Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Studies.

BACKGROUND: Hypertension imposes substantial health and economic burden worldwide. Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, causing cardiovascular events at higher risk compared with essential hypertension. However, the germline genetic contribution to the susceptibility of PA has not been well elucidated. METHOD: We conducted a genome-wide association analysis of PA in the Japanese population and a cross-ancestry meta-analysis combined with UK Biobank and FinnGen cohorts (816 PA cases and 425 239 controls) to identify genetic variants that contribute to PA susceptibility. We also performed a comparative analysis for the risk of 42 previously established blood pressure-associated variants between PA and hypertension with the adjustment of blood pressure. RESULTS: In the Japanese genome-wide association study, we identified 10 loci that presented suggestive evidence for the association with the PA risk (P<1.0×10-6). In the meta-analysis, we identified 5 genome-wide significant loci (1p13, 7p15, 11p15, 12q24, and 13q12; P<5.0×10-8), including 3 of the suggested loci in the Japanese genome-wide association study. The strongest association was observed at rs3790604 (1p13), an intronic variant of WNT2B (odds ratio, 1.50 [95% CI, 1.33-1.69]; P=5.2×10-11). We further identified 1 nearly genome-wide significant locus (8q24, CYP11B2), which presented a significant association in the gene-based test (P=7.2×10-7). Of interest, all of these loci were known to be associated with blood pressure in previous studies, presumably because of the prevalence of PA among individuals with hypertension. This assumption was supported by the observation that they had a significantly higher risk effect on PA than on hypertension. We also revealed that 66.7% of the previously established blood pressure-associated variants had a higher risk effect for PA than for hypertension. CONCLUSIONS: This study demonstrates the genome-wide evidence for a genetic predisposition to PA susceptibility in the cross-ancestry cohorts and its significant contribution to the genetic background of hypertension. The strongest association with the WNT2B variants reinforces the implication of the Wnt/ß-catenin pathway in the PA pathogenesis.

Chronic Tonsillitis and IgA Nephropathy: Findings From a Nationwide Japanese Cohort Study.

RATIONALE & OBJECTIVE: Little is known regarding the association between chronic tonsillitis and the onset of IgA nephropathy (IgAN). In the present study, we examined the potential relationship between chronic tonsillitis and a subsequent risk of developing IgAN. STUDY DESIGN: Observational cohort study. SETTING: & Participants: 4,311,393 individuals without a history of IgAN identified between January 2005 to May 2022 within a Japanese nationwide epidemiological database, the JMDC Claims Database, representing health claims to over 60 insurers. EXPOSURE: Comorbid chronic tonsillitis based on diagnosis codes. OUTCOME: IgAN occurrence. ANALYTICAL APPROACH: Cause-specific Cox proportional hazards analysis adjusting for potential confounding factors were employed to estimate hazard ratios (HRs). RESULTS: Comorbid chronic tonsillitis was identified in 12,842 individuals, constituting 0.3% of the cohort. The cohort had a median age of 44 years (interquartile range: 36-53), and males accounted for 57.9%, with a follow-up of 1,089 days (interquartile range: 532-1,797), during which 2,653 cases of IgAN developed. Cumulative incidence curve showed a higher cumulative incidence of IgAN in individuals with chronic tonsillitis compared to their counterparts without this condition. Multivariable cause-specific analysis further demonstrated that individuals with chronic tonsillitis had an elevated risk of developing IgAN, with a HR of 2.72 (95% confidence interval: 1.79-4.14). LIMITATIONS: Potential residual confounders, and lack of consideration for ethnic distinctions. CONCLUSIONS: Using a largescale epidemiological dataset, these findings suggest a relationship between chronic tonsillitis and an elevated risk of IgAN development in the general Japanese population.

Familial hypercholesterolemia is related to cardiovascular disease, heart failure and atrial fibrillation. Results from a population-based study.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with atherosclerotic cardiovascular disease (ASCVD). However, the prevalence of FH among a general population remains unknown, and it is unclear if FH is associated with other cardiovascular complications, including heart failure (HF) and atrial fibrillation (AF). METHODS: Analyses were conducted on individuals without a prior history of cardiovascular disease using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2022 (n = 4,126,642; median age, 44 years; 57.5% men). We defined FH as either LDL cholesterol ≥250 mg/dL or LDL cholesterol ≥175 mg/dL under the lipid-lowering medications under the assumption that lipid-lowering medications reduced LDL cholesterol by 30%. We assessed the associations between FH and composite outcomes, including, ASCVD (myocardial infarction, angina pectoris, and stroke), HF, and AF using Cox proportional hazard model. RESULTS: We identified 11,983 (.29%) FH patients. In total, 181,150 events were recorded during the mean follow-up period of 3.5 years. The status FH was significantly associated with composite outcomes after adjustments (hazard ratio [HR]; 1.38, 95% confidence interval [CI]: 1.30-1.47, p < .001). Interestingly, the status FH was significantly associated with HF (HR: 1.48, 95% CI: 1.36-1.61, p < .001) and AF (HR: 1.33, 95% CI: 1.08-1.64, p < .001) in addition to angina pectoris (HR: 1.45, 95% CI: 1.33-1.58, p < .001) and stroke (HR: 1.19, 95% CI: 1.04-1.36, p < .001). CONCLUSION: We found that the prevalence of FH was .29% in a general population. FH was significantly associated with a higher risk of developing cardiovascular disease, HF and AF. LAY SUMMARY: We sought to identify the prevalence of FH among a general population, and to clarify whether FH increases the risk of not only ASCVD but also HF and AF.

Association of Cancer and Its Interaction with Conventional Risk Factors on Cardiovascular Disease Risk.

Introduction We sought to examine the association of cancer history with the incidence of individual cardiovascular disease events and to clarify whether the history of cancer modifies the relationship between conventional cardiovascular risk factors and incident cardiovascular disease. Methods This retrospective cohort study used the JMDC Claims Database, including 3,531,683 individuals. The primary endpoint was the composite cardiovascular disease outcome, which included myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results During a follow-up, 144,162 composite endpoints were recorded. Individuals with a history of cancer had a higher risk of developing composite cardiovascular disease events (HR 1.26, 95% CI 1.22-1.29). The HRs for myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation were 1.11 (95% CI 0.98-1.27), 1.15 (95% CI 1.10-1.20), 1.11 (95% CI 1.05-1.18), 1.39 (95% CI 1.34-1.44), and 1.22 (95% CI 1.13-1.32), respectively. Individuals who required chemotherapy for cancer had a higher risk of developing cardiovascular disease. Although conventional risk factors (e.g., overweight/obesity, hypertension, and diabetes) were associated with incident composite cardiovascular disease even in individuals with a history of cancer, the total population-attributable fractions of conventional risk factors were less in individuals with a history of cancer. Conclusion Individuals with a history of cancer (particularly those requiring chemotherapy) have a higher risk of cardiovascular disease. Traditional risk factors are important in the development of cardiovascular disease in individuals with and without a history of cancer. In individuals with a history of cancer, however, the total population-attributable fractions of conventional risk factors decreased.

Adsorption Characteristics and Mechanical Responses of Lubricants Containing Polymer Additives under Fluid Lubrication with a Narrow Gap.

The adsorption behavior of poly(methyl acrylate) (PMA)-based polymer additives and their mechanical response under fluid lubrication in narrow gaps were investigated by using neutron reflectometry, microchannel devices, and the narrow gap viscometer. The surface adsorption layer formed by the polymer additive in a stationary field that was investigated by neutron reflectometry was only about 3 nm thick. On the other hand, when the sample oil containing the polymer additive was flowed into the microchannel device with channels about 500 nm deep, the adsorption layer grew over a long period of time and eventually formed a layer that appeared to be more than 100 nm thick. The mechanical response was measured during one-directional rotation with a constant gap length by using the narrow gap viscometer. The results showed that the effective viscosity increased in the low shear rate range. The same behavior was also observed in the reciprocating rotational tests, where the mechanical response showed a distinctive distortion only when the shear rate was low near 0 rpm. The results of the neutron reflectometer, incorporating the narrow gap viscometer, showed no effect of the rotational speed with regard to the structure of the homogeneous layer over a large area. However, the discrepancy between the reflectivity profile and the fitting curve became progressively more pronounced with time, confirming the formation of inhomogeneous structures with time. It is finally suggested that the inhomogeneous structure is due to the formation of local aggregates by PMA molecules, and it acts as flow resistance only in the low shear rate, resulting in an increase in effective viscosity.

Significance of eGFR and proteinuria for cardiovascular disease in individuals beyond 85 years.

BACKGROUND: There are limited data on how advancing age influences prediction of CVD risk based on the estimated glomerular filtration rate (eGFR) and proteinuria, especially in older adults, including those aged ≥ 85 years. This study aimed to clarify the association of eGFR and proteinuria with CVD outcomes and the impact of age on this association. METHODS: The distribution of eGFR and urine protein in Japan was assessed retrospectively using real-world administrative claims and health checkup data collected between April 2014 and November 2022. We investigated the associations of these two parameters with the incidence of CVD, with an emphasis on the impact of aging. RESULTS: We assessed 1 829 020 individuals for distribution of eGFR and proteinuria; after excluding those with known CVD, their association with CVD risk was examined in 1 040 101 individuals aged ≥ 40 years. The prevalence of impaired kidney function (eGFR <60 mL/min/1.73 m2) increased with age, being 0.7%, 9.2%, 21.9%, 40.2%, and 60.2% at the ages of 18-39, 40-64, 65-74, 75-84, and ≥ 85 years (P for trend < 0.001); similarly, the proportion with positive proteinuria increased with age, being 2.7%, 4.3%, 5.6%, 9.2%, and 15.8%, respectively (P for trend < 0.001). Both eGFR and urine protein were identified to be independent risk factors for CVD. Hazard ratios for CVD increased significantly when eGFR was <45 mL/min/1.73 m2 at the ages of 40-64, 65-74, and 75-84 and <30 mL/min/1.73 m2 at ≥ 85 years, while proteinuria remained significantly associated with a high CVD risk regardless of age. These findings were consistent even when analyzed separately by sex. CONCLUSIONS: This study identified eGFR and urine dipstick proteinuria to be independent risk factors for CVD, even among individuals aged ≥ 85 years. However, the contribution of eGFR to the CVD risk was attenuated by aging, whereas proteinuria remained less affected by advancing age.

Comparison of estimated glomerular filtration rate change with sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists among people with diabetes: A propensity-score matching study.

AIM: To compare the risk of developing kidney outcomes with use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus use of sodium-glucose cotransporter-2 (SGLT2) inhibitors among individuals with diabetes. MATERIALS AND METHODS: In this retrospective observational study, we analysed 12 338 individuals with diabetes who newly initiated SGLT2 inhibitors or GLP-1RAs using data from the JMDC claims database. The primary outcome was change in the estimated glomerular filtration rate (eGFR), estimated using a linear mixed-effects model. A 1:4 propensity-score-matching algorithm was used to compare the changes in eGFR between GLP-1RA and SGLT2 inhibitor users. RESULTS: After propensity-score matching, 2549 individuals (median [range] age 52 [46-58] years, 80.6% men) were analysed (510 GLP-1RA new users and 2039 SGLT2 inhibitor new users). SGLT2 inhibitor use was associated with a slower eGFR decline when compared with GLP-1RA use (-1.41 [95% confidence interval -1.63 to -1.19] mL/min/1.73 m2 vs. -2.62 [95% confidence interval -3.15 to -2.10] mL/min/1.73 m2). CONCLUSIONS: Our analysis demonstrates the potential advantages of SGLT2 inhibitors over GLP-1RAs in terms of kidney outcomes in individuals with diabetes.

Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease　- A 12-Year Nationwide Cohort Analysis.

BACKGROUND: Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown.Methods and Results: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. CONCLUSIONS: This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Benign Prostatic Hyperplasia and Incident Cardiovascular Disease.

BACKGROUND: Data regarding the relationship between benign prostatic hyperplasia (BPH) and incident cardiovascular disease (CVD) are scarce. We aimed to clarify the association of BPH with the risk of developing CVD using a nationwide epidemiological database.Methods and Results: This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 2,370,986 men (median age 44 years). The primary endpoints were myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), which were assessed separately. BPH was observed in 48,651 (2.1%) men. During a mean (±SD) follow-up of 1,359±1,020 days, 7,638 MI, 52,167 AP, 25,355 stroke, 58,183 HF, and 16,693 AF events were detected. Hazard ratios of BPH for MI, AP, stroke, HF, and AF were 1.04 (95% confidence interval [CI] 0.92-1.18), 1.31 (95% CI 1.25-1.37), 1.26 (95% CI 1.18-1.33), 1.21 (95% CI 1.16-1.27), and 1.15 (95% CI 1.07-1.24), respectively. We confirmed the robustness of our primary findings through a multitude of sensitivity analyses. In particular, a history of BPH was associated with a higher risk of developing CVD, even in participants without obesity, hypertension, diabetes, or dyslipidemia. CONCLUSIONS: Our analysis of a nationwide epidemiological dataset demonstrated that BPH was associated with a greater risk of developing CVD in middle-aged men.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

BACKGROUND: Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD.Methods and Results: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. CONCLUSIONS: Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Body mass index and outcomes in patients with Takotsubo syndrome: a nationwide retrospective cohort study.

BACKGROUND: Takotsubo syndrome (TTS) is a cardiac disorder that mimics acute coronary syndrome at presentation. While previous studies have demonstrated a relationship between body mass index (BMI) and outcomes in acute coronary syndrome, few have examined its relationship with TTS. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 14,551 patients admitted for TTS between 2010-2021. By applying multivariable regressions with restricted cubic splines, we examined the association between BMI and in-hospital mortality after adjusting for potential confounders. RESULTS: Mean BMI was 21.1 kg/m2, classifying patients into severe underweight (<16.0 kg/m2, 7.1%), mild/moderate underweight (16.0-18.4 kg/m2, 18.3%), normal weight (18.5-22.9 kg/m2, 46.8%), overweight (23.0-27.4 kg/m2, 22.2%), and obese (≥27.5 kg/m2, 5.6%) groups. Patients with severe or mild/moderate underweight were older and had a higher prevalence of impaired physical activity, malignancy, chronic pulmonary disease, and pneumonia. In-hospital mortality was the highest (9.4%) in the severe underweight group, followed by the mild/moderate underweight group (5.4%), with the lowest being in the obese group (2.1%). Severe underweight (adjusted odds ratio=2.05 [95% CI=1.54-2.73]) and mild/moderate underweight (1.26 [1.01-1.57]) were significantly associated with higher mortality compared with normal weight, while no significant association was noted with obesity. A nonlinear association between continuous BMI and mortality was observed, with mortality increasing when BMI decreased <20.0 kg/m2 but nearly plateauing in BMI >20 kg/m2. CONCLUSIONS: The present nationwide analysis demonstrated a nonlinear association between BMI and in-hospital mortality of TTS. BMI is an easily available and clinically relevant marker for the risk stratification of TTS.

Machine Learning-based Models for Outpatient Prescription of Kampo Formulations: An Analysis of a Health Insurance Claims Database.

BACKGROUND: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations. METHODS: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated. RESULTS: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models. CONCLUSION: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Effect of periodontal therapy on glycaemic control in type 2 diabetes.

AIM: This study aimed to elucidate the impact of periodontal therapy on glycaemic control in individuals with type 2 diabetes and various baseline blood glucose levels using a large-scale claims database from Japan. MATERIALS AND METHODS: Using the JMDC Claims Database, we identified individuals with type 2 diabetes who underwent health check-ups in the fiscal years 2018 or 2019 and were followed up until the next year's health check-up. We conducted a weighted cohort analysis using stabilized inverse probability weights for treatment and censoring to estimate the effect of periodontal therapy on changes in haemoglobin A1c levels within a year. Analysis was done for different baseline haemoglobin A1c categories: 6.5%-6.9%, 7.0%-7.9% and ≥8.0%. RESULTS: Of the 4279 insured persons included in the study, 957 received periodontal therapy. Overall, there was a tendency towards improved glycaemic control among those who received periodontal therapy. Participants with baseline haemoglobin A1c levels of 7.0%-7.9% who received periodontal therapy exhibited significantly better glycaemic control compared with those without dental visits (difference; -0.094 [95% confidence interval: -0.181 to -0.007]). CONCLUSIONS: Periodontal therapy may improve glycaemic control in individuals with diabetes, especially in those with haemoglobin A1c levels ≥7.0%.

Usability of the Japanese Late-Stage Elderly Questionnaire for screening major depression.

BACKGROUND: Older adults with major depression are at risk of frailty and long-term care needs. Consequently, screening for major depression is imperative to prevent such risks. In Japan, the Late-Stage Elderly Questionnaire was developed to evaluate older adults' holistic health, including mental well-being. It comprises one specific question to gauge life satisfaction, but the effectiveness of this question to screen for major depression remains unclear. Therefore, we aimed to assess the usability of this question to screen for major depression. METHODS: This retrospective cohort study used a large, commercially available claims database in Japan. Participants were older adults aged ≥75 years who completed the Late-Stage Elderly Questionnaire and were classified with and without new major depression within 1 year. We evaluated the questionnaire's ability to screen for major depression using C-statistics, developing three models to assess the cut-off value based on responses to the life satisfaction question ('Satisfied', 'Somewhat satisfied', 'Somewhat unsatisfied', or 'Unsatisfied'), estimating the sensitivity and specificity of each model. RESULTS: Among 11 117 older adults, 77 newly experienced major depression within 1 year. The C-statistic for screening major depression was 0.587. The model setting the cut-off between 'Somewhat unsatisfied' and 'Unsatisfied' the demonstrated lowest sensitivity and highest specificity, while the model setting the cut-off between 'Satisfied' and 'Somewhat satisfied' demonstrated highest sensitivity and lowest specificity. CONCLUSIONS: Our results suggest that due to its poor screening ability and high rate of false negatives, the question assessing life satisfaction in the Late-Stage Elderly Questionnaire may not be useful for screening major depression in older adults and may require modification.

Sex-Specific Differences in the Risk of Heart Failure following Anti-HER2 Monoclonal Antibody Therapy.

BACKGROUND: Anti-HER2 monoclonal antibody is associated with a greater risk of heart failure (HF) in female breast cancer patients. In recent years, the indication of anti-HER2 monoclonal antibodies was further expanded to stomach, colorectal, and salivary gland cancers regardless of sex in Japan. However, there have been no data on sex difference in the risk of HF after the anti-HER2 monoclonal antibody treatment. OBJECTIVES: We compared the risk of HF between male and female cancer patients treated with anti-HER2 monoclonal antibody using a nationwide population-based database. METHOD: We analyzed 4,608 cancer patients (230 men, median age; 52 years, breast cancer; 4,333) treated with HER2 monoclonal antibody enrolled in the JMDC Claims Database. The primary outcome was the incidence of HF. RESULTS: Over a mean follow-up of 917 ± 835 days, 559 HF events were documented. Kaplan-Meier curves showed no significant difference in the incidence of HF between men and women. Multivariable Cox regression analysis showed that male sex was not associated with a risk of HF compared with women (HR, 0.76; 95% CI: 0.39-1.49). CONCLUSIONS: Our analysis of a nationwide population-based database firstly revealed that no significant sex difference existed in the risk of HF among cancer patients treated with anti-HER2 monoclonal antibody. Our findings suggest that the use of anti-HER2 monoclonal antibodies in male patients may be associated with similar risks observed in female patients.

Association of four health behaviors in Life's Essential 8 with the incidence of hypertension and diabetes mellitus.

BACKGROUND: The association between health behaviors and the risk of developing hypertension and diabetes is not fully understood. We aimed to examine the association between four health behaviors involved in Life's Essential 8, the American Heart Association's key measures for improving and maintaining cardiovascular health, and the incidence of hypertension and diabetes. METHODS: This observational cohort study used the JMDC Claims Database between 2005 and 2021, which is a health check-up and claims database. We analyzed 2,912,183 participants without a history of hypertension, diabetes, cardiovascular disease, or renal failure. Non-ideal health behaviors included smoking, slow gait speed, eating fast, and poor sleep quality. RESULTS: During 1140 ± 877 days, 201,385 hypertension and 142,156 diabetes events were recorded. In a multivariable Cox regression analysis, the risk of hypertension and diabetes increased with an increasing number of non-ideal health behaviors. The hazard ratios (HRs) (95% confidence interval [CI]) per 1-point increase in non-ideal health behavior components for hypertension and diabetes were 1.11 (1.10-1.11) and 1.08 (1.08-1.09), respectively. Each health behavior was independently associated with the incidence of hypertension and diabetes. A 1-point improvement in health behaviors was associated with a lower risk of developing hypertension (HR 0.94, 95% CI 0.93-0.95) and diabetes (HR 0.95, 95% CI 0.94-0.96). CONCLUSION: Factors that can be substituted for the four health behaviors involved in Life's Essential 8 can stratify the risk of hypertension and diabetes, and improving these health behaviors is useful in preventing hypertension and diabetes in general population.

Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis.

PURPOSE: Creatinine clearance (CCr) and pharmacokinetic parameters are markedly affected by pathophysiological changes in patients with sepsis. However, only a few reports have assessed renal function in patients with sepsis using the measured CCr. Furthermore, the administration regimen has not been sufficiently evaluated using a population PK (PPK) model across renal function broad ranges. Therefore, this study was performed to construct a meropenem PPK model for patients with sepsis using the measured CCr and evaluate the optimized meropenem dosing regimen based on the CCr. METHODS: Patients with sepsis who received intravenous meropenem at the Showa University Hospital were enrolled in this prospective observational study. The PPK model was constructed using blood samples and clinical information of patients. The probability of target attainment (PTA) indicates the likelihood of achieving 50% time above the minimum inhibitory concentration (% T > MIC) based on 10,000 virtual patients using Monte Carlo simulations. The PTA for each meropenem regimen was 50% T > MIC based on different renal functions using the Monte Carlo simulation. RESULTS: One hundred samples were collected from 31 patients. The final PPK model incorporating the measured CCr as a covariate in CL displayed the best fit. The recommended dosing regimen to achieve a PTA of 50% T > MIC of 4 mcg/mL was 1 g every 8 hours as a 3-hour prolonged infusion for patients with CCr 85-130 mL/min and 1 g every 8 hours as an 8-hour continuous infusion for patients with CCr ≥ 130 mL/min. CONCLUSIONS: This model precisely predicted meropenem concentrations in patients with sepsis by accurately evaluating renal function using the measured CCr. Extended dosing was demonstrated to be necessary to achieve a PTA of 50% T > MIC for patients with CCr ≥ 85 mL/min. Meropenem effectiveness can be maximized in patients with sepsis by selecting the appropriate dosing regimen based on renal function and the MIC.

Enduring Relevance of the Stages of Change Model for Transforming Lifestyle Behaviors.

BACKGROUND: The applicability of the Stages of Change model for cardiovascular disease-related behaviors, such as smoking, exercise, diet, and sleep quality, is unclear.Methods and Results: Using a large-scale epidemiological dataset, we found that baseline behavior change intention, as per the transtheoretical model, was associated with modifications of unhealthy lifestyles including cigarette smoking, physical inactivity, skipping breakfast, and poor sleep quality. CONCLUSIONS: Our results suggest that an individual's motivation to change assessed by a general questionnaire may contribute to lifestyle modification and potentially prevent subsequent cardiovascular disease.

Association between ambient temperature and cause-specific cardiovascular disease admissions in Japan: A nationwide study.

BACKGROUND: Substantial evidence suggests that non-optimal temperatures can increase the risk of cardiovascular disease (CVD) mortality and morbidity; however, limited studies have reported inconsistent results for hospital admissions depending on study locations, which also lack national-level investigations on cause-specific CVDs. METHODS: We performed a two-stage meta-regression analysis to examine the short-term associations between temperature and acute CVD hospital admissions by specific categories [i.e., ischemic heart disease (IHD), heart failure (HF), and stroke] in 47 prefectures of Japan from 2011 to 2018. First, we estimated the prefecture-specific associations using a time-stratified case-crossover design with a distributed lag nonlinear model. We then used a multivariate meta-regression model to obtain national average associations. RESULTS: During the study period, a total of 4,611,984 CVD admissions were reported. We found cold temperatures significantly increased the risk of total CVD admissions and cause-specific categories. Compared with the minimum hospitalization temperature (MHT) at the 98th percentile of temperature (29.9 °C), the cumulative relative risks (RRs) for cold (5th percentile, 1.7 °C) and heat (99th percentile, 30.5 °C) on total CVD were 1.226 [95% confidence interval (CI): 1.195, 1.258] and 1.000 (95% CI: 0.998, 1.002), respectively. The RR for cold on HF [RR = 1.571 (95% CI: 1.487, 1.660)] was higher than those of IHD [RR = 1.119 (95% CI: 1.040, 1.204)] and stroke [RR = 1.107 (95% CI: 1.062, 1.155)], comparing to their cause-specific MHTs. We also observed that extreme heat increased the risk of HF with RR of 1.030 (95% CI: 1.007, 1.054). Subgroup analysis showed that the age group ≥85 years was more vulnerable to these non-optimal temperature risks. CONCLUSIONS: This study indicated that cold and heat exposure could increase the risk of hospital admissions for CVD, varying depending on the cause-specific categories, which may provide new evidence to reduce the burden of CVD.

Usefulness of gallium-67 scintigraphy for evaluating the histopathological activity in interstitial nephritis.

BACKGROUND: Interstitial nephritis is a common cause of renal failure. Gallium-67 scintigraphy is reportedly useful for diagnosing interstitial nephritis; however, its ability to assess disease activity remains unknown. We aimed to analyze the relationship between the renal uptake of gallium-67 and the disease activity in interstitial nephritis. METHODS: We retrospectively analyzed the data of patients who underwent gallium-67 scintigraphy at a hospital in Tokyo. The renal uptake adjusted for the soft tissues beneath the kidneys was semi-quantitatively evaluated. We compared the renal uptake levels between patients clinically diagnosed with and without interstitial nephritis. Among those undergoing renal biopsy, we evaluated the predictive ability of gallium-67 scintigraphy and analyzed the renal uptake levels regarding the disease activity through a histopathological analysis. RESULTS: We included 143 patients; among them, 30, 17, and 96 patients were clinically diagnosed with interstitial nephritis, other kidney diseases, and non-kidney diseases, respectively. The renal uptake of gallium-67 was the highest among patients with interstitial nephritis. Among the 25 patients who underwent renal biopsy, 15 were pathologically diagnosed with interstitial nephritis. The renal uptake levels showed a high discriminative ability (C-statistic: 0.83). Furthermore, net reclassification improvement with the addition of gallium-67 scintigraphy to N-acetyl-ß-D-glucosaminidase for the prediction of interstitial nephritis was 1.14. Histopathological analysis revealed a positive correlation between renal uptake and inflammation in the cortex and peritubular capillaries. CONCLUSIONS: This study confirmed the diagnostic value and potential usefulness of gallium-67 scintigraphy for evaluating interstitial nephritis.