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Arterial hypertension remains the most important modifiable cardiovascular risk factor for morbidity and mortality worldwide. This review summarizes and discusses major clinical trials published in 2023 and early 2024 in hypertension research. These trials include new epidemiological data, studies investigating the impact of blood pressure cuff size on blood pressure measurements, benefits of salt substitutes, and novel antihypertensive treatment options, including pharmacotherapy and bariatric surgery in patients with obesity. This summary reviews the major clinical trials published in 2023 and early 2024. AHT arterial hypertension, BP blood pressure, HR hazard ratio, OBP office blood pressure, PRA plasma renin activity, SBP systolic blood pressure., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension., Methods: We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data., Results: Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P <0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P <0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P <0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P =0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication ( P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P =0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P =0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P =0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P =0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups ( P for interaction, 0.84). There was significant heterogeneity between trials., Conclusions: RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medication.

Background: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce., Aims: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension., Methods: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years., Results: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m 2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up., Conclusion: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension., (© 2024. The Author(s).)

Aims: Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce., Methods and Results: Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P  < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P  = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P  < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P  = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P  < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P  = 0.000) but remained negligible., Conclusion: Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China., Methods: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months., Results: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P <0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P <0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P =0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P =0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up., Conclusions: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham., Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Background: A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches., Aims: This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries., Methods: Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres., Results: A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 μm [31-73], middle 38 μm [26-58], distal 31 μm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 μm [31-81]), followed by the LAD (42 μm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005)., Conclusions: Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.

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.)

Background: Catheter-based renal denervation (RDN) reduces blood pressure in hypertension. Urinary peptides are associated with cardiovascular and renal disease and provide prognostic information. We aimed to investigate the effect of RDN on urinary peptide-based classifiers associated with chronic kidney and heart disease and to identify urinary peptides affected by RDN., Methods: This single-arm, single-center study included patients undergoing catheter-based RDN. Urine samples were collected before and 24 months after RDN and were analyzed using capillary electrophoresis coupled with mass spectrometry. Predefined urinary peptide-based classifiers for chronic kidney disease (CKD273), coronary artery disease (CAD238), and heart failure (HF1) were applied., Results: This study included 48 patients (33% female) with uncontrolled hypertension. At 24 months after RDN, systolic blood pressure (165±17 versus 148±20 mm Hg; P <0.0001), diastolic blood pressure (90±17 versus 81±13 mm Hg; P <0.0001), and mean arterial pressure (115±15 versus 103±13 mm Hg; P <0.0001) decreased significantly. A total of 103 urinary peptides from 37 different proteins, mostly collagens, altered following RDN. CAD238, a 238 coronary artery-specific polypeptide-based classifier, significantly improved following RDN (Cohen's d , -0.632; P =0.0001). The classification scores of HF1 ( P =0.8295) and CKD273 ( P =0.6293) did not change significantly., Conclusions: RDN beneficially affected urinary peptides associated with coronary artery disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01888315., Competing Interests: Disclosures L. Lauder reports speaker honoraria from AstraZeneca, Medtronic, Pfizer, and ReCor Medical. J. Siwy and E. Mavrogeorgis are employees of the Mosaiques Diagnostics GmbH. I.E. Emrich has received speaker honoraria/consulting fees from Pharmacosmos, Astellas, Bristol Myers Squibb, AstraZeneca, and Novartis. M. Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, ReCor Medical, Servier, and Vifor during the conduct of the study. H. Mischak is cofounder and a shareholder of Mosaiques Diagnostics GmbH. F. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. The other authors report no conflicts.

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.

Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and effective in lowering blood pressure (BP) and cardiovascular disease risk, BP control remains poor, and the mortality rates associated with high BP have been steadily increasing. Device-based therapies have been investigated to overcome barriers to pharmacotherapy, including non-adherence and low rates of persistence to daily medications. Among these device-based therapies, catheter-based renal denervation (RDN) has been most extensively examined over the past 15 years. In this state-of-the-art article, we summarise the rationale for RDN, review the available evidence, provide recommendations for a safe procedure, and discuss the role of RDN in current guidelines and clinical practice.

Background: Ultrasound-assisted thrombolysis (USAT) and large-bore-thrombectomy (LBT) are under investigation for the treatment of intermediate-high and high-risk pulmonary embolisms (PE). Comparative studies investigating both devices are scarce., Aims: This study aimed to compare the safety and efficacy of the two most frequently used devices for treatment of acute PE., Methods: This multicenter, retrospective study included 125 patients undergoing LBT or USAT for intermediate- or high-risk PE between 2019 and 2023. Nearest neighbor propensity matching with logistic regression was used to achieve balance on potential confounders. The primary outcome was the change in the right to left ventricular (RV/LV) ratio between baseline and 24 h., Results: A total of 125 patients were included. After propensity score matching, 95 patients remained in the sample, of which 69 (73%) underwent USAT and 26 (27%) LBT. The RV/LV ratio decrease between baseline and 24 h was greater in the LBT than in the USAT group (adjusted between-group difference: -0.10, 95% CI: -0.16 to -0.04; p = 0.001). Both procedures were safe and adverse events occurred rarely (10% following USAT vs. 4% following LBT; p = 0.439)., Conclusion: In acute intermediate-high and high-risk PE, both LBT and USAT were feasible and safe. The reduction in RV/LV ratio was greater following LBT than USAT. Further randomized controlled trials are needed to confirm these findings., (© 2024 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Introduction: The organ donation and transplantation (ODT) system in Canada is complex and can be challenging for individuals to navigate. We thus aimed to illuminate the experiences of individuals on transplant journeys using a patient-oriented convergent parallel mixed-methods approach., Methods: We captured data on adult patients, living donors, and caregivers on transplant journeys across Canada through an online survey (n = 935) and focus groups (n = 21). The survey was comprised of 48 questions about the individuals' experiences with the living donation and transplantation system, which were analyzed descriptively. Qualitative data were analyzed using an inductive conventional content analysis approach., Results: Most participants were female (70.1%), English speaking (92.6%) and White (87.8%). Participants' experiences were represented across six key themes: holistic person-centred care, accountable care, collective impact, navigating uncertainty, connection and advocacy. Quantitative and qualitative data were integrated to identify five opportunities to improve the organ donation and transplantation system in Canada: enhancing mental health support, establishing formal peer support programmes, improving continuity of care, improving knowledge acquisition, and expanding resources and support., Conclusion: It is imperative that the ODT system commits to asking, listening, and learning from individuals on transplant journeys and to provide them opportunities to help improve it., (© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non-pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device-based neuromodulation in HF., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Resistant hypertension (RH) is a severe form of hypertension associated with increased cardiovascular risk. Although true RH affects less than 10% of the patients receiving antihypertensive therapy, the absolute number is high and continues to increase. The workup of these patients requires screening for secondary hypertension and pseudoresistance, including poor adherence to prescribed medicines and the white-coat phenomenon. The treatment of RH consists of lifestyle modifications and pharmacological therapies. Lifestyle modifications include dietary adjustments, weight loss, physical activity, and limiting alcohol consumption; pharmacological therapies include diuretics, mineralocorticoid receptor antagonists, beta blockers, angiotensin receptor-neprilysin inhibitors, and others. Over the last 15 years, interventional approaches have emerged as adjunct treatment options; we highlight catheter-based renal denervation. This review summarizes the rationales and latest clinical evidence and, based thereon, proposes an updated algorithm for the management of RH.

Background: Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown., Method: In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events., Results: During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m 2 or >60 ml/min/1.73 m 2 with an ACR ≥30 mg/g) was 37% vs. 35.3% ( P  = 0.02) vs. 46.4% ( P  < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m 2 vs. 73.2 ± 19.4 ml/min/1.73 m 2 ( P  < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m 2 ( P  < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: -9.5% (95% confidence interval (CI) -13.0% to -5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: -31.1% (95% CI -32.1% to -30.1%))., Conclusion: Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event., Competing Interests: I.E.E. received speaker honoraria from Pharmacosmos, Astellas, Bristol Myers Squibb, AstraZeneca, and Novartis. M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322 900 939) and reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Servier, Medtronic, Vifor, Novartis, and Abbott. F.M. is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. F.G. is supported by Deutsche Herzstiftung and received speaker honoraria from AstraZeneca. L.L. has received speaker honoraria from ReCor Medical and Medtronic. M.K., J.W.P., R.K., V.P., and G.H.H. declare no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Navigating the organ donation and transplantation system in Canada can be challenging for individuals on transplant journeys. Although it is likely that the COVID-19 pandemic has further contributed to these challenges, the experiences of individuals during the pandemic in Canada have not been well elicited., Objective: To illuminate how the COVID-19 pandemic has impacted individuals on transplant journeys in Canada., Design: Convergent parallel mixed-methods study., Setting: Canada., Participants: Adult patients, caregivers, and donors on transplant journeys across Canada., Data Collection: Eight focus groups and an online survey between May and November 2021. Focus group transcripts were analysed using an inductive conventional content analysis approach. Survey data were analysed using descriptive statistics. The study was guided by individuals with lived experience of organ donation and transplantation., Results: A total of 830 participants completed three COVID-19 related survey questions, with 21 participating in the focus groups. Survey results : over 50% of patients and caregivers reported that the pandemic impacted their access to their healthcare team, their mental health (60% and 65%, respectively) and their comfort going out in public (80% and 75%, respectively). Although many donors reported several factors that impacted their transplant journey, the impact appeared to be greater for patients and caregivers. Qualitative results : three themes emerged from the qualitative data that contextualise participant's experiences: compounding isolation, disruption amid uncertainty and unforeseen benefits., Conclusion: The COVID-19 pandemic has exacerbated many of the challenges that individuals on transplant journeys experience. It will be critical for transplant programmes to consider these factors in future care provision., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the past two decades the importance of trunk contribution to sporting performance has been highlighted through the expanse of literature concerning core stability and strength. However, the role of trunk motion and the abdominal muscles are yet to be established during sprint kayak performance. The purpose of this study was to determine the associations among trunk rotation, kayak velocity, and abdominal muscle activity during on-water sprint kayaking. Eight international paddlers completed five 150 m sprint trials. During each trial peak muscle activation (peak root-mean-squared electromyogram) of the latissimus dorsi, rectus abdominus, external obliques and rectus femoris for ipsilateral (stroke side) and contralateral (opposite side) were recorded as the paddler passed through a 5-m calibrated volume, in conjunction with upper and lower trunk rotation and kayak velocity. Results indicated a significant strong negative relationship between lower trunk rotation and peak velocity (r = -0.684, p < 0.05). Furthermore, a significant strong positive relationship (p < 0.05) with mean velocity was identified for the contralateral rectus abdominus and multiple significant associations between the rectus femoris, rectus abdominus and external obliques during the paddle stroke. Findings indicate that limiting the rotation of the lower trunk will increase both the peak and the mean velocity, with the rectus abdominus, external oblique and rectus femoris combining to assist in this process. Training should therefore focus on developing the strength of these muscle groups to enhance performance., Competing Interests: There were no conflicts of interest., (Copyright: © Academy of Physical Education in Katowice.)

Objective: Dietary sodium intake represents a risk factor for cardiovascular disease and mortality. The study sought to analyse the sodium content of effervescent dietary supplements and drugs in Germany and the USA., Design: Comparative cross-sectional study., Setting and Methods: The sodium content of 39 dietary supplement effervescent tablets available in Germany was measured in May and June 2022 using optical emission spectrometry with inductively coupled argon plasma. The sodium content of 33 common pharmacy-only effervescent tablets (over-the-counter (OTC) drugs) in Germany was obtained from the summary of product characteristics. We compared the sodium content of the measured German dietary supplement effervescent tablets to that of 51 dietary supplement effervescent tablets available in the USA (data: National Institutes of Health's Dietary Supplement Label Database)., Results: The measured sodium content in the German dietary supplements was 283.9±122.6 mg sodium/tablet, equivalent to 14±6% of the maximum recommended daily sodium intake (MRDSI). Vitamin products had the highest (378.3±112.8 mg, 19±6% of MRDSI), and calcium products had the lowest mean sodium content (170.4±113.2 mg, 9±6% of MRDSI). Vitamin products contained significantly more sodium than magnesium (378.3 mg vs 232.7 mg; p=0.004), calcium (378.3 mg vs 170.4 mg; p=0.006) and mineral products (378.3 mg vs 191.6 mg; p=0.048). The sodium content measured in products available in Germany was higher when compared with the declared sodium content on the label of the products sold in the USA (283.9 mg vs 190.0 mg; p<0.001). The median summary of product characteristics-declared sodium content of a single dose of the German OTC drugs was 157.0 mg (IQR: 98.9-417.3 mg); pain/common cold drugs contained the most sodium (median: 452.1 mg; IQR: 351.3-474.0 mg)., Conclusion: Effervescent tablets of nutritional supplements and OTC drugs contain high amounts of sodium, which often is not disclosed., Competing Interests: Competing interests: MB is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cytokinetic, Edwards, Medtronic, Novartis, ReCor Medical, Servier and Vifor. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219) and Deutsche Herzstiftung and has received scientific support and/or speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck and ReCor Medical. LL has received speaker honoraria from ReCor Medical and Medtronic. CU has received lecture honoraria or consulting fees from Bayer, Bristol Myers Squibb, Medtronic and ReCor Medical. UL has received speaker honoraria from Amgen, Daiichi Sankyo, Novartis and Sanofi, all outside the submitted work. MS has received speaker honoraria from BMS, Daiichi Sankyo, DGK-Academy, Pfizer and Sanofi and consulting fees from CSL Vifor, MSD and Novartis, all outside the submitted work. FG is supported by German Foundation for Heart Research (Deutsche Herzstiftung) and has received speaker honoraria from AstraZeneca. The other authors do not have conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications., Objectives: This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications., Methods: SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis., Results: The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients., Conclusions: There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775)., Competing Interests: Funding Support and Author Disclosures This study was funded by Medtronic. Dr Kandzari has received institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc, Orbus Neich, Teleflex, Medtronic, and Ablative Solutions; and has received personal consulting honoraria from Cardiovascular Systems, Inc, Medtronic, and Abbott Vascular. Dr Townsend is a consultant for Medtronic, Cytel, and Janssen. Dr Kario has received personal fees from Medtronic during the conduct of the study; has received grants from A&D Company, Omron Healthcare, Fukuda Denshi, CureApp, Sanwa Kagaku Kenkyusho, Teijin Pharma, Boehringer Ingelheim Japan, and Fukuda Lifetec; has received consulting fees from A&D Company, JIMRO, Omron Healthcare, CureApp, Terumo, and Fukuda Denshi; has received honoraria from Otsuka Pharmaceuticals and Omron Healthcare; and has participated on the Advisory Board of Fukuda Denshi, outside of the submitted work. Dr Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung; has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical; and has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. Dr Weber has received consulting fees from Medtronic, ReCor, Ablative Solutions, Johnson and Johnson, and Urovant. Dr Schmieder has received grants and personal fees from Medtronic, Recor, and Ablative Solutions. Dr Pocock has received personal fees from Medtronic outside of the submitted work. Dr Tsioufis has received institutional research/grant support from Medtronic and ReCor Medical; and has received personal consulting honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, ReCor Medical, SERVIER, WinMedica, and ELPEN. Dr Konstantinidis receives payments from Medtronic for work as research center secondary investigator. Dr Choi has received consulting fees from Medtronic, outside of the submitted work. Dr East has received consulting fees from Medtronic. Dr Lauder has received speaker fees and honoraria from Medtronic and ReCor Medical. Dr Cohen has received research support and consultant fees from Medtronic and ReCor; and receives fees from Metavention, outside of the submitted work. Dr Kobayashi is on the advisory board and Speakers Bureau for Medtronic and ReCor Medical. Dr Lee has received grants from and serves on the advisory board for Medtronic, outside of the submitted work. Dr Weil has received support from Medtronic, Recor Medical, Novartis, and AstraZeneca. Dr Agdirlioglu receives speaker honoraria from AstraZeneca, Boehringer Ingelheim, and Novartis, outside of the submitted work. Dr Schlaich has received consulting fees and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer Ingelheim. Dr Shetty has received consulting and speaker fees from Medtronic. Dr Devireddy has received personal fees from Edwards Lifesciences, Medtronic, ReCor Medical, and Shockwave Medical, outside of the submitted work. Dr Sharp has received personal fees from Medtronic, Boston Scientific, Recor Medical, and Philips, outside the submitted work. Dr Anderson has received speaker fees from Shockwave Medical, Edwards Lifesciences, and Medtronic. Mr Fahy, Mrs DeBruin, and Dr Brar are employees of Medtronic. Dr Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939); and has received personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor, Servier, and Vifor during the conduct of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro ., Methods: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis., Results: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins., Conclusion: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)