Individual versus integration of multiple components of central blood pressure and aortic stiffness in predicting cardiovascular mortality in end-stage renal diseases.

Aortic stiffness, measured by carotid-femoral pulse wave velocity (PWV), is a predictor of cardiovascular (CV) mortality in patients with end-stage renal disease (ESRD). Aortic stiffness increases aortic systolic and pulse pressures (cSBP, cPP) and augmentation index adjusted for a heart rate of 75 beats per minute (AIx@75). In this study, we examined if the integration of multiple components of central blood pressure and aortic stiffness (ICPS) into risk score categories could improve CV mortality prediction in ESRD. In a prospective cohort of 311 patients with ESRD on dialysis who underwent vascular assessment at baseline, 118 CV deaths occurred after a median follow-up of 3.1 years. The relationship between hemodynamic parameters and CV mortality was analyzed through Kaplan-Meier and Cox survival analysis. ICPS risk score from 0 to 5 points were calculated from points given to tertiles, and were regrouped into three risk categories (Average, High, Very-High). A strong association was found between the ICPS risk categories and CV mortality (High risk HR = 2.20, 95% CI: 1.05-4.62, P = 0.036); Very-High risk (HR = 4.44, 95% CI: 2.21-8.92, P < 0.001) as compared to the Average risk group. The Very-High risk category remained associated with CV mortality (HR = 3.55, 95% CI: 1.37-9.21, P = 0.009) after adjustment for traditional CV risk factors as compared to the Average risk group. While higher C-statistics value of ICPS categories (C: 0.627, 95% CI: 0.578-0.676, P = 0.001) was not statistically superior to PWV, cPP or AIx@75, the use of ICPS categories resulted in a continuous net reclassification index of 0.56 (95% CI: 0.07-0.99). In conclusion, integration of multiple components of central blood pressure and aortic stiffness may potentially be useful for better prediction of CV mortality in this cohort.

Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study.

BACKGROUND: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized. METHODS: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension. RESULTS: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP. CONCLUSIONS: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Antihypertensive treatment with hydrochlorothiazide-hydralazine combination aggravates medial vascular calcification in CKD rats with mineral bone disorder.

Background: Arterial stiffness and medial vascular calcification, leading to isolated systolic blood pressure (BP), are major cardiovascular risk factors in patients with chronic kidney disease (CKD) and mineral bone disorders (MBD). The impact of BP on MBD-induced medial vascular calcification in CKD remains uncertain. We investigated whether BP reduction improves arterial stiffness and medial vascular calcification in a rat model of CKD-MBD. Methods: CKD was induced in Wistar rats by subtotal nephrectomy. Then, MBD was generated by a Ca/P-rich diet with calcitriol supplementation to induce medial vascular calcification. Two antihypertensive treatments were evaluated: (1) the angiotensin AT1 receptor antagonist losartan, and (2) the combination of the thiazide diuretic hydrochlorothiazide and the direct vasodilator hydralazine (HCTZ/HY). After 5 weeks, mean BP (MBP), pulse pressure (PP), and pulse wave velocity (PWV) were determined. Vascular calcification was assessed in the thoracic aorta. Results: While MBP was similar in CKD-MBD and control CKD rats, PP and PWV were increased in CKD-MBD rats. The heightened arterial stiffness in CKD-MBD rats was associated with diffused medial calcification along the thoracic aorta. Although both losartan and HCTZ/HY reduced MBP in CKD-MBD rats, losartan did not affect PP and PWV nor medial vascular calcification, whereas HCTZ/HY, unexpectedly, further increased arterial stiffness and medial vascular calcification. Conclusion: In the rat model of CKD-MBD, antihypertensive treatment with losartan did not affect arterial stiffness or medial vascular calcification. However, HCTZ/HY treatment aggravated arterial stiffness and vascular calcification despite a similar reduction of MBP, suggesting a blood pressure-independent mechanism for vascular calcification.

Impact of Successive Office Blood Pressure Measurements During a Single Visit on Cardiovascular Risk Prediction: Analysis of CARTaGENE.

BACKGROUND: Multiple office blood pressure (BP) readings correlate more closely with ambulatory BP than single readings. Whether they are associated with long-term outcomes and improve cardiovascular risk prediction is unknown. Our objective was to assess the long-term impact of multiple office BP readings. METHODS: We used data from CARTaGENE, a population-based survey comprising individuals aged 40 to 70 years. Three BP readings (BP1, BP2, and BP3) at 2-minute intervals were obtained using a semiautomated device. They were averaged to generate BP1-2, BP2-3, and BP1-2-3 for systolic BP (SBP) and diastolic BP. Cardiovascular events (major adverse cardiovascular event [MACE]: cardiovascular death, stroke, and myocardial infarction) during a 10-year follow-up were recorded. Associations with MACE were obtained using adjusted Cox models. Predictive performance was assessed with 10-year atherosclerotic cardiovascular disease scores and their associated C statistics. RESULTS: In the 17 966 eligible individuals, 2378 experienced a MACE during follow-up. Crude SBP values ranged from 122.5 to 126.5 mm Hg. SBP3 had the strongest association with MACE incidence (hazard ratio, 1.10 [1.05-1.15] per SD) and SBP1 the weakest (hazard ratio, 1.06 [1.01-1.10]). All models including SBP1 (SBP1, SBP1-2, and SBP1-2-3) were underperformed. At a given SBP value, the excess MACE risk conferred by SBP3 was 2× greater than SBP1. In atherosclerotic cardiovascular disease scores, SBP3 yielded the highest C statistic, significantly higher than most other SBP measures. In contrast to SBP, all diastolic BP readings yielded similar results. CONCLUSIONS: Cardiovascular risk prediction is improved by successive office SBP values, especially when the first reading is discarded. These findings reinforce the necessity of using multiple office BP readings.

Pembrolizumab-Induced Anti-GBM Glomerulonephritis: A Case Report.

Immune checkpoint inhibitors are known to have a wide range of autoimmune toxicities, such as acute interstitial nephritis. Immunotherapy induced glomerulonephritis has been described, but anti-glomerular basement membrane disease (anti-GBM) is rarely reported. We present a case report of a 60-year-old woman with squamous cell carcinoma of the cervix who was treated with pembrolizumab, an anti-programmed cell death protein 1, and who developed severe acute kidney injury 4 months after therapy initiation. The immune workup showed a positive serum anti-GBM antibody (24 U/mL). The kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G2 glomerular basement membrane staining, compatible with anti-GBM glomerulonephritis. The patient was treated with plasmapheresis, IV steroids, and cyclophosphamide, but she developed kidney failure, necessitating dialysis. Few case reports, such as the present case, provide a possible link between anti-GBM glomerulonephritis and immune checkpoint inhibitors, warranting early clinical suspicion and investigation in patients who are treated with these agents and subsequently develop acute kidney injury.

CENtral blood pressure Targeting: a pragmatic RAndomized triaL in advanced Chronic Kidney Disease (CENTRAL-CKD): A Clinical Research Protocol.

Background: Emerging data favor central blood pressure (BP) over brachial cuff BP to predict cardiovascular and kidney events, as central BP more closely relates to the true aortic BP. Considering that patients with advanced chronic kidney disease (CKD) are at high cardiovascular risk and can have unreliable brachial cuff BP measurements (due to high arterial stiffness), this population could benefit the most from hypertension management using central BP measurements. Objective: To assess the feasibility and efficacy of targeting central BP as opposed to brachial BP in patients with CKD G4-5. Design: Pragmatic multicentre double-blinded randomized controlled pilot trial. Setting: Seven large academic advanced kidney care clinics across Canada. Patients: A total of 116 adults with CKD G4-5 (estimated glomerular filtration rate [eGFR] < 30 mL/min) and brachial cuff systolic BP between 120 and 160 mm Hg. The key exclusion criteria are 1) ≥ 5 BP drugs, 2) recent acute kidney injury, myocardial infarction, stroke, heart failure or injurious fall, 3) previous kidney replacement therapy. Methods: Double-blind randomization to a central or a brachial cuff systolic BP target (both < 130 mm Hg) as measured by a validated central BP device. The study duration is 12 months with follow-up visits every 2 to 4 months, based on local practice. All other aspects of CKD management are at the discretion of the attending nephrologist. Outcomes: Primary Feasibility: Feasibility of a large-scale trial based on predefined components. Primary Efficacy: Carotid-femoral pulse wave velocity at 12 months. Others: Efficacy (eGFR decline, albuminuria, BP drugs, and quality of life); Events (major adverse cardiovascular events, CKD progression, hospitalization, mortality); Safety (low BP events and acute kidney injury). Limitations: May be challenging to distinguish whether central BP is truly different from brachial BP to the point of significantly influencing treatment decisions. Therapeutic inertia may be a barrier to successfully completing a randomized trial in a population of CKD G4-5. These 2 aspects will be evaluated in the feasibility assessment of the trial. Conclusion: This is the first trial to evaluate the feasibility and efficacy of using central BP to manage hypertension in advanced CKD, paving the way to a future large-scale trial. Trial registration: clinicaltrials.gov (NCT05163158).

Contexte: Des données émergentes favorisent la mesure de la pression artérielle (PA) centrale plutôt que brachiale pour prédire les événements cardiovasculaires et rénaux, car la PA centrale est plus proche de la véritable PA aortique. Les patients souffrant d'insuffisance rénale chronique (IRC) de stade avancé présentent un risque cardiovasculaire élevé, et les mesures de la pression artérielle avec brassard brachial ne sont pas toujours fiables (en raison d'une rigidité artérielle élevée). La prise en charge de l'hypertension à l'aide de mesures centrales de la pression artérielle pourrait donc bénéficier à cette population de patients. Objectif: Évaluer la faisabilité et l'efficacité d'un ciblage de la PA par mesure centrale plutôt que brachiale chez les patients atteints d'IRC de stade G4-5. Conception: Essai pilote pragmatique, contrôlé et randomisé, mené en double aveugle dans plusieurs centers. Cadre: Sept grandes cliniques universitaires de soins rénaux avancés de partout au Canada. Sujets: 116 adultes atteints d'IRC de stade G4-5 (DFGe < 30 ml/min) avec une mesure de PA systolique mesurée par brassard brachial entre 120 et 160 mm Hg. Les principaux critères d'exclusion sont 1) la prise d'au moins 5 médicaments associés à la PA; 2) un épisode récent d'insuffisance rénale aiguë, d'infarctus du myocarde, d'accident vasculaire cérébral, d'insuffisance cardiaque ou une chute avec blessure; et 3) des antécédents de thérapie de remplacement rénal. Méthodologie: Randomization en double aveugle vers une cible de PA systolique centrale ou brachiale (toutes deux à < 130 mm Hg) mesurée par un appareil validé de mesure de la PA centrale. La durée de l'étude est de 12 mois avec visites de suivi tous les 2 à 4 mois, selon la pratique locale. Tous les autres aspects de la gestion de l'IRC sont à la discrétion du néphrologue traitant. Résultats: Faisabilité principale: faisabilité d'un essai à grande échelle fondé sur des paramètres prédéfinis. Efficacité principale: vitesse de l'onde de pouls carotido-fémorale à 12 mois. Autres: efficacité (déclin du DFGe, albuminurie, médicaments pour la PA, qualité de vie); événements (événements cardiovasculaires indésirables majeurs, progression de l'IRC, hospitalization, mortalité); innocuité (faible nombre d'événements liés à la PA, insuffisance rénale aiguë). Limites: Il peut être difficile de déterminer si la mesure de la PA centrale est vraiment différente de celle de la PA brachiale, et ce, au point d'influencer de manière significative les décisions de traitement. L'inertie thérapeutique peut constituer un obstacle à la réussite d'un essai randomisé dans une population de patients atteints d'IRC de stade G4-5. Ces deux aspects seront évalués dans la portion évaluant la faisabilité de l'essai. Conclusion: Il s'agit du premier essai visant à évaluer la faisabilité et l'efficacité de l'utilization de la PA centrale pour la prise en charge de l'hypertension chez les patients atteints d'IRC de stade avancé, ce qui ouvre la voie à un futur essai à grande échelle. Enregistrement de l'essai: ClinicalTrials.gov (NCT05163158).

Cerebral blood flow pulsatility and cerebral artery stiffness acutely decrease during hemodialysis.

End-stage kidney disease (ESKD) is associated with increased arterial stiffness and cognitive impairment. Cognitive decline is accelerated in ESKD patients on hemodialysis and may result from repeatedly inappropriate cerebral blood flow (CBF). The aim of this study was to examine the acute effect of hemodialysis on pulsatile components of CBF and their relation to acute changes in arterial stiffness. In eight participants (age: 63 ± 18 years, men: 5), CBF was estimated using middle cerebral artery blood velocity (MCAv) assessed with transcranial Doppler ultrasound before, during, and after a single hemodialysis session. Brachial and central blood pressure, along with estimated aortic stiffness (eAoPWV) were measured using an oscillometric device. Arterial stiffness from heart to MCA was measured as the pulse arrival time (PAT) between electrocardiogram (ECG) and transcranial Doppler ultrasound waveforms (cerebral PAT). During hemodialysis, there was a significant reduction in mean MCAv (-3.2 cm/s, p < 0.001), and systolic MCAv (-13.0 cm/s, p < 0.001). While baseline eAoPWV (9.25 ± 0.80 m/s) did not significantly change during hemodialysis, cerebral PAT increased significantly (+0.027 , p < 0.001) and was associated with reduced pulsatile components of MCAv. This study shows that hemodialysis acutely reduces stiffness of arteries perfusing the brain along with pulsatile components of blood velocity.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

BACKGROUND: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. METHODS: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. RESULTS: The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. CONCLUSIONS: The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low.

Wnt/ß-catenin pathway inhibitors, bone metabolism and vascular health in kidney transplant patients.

BACKGROUND AND OBJECTIVES: Sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23) and α-klotho have been shown to play an important role in bone and vascular disease of chronic kidney disease. We aimed to evaluate the evolution of these bone markers in newly kidney transplanted patients, and whether they are associated with bone metabolism and vascular stiffness. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a longitudinal single-center observational cohort study. Circulating levels of Wnt/ß-catenin pathway inhibitors (sclerostin, DKK1, FGF23 and α-klotho), arterial stiffness (carotid-femoral pulse-wave velocity (PWV), carotid-radial PWV, PWV ratio, augmented index) and bone parameters were assessed before (M0), and at 3 (M3) and 6 months (M6) after transplantation. Generalized estimating equations were conducted for comparative analyses between the three time points. We used a marginal structural model for repeated measures for the impact of changes in bone markers on the evolution of arterial stiffness. Multivariate linear regression analyses were performed for the associations between Wnt/ß-catenin pathway inhibitors and mineral metabolism parameters. RESULTS: We included 79 patients (70% male; median age of 53 (44-60) years old). The levels of sclerostin (2.06 ± 1.18 ng/mL at M0 to 0.88 ± 0.29 ng/mL at M6, p ≤ 0.001), DKK1 (364.0 ± 266.7 pg/mL at M0 to 246.7 ± 149.1 pg/mL at M6, p ≤ 0.001), FGF23 (5595 ± 9603 RU/mL at M0 to 137 ± 215 RU/mL at M6, p ≤ 0.001) and α-klotho (457.6 ± 148.6 pg/mL at M0 to 109.8 ± 120.7 pg/mL at M6, p < 0.05) decreased significantly after kidney transplant. Sclerostin and FGF23 were positively associated with carotid-femoral (standardized ß = 0.432, p = 0.037 and standardized ß = 0.592, p = 0.005) and carotid-radial PWV (standardized ß = 0.259, p = 0.029 and standardized ß = 0.242, p = 0.006) throughout the 6 months of follow-up. The nature of the associations between bone markers and bone metabolism parameters varies after kidney transplant. CONCLUSIONS: The circulating levels of Wnt/ß-catenin pathway inhibitors and α-klotho significantly decrease after kidney transplantation, while sclerostin and FGF23 levels might be associated with improvement of vascular stiffness and blood pressure.

Enhancing central blood pressure accuracy through statistical modeling: A proof-of-concept study.

Background: Non-invasive estimation of central blood pressure (BP) may have better prognostic value than brachial BP. The accuracy of central BP is limited in certain populations, such as in females and the elderly. This study aims to examine whether statistical modeling of central BP for clinical and hemodynamic parameters results in enhanced accuracy. Methods: This study is a cross-sectional analysis of 500 patients who underwent cardiac catheterization. Non-invasive brachial cuff and central BP were measured simultaneously to invasive aortic systolic BP (AoSBP). Central BP was calibrated for brachial systolic (SBP) and diastolic BP (Type I calibration; C1SBP) or brachial mean and diastolic BP (Type II calibration; C2SBP). Differences between central SBP and the corresponding AoSBP were assessed with linear regression models using clinical and hemodynamic parameters. These parameters were then added to C1SBP and C2SBP in adjusted models to predict AoSBP. Accuracy and precision were computed in the overall population and per age or sex strata. Results: C1SBP underestimated AoSBP by 11.2 mmHg (±13.5) and C2SBP overestimated it by 6.2 mmHg (±14.8). Estimated SBP amplification and heart rate were the greatest predictors of C1- and C2-AoSBP accuracies, respectively. Statistical modeling improved both accuracy (0.0 mmHg) and precision (±11.4) but more importantly, eliminated the differences of accuracy seen in different sex and age groups. Conclusion: Statistical modeling greatly enhances the accuracy of central BP measurements and abolishes sex- and age-based differences. Such factors could easily be implemented in central BP devices to improve their accuracy.

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

Background Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores. Conclusions Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.

Accuracy Difference of Noninvasive Blood Pressure Measurements by Sex and Height.

Importance: Women are at higher risk of cardiovascular events than men with similar blood pressure (BP). Whether this discrepancy in risk is associated with the accuracy of brachial cuff BP measurements is unknown. Objectives: To examine the difference in brachial cuff BP accuracy in men and women compared with invasively measured aortic BP and to evaluate whether noninvasive central BP estimation varies with sex. Design, Setting, and Participants: This cross-sectional study enrolled 500 participants without severe aortic stenosis or atrial fibrillation from January 1 to December 31, 2019, who were undergoing nonurgent coronary angiography at a tertiary care academic hospital. Exposures: Simultaneous measurements of invasive aortic BP and noninvasive BP. Main Outcomes and Measures: Sex differences in accuracy were determined by calculating the mean difference between the noninvasive measurements (brachial and noninvasive central BP) and the invasive aortic BP (reference). Linear regression and mediation analyses were performed to identify mediators between sex and brachial cuff accuracy. Results: This study included 500 participants (145 female [29%] and 355 male [71%]; 471 [94%] White; mean [SD] age, 66 [10] years). Baseline characteristics were similar for both sexes apart from body habitus. Despite similar brachial cuff systolic BP (SBP) (mean [SD], 124.5 [17.7] mm Hg in women vs 124.4 [16.4] in men; P = .97), invasive aortic SBP was higher in women (mean [SD], 130.9 [21.7] in women vs 124.7 [20.1] mm Hg in men; P < .001). The brachial cuff was relatively accurate compared with invasive aortic SBP estimation in men (mean [SD] difference, -0.3 [11.7] mm Hg) but not in women (mean [SD] difference, -6.5 [12.1] mm Hg). Noninvasive central SBP (calibrated for mean and diastolic BP) was more accurate in women (mean [SD] difference, 0.6 [15.3] mm Hg) than in men (mean [SD] difference, 8.3 [14.2] mm Hg). This association of sex with accuracy was mostly mediated by height (3.4 mm Hg; 95% CI, 1.1-5.6 mm Hg; 55% mediation). Conclusions and Relevance: In this cross-sectional study, women had higher true aortic SBP than men with similar brachial cuff SBP, an association that was mostly mediated by a shorter stature. This difference in BP measurement may lead to unrecognized undertreatment of women and could partly explain why women are at greater risk for cardiovascular diseases for a given brachial cuff BP than men. These findings may justify the need to study sex-specific BP targets or integration of sex-specific parameters in BP estimation algorithms.

Assessment of Stiffness of Large to Small Arteries in Multistage Renal Disease Model: A Numerical Study.

Arterial stiffness (AS), as assessed via pulse wave velocity (PWV), is a major biomarker for cardiovascular risk assessment in patients with chronic kidney disease (CKD). However, the mechanisms responsible for the changes in PWV in the presence of kidney disease are not yet fully elucidated. In the present study, we aimed to investigate the direct effects attributable to biomechanical changes in the arterial tree caused by staged renal removal, independent of any biochemical or compensatory effects. Particularly, we simulated arterial pressure and flow using a previously validated one-dimensional (1-D) model of the cardiovascular system with different kidney configurations: two kidneys (2KDN), one single kidney (1KDN), no kidneys (0KDN), and a transplanted kidney (TX) attached to the external iliac artery. We evaluated the respective variations in blood pressure (BP), as well as AS of large-, medium-, and small-sized arteries via carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and radial-digital PWV (rdPWV), respectively. Our results showed that BP was increased in 1KDN and 0KDN, and that systolic BP values were restored in the TX configuration. Furthermore, a rise was reported in all PWVs for all tested configurations. The relative difference in stiffness from 2KDN to 0KDN was higher in the case of crPWV (15%) in comparison with the increase observed for cfPWV (11%). In TX, we observed a restoration of the PWVs to values close to 1KDN. Globally, it was demonstrated that alterations of the outflow boundaries to the renal arteries with staged kidney removal led to changes in BP and central and peripheral PWV in line with previously reported clinical data. Our findings suggest that the PWV variations observed in clinical practice with different stages of kidney disease may be partially attributed to biomechanical alterations of the arterial tree and their effect on BP.

Twenty-Four-Hour Central (Aortic) Systolic Blood Pressure: Reference Values and Dipping Patterns in Untreated Individuals.

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBPMAP/DBPcal), or bSBP/diastolic blood pressure (cSBPSBP/DBPcal), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBPMAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBPSBP/DBPcal, respectively. We pragmatically propose as upper normal limit for 24-hour cSBPMAP/DBPcal 135 mm Hg and for 24-hour cSBPSBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBPSBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBPMAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

Increased Excess Pressure After Creation of an Arteriovenous Fistula in End-Stage Renal Disease.

BACKGROUND: Reservoir-wave analysis (RWA) separates the arterial waveform into reservoir and excess pressure (XSP) components, where XSP is analogous to flow and related to left ventricular workload. RWA provides more detailed information about the arterial tree than traditional blood pressure (BP) parameters. In end-stage renal disease (ESRD), we have previously shown that XSP is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). In this study, we examined whether XSP increases after creation of an AVF in ESRD. METHODS: Before and after a mean of 3.9 ± 1.2 months following creation of AVF, carotid pressure waves were recorded using arterial tonometry. XSP and its integral (XSPI) were derived using RWA through pressure wave analysis alone. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (CF-PWV). RESURLTS: In 38 patients (63% male, age 59 ± 15 years), after AVF creation, brachial diastolic BP decreased (79 ± 10 vs. 72 ± 12 mm Hg, P = 0.002), but the reduction in systolic BP, was not statistically significant (133 ± 20 vs. 127 ± 26 mm Hg, P = 0.137). However, carotid XSP (14 [12-19] to 17 [12-22] mm Hg, P = 0.031) and XSPI increased significantly (275 [212-335] to 334 [241-439] kPa∙s, P = 0.015), despite a reduction in CF-PWV (13 ± 3.6 vs. 12 ± 3.5 m/s, P = 0.025). CONCLUSIONS: Creation of an AVF resulted in increased XSP in this population, despite improvement in diastolic BP and aortic stiffness. These findings underline the complex hemodynamic impact of AVF on the cardiovascular system.

Screening Rates for Primary Aldosteronism Among Individuals With Hypertension Plus Hypokalemia: A Population-Based Retrospective Cohort Study.

Primary aldosteronism is a common, yet highly underdiagnosed, cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Hypertension plus hypokalemia is a guideline-recommended indication to screen for primary aldosteronism, yet the uptake of this recommendation at the population level remains unknown. We performed a population-based retrospective cohort study of adults ≥18 years old in Ontario, Canada, with hypertension plus hypokalemia (potassium <3.5 mEq/L) from 2009 to 2015 with follow-up through 2017. We measured the proportion of individuals who underwent primary aldosteronism screening via the aldosterone-to-renin ratio based upon hypokalemia frequency and severity along with concurrent antihypertensive medication use. We assessed clinical predictors associated with screening via Cox regression. The cohort included 26 533 adults of which only 422 (1.6%) underwent primary aldosteronism screening. When assessed by number of instances of hypokalemia over a 2-year time window, the proportion of eligible patients who were screened increased only modestly from 1.0% (158/15 983) with one instance to 4.8% (71/1494) with ≥5 instances. Among individuals with severe hypokalemia (potassium <3.0 mEq/L), only 3.9% (58/1422) were screened. Among older adults prescribed ≥4 antihypertensive medications, only 1.0% were screened. Subspecialty care with endocrinology (hazard ratio [HR], 1.52 [95% CI, 1.10-2.09]), nephrology (HR, 1.43 [95% CI, 1.07-1.91]), and cardiology (HR, 1.39 [95% CI, 1.14-1.70]) were associated with an increased likelihood of screening, whereas age (HR, 0.95 [95% CI, 0.94-0.96]) and diabetes (HR, 0.66 [95% CI, 0.50-0.89]) were inversely associated with screening. In conclusion, population-level uptake of guideline recommendations for primary aldosteronism screening is exceedingly low. Increased education and awareness are critical to bridge this gap.

Changes in arterial stiffness indices during a single haemodialysis session in end-stage renal disease population: a systematic review and meta-analysis protocol.

INTRODUCTION: Patients with end-stage renal disease are at higher risk of cardiovascular morbidity and mortality, a risk mediated in part by increased aortic stiffness. Arterial stiffness is assessed at different anatomical locations (central elastic or peripheral muscular arteries) using a variety of mechanical biomarkers. However, little is known on the robustness of each of these mechanical biomarkers following a haemodynamic stress caused by a single haemodialysis (HD) session. METHODS AND ANALYSIS: A systematic review has been designed and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A targeted search strategy applicable in key databases (PubMed, Embase, the Cochrane Library, Web of Science and grey literature) is constructed to search articles and reviews from inception to 16 October 2020. Only articles of studies conducted with adults under chronic HD for kidney failure, with repeated measures of arterial stiffness metrics (pulse wave velocity, Augmentation Index, arterial distensibility or stiffness) following a before-and-after design surrounding a HD session will be selected. The screening process, data extraction and assessment of risk bias will be done by two independent pairs of reviewers. Meta-analysis will enable adjustments for potential confounders and subgroup analyses will be performed to discriminate changes in arterial stiffness metrics from elastic, muscular or global arterial territories. ETHICS AND DISSEMINATION: This study does not require ethical approval. Findings will be submitted for publication to relevant peer-reviewed journals and will be presented at profession-specific conferences. PROSPERO REGISTRATION NUMBER: CRD42020213946.

Inaccuracy of brachial blood pressure and its potential impact on treatment and aortic blood pressure estimation.

OBJECTIVE: Although brachial cuff SBP is universally used to guide hypertension management, it can differ significantly from intraarterial SBP. We examine the potential impacts of cuff-to-intraarterial brachial SBP (bSBP) mismatch on hypertension treatment and accuracy towards central SBP. METHODS: In 303 individuals, cuff bSBP (CUFF-bSBP) and central SBP were measured using a Mobil-o-Graph simultaneously to intraarterial bSBP (IA-bSBP) and aortic SBP. According to the difference between CUFF-bSBP and IA-bSBP, we identified three phenotypes: Underestimation (CUFF-bSBP < IA-bSBP by >10 mmHg); No Mismatch (CUFF-bSBP within 10 mmHg of IA-bSBP); Overestimation (CUFF-bSBP > IA-bSBP by >10 mmHg) phenotypes. Risk of overtreatment and undertreatment, and accuracy (ARTERY society criteria: mean difference ≤5 ±â€Š8 mmHg) were determined. A multiple linear regression model was used to assess variables associated with the bSBP difference. RESULTS: Underestimation (n = 142), No Mismatch (n = 136) and Overestimation (n = 25) phenotypes had relatively similar characteristics and CUFF-bSBP (124 ±â€Š17, 122 ±â€Š14, 127 ±â€Š19 mmHg, P = 0.19) but different aortic SBP (133 ±â€Š21, 120 ±â€Š16, 112 ±â€Š18 mmHg, P < 0.001). In the underestimation phenotype, 59% were at risk of undertreatment (14% in No Mismatch), whereas 50% in the Overestimation phenotype were at risk of overtreatment (17% in No Mismatch). CUFF-bSBP accurately estimated aortic SBP only in the No Mismatch Group (mean difference 1.6 ±â€Š8.2 mmHg) whereas central BP never met the accuracy criteria. Male sex, higher height and active smoking were associated with lesser underestimation of bSBP difference. CONCLUSION: The brachial cuff lacks accuracy towards intraarterial BP in a significant proportion of patients, potentially leading to increased risks of BP mismanagement and inaccurate determination of central BP. This illustrates the need to improve the accuracy of cuff-based BP monitors.

Health literacy level in a various nephrology population from Québec: predialysis clinic, in-centre hemodialysis and home dialysis; a transversal monocentric observational study.

BACKGROUND: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. It is especially important in nephrology due to the complexity of chronic kidney disease (CKD). The present study sought to define health literacy levels in patients followed in predialysis clinic, in-center dialysis (ICHD), peritoneal dialysis (PD) and home hemodialysis (HHD). METHODS: This transversal monocentric observational study analysed 363 patients between October 2016 and April 2017. The Brief Health Literacy Screen (BHLS) and the Health Literacy Questionnaire (HLQ) were used to measure health literacy. Multivariate linear regressions were used to compare the mean scores on the BHLS and HLQ, across the four groups. RESULTS: Patients on PD had a significantly higher BHLS'score than patients on ICHD (p = 0.04). HLQ's scores differed across the groups: patients on HHD (p = 0.01) and PD (p = 0.002) were more likely to feel understood by their healthcare providers. Compared to ICHD, patients on HHD were more likely to have sufficient information to manage their health (p = 0.02), and patients in the predialysis clinic were more likely to report high abilities for health information appraisal (p < 0.001). CONCLUSION: In a monocentric study, there is a significant proportion of CKD patients, especially in predialysis clinic and in-centre hemodialysis, with limited health literacy. Patients on home dialysis (HHD and PD) had a higher level of health literacy compared to the other groups.