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.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Patient views regarding cannabis use in chronic kidney disease and kidney failure: a survey study.

BACKGROUND: Cannabis is frequently used recreationally and medicinally, including for symptom management in patients with kidney disease. METHODS: We elicited the views of Canadian adults with kidney disease regarding their cannabis use. Participants were asked whether they would try cannabis for anxiety, depression, restless legs, itchiness, fatigue, chronic pain, decreased appetite, nausea/vomiting, sleep, cramps and other symptoms. The degree to which respondents considered cannabis for each symptom was assessed with a modified Likert scale ranging from 1 to 5 (1, definitely would not; 5, definitely would). Multilevel multivariable linear regression was used to identify respondent characteristics associated with considering cannabis for symptom control. RESULTS: Of 320 respondents, 290 (90.6%) were from in-person recruitment (27.3% response rate) and 30 (9.4%) responses were from online recruitment. A total of 160/320 respondents (50.2%) had previously used cannabis, including smoking [140 (87.5%)], oils [69 (43.1%)] and edibles [92 (57.5%)]. The most common reasons for previous cannabis use were recreation [84/160 (52.5%)], pain alleviation [63/160 (39.4%)] and sleep enhancement [56/160 (35.0%)]. Only 33.8% of previous cannabis users thought their physicians were aware of their cannabis use. More than 50% of respondents probably would or definitely would try cannabis for symptom control for all 10 symptoms. Characteristics independently associated with interest in trying cannabis for symptom control included symptom type (pain, sleep, restless legs), online respondent {ß = 0.7 [95% confidence interval (CI) 0.1-1.4]} and previous cannabis use [ß = 1.2 (95% CI 0.9-1.5)]. CONCLUSIONS: Many patients with kidney disease use cannabis and there is interest in trying cannabis for symptom control.

Radial-digital pulse wave velocity: a noninvasive method for assessing stiffness of small conduit arteries.

Pulse wave velocity (PWV) is used to evaluate regional stiffness of large and medium-sized arteries. Here, we examine the feasibility and reliability of radial-digital PWV (RD-PWV) as a measure of regional stiffness of small conduit arteries and its response to changes in hydrostatic pressure. In 29 healthy subjects, we used Complior Analyse piezoelectric probes to record arterial pulse wave at the radial artery and the tip of the index. We determined transit time by second-derivative and intersecting tangents using the device-embedded algorithms and in-house MATLAB-based analyses of only reliable waves and by numerical simulation using a one-dimensional (1-D) arterial tree model coupled with a heart model. Second-derivative RD-PWV was 4.68 ± 1.18, 4.69 ± 1.21, and 4.32 ± 1.19 m/s for device-embedded, MATLAB-based, and numerical simulation analyses, respectively. Intersecting-tangent RD-PWV was 4.73 ± 1.20, 4.45 ± 1.08, and 4.50 ± 0.84 m/s for device-embedded, MATLAB-based, and numerical simulation analyses, respectively. Intersession coefficients of variation were 7.0% ± 4.9% and 3.2% ± 1.9% (P = 0.04) for device-embedded and MATLAB-based second-derivative algorithms, respectively. In 15 subjects, we examined the response of RD-PWV to changes in local hydrostatic pressure by vertical displacement of the hand. For an increase of 10 mmHg in local hydrostatic pressure, RD-PWV increased by 0.28 m/s (95% confidence interval: 0.16-0.40; P < 0.001). This study shows that RD-PWV can be used for the noninvasive assessment of regional stiffness of small conduit arteries. This finding allows for an integrated approach for assessing arterial stiffness gradient from the aorta to medium-sized arteries and now to small conduit arteries.NEW & NOTEWORTHY The interaction between the stiffness of various arterial segments is important in understanding the behavior of pressure and flow waves along the arterial tree. In this article, we provide a novel and noninvasive method of assessing the regional stiffness of small conduit arteries using the same piezoelectric sensors used for determination of pulse wave velocity over large- and medium-sized arteries. This development allows for an integrated approach for studying arterial stiffness gradient.

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis.

BACKGROUND: Patients receiving in-centre hemodialysis are at high risk of exposure to SARS-CoV-2 and death if infected. One dose of the BNT162b2 SARS-CoV-2 vaccine is efficacious in the general population, but responses in patients receiving hemodialysis are uncertain. METHODS: We obtained serial plasma from patients receiving hemodialysis and health care worker controls before and after vaccination with 1 dose of the BNT162b2 mRNA vaccine, as well as convalescent plasma from patients receiving hemodialysis who survived COVID-19. We measured anti-receptor binding domain (RBD) immunoglobulin G (IgG) levels and stratified groups by evidence of previous SARS-CoV-2 infection. RESULTS: Our study included 154 patients receiving hemodialysis (135 without and 19 with previous SARS-CoV-2 infection), 40 controls (20 without and 20 with previous SARS-CoV-2 infection) and convalescent plasma from 16 patients. Among those without previous SARS-CoV-2 infection, anti-RBD IgG was undetectable at 4 weeks in 75 of 131 (57%, 95% confidence interval [CI] 47% to 65%) patients receiving hemodialysis, compared with 1 of 20 (5%, 95% CI 1% to 23%) controls (p < 0.001). No patient with nondetectable levels at 4 weeks developed anti-RBD IgG by 8 weeks. Results were similar in non-immunosuppressed and younger individuals. Three patients receiving hemodialysis developed severe COVID-19 after vaccination. Among those with previous SARS-CoV-2 infection, median anti-RBD IgG levels at 8 weeks in patients receiving hemodialysis were similar to controls at 3 weeks (p = 0.3) and to convalescent plasma (p = 0.8). INTERPRETATION: A single dose of BNT162b2 vaccine failed to elicit a humoral immune response in most patients receiving hemodialysis without previous SARS-CoV-2 infection, even after prolonged observation. In those with previous SARS-CoV-2 infection, the antibody response was delayed. We advise that patients receiving hemodialysis be prioritized for a second BNT162b2 dose at the recommended 3-week interval.

Incidence of fractures in middle-aged individuals with early chronic kidney disease: a population-based analysis of CARTaGENE.

BACKGROUND: Previous studies evaluating fractures in chronic kidney disease (CKD) have mostly focused on hip or major fractures in aged populations with moderate to advanced CKD. We aimed at evaluating the association between early CKD and fracture incidence at all sites across age and sex in middle-aged individuals. METHODS: We analyzed CARTaGENE, a prospective population-based survey of 40- to 69-year-old individuals from Quebec (Canada). Estimated glomerular filtration rate (eGFR) at baseline was evaluated categorically or continuously using restricted cubic splines. Fractures at any site (except toes, hand and craniofacial) for up to 7 years of follow-up were identified through administrative databases using a validated algorithm. Adjusted Cox models were used to evaluate the association of CKD with fracture. Interaction terms for age and sex were also added. RESULTS: A total of 19 391 individuals (756 CKD Stage 3; 9114 Stage 2; 9521 non-CKD) were included and 829 fractures occurred during a median follow-up of 70 months. Compared with the median eGFR of 90 mL/min/1.73 m2, eGFRs of ≤60 mL/min/1.73 m2 were associated with increased fracture incidence in unadjusted and adjusted models [adjusted hazard ratio (HR) = 1.25 (95% confidence interval 1.05-1.49) for 60 mL/min/1.73 m2; 1.65 (1.14-2.37) for 45 mL/min/1.73 m2]. The eGFR was linearly associated with fracture incidence <75 mL/min/1.73 m2 [HR = 1.18 (1.04-1.34) per 10 mL/min/1.73 m2 decrease] but not above [HR = 0.98 (0.91-1.06) per 10 mL/min/1.73 m2 decrease). The effect of decreased eGFR on fracture incidence was more pronounced in younger individuals [HR = 2.45 (1.28-4.67) at 45 years; 1.11 (0.73-1.67) at 65 years] and in men. CONCLUSIONS: Even early CKD increases fracture incidence, especially in younger individuals and in men.

Formulas for Calculated Osmolarity and Osmolal Gap: A Study of Diagnostic Accuracy.

BACKGROUND: The osmolal gap has been used for decades to screen for exposure to toxic alcohols. However, several issues may affect its reliability. We aimed to develop equations to calculate osmolarity with improved performance when used to screen for intoxication to toxic alcohols. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 7,525 patients undergoing simultaneous measurements of osmolality, sodium, potassium, urea, glucose, and ethanol or undergoing similar measurements performed within 30 minutes of a measurement of toxic alcohol levels at a single tertiary-care center from April 2001 to June 2016. Patients with detectable toxic alcohols were excluded. INDEX TEST: Equations to calculate osmolarity using multiple linear regression. OUTCOMES: The performance of new equations compared with published equations developed to calculate osmolarity, and to diagnose toxic alcohol intoxications more accurately. RESULTS: We obtained 7,525 measurements, including 100 with undetectable toxic alcohols. Among them, 3,875 had undetectable and 3,650 had detectable ethanol levels. In the entire cohort, the best equation to calculate osmolarity was 2.006×Na + 1.228×Urea + 1.387×Glucose + 1.207×Ethanol (values in mmol/L, R2=0.96). A simplified equation, 2.0×Na + 1.2×Urea + 1.4×Glucose + 1.2×Ethanol, had a similar R2 with 95% of osmolal gap values between -10.9 and 13.8. In patients with undetectable ethanol concentrations, the range of 95% of osmolal gap values was narrower than previous published formulas, and in patients with detectable ethanol concentrations, the range was narrower or similar. We performed a subanalysis of 138 cases for which both the toxic alcohol concentration could be measured and the osmolal gap could be calculated. Our simplified equation had superior diagnostic accuracy for toxic alcohol exposure. LIMITATIONS: Single center, no external validation, limited number of cases with detectable toxic alcohols. CONCLUSIONS: In a large cohort, coefficients from regression analyses estimating the contribution of glucose, urea, and ethanol were higher than 1.0. Our simplified formula to precisely calculate osmolarity yielded improved diagnostic accuracy for suspected toxic alcohol exposures than previously published formulas.

Central blood pressures in early chronic kidney disease: an analysis of CARTaGENE.

BACKGROUND: Vascular stiffness and advanced chronic kidney disease (CKD) are strong determinants of higher central blood pressure (BP) and are associated with high cardiovascular morbidity and mortality. Whether mild-to-moderate CKD is associated with higher central BP independently of other comorbid conditions remains uncertain. METHODS: We evaluated the central hemodynamic profile [central systolic BP, central pulse pressure (PP), augmentation index, PP amplification, augmented pressure] of Stage 3 CKD patients and compared it with participants with estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m 2 in the CARTaGENE populational cohort through propensity score matching and multivariate regression analyses. RESULTS: Of the 20 004 participants, 13 114 had valid pulse wave analysis and eGFRs >30 mL/min/1.73 m 2 , of which 515 had Stage 3 CKD. These 515 patients had significantly higher peripheral systolic BP (127 ± 16 versus 125 ± 15 mmHg, P = 0.01) and central PP (43.0 ± 11.4 versus 39.7 ± 10.0 mmHg, P <0.001) than the control group (eGFR >60 mL/min/1.73 m 2 ). Propensity score matching allowed the creation of 500 pairs with similar clinical characteristics. In this matched cohort, central BPs were similar in Stage 3 CKD patients compared with controls (central PP 42.9 ± 11.3 versus 43.7 ± 11.3 mmHg, P = 0.3). Multivariate analysis using data from all patients also found that the higher central hemodynamic readings found in Stage 3 CKD patients disappeared after adjusting for comorbid conditions. In a subset of 609 participants in whom albuminuria levels were measured, urine albumin excretion was not independently associated with higher central hemodynamic indices. CONCLUSION: In this large cohort from the general population, early CKD and albuminuria was not independently associated with detrimental central hemodynamic parameters.

Diagnosis and outcomes of acute kidney injury using surrogate and imputation methods for missing preadmission creatinine values.

BACKGROUND: Missing preadmission serum creatinine (SCr) values are a common obstacle to assess acute kidney injury (AKI) diagnosis and outcomes. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines suggest using a SCr computed from the Modification of Diet in Renal Disease (MDRD) with an estimated glomerular filtration rate of 75 ml/min/1.73 m2. We aimed to identify the best surrogate method for baseline SCr to assess AKI diagnosis and outcomes. METHODS: We compared the use of 1) first SCr at hospital admission 2) minimal SCr over 2 weeks after intensive care unit admission 3) MDRD computed SCr and 4) Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) computed SCr to assess AKI diagnosis and outcomes. We then performed multilinear regression models to predict preadmission SCr and imputation strategies to assess AKI diagnosis. RESULTS: Our one-year retrospective cohort study included 1001 critically ill adults; 498 of them had preadmission SCr values. In these patients, AKI incidence was 25.1% using preadmission SCr. First SCr had the best agreement for AKI diagnosis (22.5%; kappa = 0.90) and staging (kappa = 0.81). MDRD, CKD-EPI and minimal SCr overestimated AKI diagnosis (26.7%, 27.1% and 43.2%;kappa = 0.86, 0.86 and 0.60, respectively). However, MDRD and CKD-EPI computed SCr had a better sensitivity than first SCr for AKI (93% and 94% vs. 87%). Eighty-eight percent of patients experienced renal recovery at least 3 months after hospital discharge. All methods except the first SCr significantly underestimated the percentage of renal recovery. In a multivariate model, age, male gender, hypertension, heart failure, undergoing surgery and log first SCr best predicted preadmission SCr (adjusted R2 = 0.56). Imputation methods with first SCr increased AKI incidence to 23.9% (kappa = 0.92) but not with MDRD computed SCr (26.7%;kappa = 0.89). CONCLUSION: In our cohort, first SCr performed better for AKI diagnosis and staging, as well as for renal recovery after hospital discharge than MDRD, CKD-EPI or minimal SCr. However, MDRD SCr and CKD-EPI SCr improved AKI diagnosis sensitivity. Imputation methods minimally increased agreement for AKI diagnosis.

Does concomitant autonomous adrenal cortisol overproduction have the potential to confound the interpretation of adrenal venous sampling in primary aldosteronism?

OBJECTIVE: Demonstration of unilateral aldosterone production by adrenal venous sampling (AVS) is required to select appropriate candidates for adrenalectomy in patients with primary aldosteronism (PA). During AVS, aldosterone and cortisol levels are measured to assess successful cannulation and lateralization. In patients with aldosterone-producing adenoma (APA), concurrent autonomous cortisol secretion might confound AVS results. DESIGN AND PATIENTS: We retrospectively examined results in eight patients with cortisol-producing adenoma (CPA), but without PA, who underwent AVS. RESULTS: In all eight, cortisol was higher on the CPA side than contralateral (CL) (median 6·7-fold [range 2·4-27·2]; P = 0·012]). By cortisol criteria, CL catheter placement would have been labelled inadequate in six despite adrenal venous aldosterone levels markedly higher than peripheral (41·6-fold [7·2-510·5]; P < 0·001), suggesting successful cannulation. In all eight, adrenal venous aldosterone/cortisol (A/C) ratios on the CL side were indicative of increased aldosterone production (≥2 times peripheral), but in only three patients on the CPA side (difference CL side 44·5-fold [6·0-109·0] vs CPA side 1·65-fold [1·0-23·0]; P = 0·017). A/C ratios were higher on the CL vs the CPA side in seven (20·0-fold [4·7-76·0]). CONCLUSION: These results in patients with CPA suggest that in patients with APA, concurrent autonomous unilateral cortisol hypersecretion could confound AVS accuracy by increasing cortisol levels (reducing A/C ratio) on the CPA side, while reducing levels (increasing A/C ratio and suggesting failed cannulation) on the CL side. Misclassification of PA subtype or repeat AVS could result, underscoring the importance of adequately assessing cortisol production prior to AVS and the need to consider alternatives.

Differences in Antihypertensive Medication Prescription Profiles Between 2009 and 2021: A Retrospective Cohort Study of CARTaGENE.

Background: Although blood pressure (BP) control is critical to prevent cardiovascular diseases, hypertension control rates in Canada are in decline. Objective: To assess this issue, we sought to evaluate the differences in antihypertensive medication prescription profiles in the province of Quebec between 2009 and 2021. Design: This is a retrospective cohort study. Setting: We used data from the CARTaGENE population-based cohort linked to administrative health databases. Patients: Participants with any drug claim in the 6 months prior to the end of follow-up were included. Measurements: Guideline-recommended antihypertensive drug prescription profiles were assessed at the time of enrollment (2009-2010) and end of follow-up (March 2021). Methods: Prescriptions practices from the 2 time periods were compared using Pearson's chi-square tests. A sensitivity analysis was performed by excluding participants in which antihypertensive drugs may not have been prescribed solely to treat hypertension (presence of atrial fibrillation/flutter, ischemic heart disease, heart failure, chronic kidney disease, or migraines documented prior to or during follow-up). Results: Of 8447 participants included in the study, 31.4% and 51.3% filled prescriptions for antihypertensive drugs at the beginning and end of follow-up. In both study periods, guideline-recommended monotherapy was applied in most participants with hypertension (77.9% vs 79.5%, P = .3), whereas optimal 2 and 3-drug combinations were used less frequently (62.0% vs 61.4%, P = .77, 51.9% vs 46.7%, P = .066, respectively). Only the use of long-acting thiazide-like diuretics (9.5% vs 27.7%, P < .001) and spironolactone as a fourth-line agent (8.3% vs 15.9%, P = .054) increased with time but nonetheless remained infrequent. Results were similar in the sensitivity analysis. Limitations: Specific indication of the prescribed antihypertensive medications and follow-up BP data was not available. Conclusions: Application of hypertension guidelines for the choice of antihypertensive drugs remains suboptimal, highlighting the need for education initiatives. This may be an important step to raise BP control rates in Canada.

Contexte: Bien que le contrôle de la pression artérielle (PA) soit essentiel pour prévenir les maladies cardiovasculaires, les taux de maitrise de l'hypertension artérielle sont en déclin au Canada. Objectifs: Pour traiter cette problématique, nous avons cherché à évaluer les différences dans les profils de prescription de médicaments antihypertenseurs dans la province de Québec entre 2009 et 2021. Conception: Étude de cohorte rétrospective. Cadre: Nous avons utilisé les données de la cohorte populationnelle CARTaGENE reliées aux bases de données administratives en santé. Sujets: Ont été inclus les participants qui ont présenté une demande de remboursement de médicament dans les six mois précédant la fin du suivi. Mesures: Les profils de prescription de médicaments antihypertenseurs recommandés dans les lignes directrices ont été évalués au moment de l'inclusion (2009-2010) et à la fin du suivi (mars 2021). Méthodologie: Les profils de prescription des deux périodes ont été comparés à l'aide des tests Chi-Square de Pearson. Une analyse de sensibilité a été réalisée en excluant les participants pour lesquels les antihypertenseurs n'avaient possiblement pas été prescrits uniquement pour traiter l'hypertension (présence de fibrillation auriculaire, cardiopathie ischémique, insuffisance cardiaque, insuffisance rénale chronique ou migraines documentées avant ou pendant le suivi). Résultats: Des 8 447 participants inclus dans l'étude, 31,4 % avait rempli des prescriptions de médicaments antihypertenseurs au début du suivi et 51,3 % à la fin du suivi. Dans les deux périodes à l'étude, la monothérapie recommandée par les directives a été appliquée chez la plupart des participants avec hypertension artérielle (77,9 % c. 79,5 %; P = 0,3), tandis que les combinaisons optimales de deux médicaments (62,0 % c. 61,4 %; P = 0,77) et de trois médicaments (51,9 % c. 46,7 % P = 0,066) ont été utilisées moins fréquemment. Seules les utilisations de diurétiques thiazidiques à action prolongée (9,5 % c. 27,7 %; P < 0,001) et de spironolactone en quatrième intention (8,3 % c. 15,9 %; P = 0,054) ont augmenté avec le temps, mais sont demeurées néanmoins peu fréquentes. Les résultats étaient similaires dans l'analyse de sensibilité. Limites: L'indication précise pour la prescription de médicaments antihypertenseurs et les données de suivi sur la pression artérielle n'étaient pas disponibles. Conclusion: L'application des lignes directrices sur l'hypertension artérielle pour le choix des médicaments antihypertenseurs reste sous-optimale, ce qui souligne un besoin pour des initiatives en matière d'éducation. Cela pourrait constituer une étape importante d'une stratégie visant l'augmentation des taux de contrôle de la PA au Canada.

Accuracy of methods to estimate central aortic SBP via upper arm cuff: a systematic review and meta-analysis.

OBJECTIVES: Central aortic BP may predict cardiovascular outcomes better than upper arm brachial BP. In recent years, technology has enabled central BP estimation by recording a peripheral BP waveform from a standard upper arm cuff. The accuracy of these devices is not well documented, and this study aimed to address this issue. METHODS: This study was a systematic review, conducted according to PRISMA guidelines, of observational studies published between 2008 and 2023 that reported accuracy testing of cuff-based central BP devices, compared with reference invasive aortic BP. The primary analysis was stratified according to each commercially available device. Pooled estimates were calculated using random-effects models based on mean differences and standard errors. RESULTS: Six thousand four hundred and fifteen studies were screened, and 27 studies met inclusion criteria (plus one unpublished study). This generated data for seven devices that are commercially available, which were tested among 2125 adult participants. There was very high heterogeneity when all devices were pooled (I2 = 97.5%), and, when stratified by device, the accuracy of estimated central BP was highly device-dependent (range of accuracy across different devices -12.4 mmHg (-16.3 to -8.5) to 3.2 mmHg (0.2-6.1). Two of the seven commercially available devices had not undergone external validation testing. CONCLUSION: The accuracy of commercially available cuff-based central BP devices is highly device-specific and not all are accurate for the estimation of central SBP. These findings have major implications for the appropriate interpretation of studies that use cuff-based estimated central BP.

Is health-related quality of life trajectory associated with dialysis modality choice in advanced chronic kidney disease?

BACKGROUND: Patients with advanced chronic kidney disease have lower health-related quality of life (HRQOL) than the general population. There is uncertainty regarding patterns of HRQOL changes before dialysis initiation. This study aimed to characterise HRQOL trajectory and assess its potential association with intended dialysis modality. METHODS: This prospective single-centre cohort study followed adults with an estimated glomerular filtration rate ≤15 mL/min/1.73 m2 for one year. Patients were allocated into one of two groups based on their intended treatment modality, 'home dialysis' (peritoneal dialysis or home haemodialysis (HD)) and 'other' (in-centre HD or conservative care). Follow-up was for up to 1 year or earlier if initiated on kidney replacement therapy or died. Kidney Disease Quality of Life - Short Form (KDQOL-SF) was completed every 6 months. Predictors of changes in KDQOL-SF components were modelled using mixed effect multivariable linear regressions. RESULTS: One hundred and nine patients were included. At baseline, crude physical composite summary (PCS) (45 ± 10 vs. 39 ± 8) was higher in patients choosing home dialysis (n = 41), while mental composite summary (MCS) was similar in both groups. After adjustment, patients choosing home dialysis had an increase in MCS (B = 8.4 per year, p = 0.007) compared to those selecting in-centre HD/conservative care. This translates into an annual increase in MSC by 3 points for the 'home dialysis' group, compared to an annual decline by 5.4 points in the 'other' group. There was no difference in PCS trajectory through time. CONCLUSIONS: Patients choosing home dialysis had improved MCS over time compared to those not selecting home dialysis. More work is needed to determine how differences in processes of care and/or unmeasured patient characteristics modulate this association.

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.

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).

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.

Accuracy of cuff blood pressure and systolic blood pressure amplification.

Automated cuff measured blood pressure (BP) is the global standard used for diagnosing hypertension, but there are concerns regarding the accuracy of the method. Individual variability in systolic BP (SBP) amplification from central (aorta) to peripheral (brachial) arteries could be related to the accuracy of cuff BP, but this has never been determined and was the aim of this study. Automated cuff BP and invasive brachial BP were recorded in 795 participants (74% male, aged 64 ± 11 years) receiving coronary angiography at five independent research sites (using seven different automated cuff BP devices). SBP amplification was recorded invasively by catheter and defined as brachial SBP minus aortic SBP. Compared with invasive brachial SBP, cuff SBP was significantly underestimated (130 ± 18 mmHg vs. 138 ± 22 mmHg, p < 0.001). The level of SBP amplification varied significantly among individuals (mean ± SD, 7.3 ± 9.1 mmHg) and was similar to level of difference between cuff and invasive brachial SBP (mean difference -7.6 ± 11.9 mmHg). SBP amplification explained most of the variance in accuracy of cuff SBP (R2 = 19%). The accuracy of cuff SBP was greatest among participants with the lowest SBP amplification (ptrend < 0.001). After cuff BP values were corrected for SBP amplification, there was a significant improvement in the mean difference from the intra-arterial standard (p < 0.0001) and in the accuracy of hypertension classification according to 2017 ACC/AHA guideline thresholds (p = 0.005). The level of SBP amplification is a critical factor associated with the accuracy of conventional automated cuff measured BP.

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile.

Cellular immune defects associated with suboptimal responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4+, and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses, and enhances comparatively more T helper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.

Gene polymorphisms as clinical tools in chronic glomerulopathies: a prospective study.

BACKGROUND/AIMS: Studies have proposed various polymorphisms of genes implicated in the physiopathology of chronic kidney disease as risk factors of progression and potential clinical tools. We sought to validate and simultaneously compare their predictive value in a prospective cohort of chronic glomerulopathies receiving recommended antihypertensive and antiproteinuric therapies. METHODS: Using PubMed, we identified 9 polymorphisms previously associated with progression. These were mostly of the renin-angiotensin-aldosterone and inflammation pathways: MCP-1 A2518G, TGF-ß1 T869C and C-509T, ACE I/D, AGT M235T, AT1R A1166C, TSC-22 A-396G, eNOS 4b/a and CYP11ß2 C-344T. We hypothesized that their determination would identify individuals at higher risk of progression. RESULTS: We recruited 93 predominantly male and Caucasian patients with a mean age of 63 and baseline eGFR of 33 ml/min/1.73 m(2) followed prospectively over a median of 36 months. 61% of patients had diabetic nephropathy, almost all received RAA blockade (90%) and none immunosuppressive therapy. The average blood pressure during follow-up was 140/72 mm Hg, the urinary protein to creatinine ratio 0.15 g/mmol and the rate of renal function decline -3.2 ± 4.1 ml/min/1.73 m(2)/year. Proteinuria and blood pressure strongly predicted progression. However, under recommended therapy, none of the proposed polymorphisms predicted renal function decline. In addition, none showed simple or partial correlations with the severity of proteinuria or blood pressure. Finally, summation variable of risk polymorphisms did not predict progression. CONCLUSION: This study does not validate the use of these 9 polymorphisms as individual clinical tools in patients with chronic glomerulopathies on recommended antihypertensive and antiproteinuric therapies.

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.