en charge basée sur le pronostic individuel plutôt que sur une norme biologique arbitraire.

[Hypertension: novelties 2021]. / Hypertension artérielle.

The past year has been particularly rich in the field of arterial hypertension. Our annual review covers the latest epidemiological studies which show that more than 1.2 billion people have high blood pressure, half of them are unaware of it and that only a quarter of treated patients reach the recommended targets. The impact of poor adherence in young hypertensive patients on cardiovascular events and the effects of intensive treatment in patients over 60 years of age will be discussed. Finally, the adjustment of anti hypertensive treatment in pregnant women with a history of pre-eclampsia according to hemodynamic parameters measured during pregnancy and the effects of potassium supplementation in table salt on cardiovascular events will be presented.

L'année écoulée a été particulièrement riche dans le domaine de l'hypertension artérielle (HTA). Notre revue annuelle couvre les dernières études épidémiologiques qui montrent que plus de 1,2 milliard de personnes sont atteintes d'HTA, que la moitié d'entre elles l'ignore et finalement qu'un quart des patient·e·s atteignent les cibles recommandées. L'impact d'une mauvaise adhésion chez des jeunes patients hypertendus sur les événements cardiovasculaires ainsi que les effets d'un traitement intensif chez des patients de plus de 60 ans seront abordés. Finalement, l'ajustement d'un traitement antihypertenseur chez des femmes enceintes avec antécédents de prééclampsie en fonction des paramètres hémodynamiques mesurés en cours de grossesse et les effets d'une supplémentation de potassium dans le sel de table sur les événements cardiovasculaires seront présentés.

[Sodium, potassium and arterial hypertension: what's new?] / Sodium, potassium et hypertension artérielle: quoi de neuf?

High blood pressure is a public health problem, causing high morbidity and mortality. Its prevalence could exceed 1.5 billion of cases by 2025. High-salt diets have been recognized for several years as a major contributor to elevated blood pressure, with a curvilinear relationship between salt load and increased systolic and diastolic values. On the contrary, potassium is considered as protective, with lower blood pressure values in populations consuming a lot of fruits and vegetables. The World Health Organisation has established recommendations, with a target consumption of less than 218 mmol and more than 90 mmol per day, of salt and potassium, respectively. In this review article, we cover the most recent evidence allowing to sustain those recommendations.

L'hypertension artérielle est un problème de santé publique entraînant une grande morbi-mortalité. Sa prévalence pourrait dépasser 1,5 milliard de cas en 2025. L'alimentation riche en sel est reconnue depuis plusieurs années comme un pourvoyeur important d'augmentation de la tension artérielle, avec une relation curvilinéaire entre la charge en sel et la hausse des valeurs systoliques et diastoliques. Au contraire, le potassium est considéré comme protecteur, avec des valeurs tensionnelles inférieures dans les populations consommant beaucoup de fruits et légumes. L'OMS a établi des recommandations, avec comme cible moins de 218 mmol (5 g) et plus de 90 mmol (3,5 g) par jour de sel (NaCl) et de potassium, respectivement. Dans cet article, nous revoyons les évidences récentes permettant de soutenir ces recommandations.

[How to manage hypertension after an ischemic or hemorrhagic stroke?] / Hypertension artérielle après un accident vasculaire cérébral: quelle prise en charge?

The sometimes-divergent results of studies on the management of blood pressure in the acute phase of stroke have not led to strong and generalizable recommendations. Indeed, an individualized approach seems to be necessary. Depending on the etiology of the stroke, the time to introduce blood pressure lowering therapy differs. In hemorrhagic stroke, it is recommended that intensive hypotensive therapy be started immediately aiming a systolic blood pressure of 130-140mmHg, whereas in the management of ischemic stroke, no hypotensive therapy should be introduced within the first 24 hours except if thrombectomy or thrombolysis are performed. No antihypertensive agent has clearly demonstrated superiority over other classes. However, abrupt changes in blood pressure should be avoided.

Les résultats, parfois divergents, des études évaluant la prise en charge de la tension artérielle en phase aiguë d'un accident vasculaire cérébral (AVC) n'ont pas permis d'établir avec certitude les stratégies thérapeutiques optimales. Néanmoins, ces études mettent en évidence des différences majeures selon le type d'AVC. En cas d'AVC hémorragique, il est recommandé de débuter immédiatement un traitement hypotenseur intensif en visant une tension artérielle systolique (TAS) entre 130 et 140 mmHg, alors que, lors de la prise en charge d'un AVC ischémique, aucun traitement hypotenseur ne devrait être instauré, sauf en cas de thrombectomie ou de thrombolyse. Aucun agent antihypertenseur n'a clairement démontré une supériorité sur les autres classes. Il faut toutefois éviter toute variation brutale de la tension artérielle.

Mendelian randomization to assess causality between uromodulin, blood pressure and chronic kidney disease.

UMOD variants associated with higher levels of urinary uromodulin (uUMOD) increase the risk of chronic kidney disease (CKD) and hypertension. However, uUMOD levels also reflect functional kidney tubular mass in observational studies, questioning the causal link between uromodulin production and kidney damage. We used Mendelian randomization to clarify causality between uUMOD levels, kidney function and blood pressure in individuals of European descent. The link between uUMOD and estimated glomerular filtration rate (eGFR) was first investigated in a population-based cohort of 3851 individuals. In observational data, higher uUMOD associated with higher eGFR. Conversely, when using rs12917707 (an UMOD polymorphism) as an instrumental variable in one-sample Mendelian randomization, higher uUMOD strongly associated with eGFR decline. We next applied two-sample Mendelian randomization on four genome wide association study consortia to explore causal links between uUMOD and eGFR, CKD risk (567,460 individuals) and blood pressure (757,461 individuals). Higher uUMOD levels significantly associated with lower eGFR, higher odds for eGFR decline or CKD, and higher systolic or diastolic blood pressure. Each one standard deviation (SD) increase of uUMOD decreased log-transformed eGFR by -0.15 SD (95% confidence interval -0.17 to -0.13) and increased log-odds CKD by 0.13 SD (0.12 to 0.15). One SD increase of uUMOD increased systolic blood pressure by 0.06 SD (0.03 to 0.09) and diastolic blood pressure by 0.08 SD (0.05 to 0.12). The effect of uUMOD on blood pressure was mediated by eGFR, whereas the effect on eGFR was not mediated by blood pressure. Thus, our data support that genetically driven levels of uromodulin have a direct, causal and adverse effect on kidney function outcome in the general population, not mediated by blood pressure.

Relationship between renal function and blood pressure dipping status in renal transplant recipients: a longitudinal study.

BACKGROUND: Hypertension (HT) is associated with adverse outcomes in kidney transplant (KTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in KTX patients is unknown. METHODS: We retrospectively screened KTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, 1 (T2) and 2 (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable. RESULTS: A total of 123 patients were included with a mean follow-up of 2.12 ± 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 ± 15.1 and 54.9 ± 20.0 mL/min/1.73m2 respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p = 0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2 higher eGFR. HT was negatively associated with eGFR (p = 0.003). CONCLUSIONS: We confirm a high prevalence of non-dippers in KTX recipients. We suggest that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.

Assessment of a strategy combining ambulatory blood pressure, adherence monitoring and a standardised triple therapy in resistant hypertension.

PURPOSE: Poor adherence to drug therapy and inadequate drug regimens are two frequent factors responsible for the poor blood pressure (BP) control observed in patients with apparent resistant hypertension. We evaluated the efficacy of an antihypertensive management strategy combining a standardised therapy with three long acting drugs and electronic monitoring of drug adherence in patients with apparent resistant hypertension. MATERIALS AND METHODS: In this multicentric observational study, adult patients with residual hypertension on 24 h ambulatory BP monitoring (ABMP) despite the use of three or more antihypertensive drugs could be included. Olmesartan/amlodipine (40/10 mg, single pill fixed-dose combination) and chlorthalidone (25 mg) were prescribed for 3 months in two separated electronic pills boxes (EPB). The primary outcome was 24 h ambulatory systolic BP (SBP) control at 3 months, defined as mean SBP <130 mmHg. RESULTS: We enrolled 48 patients (36.0% women) of whom 35 had complete EPB data. After 3 months, 52.1% of patients had 24 h SBP <130 mmHg. 24 h SBP decreased by respectively -9.1 ± 15.5 mmHg, -22.8 ± 30.6 mmHg and -27.7 ± 16.6 mmHg from the tertile with the lowest adherence to the tertile with the highest adherence to the single pill combination (p = 0.024). A similar trend was observed with tertiles of adherence to chlorthalidone. Adherence superior to 90% was associated with 24 h systolic and diastolic blood pressure control in multiple logistic regression analysis (odds ratio = 14.1 (95% confidence interval 1.1-173.3, p = 0.039). CONCLUSIONS: A simplified standardised antihypertensive therapy combined with electronic monitoring of adherence normalises SBP in about half of patients with apparent resistant hypertension. Such combined management strategy enables identifying patients who need complementary investigations and those who rather need a long-term support of their adherence.