Juan Jesús Carrero

Background: Most eligible patients are not prescribed guideline‐directed medical therapy for heart failure with reduced ejection fraction (EF). Increased time pressures for providers in the ambulatory setting may contribute to these shortfalls. We assessed the association between cardiologist ambulatory workload and guideline‐directed medical therapy prescription for patients with heart failure with reduced EF. Methods: This was a cross‐sectional study of patients with heart failure with reduced EF (EF ≤40%) seen by a cardiologist from October 1, 2022, to September 30, 2023, using deidentified administrative and electronic health record data from Optum Labs Data Warehouse, which includes data from multiple health systems across the United States. The primary exposure was ambulatory workload, measured as the average number of visits per day, categorized into quartiles. The primary outcome was “comprehensive quadruple therapy,” defined as prescription for all 4 guideline‐directed medical therapies: β‐blocker; angiotensin receptor–neprilysin inhibitor; mineralocorticoid receptor antagonist; and sodium‐glucose cotransporter 2 inhibitor. Analyses were conducted using generalized estimating equations, adjusted for demographic and clinical variables. Results: Overall, 40 173 patients were seen by 881 cardiologists (median ambulatory workload, 9.1 patients per day; interquartile range=5.1–13.0). The percentage of patients prescribed comprehensive quadruple therapy was higher among patients in lower quartiles (quartile 1: 14%; quartile 2: 9.7%; quartile 3: 8.9%; quartile 4: 7.4%; P P value=quartile 1: 1.35 [1.09–1.66], 0.008; quartile 2: 1.20 [1.00–1.43], 0.050; quartile 3: 1.11 [0.93–1.32], 0.28; quartile 4 [reference]). Conclusions: Seeing a cardiologist with lower ambulatory workload was associated with increased prescribing of guideline‐recommended, life‐saving therapy in patients with heart failure with reduced EF. Current models that incentivize more visits per day may negatively impact care in the ambulatory setting.

Background and hypothesis: The burden and prognostic significance of inflammation in chronic kidney disease (CKD) remains poorly characterized, with prior studies yielding conflicting estimates of the association between elevated high-sensitivity C-reactive protein (hsCRP) and cardio-kidney outcomes. Methods: Observational nationwide study of 23 008 adults with CKD stages 3–5 attending nephrology care and enrolled in the Swedish Renal Registry (2008–2023). Inflammation was assessed longitudinally via 94 500 repeated hsCRP registrations. Time-varying, cause-specific Cox models accounting for competing risks estimated associations with study outcomes, which included major adverse cardiovascular events (MACE), heart failure (HF) hospitalization, acute kidney injury (AKI), kidney failure requiring replacement therapy (KFRT), and all-cause mortality. Pre-defined stratifiers were atherosclerotic cardiovascular disease (ASCVD) history and CKD stage. Results: Mean age was 71 years, 65% were male, and median estimated glomerular filtration rate was 25 ml/min/1.73 m². Median hsCRP was 4.0 (interquartile range [IQR] 1.9–7.0) mg/l, and 75% of participants had hsCRP ≥2. Over median 3.9 (IQR 2.0–6.7) years, hsCRP ≥2 mg/l was associated with higher rates of all outcomes: hazard ratio 1.20 (95% confidence interval 1.12–1.28) for MACE (n = 5480 events), 1.29 (1.22–1.37) for HF hospitalization (n = 8173), 1.28 (1.18–1.38) for AKI (n = 3943), 1.09 (1.02–1.15) for KFRT (n = 6177), and 1.43 (1.37–1.50) for mortality (n = 12 645). In spline analyses, associations were steeper at lower hsCRP levels and flatter thereafter for all outcomes except KFRT, where the hsCRP-response relationship was relatively flat. Associations with MACE, HF, AKI, and mortality were consistent regardless of ASCVD status and CKD stage. Associations with KFRT were inconsistent across CKD stages. Conclusion: In this nationwide cohort of adults with moderate to severe CKD receiving nephrology care, inflammation was common, and higher hsCRP levels were associated with adverse cardiovascular and kidney outcomes, as well as mortality. Although associations were less consistent for KFRT, these findings collectively support the utility of hsCRP monitoring in this population.

Chronic kidney disease (CKD) is a leading cause of premature death due to the loss of kidney function and development of kidney failure, and because of attendant major adverse cardiovascular events. High-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, is associated with increased risks of cardiovascular events and CKD progression. CKD is characterized by a pro-inflammatory state with upregulation of inflammatory pathways and disruption of anti-inflammatory mechanisms. The resulting systemic inflammation, along with local tissue-based inflammatory mechanisms, are key contributors to kidney damage, atherosclerosis and cardiac dysfunction. As a result, a series of inflammatory pathways and mediators have emerged as potential therapeutic targets for CKD and its major cardiovascular complications. Investigational treatments that have targeted inflammation include inhibition of apoptosis signal-regulating kinase-1 (ASK1) by selonsertib, Janus kinase (JAK) 1/2 inhibition with baricitinib, protein kinase C-β (PKCβ) inhibition with ruboxistaurin, nuclear factor erythroid 2-related factor 2 (Nrf2) activation with bardoxolone, phosphodiesterase inhibition with pentoxifylline and monoclonal antibodies against IL-1β and IL-6. Furthermore, proven therapies for CKD, including renin–angiotensin–aldosterone system inhibitors, sodium–glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid antagonists, possess anti-inflammatory properties that might contribute to their previously established clinical benefits.

Background: Although women have more prevalent chronic kidney disease (CKD) they less often have recommended therapy or a documented CKD diagnosis in primary care. This study investigates whether gender disparities remain in specialized nephrology care as a possible expression of gender bias. Methods: Patients with incident estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 registered in the Swedish Renal Registry between 2010 and 2020 were included. Logistic regression investigated gender differences in having a CKD diagnosis, kidney biopsy, blood pressure (BP) <140/90 mmHg and guideline-recommended medications. Gender disparities regarding kidney replacement therapy (KRT) initiation, including preemptive kidney transplantation and initiating dialysis with a planned access, were investigated using flexible parametric regression and Cox regression. Results: Of 25 478 included patients 37% were female. Women were less likely to have a CKD diagnosis [odds ratio (OR) 0.81, 95% confidence interval 0.73–0.90], a renin–angiotensin–aldosterone inhibitor (OR 0.94, 0.89–0.99), lipid-lowering agent (OR 0.93, 0.88–0.99) or BP <140/90 mmHg (OR 0.91, 0.86–0.97). Women had borderline-significantly lower odds of having a kidney biopsy (OR 0.93, 0.86–1.00). Women were less likely to initiate KRT, [hazard ratio (HR) 0.75, 0.70–0.80] or to initiate dialysis with a planned access (HR 0.82, 0.78–0.85). No significant gender differences were seen regarding preemptive transplantation and conservative kidney management decision. Women less often died before KRT initiation (HR 0.81, 0.77–0.85). Conclusions: Swedish women with advanced CKD in specialized nephrology remain underdiagnosed, undertreated and less likely to reach BP targets. Although these gender differences did not translate to increased KRT and mortality rates, they highlight the need for nephrologists to maintain awareness and strive for health equity.

Background: In advanced chronic kidney disease (CKD) evidence for lower systolic blood pressure (SBP) targets is limited and guideline recommendations are conflicting. We investigated the association between achieved SBP and major adverse cardiovascular events (MACE) in nephrology-referred patients with CKD. Methods: In this nationwide, observational cohort from the Swedish Renal Register–chronic kidney disease (SRR-CKD), we included adults with CKD stages 3–5 referred to nephrology outpatient clinics between 2006 and 2017. Mean office SBP during the first year was categorized in incrementally higher SBP groups with 130–<140 mmHg as reference. The primary outcome was MACE; secondary outcomes were its components and all-cause death, analyzed using cause-specific multivariable-adjusted flexible parametric survival models. Results: Among 23 317 patients (median age 72 years; 64% men; median estimated glomerular filteration rate (eGFR) 24 ml/min/1.73 m²), over a median follow-up of 2.5 years, 8556 (37%) experienced MACE and 7686 (33%) died. Compared with SBP 130–<140 mmHg, SBP 120–<130 mmHg was associated with lower risks of MACE [adjusted hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.87–0.99] and all-cause mortality (HR 0.93, 95% CI 0.87–0.99), whereas SBP ≥160 mmHg was associated with higher risks of MACE (HR 1.38, 95% CI 1.28–1.49) and death (HR 1.29, 95% CI 1.20–1.38). MACE risk was nonproportional and declined over time in patients with SBP 100–<120 mmHg, demonstrating lower MACE risk compared to 130–<140 after 3 years. In continuous analyses, MACE risk was lowest around 125 mmHg and increased at higher SBP levels. Conclusions: In nephrology-referred patients with advanced CKD, achieved SBP around 120–<130 mmHg (near 125 mmHg) was associated with the lowest cardiovascular and mortality risk, while SBP ≥140 mmHg, especially ≥160 mmHg, was consistently associated with higher MACE risk.

Acute kidney injury (AKI) is a common and potentially serious complication, yet population-level data on its burden and determinants remain limited. We quantified AKI incidence, temporal trends, and risk factors across a complete healthcare system. We conducted a population-based cohort study including all adult residents of Stockholm, Sweden (2017–2021) using the SCREAM project. AKI events requiring hospitalization or occurring during hospital stays were identified using a composite algorithm incorporating laboratory-based KDIGO creatinine criteria, ICD-10 diagnoses, and acute dialysis procedure codes. We calculated annual incidence rates, temporal trends using Poisson regression, and incidence rate ratios for selected demographic, clinical, and laboratory-defined risk factors. Among approximately 1.9 million adults annually, 0.6–0.7% experienced AKI each year (71–95 per 10,000 person-years). AKI occurred in 5.8–7.8% of hospitalizations, with only 30% reaching KDIGO stage 2–3. From 2017 to 2021, AKI incidence increased by 26% (95% CI 1.23–1.29). Populations at highest risk of AKI were largely consistent over the years, and included older adults, men, and individuals with uncontrolled diabetes, prior AKI, hypertension, heart failure, kidney transplantation, and multiple myeloma. Lower eGFR and higher albuminuria were associated with markedly higher AKI risk in a graded manner. COVID-19 infection was associated with a six-fold higher AKI risk in 2020, but marked attenuation in 2021 suggests it does not explain the overall upward trend. This region-wide analysis quantifies the contemporary burden of AKI and identifies high-risk populations that may benefit from targeted prevention and monitoring strategies.

Introduction: Patients with myocardial infarction (MI) or heart failure (HF) often have concomitant chronic kidney disease (CKD). These patients are perceived as ‘complex’, but empirical evidence quantifying this complexity or exploring the diseases and problems they experience is scarce. We aimed here to comprehensively characterize the complexity of care among patients with MI/HF across the spectrum of CKD severity and to identify frequent longitudinal disease accrual trajectories associated with all-cause mortality. Methods: Retrospective cohort of 29 901 adults surviving an incident MI/HF hospitalization from the Stockholm CREAtinine Measurements (SCREAM, 2006–2021) project. KDIGO CKD stages were classified as no CKD, mild CKD, or moderate-to-severe CKD using plasma creatinine and urinary albumin at hospital admission. Care complexity was evaluated through multidimensional indicators encompassing comorbid conditions, treatments, healthcare use, and mortality. Process mining identified longitudinal trajectories of disease accrual and associated mortality risks. Results: Increasing CKD severity was associated with greater comorbidities, polypharmacy, healthcare use, and higher observed rate of recurrent MI/HF and death. We identified 8927 hospitalizations and 20 805 outpatient disease trajectories during follow-up. CKD patients more often accumulated multiple circulatory diagnoses, significantly increasing mortality hazards compared with those without CKD. Trajectories involving progression to endocrine/metabolic, respiratory, neoplastic, and genitourinary diseases became more frequent with advancing CKD and were strongly associated with death. Conclusions: Among MI/HF survivors, those with CKD are the most complex and resource-demanding. We identified key comorbidity patterns that provide opportunities for earlier, targeted interventions—particularly addressing endocrine, respiratory, and neoplastic complications—to reduce their adverse outcomes and premature mortality.