Genki Plaza Medical Center for Health Care

IntroductionNovel therapies are emerging for the prevention of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). Within the FOUNTAIN platform (NCT05526157; EUPAS48148), this real-world study aimed to characterize cohorts of adults with CKD and T2D starting therapy with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in Europe, Japan, and the United States (US) during 2012–2021.MethodsThis multinational, multicohort study was conducted in five data sources: the Danish National Health Registers (DNHR) (Denmark), PHARMO Data Network (PHARMO) (The Netherlands), Valencia Health System Integrated Database (VID) (Spain), Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex) (Japan), and Optum’s de-identified Clinformatics® Data Mart Database (CDM) (US). Eligible patients had T2D (defined by data source-specific algorithms) and CKD (based on diagnosis codes, estimated glomerular filtration rate values, and/or urine albumin-to-creatinine ratio) and initiated an GLP-1 RA during 2012–2021. Baseline demographic, lifestyle, and clinical characteristics were analyzed, and treatment patterns were described.ResultsStudy cohorts included 18,929 GLP-1 RA initiators in DNHR; 476 in PHARMO; 11,798 in VID; 329 in J-CKD-DB-Ex; and 70,158 in CDM. Across cohorts, mean age ranged from 66.1 years in J-CKD-DB-Ex to 67.9 years in CDM, and between 46.6% (PHARMO) and 59.6% (J-CKD-DB-Ex) of patients were men. There was a steady increase in GLP-1 RA initiators from 2012 (when 1.6–4.8% of GLP-1 RA initiators started therapy) to 2019 (when 19.8–31.5% started therapy). The median duration of initial treatment with a GLP-1 RA ranged from 2.3 months (PHARMO) to 12.4 months (VID). At 1-year follow-up, between 52% (CDM) and 78% (DNHR) of patients were receiving treatment. Findings suggested that GLP-1 RA use was independent of CKD severity.ConclusionsDuring 2012–2021, GLP-1 RA use steadily increased across multinational cohorts of patients with T2D and CKD, and persistence with treatment was high. GLP-1 use was independent of CKD severity.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-025-01717-8.

Background: Clinical implications of high peak nighttime home blood pressure (BP) are currently unknown. This analysis investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in individuals with ≥1 cardiovascular risk factor. Methods: In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times every night for 14 days at baseline using a nighttime home BP monitoring device (HEM-5001, Omron Healthcare). Peak nighttime home SBP was defined as average of the highest three values over the 14-night measurement period. Occurrence of cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) was determined over a mean 7.1 years’ follow-up. Results: This analysis included 2545 individuals (mean age 63.3±10.3 years, 49% male). After adjustment for covariates (including age, sex, and average office, morning, evening, and nighttime home SBP), stroke risk was significantly higher in individuals with peak nighttime home SBP in the highest (Q5, ≥149.0 mmHg) versus lowest quintile (Q1, <119.3 mmHg) (hazard ratio [HR] 4.24, 95% confidence interval [CI] 1.07–16.77; p=0.039 overall and 8.92, 1.49–53.43; p=0.017 in the subgroup with ≥6 nighttime home SBP measurements). This increased stroke risk remained significant after controlling for day-by-day average real variability of nighttime BP. The average peak nighttime home SBP cut-off value for predicting an increased risk of incident stroke was 136 mmHg. Conclusions: We propose exaggerated peak nighttime home SBP determined from ≥6 measurements as a novel risk factor for stroke, independent of conventional office and home BP values.

IntroductionWe compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.Research design and methodsUsing the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.ResultsAt baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m2 and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was −0.80 mL/min/1.73 m2/year (95% CI −1.05 to −0.54) among SGLT2 inhibitors group and −1.78 mL/min/1.73 m2/year (95% CI −2.08 to −1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m2/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.ConclusionsThe benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Obesity with increased high-sensitive cardiac troponin T (hs-cTnT) has been reported to be more likely to progress cardiovascular disease (CVD) events, which suggests that hs-cTnT may identify a "malignant" phenotype of obesity. We classified 3513 hypertensive patients from the Japan Morning Surge-Home Blood Pressure (J-HOP) study into groups based on body mass index (BMI) (normal weight: <25 kg/m2, overweight: 25-29.9 kg/m2, obesity: ≥30 kg/m2) and elevations in biomarker levels (hs-cTnT ≥3 ng/mL: 51.3%, 54.9%, 53.3%, and N-terminal pro-brain natriuretic peptide [NT-ProBNP] ≥55 pg/mL: 51.1%, 40.7%, 36.0% in each BMI category). We evaluated the independent and combined associations of BMI and each hs-cTnT/NT-proBNP or both with CVD events (fatal and nonfatal coronary artery disease, stroke, and hospitalized heart failure). During the mean 6.4 ± 3.9-year follow-up, 232 CVD events occurred. Obesity with elevated hs-cTnT was associated with a risk of CVD events compared to normal weight without elevated hs-cTnT (hazard ratio 3.22, 95% confidence interval: 1.83-5.68). A similar pattern of results was also observed across the status of obesity and elevated NT-proBNP. There was a significant interaction between hs-cTnT and CVD events according to the obesity status (p = 0.039), while this association was marginal in NT-proBNP (p = 0.060). The magnitude of the mediation of hs-cTnT for the association between obesity and CVD risk was 41.2%, and that for NT-proBNP was 8.1%. In this Japanese hypertensive population, the elevation of hs-cTnT identified obese patients at particularly high risk for developing CVD events, suggesting that hs-cTnT may identify a 'malignant' phenotype of obesity.

The aim of this study was to clarify the characteristics of individuals with prediabetes who developed type 2 diabetes despite undergoing interventions, and to evaluate the performance of urinary myo-inositol (UMI) as a noninvasive indicator for the risk of developing diabetes. A total of 51 individuals with prediabetes who underwent a 75-g oral glucose tolerance test, ΔUMI (the difference in the UMI : creatinine ratio between before and 120 min after 75-g glucose loading), fasting plasma glucose, insulin, hemoglobin A1c, noninvasive testing (age, body mass index, blood pressure) and general blood tests were measured at baseline, and underwent dietary/exercise guidance for 8 years were studied. A total of 31 participants developed diabetes in 8 years. At baseline, the group that developed diabetes was characterized by high ΔUMI, hemoglobin A1c, fasting plasma glucose and low high-density lipoprotein cholesterol, and insulinogenic index (I.I.). I.I and ΔUMI showed a higher correlation than fasting plasma glucose and hemoglobin A1c. Regarding diabetes onset within 8 years, Cox regression analysis of diabetes onset showed the baseline ΔUMI is an independent predictor, adjusted for the result of not only noninvasive markers, but also that of noninvasive and general blood markers. The log-rank test showed that all glycemic indicators were significantly associated with diabetes onset. Participants who developed type 2 diabetes from prediabetes despite undergoing interventions were characterized by high glycemic control markers and low I.I. As noninvasive measurement of ΔUMI is associated with I.I. and diabetes onset, it could be a useful indicator for identifying individuals with a high risk of diabetes onset.

BACKGROUNDOur aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD).METHODSWe analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. We compared 2 groups of CAVI measurements—the highest quartile (≧8.1) and the combined lower 3 quartiles (<8.1). We used Cox proportional hazards models to assess associations between these 2 groups and subsequent CKD events, proteinuria, eGFR <60 ml/min/1.73 m2, and rapid eGFR decline (greater than or equal to −3 ml/min/1.73 m2 per year).RESULTSThe mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR <60 ml/min/1.73 m2, and the odds ratio with 95% CI was 1.3 (1.1, 1.4) for rapid eGFR decline.CONCLUSIONSPersons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements <8.1. Greater arterial stiffness among adults without CKD may be associated with kidney dysfunction.

Hypertension is an important risk factor for non-valvular atrial fibrillation (NVAF) and its prognosis. However, there is no study to clarify the impact of pre-existing hypertension and BP control status before the onset of AF on the prognosis after the onset of AF. This retrospective real-world cohort analysis used data from the Japan Medical Data Center Co., Ltd database. The presence of NVAF and hypertension, plus the occurrence of adverse events, was based on ICD-10 codes in the database. The primary composite AF-related cardiovascular event end point included ischemic stroke, hemorrhagic stroke, and acute myocardial infarction. Of the 21523 patients identified as having new-onset NVAF between January 2005 and June 2016, 7885 had blood pressure (BP) data before the onset of NVAF available and were included in the analysis (4001 with pre-existing hypertension and 3884 without pre-existing hypertension). The rate of primary composite end point events was 10.3 and 4.4 per 1000 patient-years in patients with and without hypertension, respectively (P<.001). In addition, lower systolic BP (<120mmHg) before the onset of NVAF was associated with a lower incidence of cardiovascular events after the development of NVAF (P<.001). This highlights the importance of earlier and tighter 24-hour BP control before the onset of NVAF in patients with hypertension, not only for reducing the occurrence of new-onset of NVAF, but also for reducing both hemorrhagic and ischemic cardiovascular events after the onset of NVAF.

We developed an innovative automated home blood pressure (BP) monitoring method that measures BP while asleep repeatedly over several days. Our aim was to assess the predictive ability of nighttime BP obtained using the home BP device for incident cardiovascular disease (CVD) in general practice patients. We used data from the nationwide practice-based J-HOP (Japan Morning Surge-Home Blood Pressure) Nocturnal BP Study, which recruited 2545 Japanese with a history of or risk factors for CVD (mean age 63 years; antihypertensive medication use 83%). The associations between nighttime home BPs (measured at 2:00, 3:00, and 4:00 am using validated, automatic, and oscillometric home BP devices) and incident CVD, including coronary disease and stroke events, were assessed with Cox proportional hazards models. The mean±SD office, morning home, and nighttime home systolic BP (SBP)/diastolic BP were 140±15/82±10, 137±15/79±10, and 121±15/70±9 mm Hg, respectively. During a follow-up of 7.1±3.8 years (18,116 person-years), 152 CVD events occurred. A 10-mm Hg increase of nighttime home SBP was associated with an increased risk of CVD events (hazard ratios [95% CIs]: 1.201 [1.046-1.378]), after adjustments for covariates including office and morning home SBPs. The model fit assessed by the change in Goodness-of-Fit was improved when we added nighttime home SBP into the base models including office and morning home SBPs (Δ6.838 [5.6%]; P=0.009). This is among the first and largest nationwide practice-based study demonstrating that nighttime SBP obtained using a home device is a predictor of incident CVD events, independent of in-office and morning in-home SBP measurement. Clinical Trial Registration- URL: http://www.umin.ac.jp/icdr/index.html . Unique identifier: UMIN000000894.

The clinical outcomes associated with masked hypertension defined by home blood pressure monitoring (HBPM) in clinical settings remain uncertain. To assess the association between masked hypertension and cardiovascular disease events in clinical settings. This observational cohort study used data from 4261 outpatients treated at 71 primary practices or university hospitals throughout Japan who were enrolled in the Japan Morning Surge-Home Blood Pressure study between January 1, 2005, and December 31, 2012. Participants had a history of or risk factors for cardiovascular disease and were followed up through March 31, 2015. Participants underwent clinic blood pressure (BP) measurements on 2 occasions as well as HBPM measurements in the morning and evening for a 14-day period. Urine albumin to creatinine ratio and circulating brain (or B-type) natriuretic peptide levels were quantified at baseline as a marker of cardiovascular end-organ damage. Data were analyzed from July 1, 2017, to October 31, 2017. Participants were categorized into 4 BP groups: (1) masked hypertension-hypertensive home BP levels (systolic, ≥135 mm Hg; diastolic, ≥85 mm Hg) and nonhypertensive clinic BP levels (systolic, <140 mm Hg; diastolic, <90 mm Hg); (2) white-coat hypertension-nonhypertensive home BP levels (systolic, <135 mm Hg; diastolic, <85 mm Hg) and hypertensive clinic BP levels (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg); (3) sustained hypertension-hypertensive home and clinic BP levels; and (4) controlled BP-nonhypertensive home and clinic BP levels. Incident stroke and coronary heart disease. Of the 4261 participants, 2266 (53.2%) were women, 3374 (79.2%) were taking antihypertensive medication, and the mean (SD) age was 64.9 (10.9) years. During a median (interquartile range) follow-up of 3.9 (2.4-4.6) years, 74 stroke (4.4 per 1000 person-years) and 77 coronary heart disease (4.6 per 1000 person-years) events occurred. The masked hypertension group had a greater risk for stroke compared with the controlled BP group (hazard ratio, 2.77; 95% CI, 1.20-6.37), independent of traditional cardiovascular risk factors, urine albumin to creatinine ratio, and circulating B-type natriuretic peptide levels. Conversely, masked hypertension yielded no association with coronary heart disease risk. In the Japanese general practice population, masked hypertension defined by HBPM may be associated with an increased risk for stroke events. Use of HBPM may improve the assessment of BP-related risks and identify new therapeutic interventions aimed at preventing cardiovascular disease events.