Chronic Kidney Disease (CKD) is associated with high cardiovascular disease (CVD) risk, and require specific interventions to decreases CVD risk.The guidelines indicate that systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. The European Society Cardiology (ESC) guidelines, he European Renal Association (ERA) Council and the Spanish Society of Nephrology (S.E.N.) in collaboration with 15 Scientific Societies recommend assessing albuminuria in all these populations.We have evaluated current clinical practice regarding the assessment of CVD risk factors (blood pressure, albuminuria, serum cholesterol, glycemia and creatinine) in different adult health user populations, analyzing the results separately for men and women, given recent evidence on gender differences in the recognition, monitoring, and management of CKD.Methods: Observational, retrospective, non-interventional single centre study performed in a hospital using Electronic Health Record(EHR) data.Results: Among 707,493 healthcare users, 612,619 were adults, and of these 332,943 (54.3%) females; 73,632 (12.0%) had DM and 121,445 (19.8%) hypertension. Mean (SD) age was 68,91±21,4 years; 261,694 (36.9%) were older than 50 years.Only 8,522 (1.39%) had undergone albuminuria testing as compared with 264,684 (43.21%) tested for serum creatinine, 140,492 (22.93%) for serum cholesterol, 263,381 (42.99%) for serum glucose, and 226,448 (36.96%) for blood pressure. Albuminuria was the only cardiovascular risk factor assessed more frequently in men than in women.Albuminuria, as other CVD risk factors, was more frequently assessed in patients with DM (6.71% of patients) or hypertension (4.81%), but albuminuria assessment remained suboptimal compared with 58% to 87% for other cardiovascular risk factors. For adults with diabetes or hypertension, albuminuria was assessed more frequently in men than in women.Albuminuria assessment in those older than 50 years was also suboptimal at 2.24%, as compared with 31% to 47% for other CVD risk factors.Albuminuria and EGFR are needed to screen for CKD, meaning that a urine test for albumin and creatinine and a serum test for creatinine are needed. To these, we may add assessment of Blood pressure, serum Cholesterol (for familial hypercholesterolemia) and serum glucose for Diabetes. Albuminuria was the only cardiovascular risk factor that was assessed more frequently in men (up to nearly 60% more frequently), indicating that screening for CKD and CVD risk in women is suboptimal. This result is surprisingly consistent across time and in all age groups. This is the first time that gender disparities in the assessment of albuminuria has been revealed.Conclusion: Albuminuria is assessed infrequently, even in patients with a high cardiovascular risk, especially in women.

Myokines are signalling moieties released by the skeletal muscle in response to acute and/or chronic exercise, which exert their beneficial or detrimental effects through paracrine and/or autocrine pathways on the skeletal muscle and through endocrine pathways in many other organs (e.g. the heart). Interestingly, alterations in myokines have been described in patients with heart failure (HF) that are associated with adverse structural and functional left ventricular remodelling and poor cardiac outcomes. Recent experimental and clinical studies have shown that the muscle regulation of a number of myokines is altered in chronic kidney disease (CKD) thus representing a new molecular aspect of the pathophysiology of skeletal myopathy present in patients with CKD. Muscle dysregulation of myokines may contribute to a number of disorders in non-dialysis and dialysis patients with CKD, including the high risk of developing HF. This possibility would translate into a range of new diagnostic and therapeutic options. In fact, the measurement of circulating myokines opens their possible usefulness as biomarkers to personalize exercise training and pharmacological therapies for the prevention and treatment of HF in patients with CKD and skeletal myopathy. This review will analyse information on some myokines that target the heart and are altered at the level of skeletal muscle and circulation in patients with CKD.

Background: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. Summary: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. Key Messages: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and constitutes a central pathophysiological process that underlies tissue dysfunction, across organs, in multiple chronic diseases and during aging. Myocardial fibrosis is a key contributor to dysfunction and failure in numerous diseases of the heart and is a strong predictor of poor clinical outcome and mortality. The excess structural and matricellular ECM proteins deposited by cardiac fibroblasts, is found between cardiomyocytes (interstitial fibrosis), in focal areas where cardiomyocytes have died (replacement fibrosis), and around vessels (perivascular fibrosis). Although myocardial fibrosis has important clinical prognostic value, access to cardiac tissue biopsies for histological evaluation is limited. Despite challenges with sensitivity and specificity, cardiac magnetic resonance imaging (CMR) is the most applicable diagnostic tool in the clinic, and the scientific community is currently actively searching for blood biomarkers reflecting myocardial fibrosis, to complement the imaging techniques. The lack of mechanistic insights into specific pro- and anti-fibrotic molecular pathways has hampered the development of effective treatments to prevent or reverse myocardial fibrosis. Development and implementation of anti-fibrotic therapies is expected to improve patient outcomes and is an urgent medical need. Here, we discuss the importance of the ECM in the heart, the central role of fibrosis in heart disease, and mechanistic pathways likely to impact clinical practice with regards to diagnostics of myocardial fibrosis, risk stratification of patients, and anti-fibrotic therapy.

European Journal of Heart FailureEarly View Viewpoint Reassessing the management of hypertension: Time to prevent aldosterone-mediated heart failure Bertram Pitt, Bertram Pitt Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USASearch for more papers by this authorJenifer M. Brown, Jenifer M. Brown Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USASearch for more papers by this authorAnand Vaidya, Anand Vaidya Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USASearch for more papers by this authorJavier Diez, Corresponding Author Javier Diez [email protected] Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Pamplona, Spain Center for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain Corresponding author. Edificio CIMA, Av Pío XII 55, 31008 Pamplona, Spain. Email: [email protected]Search for more papers by this author Bertram Pitt, Bertram Pitt Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USASearch for more papers by this authorJenifer M. Brown, Jenifer M. Brown Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USASearch for more papers by this authorAnand Vaidya, Anand Vaidya Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USASearch for more papers by this authorJavier Diez, Corresponding Author Javier Diez [email protected] Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Pamplona, Spain Center for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain Corresponding author. Edificio CIMA, Av Pío XII 55, 31008 Pamplona, Spain. Email: [email protected]Search for more papers by this author First published: 18 January 2024 https://doi.org/10.1002/ejhf.3141Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1Diez J, Butler J. Growing heart failure burden of hypertensive heart disease: A call to action. Hypertension 2023; 80: 13–21. https://doi.org/10.1161/HYPERTENSIONAHA.122.19373 10.1161/HYPERTENSIONAHA.122.19373 CASPubMedGoogle Scholar 2 World Health Organization. Global report on hypertension: The race against a silent killer. Geneva: WHO; 2023. Google Scholar 3Díez J, Rosano G, Butler J. Time to reconsider the perception and management of hypertensive heart disease. Eur J Heart Fail 2023; 25: 450–453. https://doi.org/10.1002/ejhf.2811 10.1002/ejhf.2811 PubMedWeb of Science®Google Scholar 4Cannone V, Buglioni A, Sangaralingham J, Scott C, Bailey KR, Rodeheffer R, et al. Aldosterone, hypertension, and antihypertensive therapy: Insights from a general population. Mayo Clin Proc 2018; 93: 980–990. https://doi.org/10.1016/j.mayocp.2018.05.027 10.1016/j.mayocp.2018.05.027 CASPubMedWeb of Science®Google Scholar 5Baudrand R, Vaidya A. The low-renin hypertension phenotype: Genetics and the role of the mineralocorticoid receptor. Int J Mol Sci 2018; 19:546. https://doi.org/10.3390/ijms19020546 10.3390/ijms19020546 PubMedWeb of Science®Google Scholar 6Brown JM, Siddiqui M, Carey R, Siddiqui M, Williams GH. The unrecognized prevalence of primary aldosteronism: A cross-sectional study. Ann Intern Med 2020; 173: 10–20. https://doi.org/10.7326/M20-0065 10.7326/M20-0065 PubMedWeb of Science®Google Scholar 7Brown JM, Robinson-Cohen C, Luque-Fernandez MA Allison MA, Baudrand R, Ix JH, et al. The spectrum of subclinical primary aldosteronism and incident hypertension: A cohort study. Ann Intern Med 2017; 167: 630–641. https://doi.org/10.7326/M17-0882 10.7326/M17-0882 PubMedWeb of Science®Google Scholar 8Inoue K, Goldwater D, Allison M, Seeman T, Kestenbaum BR, Watson KA. Serum aldosterone concentration, blood pressure, and coronary artery calcium: The Multhi-Ethnic Study of Atherosclerosis. Hypertension 2020; 76: 113–120. https://doi.org/10.1161/HYPERTENSIONAHA.120.15006 10.1161/HYPERTENSIONAHA.120.15006 CASPubMedWeb of Science®Google Scholar 9Gray Z, Tu W, Chertow GM, Bhalla V. Aldosterone sensitivity: An opportunity to explore the pathogenesis of hypertension. Am J Physiol Renal Physiol 2021; 320: F325–F335. https://doi.org/10.1152/ajprenal.00415.2020 10.1152/ajprenal.00415.2020 CASPubMedGoogle Scholar 10Brown JM, Wijkman MO, Claggett BL, Shah AM, Ballantyne CM, Coresh J, et al. Cardiac structure and function across the spectrum of aldosteronism: The Atherosclerosis Risk in Communities study. Hypertension 2022; 79: 1984–1993. https://doi.org/10.1161/HYPERTENSIONAHA.122.19134 10.1161/HYPERTENSIONAHA.122.19134 CASPubMedGoogle Scholar 11Bauersachs J, López-Andrés N. Mineralocorticoid receptor in cardiovascular diseases – Clinical trials and mechanistic insights. Br J Pharmacol 2022; 179: 3119–3134. https://doi.org/10.1111/bph.15708 10.1111/bph.15708 CASPubMedWeb of Science®Google Scholar 12Mancia G, Kreutz R, Brunström M, Burnier M, Grassi G, Januszewicz A, et al. 2023 ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023; 41: 1874–2071. https://doi.org/10.1097/HJH.0000000000003480 10.1097/HJH.0000000000003480 CASPubMedWeb of Science®Google Scholar 13Williams B, MacDonald TM, Morant SV, Webb DJ, Sever P, McInnes GT, et al. Endocrine and haemodynamic changes in resistant hypertension, and blood pressure responses to spironolactone or amiloride: The PATHWAY-2 mechanisms substudies. Lancet Diabetes Endocrinol 2018; 6: 464–475. https://doi.org/10.1016/S2213-8587(18)30071-8 10.1016/S2213-8587(18)30071-8 PubMedWeb of Science®Google Scholar 14Agarwal R, Ruilope LM, Ruiz-Hurtado G, Haller H, Schmieder RE, Anker SD, et al. Effect of finerenone on ambulatory blood pressure in chronic kidney disease in type 2 diabetes. J Hypertens 2023; 41: 295–302. https://doi.org/10.1097/HJH.0000000000003330 10.1097/HJH.0000000000003330 CASPubMedWeb of Science®Google Scholar 15Freeman MW, Halvorsen YD, Marshall W, Pater M, Isaacsohn J, Pearce C, et al.; BrigHTN Investigators. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med 2023; 388: 395–405. https://doi.org/10.1056/NEJMoa2213169 10.1056/NEJMoa2213169 CASPubMedWeb of Science®Google Scholar 16Laffin LJ, Rodman D, Luther JM, Vaidya A, Weir MR, Rajicic N, et al.; Target-HTN Investigators. Aldosterone synthase inhibition with lorundrostat for uncontrolled hypertension: The Target-HTN randomized clinical trial. JAMA 2023; 330: 1140–1150. https://doi.org/10.1001/jama.2023.16029 10.1001/jama.2023.16029 CASPubMedGoogle Scholar 17Serenelli M, Jackson A, Dewan P, Jhund PS, Petrie MC, Rossignol P, et al. Mineralocorticoid receptor antagonists, blood pressure, and outcomes in heart failure with reduced ejection fraction. JACC Heart Fail 2020; 8: 188–198. https://doi.org/10.1016/j.jchf.2019.09.011 10.1016/j.jchf.2019.09.011 PubMedWeb of Science®Google Scholar 18Selvaraj S, Claggett B, Shah SJ, Anand I, Rouleau JL, Desai AS, et al. Systolic blood pressure and cardiovascular outcomes in heart failure with preserved ejection fraction: An analysis of the TOPCAT trial. Eur J Heart Fail 2018; 20: 483–490. https://doi.org/10.1002/ejhf.1060 10.1002/ejhf.1060 CASPubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL.

ObjectiveHeart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone.MethodsIn this substudy (n=290) to the Heart ‘Omics’ in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25–50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher’s Z transform.ResultsMultivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66–95) to 75 (61–90) µg/L and PICP/CITP from 22 (17–28) to 18 (13–26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of −0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio.ConclusionsSpironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs.Trial registration numberNCT02556450.

El exceso de volumen en la insuficiencia cardiaca explica la mayoría de los síntomas y signos, y está relacionado con la progresión de la enfermedad. Es un fenómeno complejo que va más allá del incremento de presiones intravasculares, lo que dificulta su correcto diagnóstico y supone un gran reto terapéutico. En la actualidad, se recomienda un abordaje multiparamétrico que incluya datos clínicos (síntomas y signos), pruebas de imagen y biomarcadores. El presente artículo propone un enfoque terapéutico práctico de la sobrecarga hidrosalina en la insuficiencia cardiaca tanto en el ámbito hospitalario como en el ambulatorio. Este documento es una iniciativa de la Sociedad Española de Medicina Interna en colaboración con la Sociedad Española de Cardiología y la Sociedad Española de Nefrología. Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine in collaboration with the Spanish Society of Cardiology and the Spanish Society of Nephrology.

Myocardial remodelling, entailing cellular and molecular changes in the different components of the cardiac tissue in response to damage, underlies the morphological and structural changes leading to cardiac remodelling, which in turn contributes to cardiac dysfunction and disease progression. Since cardiac tissue is not available for histomolecular diagnosis, surrogate markers are needed for evaluating myocardial remodelling as part of the clinical management of patients with cardiac disease. In this setting, circulating biomarkers, a component of the liquid biopsy, provide a promising approach for the fast, affordable and scalable screening of large numbers of patients, allowing the detection of different pathological features related to myocardial remodelling, aiding in risk stratification and therapy monitoring. However, despite the advances in the field and the identification of numerous potential candidates, their implementation in clinical practice beyond natriuretic peptides and troponins is mostly lacking. In this review, we will discuss some biomarkers related to alterations in the main cardiac tissue compartments (cardiomyocytes, extracellular matrix, endothelium and immune cells) which have shown potential for the assessment of cardiovascular risk, cardiac remodelling and therapy effects. The hurdles and challenges for their translation into clinical practice will also be addressed.

INTRODUCTION:Renal trauma is the most common of urological trauma and accounts for up to 5% of all. The AAST scale is the most widely used to assess renal trauma. This study focuses on high-grade trauma, whose treatment has evolved towards a conservative approach, with techniques such as angioembolization. The aim is to describe the evolution in the management of high-grade renal trauma in all patients treated at La Paz University Hospital from 2001 to 2022. METHODS:A descriptive retrospective study was conducted on patients treated at the hospital. The study was divided into two periods (2001-2010 and 2011-2022). A total of 285 patients with renal trauma were collected, of which 54 were high grade. The main variable is the type of management, conservative (embolization) or interventional through nephrectomy. RESULTS:In the completed series, there was a decrease in radical nephrectomy in high-grade renal trauma from 50% to 13.8% over time, with an increase in embolization from 23,1% to 44,8%. In patients with isolated renal trauma, those treated with embolization increased from 28.6% to 69.2%, while those undergoing radical/partial nephrectomy decreased from 42.8% to 7.69%. CONCLUSION:The management of renal trauma has evolved over the years in our center. The number of patients treated by embolization has increased, while the number of complications and nephrectomies has decreased.

Introducción: El traumatismo renal es más común dentro de los urológicos y representa hasta un 5%. La escala de AAST es la más utilizada para valorarlo. Este trabajo, se centra en los traumatismos de alto grado cuyo tratamiento ha evolucionado hacia el manejo conservador, utilizando técnicas como la angioembolización. Se busca describir la evolución en el manejo del traumatismo renal de alto grado en todos los pacientes tratados en el Hospital Universitario La Paz desde 2001 hasta 2022.

Introduction: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. Methods: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Results: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. Conclusions: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Epidemiological studies have revealed that hypertensive heart disease is a major risk factor for heart failure, and its heart failure burden is growing rapidly. The need to act in the face of this threat requires first an understanding of the multifactorial origin of hypertensive heart disease and second an exploration of new mechanistic pathways involved in myocardial alterations critically involved in cardiac dysfunction and failure (eg, myocardial interstitial fibrosis). Increasing evidence shows that alterations of gut microbiota composition and function (ie, dysbiosis) leading to changes in microbiota-derived metabolites and impairment of the gut barrier and immune functions may be involved in blood pressure elevation and hypertensive organ damage. In this review, we highlight recent advances in the potential contribution of gut microbiota alterations to myocardial interstitial fibrosis in hypertensive heart disease through blood pressure-dependent and blood pressure-independent mechanisms. Achievements in this field should open a new path for more comprehensive treatment of myocardial interstitial fibrosis in hypertensive heart disease and, thus, for the prevention of heart failure.

European Journal of Heart FailureVolume 26, Issue 2 p. 285-287 Invited Editorial Advancing the fight against fibrosis in patients with heart failure: The contribution of sodium–glucose cotransporter 2 inhibition Rudolf A. de Boer, Rudolf A. de Boer Thorax Center, Department of Cardiology, Erasmus Medical Center, Erasmus MC, Cardiovascular Institute, Rotterdam, The NetherlandsSearch for more papers by this authorJavier Díez, Corresponding Author Javier Díez [email protected] Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Pamplona, Spain Center for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain Corresponding author. Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Edificio CIMA, Av Pío XII 55, 31008 Pamplona, Spain. Email: [email protected]Search for more papers by this author Rudolf A. de Boer, Rudolf A. de Boer Thorax Center, Department of Cardiology, Erasmus Medical Center, Erasmus MC, Cardiovascular Institute, Rotterdam, The NetherlandsSearch for more papers by this authorJavier Díez, Corresponding Author Javier Díez [email protected] Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Pamplona, Spain Center for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain Corresponding author. Center for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Edificio CIMA, Av Pío XII 55, 31008 Pamplona, Spain. Email: [email protected]Search for more papers by this author First published: 09 January 2024 https://doi.org/10.1002/ejhf.3125 The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Heart Failure or of the European Society of Cardiology. doi: 10.1002/ejhf.3101. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Frangogiannis NG, Kovacic JC. Extracellular matrix in ischemic heart disease, part 4/4: JACC focus seminar. J Am Coll Cardiol 2020; 75: 2219–2235. https://doi.org/10.1016/j.jacc.2020.03.020 10.1016/j.jacc.2020.03.020 PubMedWeb of Science®Google Scholar 2Díez J, González A, Kovacic JC. Myocardial interstitial fibrosis in nonischemic heart disease, part 3/4: JACC focus seminar. J Am Coll Cardiol 2020; 75: 2204–2218. https://doi.org/10.1016/j.jacc.2020.03.019 10.1016/j.jacc.2020.03.019 CASPubMedWeb of Science®Google Scholar 3de Boer RA, de Keulenaer G, Bauersachs J, Brutsaert D, Cleland JG, Diez J, et al. Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology. Eur J Heart Fail 2019; 21: 272–285. https://doi.org/10.1002/ejhf.1406 10.1002/ejhf.1406 PubMedWeb of Science®Google Scholar 4Díez J, de Boer RA. Management of cardiac fibrosis is the largest unmet medical need in heart failure. Cardiovasc Res 2022; 118: e20–e22. https://doi.org/10.1093/cvr/cvab228 10.1093/cvr/cvab228 CASPubMedWeb of Science®Google Scholar 5Wang H, Ding L, Tian L, Tian Y, Liao L, Zhao J. Empagliflozin reduces diffuse myocardial fibrosis by extracellular volume mapping: A meta-analysis of clinical studies. Front Endocrinol (Lausanne) 2022; 13:917761. https://doi.org/10.3389/fendo.2022.917761 10.3389/fendo.2022.917761 PubMedWeb of Science®Google Scholar 6Ferreira JP, Butler J, Anker SD, Januzzi JL, Panova-Noeva M, Reese-Petersen AL, et al.; EMPEROR Committees and Investigators. Effects of empaglifozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials. Eur J Heart Fail 2024; 26: 274–284. https://doi.org/10.1002/ejhf.3101 10.1002/ejhf.3101 Google Scholar 7López B, González A, Ravassa S, Beaumont J, Moreno MU, San José G, et al. Circulating biomarkers of myocardial fibrosis: The need for a reappraisal. J Am Coll Cardiol 2015; 65: 2449–2456. https://doi.org/10.1016/j.jacc.2015.04.026 10.1016/j.jacc.2015.04.026 CASPubMedWeb of Science®Google Scholar 8López B, Querejeta R, González A, Larman M, Díez J. Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage C heart failure: Potential role of lysyl oxidase. Hypertension 2012; 60: 677–683. https://doi.org/10.1161/HYPERTENSIONAHA.112.196113 10.1161/HYPERTENSIONAHA.112.196113 CASPubMedWeb of Science®Google Scholar 9Raafs AG, Verdonschot JAJ, Henkens MTHM, Adriaans BP, Wang P, Derks K, et al. The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy – A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy. Eur J Heart Fail 2021; 23: 933–944. https://doi.org/10.1002/ejhf.2201 10.1002/ejhf.2201 CASPubMedWeb of Science®Google Scholar 10Klappacher G, Franzen P, Haab D, Mehrabi M, Binder M, Plesch K, et al. Measuring extracellular matrix turnover in the serum of patients with idiopathic or ischemic dilated cardiomyopathy and impact on diagnosis and prognosis. Am J Cardiol 1995; 75: 913–918. https://doi.org/10.1016/S0002-9149(99)80686-9 10.1016/S0002-9149(99)80686-9 CASPubMedWeb of Science®Google Scholar 11Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: Insights from the Randomized Aldactone Evaluation Study (RALES). RALES Investigators. Circulation 2000; 102: 2700–2706. https://doi.org/10.1161/01.CIR.102.22.2700 10.1161/01.CIR.102.22.2700 CASPubMedWeb of Science®Google Scholar 12Ravassa S, Trippel T, Bach D, Bachran D, González A, López B, et al. Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: Results from the Aldo-DHF trial. Eur J Heart Fail 2018; 20: 1290–1299. https://doi.org/10.1002/ejhf.1194 10.1002/ejhf.1194 CASPubMedWeb of Science®Google Scholar 13Canty EG, Kadler KE. Procollagen trafficking, processing and fibrillogenesis. J Cell Sci 2005; 118: 1341–1353. https://doi.org/10.1242/jcs.01731 10.1242/jcs.01731 CASPubMedWeb of Science®Google Scholar 14Querejeta R, López B̃, González A, Sánchez E, Larman M, Martínez Ubago J́L, et al. Increased collagen type I synthesis in patients with heart failure of hypertensive origin: Relation to myocardial fibrosis. Circulation 2004; 110: 1263–1268. https://doi.org/10.1161/01.CIR.0000140973.60992.9A 10.1161/01.CIR.0000140973.60992.9A CASPubMedWeb of Science®Google Scholar 15Kaye DM, Khammy O, Mariani J, Maeder MT. Relationship of circulating matrix biomarkers to myocardial matrix metabolism in advanced heart failure. Eur J Heart Fail 2013; 15: 292–298. https://doi.org/10.1093/eurjhf/hfs179 10.1093/eurjhf/hfs179 CASPubMedWeb of Science®Google Scholar 16Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Ishikawa K, Watanabe S, Picatoste B, et al. Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol 2019; 73: 1931–1944. https://doi.org/10.1016/j.jacc.2019.01.056 10.1016/j.jacc.2019.01.056 CASPubMedWeb of Science®Google Scholar 17Chung CC, Lin YK, Chen YC, Kao YH, Yeh YH, Trang NN, et al. Empagliflozin suppressed cardiac fibrogenesis through sodium-hydrogen exchanger inhibition and modulation of the calcium homeostasis. Cardiovasc Diabetol 2023; 22: 27. https://doi.org/10.1186/s12933-023-01756-0 10.1186/s12933-023-01756-0 CASPubMedWeb of Science®Google Scholar Volume26, Issue2February 2024Pages 285-287 ReferencesRelatedInformation

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

The estimated glomerular filtration rate (eGFR) provides insight into cardiovascular disease (CVD) risk stratification and proactive management. Accumulating evidence suggests that combining eGFR calculated from serum cystatin C (eGFRcys) and from serum creatinine (eGFRcrea) improves CVD risk stratification over eGFRcrea alone. The term selective glomerular hypofiltration syndrome (SGHS) or shrunken pore syndrome has been proposed to define an eGFRcys:eGFRcrea ratio <1, which is hypothesized to result from a reduced glomerular filtration of 5- to 30-kDa molecules as compared with smaller molecules. SGHS may be identified in people with normal or reduced measured GFR, but the prevalence depends on the cut-off value of the eGFRcys:eGFRcrea ratio used, which is not yet standardized. SGHS is strongly associated with increased CVD and mortality risks and it may offer an opportunity to expand our understanding of the mechanisms linking GFR disorders with CVD risk (e.g. an altered plasma proteome), which may guide treatment decisions. However, muscle wasting may also contribute to a reduced eGFRcys:eGFRcrea ratio and there are open questions regarding the pathophysiology of a reduced eGFRcys:eGFRcrea ratio, the reference cut-off values of the ratio to define the syndrome and its clinical implications. We now critically review the SGHS concept, its pathophysiological basis and links to CVD and the potential consequences for clinical practice and propose a research agenda.