Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Birth Weight and Maternal Body Size as Determinants of Blood Pressure at Age 17: Results from the Jerusalem Perinatal Study Cohort.

OBJECTIVES: To investigate the effect of birth weight (BW) and maternal pre-pregnancy BMI (mBMI) on blood pressure (BP) in adolescence. METHODS: A Population-based cohort of 11,729 births in Jerusalem during 1974-1976, with archival data on maternal and birth characteristics was performed. Measurements at age 17 were assessed and linear regression models were used to evaluate the associations of birth characteristics with BP outcomes. RESULTS: BW was inversely associated with both systolic (SBP) and diastolic (DBP) BP at age 17 (SBP: B = - 0.829, p = 0.002; DBP: B = - 0.397, p = 0.033). The interaction term between BW and weight at age 17 was significant for DBP (p = 0.017) and pulse pressure (p = 0.005). mBMI yielded significant positive associations with BP, independent of BW. CONCLUSIONS FOR PRACTICE: Our findings indicate that there are at least two distinct pathways linking early life characteristics with subsequent BP: Intrauterine growth, as reflected by BW and other genetic or environmental factors, reflected by mBMI and maternal education, contribute to offspring adolescent BP. These results warrant replication in other birth cohorts and underline the need to explore specific mechanisms that account for these associations.

Prognostic Relevance of Short-Term Blood Pressure Variability. The Spanish ABPM Registry.

BACKGROUND: The prognostic relevance of short-term blood pressure (BP) variability in hypertension is not clearly established. We aimed to evaluate the association of short-term BP variability, with all-cause and cardiovascular mortality in a large cohort of patients with hypertension. METHODS: We selected 59 124 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry from 2004 to 2014 (median follow-up: 9.7 years). Systolic and diastolic BP SD and coefficient of variation from daytime and nighttime, weighted SD, weighted coefficient of variation, average real variability (mean of differences between consecutive readings), and BP variability ratio (ratio between systolic and diastolic 24-hour SD) were calculated through baseline 24-hour ambulatory BP monitoring. Association with all-cause and cardiovascular mortality were assessed by Cox regression models adjusted for clinical confounders and BP. RESULTS: Patients who died during follow-up had higher values of BP variability compared with those remaining alive. In adjusted models systolic and diastolic daytime and weighted SD and coefficient of variation, average real variability, as well as systolic nighttime SD and BP variability ratio were all significantly associated with all-cause and cardiovascular mortality. Hazard ratios for 1-SD increase in the systolic components ranged from 1.05 to 1.12 for all-cause mortality and from 1.07 to 1.17 for cardiovascular mortality. A daytime SD≥13 mm Hg, a nighttime and a weighted SD≥12 mm Hg, and an average real variability ≥10 mm Hg, all systolic, were independently associated with mortality. CONCLUSIONS: Short-term blood pressure variability shows a relatively weak but significant association with all-cause and cardiovascular mortality in patients with hypertension.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Plasma-free vs deconjugated metanephrines for diagnosis of phaeochromocytoma.

BACKGROUND: The diagnosis of phaeochromocytoma is commonly performed by the measurements of plasma-free normetanephrine and metanephrine. Plasma-deconjugated normetanephrine and metanephrine have been proposed as alternative, equivalent, but easier to measure biomarkers. OBJECTIVE: The aim of this study was to compare the diagnostic performance of plasma-free vs deconjugated normetanephrine and metanephrine in patients tested for phaeochromocytoma. METHODS: The study population included a reference group of 262 normotensive and hypertensive volunteers, 198 patients with phaeochromocytoma and 528 patients initially suspected of having the tumour, but with negative investigations after at least 2 years of follow-up. Measurements were performed using liquid chromatography with electrochemical detection. RESULTS: Plasma concentrations of free normetanephrine were 17-fold higher in patients with phaeochromocytoma than in the reference population, a 72% larger (P < 0·001) difference than that for the 10-fold higher levels of plasma-deconjugated normetanephrine. In contrast, relative increases in plasma concentrations of free and deconjugated metanephrine were similar. Using upper cut-offs established in the reference population, measurements of plasma-free metabolites provided superior diagnostic performance than deconjugated metabolites according to measures of both sensitivity (97% vs 92%, P = 0·002) and specificity (93% vs 89%, P = 0·012). The area under the receiver operating characteristic curve for the free metabolites was larger than that for the deconjugated metabolites (0·986 vs 0·965, P < 0·001). CONCLUSION: Measurements of plasma-free normetanephrine and metanephrine are superior to the deconjugated metabolites for diagnosis of phaeochromocytoma.

Comparison of systolic blood pressure values obtained by photoplethysmography and by Korotkoff sounds.

In the current study, a non-invasive technique for systolic blood pressure (SBP) measurement based on the detection of photoplethysmographic (PPG) pulses during pressure-cuff deflation was compared to sphygmomanometry-the Korotkoff sounds technique. The PPG pulses disappear for cuff-pressures above the SBP value and reappear when the cuff-pressure decreases below the SBP value. One hundred and twenty examinations were performed on forty subjects. In 97 examinations the two methods differed by less than 3 mmHg. In nine examinations the SBP value measured by PPG was higher than that measured by sphygmomanometry by 5 mmHg or more. In only one examination the former was lower by 5 mmHg or more than the latter. The appearance of either the PPG pulses or the Korotkoff sounds assures that the artery under the cuff is open during systolic peak pressure. In the nine examinations mentioned above the PPG pulses were observed while Korotkoff sounds were not detected, despite the open artery during systole. In these examinations, the PPG-based technique was more reliable than sphygmomanometry. The high signal-to-noise ratio of measured PPG pulses indicates that automatic measurement of the SBP by means of automatic detection of the PPG signals is feasible.

Changing profile of health and function from age 70 to 85 years.

BACKGROUND: Old age has traditionally been considered to begin at age 65. The improving health and functional status observed among older people may necessitate reevaluation of this cut-off point. OBJECTIVE: To present the changing prevalence of common geriatric syndromes, functional parameters, common disease status and health care utilization, at ages 70, 78 and 85, in order to help address the question of when does contemporary aging actually begin. METHODS: Medical, psychosocial, cognitive, and functional status, and health service utilization at age 70, 78 and 85 were assessed through the Jerusalem Longitudinal Cohort Study (1990-2010), which prospectively followed a representative sample (born 1920-1921), of 1,861 people, all of whom underwent home-based comprehensive assessment. RESULTS: At age 70, the cohort had good health, low comorbidity, preserved cognition, mobility and independence in basic and instrumental activities of daily activities (ADL). Rising comorbidity, declining cognitive status, increasing depression, and difficulty in ADLs were seen at 78. By age 85, compared to age 70, comorbidity had tripled, depression, hearing and visual impairment, falls, dizziness and mobility problems had doubled; 23% of subjects had cognitive impairment, 42.5% suffered urinary incontinence, and dependence in basic and instrumental ADLs was common (37.8 and 51.7%, respectively). Home care was 4.5, 10.1, and 24.6%, and hospitalization in the previous year occurred among 12.3, 18.8 and 27.8% at ages 70, 78 and 85, respectively. CONCLUSIONS: At age 70, the overall health profile was favorable, prevalence of geriatric syndromes was low, cognitive and functional status was preserved, and health service utilization was low. The progressive deterioration seen at ages 78 and more profoundly so at age 85, suggest that a cut-off point beyond age 70 years may serve to better define entry into old age.

Renal artery stenosis with significant proteinuria may be reversed after nephrectomy or revascularization in patients with the antiphospholipid antibody syndrome: a case series and review of the literature.

Renal artery stenosis (RAS) is a disease which might present as hypertension, renal insufficiency or proteinuria and even as nephrotic syndrome. While 90% of cases are secondary to atherosclerosis, the rest of the cases are usually related to fibromuscular dysplasia. Recently, RAS has also been documented in patients with the antiphospholipid syndrome (APS). Although cases of nephrotic syndrome induced by RAS have been published, cases of patients with APS and nephrotic syndrome attributed to RAS were not reported in the literature. In this paper, three young male patients with APS, hypertension and significant proteinuria secondary to RAS are presented. The patients were treated with nephrectomy or revascularization in addition to prior treatment with warfarin, with improvement of the hypertension and the proteinuria. The relationship between renal artery stenosis, nephrotic range proteinuria and APS is reviewed. We suggest that renal artery stenosis should be included in the differential diagnosis of the nephrotic syndrome and that APS should be included in the differential diagnosis of renal artery stenosis especially in young male patients with proteinuria.

Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension.

Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, nondipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours. These observations provide justification for complete 24-h BP control as being the primary goal of antihypertensive treatment. Bedtime administration of antihypertensive drugs has also been proposed as a potentially more effective treatment strategy than morning administration. This Position Paper by the International Society of Hypertension reviewed the published evidence on the clinical relevance of the diurnal variation in BP and the timing of antihypertensive drug treatment, aiming to provide consensus recommendations for clinical practice. Eight published outcome hypertension studies involved bedtime dosing of antihypertensive drugs, and all had major methodological and/or other flaws and a high risk of bias in testing the impact of bedtime compared to morning treatment. Three ongoing, well designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing. Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose.

Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

BACKGROUND: The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality and composite cardiovascular events in different age classes. METHOD: Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age classes were age 40 or less, 40-50, 50-60, 60-70, and over 70 years. Co-primary endpoints were total mortality and composite cardiovascular events. The relative risk expressed by hazard ratio per 1SD increase for each of the PP variables was calculated from multivariable-adjusted Cox regression models. RESULTS: The 11 848 participants from 13 cohorts (age 53 ±â€Š16 years, 50% men) were followed for up for 13.7 ±â€Š6.7 years. A total of 2946 participants died (18.1 per 1000 person-years) and 2093 experienced a fatal or nonfatal cardiovascular event (12.9 per 1000 person-years). Mean PP, elPP, and stPP were, respectively, 49.7, 43.5, and 6.2 mmHg, and elPP and stPP were uncorrelated ( r  = -0.07). At age 50-60 years, all PP variables displayed association with risk for almost all outcomes. From age over 60 years to age over 70 years, hazard ratios of of PP and elPP were similar and decreased gradually but differently for pulse rate lower than or higher than 70 bpm, whereas stPP lacked predictive power in most cases. For age 40 years or less, elPP showed protective power for coronary events, whereas stPP and PP predicted stroke events. Adjusted and unadjusted hazard ratio variations were similar over the entire age range. CONCLUSION: This study provides a new basis for associating PP components with outcome and arterial properties in different age groups and at different pulse rates for both old and young age. The similarity between adjusted and unadjusted hazard ratios supports the clinical usefulness of PP components but further studies are needed to assess the prognostic significance of the PP components, especially at the young age.

Abnormal liver tests in patients with SARS-CoV-2 or influenza - prognostic similarities and temporal disparities.

BACKGROUND & AIMS: Abnormal liver tests are common in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but a possible direct role of the virus in liver injury and its association with short-term outcomes are controversial. Therefore, we aimed to compare the pattern of abnormal liver tests in patients with SARS-CoV-2 with those of patients infected with influenza, a non-hepatotropic respiratory virus, and their association with worse outcomes during hospitalisation. METHODS: We performed a retrospective cohort study of 1,737 hospitalised patients (865 with influenza and 872 with SARS-CoV-2) in a tertiary medical centre. We defined abnormal liver tests as alanine transaminase or aspartate transaminase ≥40 IU/ml at any time-point during hospitalisation. RESULTS: Abnormal liver tests were mild to moderate in most patients regardless of infection type, but the majority of patients with influenza had a transaminase peak earlier during hospitalisation compared with patients with SARS-CoV-2. Abnormal liver tests correlated with markers of severe disease in either influenza or SARS-CoV-2 infections, and were associated with death, occurring mainly in patients with severe liver test abnormalities (>200 IU/L) (38.7% and 60% of patients with influenza or SARS-CoV-2, respectively). In multivariate analysis, controlling for age, sex, lymphopaenia, and C-reactive protein, liver test abnormalities remained significantly associated with death for influenza (odds ratio 4.344; 95% CI 2.218-8.508) and SARS-CoV-2 (odds ratio 3.898; 95% CI 2.203-6.896). These results were confirmed upon propensity score matching. CONCLUSIONS: Abnormal liver tests during hospitalisation with SARS-CoV-2 or influenza infections are common, may differ in their time course, and reflect disease severity. They are associated with worse outcomes, mainly in patients with severe liver test abnormalities, regardless of infection type. LAY SUMMARY: Coronavirus disease 2019 (COVID-19) is a serious global health pandemic, the causative agent of which is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Abnormal liver tests are common among SARS-CoV-2 infected patients and are often associated with worse outcomes. Herein, we compare the pattern of abnormal liver tests and their association with disease severity between 2 major non-hepatotropic respiratory viruses: SARS-CoV-2 and influenza. We show that abnormal liver tests are common in both infections, may slightly differ in their kinetics, and are associated with worse outcomes, especially in patients with severe liver test abnormalities. These results strongly suggest that abnormal liver tests in SARS-CoV-2 patients reflect disease severity, rather than a virus-mediated direct liver injury, and should be closely followed in admitted patients.

Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor.

BACKGROUND: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan. METHODS: In 4,663 young (18-49 years) and 7,185 older adults (≥50 years), brachial PP was recorded over 24 hours. Total mortality and all major cardiovascular events (MACEs) combined were coprimary endpoints. Cardiovascular death, coronary events, and stroke were secondary endpoints. RESULTS: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mm Hg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1,000 person-years. The adjusted hazard ratios expressed per 10-mm Hg PP increments were less than unity (P ≤ 0.027) for MACE (0.67; 95% confidence interval [CI], 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mm Hg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1,000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P < 0.0001). The PP-related relative risks of death, MACE, and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3. CONCLUSIONS: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.

High prevalence of left ventricular hypertrophy in octogenarian women: The Jerusalem Longitudinal Cohort Study.

BACKGROUND: Left ventricular hypertrophy (LVH) is more frequent in women and increases with age; however, it is unclear whether this finding is true in the very elderly. The objective of this study was to examine gender differences in the prevalence of LVH in a very elderly cohort. METHODS: Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Three hundred and thirty-nine of the subjects from the most recent set of data collection in 2005-2006 underwent echocardiography in addition to structured interviews and physical examination. RESULTS: The overall prevalence of LVH was high and significantly higher among women (60% vs 43%, p=0.0023). Systolic blood pressure (SBP) was significantly higher in women with LVH compared with women without LVH (p<0.01) and both groups of men (p<0.005). Women with LVH were three times more likely than women without LVH and 6.5 times more likely than men with LVH to believe that a BP of 160/100 mmHg represents their BP goal (p<0.05). CONCLUSIONS: This study demonstrates a high prevalence of LVH in a very elderly population, a finding significantly more pronounced in women and related to SBP.

Occupational and environmental influences on hypertension.

In this review I try to summarize concisely available information on common effectors on blood pressure, occupational, and environmental ones, which are sometimes overlooked, so that clinicians involved in caring for patients with hypertension may have somewhat better vision of what our patients are exposed to.

Aberrant corin and PCSK6 in placentas of the maternal hyperinsulinemia IUGR rat model.

OBJECTIVES: Corin is a protease that converts pro-atrial natriuretic peptide (pro-ANP) to ANP. While the involvement of ANP in the cardiovascular regulation is well established, there is increasing evidence that the pregnant uterus produces ANP, which promotes spiral artery remodeling. The present study examines the alterations in corin and PCSK6, a key enzyme in the conversion of pro-corin to corin, in the placenta of hyperinsulinemic dams (HD) featuring pregnancy-induced hypertension (PIH). MATERIALS AND METHODS: The study was conducted on female Wistar rats. Rats were rendered hyperinsulinemic by subcutaneous insulin pellet, mated and followed to the twenty-first day of pregnancy. Normal pregnant dams (NPD) served as controls. Both groups were sacrificed on day 21 of gestation and their placentas were dissected along with the mesometrial triangle (MT). The tissue was then sectioned from the maternal surface to the base of the MT, and processed for histological and molecular biology analysis of Corin, PCSK6 and ANP expression/immunoreactivity. RESULTS: Hyperinsulinemic dams developed PIH, along lower placental and fetal weights. Corin expression and immunoreactivity were significantly decreased in the placenta by ~40-50%, but not in the MT. Similarly, placental but not MT PCSK6 immunoreactivity was lower in HD. Concomitantly with the downregulation of corin/PCSK6, proANP levels increased in the placenta of HD. CONCLUSIONS: Corin and PCSK6 are expressed in the placenta and MT. The decline in these two enzymes in the placenta of HD suggests a role of corin/PCSK6 machinery in the development of PIH and intrauterine growth restriction characterizing hyperinsulinemia.