Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Kidney outcomes associated with haematuria and proteinuria trajectories among patients with IgA nephropathy in real-world clinical practice: The Japan Chronic Kidney Disease Database.

AIM: Among patients with Immunoglobulin A (IgA) nephropathy, we aimed to identify trajectory patterns stratified by the magnitude of haematuria and proteinuria using repeated urine dipstick tests, and assess whether the trajectories were associated with kidney events. METHODS: Using a nationwide multicentre chronic kidney disease (CKD) registry, we analysed data from 889 patients with IgA nephropathy (mean age 49.3 years). The primary outcome was a sustained reduction in eGFR of 50% or more from the index date and thereafter. During follow-up (median 49.0 months), we identified four trajectories (low-stable, moderate-decreasing, moderate-stable, and high-stable) in both urine dipstick haematuria and proteinuria measurements, respectively. RESULTS: In haematuria trajectory analyses, compared to the low-stable group, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) for kidney events were 2.59 (95% CI, 1.48-4.51) for the high-stable, 2.31 (95% CI, 1.19-4.50) for the moderate-stable, and 1.43 (95% CI, (0.72-2.82) for the moderate-decreasing groups, respectively. When each proteinuria trajectory group was subcategorized according to haematuria trajectories, the proteinuria group with high-stable and with modest-stable haematuria trajectories had approximately 2-times higher risk for eGFR reduction ≥50% compared to that with low-stable haematuria trajectory. CONCLUSION: Assessments of both haematuria and proteinuria trajectories using urine dipstick could identify high-risk IgA nephropathy patients.

Nighttime Blood Pressure Phenotype and Cardiovascular Prognosis: Practitioner-Based Nationwide JAMP Study.

BACKGROUND: Ambulatory and home blood pressure (BP) monitoring parameters are better predictors of cardiovascular events than are office BP monitoring parameters, but there is a lack of robust data and little information on heart failure (HF) risk. The JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) used the same ambulatory BP monitoring device, measurement schedule, and diary-based approach to data processing across all study centers and determined the association between both nocturnal hypertension and nighttime BP dipping patterns and the occurrence of cardiovascular events, including HF, in patients with hypertension. METHODS: This practitioner-based, nationwide, multicenter, prospective, observational study included patients with at least 1 cardiovascular risk factor, mostly hypertension, and free of symptomatic cardiovascular disease at baseline. All patients underwent 24-hour ambulatory BP monitoring at baseline. Patients were followed annually to determine the occurrence of primary end point cardiovascular events (atherosclerotic cardiovascular disease and HF). RESULTS: A total of 6,359 patients (68.6±11.7 years of age, 48% men) were included in the final analysis. During a mean±SD follow-up of 4.5±2.4 years, there were 306 cardiovascular events (119 stroke, 99 coronary artery disease, 88 HF). Nighttime systolic BP was significantly associated with the risk of atherosclerotic cardiovascular disease and HF (hazard ratio adjusted for demographic and clinical risk factors per 20-mm Hg increase: 1.18 [95% CI, 1.02-1.37], P=0.029; and 1.25 [95% CI, 1.00-1.55], P=0.048, respectively). Disrupted circadian BP rhythm (riser pattern, nighttime BP higher than daytime BP) was significantly associated with higher overall cardiovascular disease risk (1.48 [95% CI, 1.05-2.08]; P=0.024), and especially HF (2.45 [95% CI, 1.34-4.48]; P=0.004) compared with normal circadian rhythm. CONCLUSIONS: Nighttime BP levels and a riser pattern were independently associated with the total cardiovascular event rate, in particular for HF. These findings suggest the importance of antihypertensive strategies targeting nighttime systolic BP. Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000020377.

Twenty-Four-Hour Blood Pressure-Lowering Effect of a Sodium-Glucose Cotransporter 2 Inhibitor in Patients With Diabetes and Uncontrolled Nocturnal Hypertension: Results From the Randomized, Placebo-Controlled SACRA Study.

BACKGROUND: The risk of cardiovascular disease and mortality in salt-sensitive patients with diabetes mellitus and uncontrolled nocturnal hypertension is high. The SACRA (Sodium-Glucose Cotransporter 2 [SGLT2] Inhibitor and Angiotensin Receptor Blocker [ARB] Combination Therapy in Patients With Diabetes and Uncontrolled Nocturnal Hypertension) study investigated changes in blood pressure (BP) with empagliflozin plus existing antihypertensive therapy. METHODS: This multicenter, double-blind, parallel study was conducted in Japan. Adult patients with type 2 diabetes mellitus and uncontrolled nocturnal hypertension receiving stable antihypertensive therapy including angiotensin receptor blockers were randomized to 12 weeks' treatment with empagliflozin 10 mg once daily or placebo. Clinic BP was measured at baseline and weeks 4, 8, and 12; 24-hour ambulatory BP monitoring was performed at baseline and week 12; and morning home BP was determined for 5 days before each visit. The primary efficacy end point was change from baseline in nighttime BP (ambulatory BP monitoring). RESULTS: One hundred thirty-two nonobese, older patients with well-controlled blood glucose were randomized (mean age 70 years, mean body mass index 26 kg/m2). Empagliflozin, but not placebo, significantly reduced nighttime systolic BP versus baseline (-6.3 mm Hg; P=0.004); between-group difference in change from baseline was -4.3 mm Hg (P=0.159). Reductions in daytime, 24-hour, morning home, and clinic systolic BP at 12 weeks with empagliflozin were significantly greater than with placebo (-9.5, -7.7, -7.5, and -8.6 mm Hg, respectively; all P≤0.002). Between-group differences in body weight and glycosylated hemoglobin reductions were significant, but small (-1.3 kg and -0.33%; both P<0.001). At 4 weeks, N-terminal pro-B-type natriuretic peptide levels were reduced to a greater extent in the empagliflozin versus placebo group (-12.1%; P=0.013); atrial natriuretic peptide levels decreased with empagliflozin versus placebo at weeks 4 and 12 (-8.2% [P=0.008] and -9.7% [P=0.019]). Changes in antihypertensive medication during the study did not differ significantly between groups. CONCLUSIONS: Nonseverely obese older diabetes patients with uncontrolled nocturnal hypertension showed significant BP reductions without marked reductions in glucose with the addition of empagliflozin to existing antihypertensive and antidiabetic therapy. Use of sodium-glucose cotransporter 2 inhibitors in specific groups (eg, those with nocturnal hypertension, diabetes, and high salt sensitivity) could help reduce the risk of heart failure and cardiovascular mortality. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03050229.

Maximum home systolic blood pressure is a marker of carotid atherosclerosis.

Background: Maximum home systolic blood pressure (maximum SBP) has been reported as a parameter of blood pressure (BP) variability. We tested the hypothesis that maximum SBP is one of the risk factors of hypertensive target organ damage (TOD).Methods: We conducted a cross-sectional study of 4,310 subjects with>1 cardiovascular risk factor. The subjects measured their home BP for 14 consecutive days. Mean and maximum SBPs were used as independent variables. As dependent variables, we used left ventricular mass index (LVMI), brachial-ankle pulse wave velocity (baPWV), maximum carotid intima-media thickness (CIMT), and urine albumin creatinine ratio (UACR).Results: In a multiple regression analysis, the subjects' mean and maximum SBPs were significantly associated with the above TOD markers. Compared to mean SBP, maximum SBP demonstrated a significantly stronger association with CIMT (p<0.001).Conclusion: Based on its clinical significance herein, measurement of maximum home SBP is warranted in addition to measurement of mean home SBP.

Should Pre-hypertension Be Treated?

Hypertension is an important preventable risk factor for disease and death worldwide. In light of the world's population growth and aging, hypertension is a global public health issue. Many studies have shown associations between pre-hypertension and a higher risk of the future development of hypertension and cardiovascular disease in general populations. However, pre-hypertension per se is not a disease with an immediate high risk, and the clinical value of the identification of pre-hypertension is the potential detection of the early stage of the risk of hypertension and/or cardiovascular disease over an individual's lifespan. We recently assessed the impacts of age-related differences in risk factors on new-onset hypertension among normotensive individuals. As risk factors of the new onset of hypertension, the impact of diastolic blood pressure compared with systolic blood pressure (SBP), men compared with women, and higher body mass index were greater in the younger adults, whereas in the older adults, the impact of SBP and female sex were greater. Proteinuria was a risk factor for hypertension in both younger and older adults. Non-pharmacological approaches such as body weight reduction, low-salt diet, physical exercise, and good sleep hygiene should be first-line treatments for pre-hypertension. In addition, careful observation to detect the new onset of hypertension and the identification of the appropriate timing of pharmacologic treatment should be conducted, especially in adults with pre-hypertension and the risk factors mentioned above.

Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring　- The NOCTURNE Study.

BACKGROUND: Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled. The ARB/CCB combination therapy (irbesartan 100 mg+amlodipine 5 mg) achieved a significantly greater reduction in nocturnal home systolic BP (primary endpoint) than the ARB/diuretic combination (daily irbesartan 100 mg+trichlormethiazide 1 mg) (-14.4 vs. -10.5 mmHg, P<0.0001), independently of urinary sodium excretion and/or nocturnal BP dipping status. However, the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity (diabetes, chronic kidney disease, and elderly patients). CONCLUSIONS: This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM. The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake, despite the similar impact of the 2 combinations in patients with higher salt sensitivity.

Home blood pressure stability score is associated with better cardiovascular prognosis: data from the nationwide prospective J-HOP study.

A home blood pressure (BP)-centered strategy is emerging as the optimal approach to achieve adequate BP control in individuals with hypertension, but a simple cardiovascular risk score based on home BP level and variability is lacking. This study used prospective data from the Japan Morning Surge-Home Blood Pressure (J-HOP) extended study to develop a simple home BP stability score for the prediction of cardiovascular risk. The J-HOP extended study included 4070 participants (mean age 64.9 years) who measured home BP three times in the morning and evening for 14 days at baseline. During the mean 6.3-year follow-up, there were 260 cardiovascular events. A home BP stability score was calculated based on the average of morning and evening systolic BP (SBP; MEave), and three home BP variability metrics: average real variability (average absolute difference between successive measurements); average peak (average of the highest three SBP values for each individual), and time in therapeutic range (proportion of time spent with MEave home SBP 100-135 mmHg). There was a curvilinear association between the home BP stability score and the risk of cardiovascular events. Compared with individuals in the optimal home SBP stability score group (9-10 points), those in the very high-risk group (0 points) had significantly higher cardiovascular event risk during follow-up (adjusted hazard ratio 3.97, 95% confidence interval 2.22-7.09; p < 0.001), independent of age, sex, medication, cardiovascular risk factors, and office BP. These data show the potential for a simple home BP-based score to predict cardiovascular event risk in people with hypertension.

Potential Long-Term Benefit of Home Systolic Blood Pressure Below 125 mm†Hg for Cardiovascular Risk Reduction: The J-HOP Study Extended.

BACKGROUND: The long-term benefit of achieving the Japanese Society of Hypertension home systolic blood pressure (SBP) target of <125 mm Hg has not been fully evaluated. This study investigated the long-term risk of cardiovascular disease events in individuals with home SBP <125 versus 125 to <135 or ≥135 mm Hg who participated in the J-HOP study (Japan Morning Surge-Home Blood Pressure). METHODS: The J-HOP study enrolled outpatients with ≥1 cardiovascular risk factor between 2005 and 2012, with follow-up until March 2015 and extended follow-up from December 2017 to May 2018. Cardiovascular disease events (stroke, coronary artery disease, congestive heart failure, and aortic dissection) were compared between home SBP subgroups. RESULTS: During mean 5.9 years of follow-up in 4231 participants (mean age, 65 years), cardiovascular events included stroke (n=89), coronary artery disease (n=116), congestive heart failure (n=37), and aortic dissection (n=8). The adjusted 10-year risk of total cardiovascular disease was slightly higher, and stroke risk was significantly higher when baseline home SBP was ≥135 versus <125 mm Hg (adjusted hazard ratio, 1.39 [95% CI, 0.97-2.00] for overall cardiovascular disease and 2.68 [95% CI, 1.34-5.38] for stroke; this was largely due to between-group differences in the first 5 years of follow-up, which were maintained over the subsequent 5 years). Findings were similar in the subgroup of high-risk patients (those with diabetes or stroke history). CONCLUSIONS: These data highlight the potential long-term benefit of strict home SBP control and validate this as an appropriate Japanese Society of Hypertension guideline target although confirmation in larger populations is needed. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; University Hospital Medical Information Network Clinical Trials Registry; Unique identifier: UMIN000000894 (Japan Morning Surge-Home Blood Pressure study).

Home blood pressure measurement consistency and cognitive impairment.

Cognitive function tends to decline with age, and individuals with mild cognitive impairment (MCI) often have difficulty completing established self-management tasks. The aim of this study was to investigate the association between the number of days within a 5-and-a-half-day period that patients took their home blood pressure (BP) as instructed and MCI assessed by the Japanese version of the Montreal Cognitive Assessment (MoCA-J) in an elderly clinical population. We analyzed 303 ambulatory patients (mean age 77.3 ± 8.2 years) in whom MoCA-J had been assessed, who were instructed to take home BP for 1 evening and twice a day for the next five days, and who had at least one morning home BP measurement. After accounting for patient characteristics including age, sex, body mass index, drinking, smoking, prevalent cardiovascular disease, morning systolic BP and diastolic BP, and the use of antihypertensive drugs, the number of days home BP was measured was independently associated with both total MoCA-J score (estimate, 0.82; 95% confidence interval [CI], 0.43-1.21; P < 0.001) and the lowest quartile of MoCA-J score (13 or below) (odds ratio [OR], 0.72; 95%CI, 0.59-0.87; P = 0.001). Home BP measurement noncompliance (<5 days' measurement) was also independently associated with the total MoCA-J score (estimate, -2.56; 95%CI, -4.09 to -1.03; P = 0.001) and the lowest quartile of MoCA-J score (OR, 3.32; 95%CI, 1.59-6.96; P = 0.001). In conclusion, poor compliance with home BP monitoring was associated with cognitive impairment in elderly cases who had been specifically instructed to perform home BP monitoring during a designated period.

Daytime actisensitivity predicts nocturnal dipping patterns and morning surge in blood pressure: the Home-Activity ICT-based Japan Ambulatory Blood Pressure Monitoring Prospective study.

BACKGROUND: Ambulatory blood pressure (BP) is influenced by physical activity and the BP response to physical activity (actisensitivity) differs between individuals. This study investigated associations between daytime actisensitivity and nighttime BP dipping status and morning BP surge. METHODS: Twenty-four-hour ambulatory BP monitoring (ABPM) with simultaneously monitored physical activity using a multisensor all-in-one device (TM-2441; A&D Company) was performed at baseline in HI-JAMP study participants. Those with complete BP measurements and complete physical activity monitoring data were included in this analysis. Actisensitivity was calculated as the slope of the regression line between daytime SBP and log-transformed physical activity over a 5 min period before each BP reading. Hyper and negative reactivity were defined as actisensitivity greater than 90th and less than 10th percentile, respectively. RESULTS: Data from 2692 individuals (mean age 69.9 ±â€Š11.9 years; mean BMI 24.8 ±â€Š4.1 kg/m2, 53.6% men) were analyzed. Those with hyper reactivity had a high prevalence of the extreme dipper pattern of nighttime BP and exaggerated morning BP surge; those with negative reactivity had higher nighttime BP and a riser pattern of nighttime BP. Results remained significant after adjusting for 24-h physical activity. Differences in diurnal BP variability based on actisensitivity were augmented in individuals aged at least 75 years. CONCLUSION: This study is the first to investigate associations between actisensitivity and 24-h ambulatory BP profiles using an all-in-one multisensor device in a large real-world population. The associations seen between either hyper or negative actisensitivity and abnormal diurnal BP variability, especially in the elderly, could contribute to increased cardiovascular event risk. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000029151 (HI-JAMP study).

Home systolic blood pressure time in therapeutic range and cardiovascular risk: the practitioner-based nationwide J-HOP study extended.

Time in therapeutic range (TTR) for office systolic blood pressure (SBP) is an independent predictor of major cardiovascular events. However, the clinical implications of TTR for home SBP have not yet been investigated. This study determined the association between TTR of home SBP and cardiovascular events in individuals with ≥1 cardiovascular risk factor who were enrolled in The Japan Morning Surge-Home Blood Pressure (J-HOP) study. The therapeutic range for home SBP was defined as home SBP of 100-135 mmHg during the 13-day baseline period of the J-HOP study. Participants were divided into subgroups based on quartiles of TTR for home SBP, and the risk of cardiovascular events was determined in each quartile. During a mean 6.3 years of follow-up in 4070 participants (mean age 65 years), cardiovascular events included stroke in 92, coronary artery disease in 119, heart failure in 41 and aortic dissection in 8. The adjusted hazard ratio (95% confidence interval) for the risk of total cardiovascular events in participants with home SBP TTR in the lowest (100%) versus highest quartile (<15.3%) was 1.74 (1.16-2.61); the corresponding hazard ratio for stroke events was 2.11 (1.06-4.21). A 10% decrease in home SBP TTR was associated with a 4% increase in the risk of total cardiovascular events (p = 0.033) and a 9% increase in the risk of stroke (p = 0.004). The significant association seen between home SBP TTR and the occurrence of cardio- and cerebrovascular events highlights the importance of achieving stable reductions in home SBP and minimizing day-by-day home BP variability.Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000000894 (J-HOP study).

Precise risk-prediction model including arterial stiffness for new-onset atrial fibrillation using machine learning techniques.

Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia and is an important risk factor for ischemic cerebrovascular events. This study used machine learning techniques to develop and validate a new risk prediction model for new-onset AF that incorporated the use electrocardiogram to diagnose AF, data from participants with a wide age range, and considered hypertension and measures of atrial stiffness. In Japan, Industrial Safety and Health Law requires employers to provide annual health check-ups to their employees. This study included 13 410 individuals who underwent health check-ups on at least four successive years between 2005 and 2015 (new-onset AF, n = 110; non-AF, n = 13 300). Data were entered into a risk prediction model using machine learning methods (eXtreme Gradient Boosting and Shapley Additive Explanation values). Data were randomly split into a training set (80%) used for model construction and development, and a test set (20%) used to test performance of the derived model. The area under the receiver operator characteristic curve for the model in the test set was 0.789. The best predictor of new-onset AF was age, followed by the cardio-ankle vascular index, estimated glomerular filtration rate, sex, body mass index, uric acid, γ-glutamyl transpeptidase level, triglycerides, systolic blood pressure at cardio-ankle vascular index measurement, and alanine aminotransferase level. This new model including arterial stiffness measure, developed with data from a general population using machine learning methods, could be used to identify at-risk individuals and potentially facilitation the prevention of future AF development.

Peak nocturnal home blood pressure as an early and strong novel risk factor for stroke: the practitioner-based nationwide J-HOP Nocturnal BP study.

Clinical implications of high peak nighttime home blood pressure (BP) are currently unknown. This study investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in individuals with at least one cardiovascular risk factor. In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times each 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. Cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) were tracked over a mean follow-up period of 7.1 years. This analysis included 2545 individuals (mean age 63.3 ± 10.3 years, 49% male). After adjusting 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 quintile (≥149.0 mmHg) compared to the lowest quintile (<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. We propose that exaggerated peak nighttime home SBP, determined from ≥6 measurements, is a novel risk factor for stroke, independent of conventional office and home BP values. The exaggerated peak nighttime home systolic blood pressure (HSBP) determined from six or more measurements as a novel risk factor for stroke, independent of conventional office and home blood pressure (BP) values.

Home Blood Pressure Variability Risk Prediction Score for Cardiovascular Disease Using Data From the J-HOP Study.

BACKGROUND: Home blood pressure (BP) is more closely associated with cardiovascular event risk than office BP, but cardiovascular risk prediction based on home BP variability is lacking. This study developed a simple cardiovascular event prediction score, including home BP variability data, from the J-HOP study (Japan Morning Surge-Home Blood Pressure). METHODS: The J-HOP study extended follow-up from December 2017 to May 2018 generated the study data set (4231 patients). Cardiovascular events included fatal/nonfatal stroke (n=94), coronary heart disease (n=124), heart failure (n=42), and aortic dissection (n=8). Cox proportional hazards models were used to predict overall cardiovascular risk. Potential covariates included age, sex, body mass index, smoking, history of diabetes, statin use, history of cardiovascular disease, total cholesterol:high-density lipoprotein cholesterol ratio, office systolic BP (SBP), mean of morning-evening average (MEave), home SBP, and average real variability of MEave home SBP. A risk score and models were constructed, and model performance was assessed. RESULTS: Model performance was best when average real variability of MEave SBP was included (C statistic, 0.760). The risk score assigns points for age (5-year bands), sex, cardiovascular disease history, high-density lipoprotein cholesterol, mean MEave home SBP, and average real variability of MEave home SBP. Estimated 10-year cardiovascular risk ranged from ≤0.6% (score ≤0) to >32% (score ≥26). Calibration 2 statistics values for the model (2.66) and risk score (5.29) indicated excellent goodness of fit. CONCLUSIONS: This simple cardiovascular disease prediction algorithm, including day-by-day home BP variability, could be used as part of a home BP-centered approach to hypertension management in clinical practice.

Kidney outcomes of SGLT2 inhibitors among older patients with diabetic kidney disease in real-world clinical practice: the Japan Chronic Kidney Disease Database Ex.

INTRODUCTION: We 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 METHODS: Using 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. RESULTS: At 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. CONCLUSIONS: The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.

The association between employee lifestyles and the rates of mental health-related absenteeism and turnover in Japanese companies.

We assessed the association of employee lifestyles (e.g., smoking, exercise, drinking, and sleep habits) with mental health-related absenteeism and turnover rates utilizing data from the annual Health and Productivity Management survey by Japan's Ministry of Economy, Trade and Industry. This analysis included data from 1,748 companies, encompassing 4,199,021 employees. The average proportions of mental health-related absenteeism and employee turnover rates were 1.1±1.0% and 5.0±5.0%, respectively. In multivariable regression models that incorporated all lifestyle factors and confounders, a 1 percentage point increase in the proportion of employees who slept well was associated with reductions in their turnover rate (mean, -0.020%; 95% confidence interval [CI], -0.038 to -0.002) and in mental health-related absenteeism (mean, -0.005%; 95% CI, -0.009 to 0.001). A similar increase in the proportion of employees engaging in regular physical activity corresponded with a 0.005% decrease in the prevalence of mental health-related absenteeism (95% CI, -0.010 to -0.001). A 1 percentage point increase in the proportion of employees who smoked was associated with a 0.013% reduction in mental health-related absenteeism (95% CI, -0.017 to -0.008). Nonetheless, the current study's observational and cross-sectional design restricted the ability to establish causality between employee lifestyle factors and mental health issues.

Impact of vascular biomarkers and supine hypertension on cardiovascular outcomes in hypertensive patients: first results from the Cardiovascular Prognostic COUPLING Study in Japan.

The prognostic impact of vascular biomarkers and supine blood pressure (BP) is not well understood. The multicenter, prospective Coupling study determined the prognostic impact of vascular biomarkers and supine BP in outpatients aged ≥30 years with ≥1 cardiovascular risk factor. Occurrence of major cardiovascular events during follow-up was recorded. The primary outcome was time to onset of a major cardiovascular event. Office and supine BP, the cardio-ankle vascular index (CAVI), and the ankle-brachial index (ABI) were determined annually. Of the 5109 participants in the Coupling study, 4716 were analyzed (51.9% male, mean age 68.5 ± 11.4 years); participants mostly had hypertension treated based on seated office/home BP according to relevant guidelines. During a median follow-up of 5.0 years (interquartile range 3.6-5.2), 231 major cardiovascular events occurred. After adjustment for age, sitting office systolic BP, and other covariates, a 1-unit increase in CAVI (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.01-1.24) and a 0.1-unit decrease in ABI (HR 1.41, 95% CI 1.18-1.68) were significantly associated with cardiovascular event risk; risk was greatest when CAVI was ≥8.0 and ABI was ≤1.10. Uncontrolled supine hypertension (≥140/90 mmHg) was also significantly associated with adjusted cardiovascular event risk (HR 1.36, 95% CI 1.02-1.81); seated office BP control was not significantly associated with cardiovascular event risk. Increased arterial stiffness, mildly lower ABI, and supine hypertension are risk factors for cardiovascular events during standard clinical practice. Supine evaluation of BP and vascular biomarkers has highlighted a blind spot in current hypertension management (Clinical trial registration: University Hospital Medical Information Network Clinical Trials Registry, UMIN000018474).

Evaluating the associations between compliance with CKD guideline component metrics and renal outcomes.

Understanding the association between compliance to the Chronic Kidney Disease (CKD) guidelines in real-world clinical settings and renal outcomes remains a critical gap in knowledge. A comprehensive analysis was conducted using data from a national, multicenter CKD registry. This study included 4,455 patients with an estimated glomerular filtration rate (eGFR) measurement on the index date and eight additional metrics recorded within six months. These metrics comprised serum electrolyte levels, low-density lipoprotein cholesterol, hemoglobin, and the use of renin-angiotensin system inhibitors. The primary outcome was a composite of renal events, defined by a decline in eGFR to < 15 mL/min/1.73 m2 or a reduction of ≥ 30% in eGFR, confirmed by follow-up tests. Over a median follow-up of 513 days, 838 renal events were observed. High serum potassium levels (> 5.4 mmol/L) were associated with increased event rates compared to lower levels. Similarly, low serum sodium-chloride levels (< 33) correlated with higher event rates. Usage of renin-angiotensin system inhibitors, low serum calcium (< 8.4 mg/dL), and high uric acid levels (> 7.0 mg/dL) were also linked to increased events. Conversely, higher hemoglobin levels (≥ 13 g/dL) were associated with lower event rates. Compliance to guidelines, categorized into quartiles based on the number of met metrics, revealed a significantly reduced risk of events in the highest compliance group (meeting 8 metrics) compared to the lowest (0-5 metrics). Compliance to CKD guidelines in clinical practice is significantly associated with improved renal outcomes, emphasizing the need for guideline-concordant care in the management of CKD.