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Background: Resistant hypertension is characterized by elevated blood pressure (BP) despite using 3 antihypertensive agents. Ambulatory BP monitoring (ABPM) detects the presence of white-coat resistant hypertension (24-hour BP <130/80 mm Hg). The aim of the study was to evaluate risks of death in resistant hypertension compared with controlled hypertension, as well as in ABPM-confirmed (24-hour BP ≥130 or 80 mm Hg), versus white-coat resistant hypertension., Methods: We selected 8146 patients with controlled hypertension (office BP <140/90 mm Hg while being treated with ≤3 antihypertensive drugs) and 8577 with resistant hypertension (BP ≥140 or ≥90 mm Hg while being treated with ≥3 drugs). All-cause and cardiovascular mortalities (median follow-up, 9.7 years) were compared between groups, as well as between patients with white-coat (3289) and ABPM-confirmed (5288) resistant hypertension. Hazard ratios (HRs) from Cox models after adjustment for clinical confounders were used for comparisons., Results: Compared with controlled hypertension, resistant hypertension was associated with an increased risk in all-cause (HR, 1.21 [95% CI, 1.12-1.30]) and cardiovascular mortalities (HR, 1.33 [95% CI, 1.17-1.51]) in confounder-adjusted models. Compared with white-coat, ABPM-confirmed resistant hypertension was associated with an increased risk of all-cause (HR, 1.45 [95% CI, 1.32-1.60]) and cardiovascular (HR, 1.68 [95% CI, 1.43-1.98]) mortalities. When ABPM-confirmed and white-coat resistant hypertension were separately compared with controlled hypertension, only the former was associated with an increased risk of death and cardiovascular death (HR, 1.36 [95% CI, 1.26-1.48] and 1.56 [95% CI, 1.36-1.79]), respectively., Conclusions: ABPM-confirmed resistant hypertension is associated with an increased risk of death and cardiovascular death with respect to both controlled hypertension and white-coat resistant hypertension.

Aims: Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline., Methods and Results: A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (P interaction  = 0.1075 for composite CV outcome and P interaction  = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (P interaction  = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups., Conclusions: In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiovascular-kidney-metabolic syndrome is an emerging entity that connects cardiovascular diseases, chronic kidney disease, and diabetes. The non-steroidal mineralocorticoid receptor antagonist, finerenone, has been studied in three prospective randomized clinical trials of patients with cardio-kidney-metabolic syndrome: FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF. In light of the strong epidemiological overlap and shared mechanistic drivers of clinical outcomes across cardio-kidney-metabolic syndrome, we summarize the efficacy and safety of finerenone on cardiovascular, kidney, and mortality outcomes in this prespecified participant-level pooled analysis. The three trials included 18,991 participants (mean age 67 ± 10 years; 35% women). During 2.9 years median follow-up, the primary outcome of cardiovascular death occurred in 421 (4.4%) assigned to finerenone and 471 (5.0%) assigned to placebo (HR 0.89; 95% CI 0.78-1.01; P = 0.076). Death from any cause occurred in 1,042 (11.0%) participants in the finerenone arm and 1,136 (12.0%) in the placebo arm (HR 0.91; 95% CI 0.84-0.99; P = 0.027). Finerenone further reduced the risk of HF hospitalization (HR 0.83; 95% CI 0.75-0.92; P < 0.001) and the composite kidney outcome (HR 0.80; 95% CI 0.72-0.90; P < 0.001). While this pooled analysis failed to demonstrate significant reductions in cardiovascular death, finerenone was associated with significantly lower deaths of any cause, cardiovascular events, and kidney outcomes. PROSPERO identifier: CRD42024570467., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Guidelines suggest similar blood pressure (BP) targets in patients with and without diabetes and recommend ambulatory BP monitoring (ABPM) to diagnose and classify hypertension. It was explored whether different levels of ambulatory and office BP and different hypertension phenotypes associate with differences of risk in diabetes and no diabetes., Methods: This analysis assessed outcome data from the Spanish ABPM Registry in 59 124 patients with complete available data. The associations between office, mean, daytime, and nighttime ambulatory BP with the risk in patients with or without diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes, i.e. sustained hypertension, white-coat hypertension, and masked hypertension, compared with normotension were studied. Analyses were done with Cox regression analyses and adjusted for demographic and clinical confounders., Results: A total of 59 124 patients were recruited from 223 primary care centres in Spain. The majority had an office systolic BP >140 mmHg (36 700 patients), and 23 128 (40.6%) patients were untreated. Diabetes was diagnosed in 11 391 patients (19.2%). Concomitant cardiovascular (CV) disease was present in 2521 patients (23.1%) with diabetes and 4616 (10.0%) without diabetes. Twenty-four-hour mean, daytime, and nighttime ambulatory BP were associated with increased risk in diabetes and no diabetes, while in office BP, there was no clear association with no differences with and without diabetes. While the relative association of BP to CV death risk was similar in diabetes compared with no diabetes (mean interaction P = .80, daytime interaction P = .97, and nighttime interaction P = .32), increased event rates occurred in diabetes for all ABPM parameters for CV death and all-cause death. White-coat hypertension was not associated with risk for CV death (hazard ratio 0.86; 95% confidence interval 0.72-1.03) and slightly reduced risk for all-cause death in no diabetes (hazard ratio 0.89; confidence interval 0.81-0.98) but without significant interaction between diabetes and no diabetes. Sustained hypertension and masked hypertension in diabetes and no diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no diabetes and CV death risk (interaction P = .26), while some interaction was present for all-cause death (interaction P = .043) and non-CV death (interaction P = .053)., Conclusions: Diabetes increased the risk for all-cause death, CV, and non-CV death at every level of office and ambulatory BP. Masked and sustained hypertension confer to the highest risk, while white-coat hypertension appears grossly neutral without interaction of relative risk between diabetes and no diabetes. These results support recommendations of international guidelines for strict BP control and using ABPM for classification and assessment of risk and control of hypertension, particularly in patients with diabetes., Clinical Trial Registration: Not applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: It has been suggested that a blunted nocturnal blood pressure (BP) decline is associated with a poor prognosis. Nevertheless, it remains unclear if an abnormal dipping is deleterious per se or it merely reflects an elevated BP during sleep. We aimed to assess the prognostic value of nocturnal BP decline, with or without concomitant elevated nocturnal BP., Methods: Vital status and cause of death were obtained from death certificates in 59 124 patients, enrolled in the Spanish ABPM Registry between 2004 and 2014 (median follow-up: 10 years). The association between night-to-day ratio (NDR) and dipping patterns (extreme dippers, dippers, reduced dippers, and risers) with all-cause and cardiovascular mortality were evaluated by Cox-proportional models adjusted for clinical confounders and 24 h blood pressure., Results: NDR was associated with all-cause mortality [hazard ratio for 1SD change: 1.15; 95% confidence interval (CI) 1.13-1.17]. Reduced dippers (1.13; 1.06-1.20) and risers (1.41; 1.32-1.51) were associated with an increased risk of all-cause death, whereas extreme dippers (0.90; 0.79-1.02) were not. Elevated NDR (≥0.9) in the absence of elevated night SBP (<120 mmHg) was associated with an increased risk of death (1.13; 1.04-1.22), as well as elevated night SBP but normal NDR (1.38; 1.26-1.50), and the combination of both abnormalities (1.56; 1.46-1.66). Similar results were obtained for cardiovascular mortality., Conclusion: Abnormalities in the circadian pattern are associated with an increased risk of all-cause and cardiovascular mortality. This is maintained even in the absence of nocturnal BP elevation., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

Introduction: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear., Methods: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%])., Results: There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients., Conclusion: DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients., (© 2024 S. Karger AG, Basel.)

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., Competing Interests: Disclosures None.

Background: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning-derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP)., Methods: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used., Results: For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865; P =3.61×10 - 28 ), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited., Conclusions: The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics.

Objectives: This study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or sex., Design: FIDELITY post hoc analysis; median follow-up of 3 years., Setting: FIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials., Participants: Adults with type 2 diabetes and chronic kidney disease receiving optimised renin-angiotensin system inhibitors (N=13 026)., Interventions: Randomised 1:1; finerenone or placebo., Primary and Secondary Outcome Measures: Cardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes., Results: Mean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65-74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65-74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); P interaction =0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); P interaction =0.99). Effects on HHF reduction were not modified by age (P interaction =0.70) but appeared more pronounced in males (P interaction =0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65-74 but not ≥75; no heterogeneity in treatment effect was observed (P interaction =0.51). In sex subgroups, finerenone consistently reduced kidney events (P interaction =0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups., Conclusions: Finerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups., Trial Registration Numbers: NCT02540993, NCT02545049., Competing Interests: Competing interests: SB reports research support from 3ive, Bayer, Boehringer Ingelheim, Novartis and Novo Nordisk; honorarium from UpToDate; consultancy fees from Baxter; and speaker bureau fees from Home Dialysis University and PD Excellence Academy. MEFC reports consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Fresenius Medical Care, and research support from Baxter and Fresenius. RB reports consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, MSD, Mundipharma, Sanofi and Servier. SDA reports grants from Abbott Vascular and Vifor International; and personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BioVentrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Impulse Dynamics, Janssen, Novartis, Occlutech, Respicardia, Servier, Vectorious and V-Wave. GLB reports consultancy fees from Alnylam, Ionis and Merck. GF is a trial committee member for Amgen, Bayer (no fees received), Boehringer Ingelheim, Medtronic, Novartis, Servier and Vifor. PR reports personal fees from Bayer during the conduct of the study; he has received research support and personal fees from AstraZeneca and Novo Nordisk, and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi and Vifor; all fees are given to Steno Diabetes Center Copenhagen. LMR reports consultancy fees from Bayer. AEF, PK, AL and MB are all full-time employees of Bayer. BP reports consultant fees for AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, and Vifor/Relypsa; he has stock options for Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida, and Vifor/Relypsa; he also holds a patent for site-specific delivery of eplerenone to the myocardium (US patent #9931412) and a provisional patent for histone-acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045784)., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk., Methods: The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk., Results: At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome ( P  = .31)., Conclusions: Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression., Competing Interests: N.T. reports having consultancy agreements with Marizyme, Mesentech, PulseData and Renibus; an ownership interest in ClinPredict, Klinrisk, Marizyme, Mesentech, PulseData, Quanta and Renibus; receiving research funding from AstraZeneca, Bayer, BI-Lilly, Janssen and Otsuka; receiving honoraria from AstraZeneca, Bayer, BI-Lilly, Janssen, Otsuka Pharmaceuticals and Pfizer; patents or royalties with Klinrisk and Marizyme; an advisory or leadership role with ClinPredict and Klinrisk; other interests or relationships with the National Kidney Foundation; and being the founder of ClinPredict and Klinrisk. T.F. reports personal fees from Baxter, ClinPredict, Quanta Dialysis Technologies and Strategic Health Resources, and personal fees/other from Klinrisk. S.J.L. reports personal fees from Quanta Dialysis Technologies. S.D.A. reports grants from Abbott Vascular and Vifor International, and personal fees from Amgen, AstraZeneca, Bayer, BioVentrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Impulse Dynamics, Janssen, Novartis, Occlutech, Respicardia, Servier, Vectorious and V-Wave. G.F. reports lecture fees and/or being a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier and Vifor Pharma. He is a senior consulting editor for JACC: Heart Failure and has received research support from the EU. B.P. reports consultant fees for AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; has stock options for Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; and holds a patent for site-specific delivery of eplerenone to the myocardium (US patent 9931412) and a provisional patent for histone acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045,784). P.R. reports personal fees from Bayer during the conduct of the study; research support and personal fees from AstraZeneca and Novo Nordisk and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor. All fees are given to Steno Diabetes Center Copenhagen. L.M.R. reports consultancy fees from Bayer. A.E.F. is a full-time employee of Bayer PL, Germany. Y.M.K.F. is a full-time employee of Bayer US. P.S. is a part-time employee of Bayer AG, Pharmaceuticals Division, Germany. R.L. and K.R. are full-time employees of Bayer AG, Pharmaceuticals Division, Germany. G.L.B. reports research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; acted as a consultant and received personal fees from Alnylam, Merck and Relypsa; is an Editor of the American Journal of Nephrology, Nephrology and Hypertension, Section Editor of UpToDate and an Associate Editor of Diabetes Care and Hypertension Research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objective: To explore whether insulin resistance, assessed by estimated glucose disposal rate (eGDR), is associated with cardiorenal risk and whether it modifies finerenone efficacy., Research Design and Methods: In FIDELITY (N = 13,026), patients with type 2 diabetes, either 1) urine albumin-to-creatinine ratio (UACR) of ≥30 to <300 mg/g and estimated glomerular filtration rate (eGFR) of ≥25 to ≤90 mL/min/1.73 m2 or 2) UACR of ≥300 to ≤5,000 mg/g and eGFR of ≥25 mL/min/1.73 m2, who also received optimized renin-angiotensin system blockade, were randomized to finerenone or placebo. Outcomes included cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney (kidney failure, sustained decrease of ≥57% in eGFR from baseline, or renal death) composites. eGDR was calculated using waist circumference, hypertension status, and glycated hemoglobin for 12,964 patients., Results: Median eGDR was 4.1 mg/kg/min. eGDR

Introduction and Objectives: This study aimed to describe the cardiovascular risk profile of working young adults from Spain and its association with lifestyle., Methods: Participants (18-30 years) were recruited from a nationwide cohort of economically active adults insured by a large occupational risk prevention company, with data obtained from routine medical assessments. The participants were categorized as having an "unhealthy" cardiovascular risk profile based on the presence of prediabetes/diabetes, prehypertension/hypertension, or hypercholesterolemia, or a "healthy" profile if these conditions were completely absent. The association with lifestyle factors (weight, physical activity, sleeping characteristics, alcohol consumption, smoking) was assessed., Results: A total of 78 421 young adults (27±2 years, 36% female) were evaluated at baseline. The "unhealthy" cardiovascular risk profile was prevalent (18%) and inversely associated (OR, 0.64; 95%CI, 0.57-0.80) with an optimal lifestyle (normal weight, regular physical activity, no drinking/smoking, and good sleep). The latter condition was found in only 3.5% of the participants. On the other hand, prospective analyses in 44 776 participants (median follow-up=2 [range 2-5] years) showed that 2.0% transitioned from a "healthy" to an "unhealthy" profile. Being physically active (OR, 0.95; 95%CI, 0.81-0.99) and having a normal weight (OR, 0.61; 95%CI, 0.51-0.70) were associated with a lower likelihood of this transition. No consistent associations were found for other lifestyle factors., Conclusions: The prevalence of cardiovascular risk factors is high in economically active young Spanish adults. An unhealthy cardiovascular risk profile is inversely associated with an optimal lifestyle, but the latter is highly infrequent in this population., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Whether bedtime versus morning administration of antihypertensive therapy is beneficial on outcomes is controversial. We evaluated the risk of total and cardiovascular mortality in a very large observational cohort of treated hypertensive patients, according to the timing of their usual treatment administration (morning versus evening)., Methods: Vital status and cause of death were obtained from death certificates of 28 406 treated hypertensive patients (mean age 62 years, 53% male individuals), enrolled in the Spanish Ambulatory Blood Pressure Monitoring (ABPM) Registry between 2004 and 2014. Among the 28 406 patients, most (86%) received their medication exclusively in the morning; whilst 13% were treated exclusively in the evening or at bedtime. Follow-up was for a median of 9.7 years and 4345 deaths occurred, of which 1478 were cardiovascular deaths., Results: Using Cox-models adjusted for clinical confounders and 24-h SBP, and compared with patients treated in the morning (reference group), all-cause mortality [hazard ratio 1.01; 95% CI 0.93-1.09) and cardiovascular mortality (hazard ratio 1.04; 95% CI 0.91-1.19) was not significantly different in those receiving evening medication dosing. The results were consistent in all the subgroups of patients analysed., Conclusion: In this very large observational study, morning versus bedtime dosing of antihypertensive medication made no difference to the subsequent risk of all-cause or cardiovascular mortality. These findings are in accordance with results from a recent randomized controlled trial and do not support the hypothesis of a specific beneficial effect of night-time antihypertensive treatment dosing on risk of all-cause or cardiovascular death., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis., Materials and Methods: Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure., Results: ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively)., Conclusions: Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self-reported physical activity (PA) and CKD and also studied whether PA attenuates CKD-associated CVD risk., Methods: A cohort of Spanish adults (18-64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m 2 ) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow-up., Results: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow-up = 2 years, range = 2-5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross-sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79-0.81), but not insufficient PA (1.02; 0.99-1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow-up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (-45% to -7%) and incidence (-38% to -4%) of all CVD risk factors., Conclusion: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)