桑原 政成

Losartan has a unique uricosuric property among angiotensin II receptor blockers and may therefore be advantageous in patients with hypertension and hyperuricemia or gout. The study by Xu et al. combined a meta-analysis of placebo-controlled randomized trials with a target trial emulation using UK Biobank data and demonstrated that losartan reduced serum uric acid by approximately 0.3 mg/dL. Although this effect is modest and substantially smaller than that of established uric acid-lowering therapies, it may be clinically relevant when selecting antihypertensive treatment for patients with borderline hyperuricemia, gout risk, or diuretic-associated uric acid elevation. Losartan may partially counterbalance the uric acid-raising effect of thiazide diuretics, but it should not replace appropriate treat-to-target therapy in patients with gout or marked hyperuricemia. The study is limited by the small emulated cohort and the possibility of residual confounding and selection bias. Nevertheless, the consistency of the findings across different analytical approaches supports a genuine uric acid-lowering effect. Future studies should determine whether this biochemical effect translates into fewer gout flares, improved attainment of serum uric acid targets, or reduced cardiovascular and cardiometabolic events. Overall, losartan should be regarded as an effective antihypertensive agent with a modest but favorable uric acid profile. Clinical interpretation of losartan's uric acid-lowering effect in hypertension care. ARB, angiotensin II receptor blocker; RCT, randomized controlled trial; URAT1, urate transporter 1.

BACKGROUND: Coronary artery (CA) lesions (CALs) are major complications of Kawasaki disease (KD). Studies have reported that coronary outcomes (CAL regression and progression) are associated with age; however, age-stratified data remain limited. METHODS: We analyzed data from 129,950 patients with KD in Japan (2011-2022). CALs were classified as CA dilatation, CA aneurysm, or giant CA aneurysm. Coronary outcomes were assessed by comparing echocardiographic findings between baseline and the subacute phase. Patients were stratified into nine 6-month age groups. Restricted cubic splines (RCS) were used to assess nonlinear associations between age and coronary outcomes. Multivariable logistic regression analyses assessed age-specific associations using the RCS-identified reference group. RESULTS: Among patients without CALs at initial echocardiography, the 0 to 6-month group had the highest proportion with subsequent CAL development (2.8%). Among patients with CA dilatation, the 0 to 6-month group showed the lowest proportion of patients with CA regression (75.5%). RCS analyses identified the 25 to 30-month group as the most likely to show CA dilatation regression and the least likely to experience CAL progression. Multivariable analysis demonstrated that patients aged 0 to 6 months were significantly less likely to show CA dilatation regression (adjusted odds ratio [95% confidence interval]: 0.44 [0.30-0.63], reference: 25-30 months) and more likely to experience CAL progression (3.84 [3.03-4.86]). CONCLUSIONS: Coronary outcomes differed substantially across age groups; patients aged 0 to 6 months had the most adverse coronary outcomes. Even without CALs at initial echocardiography, this age group had the highest risk of subsequent CAL development.

IMPORTANCE: The COVID-19 pandemic may serve as a natural experiment, with pandemic-associated changes in the epidemiology of Kawasaki disease (KD) potentially informing understanding of KD pathogenesis. OBJECTIVES: To assess long-term KD incidence across 50 years and to examine pandemic-associated changes in KD epidemiology across age groups. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a descriptive epidemiologic analysis of data from the Japanese Nationwide Survey of Kawasaki Disease conducted from 2023 to 2024, along with 50 years of historical data. Data were included from patients with KD in the current 2023-2024 survey (n = 29 841) and historical and current survey data from 1975 through 2024 (n = 467 456) for trend analysis. MAIN OUTCOMES AND MEASURES: Annual KD incidence overall and stratified by 3 age groups: infants (<1 year), 1 to 4 years, and 5 to 9 years. RESULTS: The current survey registered 15 032 and 14 809 patients with KD in 2023 and 2024, respectively (overall, 57.3% male; median [IQR] age, 2 [1-4] years). Across the 50-year study period, despite the population under 5 years of age declining in Japan by 61.6%, KD incidence rates increased 16.1-fold. Across the COVID-19 pandemic period, patient numbers reached a nadir of 10 333 in 2022, then rebounded to 15 032 cases (45.5% increase) in 2023. Notably, decline and rebound patterns differed by age. Indexed incidence rates (using 2017 as a baseline of 100) demonstrated that patients 5 to 9 years of age had the largest decline (nadir of 54.2 in 2021, 45.8% below baseline) and the largest rebound (134.8 in 2024, 34.8% above baseline). In contrast, patients younger than 1 year showed the smallest decline (nadir of 73) and incidence rates did not return to baseline levels. When comparing the magnitude of rebound in KD incidence, a distinct age-dependent dose-response pattern was observed: 26.1% for infants, 38.9% for patients aged 1 year, 42.7% for patients aged 2 years, 85.8% for patients aged 3 years, 105.3% for patients aged 4 years, and 166.7% for patients aged 5 to 9 years. CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of KD in Japan, KD incidence rebounded after the relaxation of COVID-19 pandemic-related restrictions, with age-dependent patterns. Nonpharmaceutical interventions (eg, mask-wearing) during the pandemic may explain the greater rebound pattern observed in older children; however, the minimal changes in infants suggest different exposure pathways to potential KD triggers. These findings support an age-stratified approach to KD pathogenesis research, distinguishing infants from older children.

BACKGROUND: Although intensive care is considered important for cardiovascular emergencies, large-scale evidence comparing outcomes by initial admission ward remains limited in Japan. METHODS AND RESULTS: Using the JROAD database, we identified patients hospitalized for cardiovascular emergencies after ambulance transport between April 2016 and March 2024 and classified patients by initial ward (intensive care unit [ICU], high care unit [HCU], or general ward [GW]). Deaths within 24 h were excluded. Multivariable logistic regression analysis was performed with adjustment for demographics, comorbidities, acute therapies, and hospital cardiologist staffing. Among 1,211,636 admissions, there were 323,220 (26.7%) deaths within 24 h; thus, 888,416 admissions (ICU, 212,059; HCU, 124,468; GW, 551,889) were analyzed. In-hospital mortality was 10.8%, 9.7%, and 12.2% for patients admitted to the ICU, HCU, and GW, respectively. Compared with the GW, the adjusted odds of death were lower for the ICU (odds ratio [OR] 0.718; 95% confidence interval [CI] 0.703-0.734) and HCU (OR 0.928; 95% CI 0.906-0.950). A higher number of board-certified cardiologists was independently associated with lower in-hospital mortality (OR 0.977 per additional board-certified cardiologist; 95% CI 0.976-0.978). Findings were consistent for acute myocardial infarction, acute heart failure, aortic dissection, and pulmonary embolism. CONCLUSIONS: Higher-acuity admission and a higher number of cardiologists were independently associated with lower in-hospital mortality, supporting optimization of critical care access for high-risk cardiovascular emergencies in Japan.