Contrast-enhanced ultrasonography reveals a lower cortical perfusion and a decreased renal flow reserve in hypertensive patients.

BACKGROUND: Microvascular structural alteration and dysfunction is a hallmark of arterial hypertension. So far, the visualization and the quantification of renal microcirculation in humans has been hampered by the lack of non-nephrotoxic and non-invasive radiologic techniques. Contrast-enhanced ultrasonography (CEUS) is an appealing method to investigate renal microcirculation and has not been investigated in this setting. We aimed to compare renal microcirculation in normotensive (NT) and hypertensive (HT) participants using CEUS at rest and during a sympathetic stress test. METHODS: We measured the renal perfusion index (PI, primary outcome), the renal resistive index (RRI), beat-to-beat systemic hemodynamics and plasma catecholamines before and during a 2-min cold pressor test (CPT) in NT and HT participants. Linear mixed model analysis was used to compare the effect of the CPT on the variables of interest. RESULTS: Seventy-three participants (32 HT) with normal kidney function were included. HT participants had a lower baseline PI compared with NT participants [median (interquartile range) 1476 (959-2155) arbitrary units (a.u.) vs 2062 (1438-3318) a.u., P < .001]. The CPT increased blood pressure, heart rate and catecholamines in all participants. The increase in PI observed in NT during the CPT was blunted in HT [+504 (117-920) a.u. vs +1159 (678-2352) a.u in NT, interaction P = .013]. Age, sex and body mass index did not modify these results. CONCLUSIONS: HT patients had a lower basal renal cortical perfusion. During the cold pressor test, HT participants had a smaller increase in the PI, suggesting that renal cortical flow reserve is impaired.

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.

[Hypertension in the elderly†: have new guidelines changed the management†?] / Hypertension de la personne âgée†: les nouvelles recommandationsont-elles changé la prise en charge†?

Hypertension is highly prevalent in elderly and represents the number one risk factor for cardiac and cerebrovascular complications including cognitive dysfunction. Recently published AHA/ACC and ESC/ESH guidelines for the management of hypertension in adults have modified the approach of hypertension in patients older than 65 years and particularly in those older than 85. The new concepts are the following: the thresholds and target blood pressures for patients older than 65 years are less conservative; emphasis is made on biological rather than chronological age; the use of single pill combinations is favored to simplify treatment algorithms and increase long-term drug adherence. At last, a regular assessment of adherence in collaboration with health care partners is highlighted.

L'hypertension est très fréquente chez les personnes âgées et représente le premier facteur de risque de complications cardio et cérébrovasculaires, y compris les atteintes cognitives. Les recommandations AHA/ACC et ESC/ESH, récemment publiées, ont modifié la prise en charge des patients de plus de 65 ans et en particulier ceux âgés de plus de 85 ans. Les nouveaux concepts sont les suivants : le seuil diagnostique est moins conservateur ; la pression artérielle cible pour les patients âgés de plus de 65 ans rejoint celle des adultes plus jeunes ; l'accent est mis sur l'âge biologique plutôt que chronologique et la tolérance du traitement ; l'utilisation de combinaisons fixes est favorisée afin d'améliorer l'adhérence et, finalement, l'évaluation régulière de l'adhérence thérapeutique en collaboration avec les partenaires de soins est encouragée.

[Hypertension management : from medical inertia to patient autonomy]. / Prise en charge de l'hypertension artérielle : de l'inertie thérapeutique à l'autonomie des patients.

The percentage of patients treated for hypertension with a well-controlled blood pressure (< 140/90 mmHg) remains disappointedly low, in general way below 50 %, despite all national and international recommendations. Among the causes explaining this insufficient control, therapeutic inertia has been identified as an important determinant, which unfortunately did not improve over the last 10­20 years. Patients' empowerment through home blood pressure monitoring and perhaps self-titration according to a well pre-specified scheme supported by telemedicine could represent news avenues to fight against therapeutic inertia.

Le pourcentage de patients hypertendus traités qui atteignent les cibles de pression artérielle (< 140/90 mmHg) recommandées par la majorité des recommandations nationales et internationales reste bas, souvent bien inférieur à 50 %. Parmi les causes de ce contrôle insuffisant, l'inertie thérapeutique des prestataires de soins a été identifiée comme un déterminant important qui ne s'est pas amélioré au cours des 10­20 dernières années. Le renforcement de l'autonomie du patient par l'encouragement à l'automesure de la pression artérielle à domicile, mais peut-être aussi l'autotitration des médicaments selon un schéma bien défini et soutenu par la télémédecine, pourraient représenter de nouvelles voies pour lutter contre l'inertie thérapeutique en impliquant plus les patients eux-mêmes.

SGLT2 inhibitors in diabetic and non-diabetic kidney transplant recipients: current knowledge and expectations.

The beneficial effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown recently in numerous randomized controlled trials (RCT) and systematic reviews. According to KDIGO guidelines, SGLT2i currently represent a first choice for diabetic patients with chronic kidney disease (CKD). In addition, a recent meta-analysis of 13 large led by the 'SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium' (SMART-C) provided solid evidence of SGLT2i beneficial effects in CKD or in patients with heart failure, with and without diabetes. Collectively, the patients treated with SGLT2i had a decreased risk of CKD progression, acute kidney injury (AKI), end-stage kidney disease (ESKD) or death from heart failure. Whether these cardio-renal benefits should be extrapolated to kidney transplant recipients (KTR) needs to be assessed in further studies. In this article, we report recent data accumulated so far in the literature, looking at the efficacy and safety of SGLT2i in diabetic and non-diabetic KTR. We found encouraging data regarding the use of SGLT2i in KTR with diabetes. These agents appeared to be safe, and they reduced body weight and blood pressure in this group of patients. Potential effects on kidney graft function and survival are yet to be investigated.

New Aspects in the Management of Hypertension in Patients with Chronic Kidney Disease not on Renal Replacement Therapy.

With chronic kidney disease (CKD) being a global arising health problem, strategies for delaying kidney disease progression and reducing the high cardiovascular risk inherent to CKD, are the main objectives of the actual management of patients with kidney diseases. In these patients, the control of arterial hypertension is essential, as high blood pressure (BP) is a strong determinant of worst cardiovascular and renal outcomes. Achieving target blood pressures recommended by international guidelines is mandatory and often demands a multiple levels management, including several pharmacological and lifestyle measures. Even in the presence of adequate BP control, the residual cardiovascular risk remains high. In this respect, the recent demonstration that novel agents such as sodium glucose transporter 2 (SGLT2) inhibitors or the new non-steroidal mineralocorticoid antagonist finerenone can retard the progression of kidney diseases and reduce cardiovascular mortality on top of standard of care treatment with renin-angiotensin system inhibitors represent enormous progresses. These studies also demonstrate that cardiovascular and renal protection can be obtained beyond blood pressure control. Other promising novelties are still to come such as renal denervation and endothelin receptor antagonists in the setting of diabetic and non-diabetic kidney diseases. In the present review, we shall discuss the classic and the new aspects for the management of hypertension in CKD, integrating the new data from recent clinical studies.

Contrast-Enhanced Ultrasonography Enables the Detection of a Cold Pressor Test-Induced Increase in Renal Microcirculation in Healthy Participants.

Background: Renal microcirculation is essential for regulation of the glomerular filtration rate, the reabsorption of salt and water from the interstitium, and hence the blood pressure. Renal ultrasonography coupled to Doppler analysis and contrast-enhanced ultrasound enables the study of renal perfusion. So far, physiologic interventions have rarely been performed to assess the renal perfusion. The objective of our study was to measure the renal perfusion in response to a cold pressor test (CPT). Methods: Healthy adult participants were exposed to a 2 min CPT or a sham exposure (body temperature). Systemic hemodynamics, renal resistive index (RRI) and renal perfusion index (PI) were measured before and during the CPT or the sham exposure. Renal responses were compared using a paired Student's t-test or Wilcoxon signed rank test. Pearson correlation test was used to test association of variables of interest. Results: Forty-one normotensive participants (21 women) were included in the study. Mean blood pressure and heart rate both increased with the CPT. The RRI decreased from 0.60 ± 0.05 arbitrary units (AU) to 0.58 ± 0.05 AU (p < 0.05) and the PI increased from 2,074 AU (1,358-3,346) to 3,800 AU (2,118-6,399) (p < 0.05) (+66% (24-106%)). Compared to the sham exposure, the increase in PI with the CPT was more marked. There was a negative association between the increase in heart rate and mean blood pressure with the RRI (r: -0.550, p = 0.002 and r: -0.395, P = 0.016), respectively. Conclusion: Doppler Ultrasound and CEUS enable the detection of physiological changes within the macro- and microvascular renal circulation. The CPT decreases the RRI and increases the PI. Whether these changes are present in pathological states such as diabetes or hypertension will need additional studies.

How Do I Manage Hypertension in Patients with Advanced Chronic Kidney Disease Not on Dialysis? Perspectives from Clinical Practice.

In the general population, the prevalence of moderate and severe chronic kidney disease (CKD) is usually below 5% but this figure is often higher in specific groups of patients such as those with type 2 diabetes. Patients with advanced CKD (CKD stage 3b and 4) are at high or very high cardiovascular risk, and their risk of progressing towards end-stage kidney disease (CKD stage 5) and the need of renal replacement therapy are elevated. Hypertension is a major cause of poor cardiovascular and renal outcomes in severe CKD. Therefore, an adequate control of blood pressure (BP) is mandatory. However, normalizing BP is often challenging in these patients because the clinical management of hypertension in advanced CKD is not well defined and rarely supported by large randomized controlled trials. In the present review, we discuss the characteristics of hypertension in advanced CKD, excluding dialysis, and its management integrating data from recent clinical studies and a pragmatic approach enriched by a long-standing clinical experience.

Validation of the optical Aktiia bracelet in different body positions for the persistent monitoring of blood pressure.

The diagnosis of hypertension and the adjustment of antihypertensive drugs are evolving from isolated measurements performed at the physician offices to the full phenotyping of patients in real-life conditions. Indeed, the strongest predictor of cardiovascular risk comes from night measurements. The aim of this study was to demonstrate that a wearable device (the Aktiia Bracelet) can accurately estimate BP in the most common body positions of daily life and thus become a candidate solution for the BP phenotyping of patients. We recruited 91 patients with BP ranging from low to hypertensive levels and compared BP values from the Aktiia Bracelet against auscultatory reference values for 4 weeks according to an extended ISO 81060-2 protocol. After initializing on day one, the observed means and standard deviations of differences for systolic BP were of 0.46 ± 7.75 mmHg in the sitting position, - 2.44 ± 10.15 mmHg in the lying, - 3.02 ± 6.10 mmHg in the sitting with the device on the lap, and - 0.62 ± 12.51 mmHg in the standing position. Differences for diastolic BP readings were respectively of 0.39 ± 6.86 mmHg, - 1.93 ± 7.65 mmHg, - 4.22 ± 6.56 mmHg and - 4.85 ± 9.11 mmHg. This study demonstrates that a wearable device can accurately estimate BP in the most common body positions compared to auscultation, although precision varies across positions. While wearable persistent BP monitors have the potential to facilitate the identification of individual BP phenotypes at scale, their prognostic value for cardiovascular events and its association with target organ damage will need cross-sectional and longitudinal studies. Deploying this technology at a community level may be also useful to drive public health interventions against the epidemy of hypertension.

Blood pressure from the optical Aktiia Bracelet: a 1-month validation study using an extended ISO81060-2 protocol adapted for a cuffless wrist device.

OBJECTIVE: The objective of this study (NCT04027777) was to assess the accuracy and precision of the Aktiia Bracelet, a CE-marked noninvasive optical blood pressure (BP) monitor worn at the wrist, over a period of 1 month. METHODS: In this study, participants aged between 21 and 65 years were recruited. The clinical investigation extended the ISO81060-2:2013 standard to the specificities of cuffless devices. Each BP assessment consisted of the simultaneous recording of optical signals with Aktiia Bracelet and double-blinded auscultation by two trained observers in the standard sitting position. The algorithms of Aktiia Bracelet further processed the recorded optical signals to perform a signal quality check and to calculate uncalibrated estimates of systolic BP (SBP) and diastolic BP (DBP). These estimates were transformed into mmHg using a subject-dependent calibration parameter, which was calculated using the first two available reference measurements per subject. RESULTS: Eighty-six participants were included in the analysis. The mean and SD of the differences between Aktiia Bracelet estimates and the reference (ISO81060-2 criterion 1) were 0.46 ± 7.75 mmHg for SBP and 0.39 ± 6.86 mmHg for DBP. The SD of the averaged paired difference per subject (ISO81060-2 criterion 2) were 3.9 mmHg for SBP and 3.6 mmHg for DBP. CONCLUSION: After initialization and during 1 month, the overall accuracy of Aktiia Bracelet satisfied validation criteria 1 and 2 of ISO81060-2 in the sitting position. The Aktiia Bracelet can be recommended for BP measurement in the adult population.

Hypertension and Drug Adherence in the Elderly.

Hypertension is highly prevalent after the age of 65 years affecting more than 60% of individuals in developed countries. Today, there is sufficient evidence from clinical trials that treating elderly subjects with hypertension with antihypertensive medications has a positive benefit/risk ratio even in very elderly patients (>80 years). In recent years, partial or total non-adherence has been recognized as major issues in the long-term management of hypertension in all age categories. However, whether non-adherence is more frequent in hypertensive patients older than 65 years or not is still a matter of debate and the common belief is that adherence is lower in older than in younger patients. Are clinical data supporting this belief? In this brief review, we discuss the topic of drug adherence in elderly in the context of the medical treatment of hypertension. Studies show that drug adherence is actually better in patients aged 65 to 80 years when compared to younger hypertensive patients (<50 years). However, in very old patients (>80 years) the prevalence of non-adherence does increase. In this patients' group, there are specific risk factors for non-adherence such as cognitive ability, depression, and health believes, in addition to classical risk factors for non-adherence. One important aspect in the elderly is the prescription of potentially inappropriate medications that will interfere with the adherence to necessary treatments. In this context, an interesting new concept was developed few years ago, i.e., the process of deprescribing. Thus, today, in addition to conventional guidelines recommendations (use of single pill combinations, individualization of treatments), the evaluation of cognitive abilities, the regular assessment of potentially inappropriate medications, and the process of deprescribing appear to be three new additional steps to improve drug adherence in the elderly and thereby ameliorate the global management of hypertension.

New Insights on the Role of Sodium in the Physiological Regulation of Blood Pressure and Development of Hypertension.

A precise maintenance of sodium and fluid balance is an essential step in the regulation of blood pressure and alterations of this balance may lead to the development of hypertension. In recent years, several new advances were made in our understanding of the interaction between sodium and blood pressure regulation. The first is the discovery made possible with by new technology, such as 23Na-MRI, that sodium can be stored non-osmotically in tissues including the skin and muscles particularly when subjects are on a high sodium diet or have a reduced renal capacity to excrete sodium. These observations prompted the refinement of the original model of regulation of sodium balance from a two-compartment model comprising the extracellular fluid within the intravascular and interstitial spaces to a three-compartment model that includes the intracellular space of some tissues, most prominently the skin. In this new model, the immune system plays a role, thereby supporting many previous studies indicating that the immune system is a crucial co-contributor to the maintenance of hypertension through pro-hypertensive effects in the kidney, vasculature, and brain. Lastly, there is now evidence that sodium can affect the gut microbiome, and induce pro-inflammatory and immune responses, which might contribute to the development of salt-sensitive hypertension.

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis.

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis.