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.

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.

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.

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.

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.

The effect of psychological stress and physical activity on ambulatory blood pressure variability detected by a multisensor ambulatory blood pressure monitoring device.

Psychological stress and physical activity contribute to blood pressure (BP) variability, which is a significant and independent risk factor for cardiovascular events. We examined the effects of physical activity level in the 5 min before each BP measurement and psychological stress on ambulatory BP and pulse rate variability in daily life. During a 24 h monitoring period, BP and pulse rate were measured by a multisensor ABPM device (TM-2441; A&D Co.) at 30 min intervals, and physical activity was continuously recorded by an actigraph built into the ABPM device. Psychological stress was assessed from negative emotions or worksite location in the participants' situational information at each BP measurement, which was self-reported on a paper pad immediately (or as soon as possible) after the measurement. A total of 642 ABPM readings with corresponding situational information were obtained from 50 high-risk patients and showed that BP and pulse rate were significantly associated with actigraph-recorded physical activity (increase against the physical-activity-above-walking level: 4.2 ± 2.0 mmHg, p = 0.036 for SBP; 5.4 ± 1.1 bpm, p < 0.001 for pulse rate). When self-reported situational factors were additionally included in the analysis model as variables, negative emotions (7.4 ± 2.5 mmHg, p = 0.003 for SBP) and worksite location (5.8 ± 2.1 mmHg, p = 0.005 for SBP) were significantly associated with BP increase, while the association between BP and physical activity was weakened (p > 0.05). The pulse rate increased against the physical-activity-above-walking level but did not change for negative emotions. In conclusion, the effect of negative emotions on BP was greater than that of physical activity, whereas no similar effect on pulse rate was found. Simultaneous monitoring of BP, pulse rate, and actigraph-recorded physical activity could detect psychological stress-induced BP elevation.

Concept, study design, and baseline blood pressure control status of the nationwide prospective HI-JAMP study using multisensor ABPM.

The Home-Activity Information and Communication Technology (ICT)-based Japan Ambulatory Blood Pressure Monitoring Prospective (HI-JAMP) study is a nationwide general practitioner-based cohort of medicated hypertensive patients that began in 2017. The primary objective of this study is to clarify which blood pressure (BP) measure is the best predictor of cardiovascular disease: office, home, or ambulatory BP. To this end, we used a newly developed ICT-based multisensor ambulatory BP monitoring (IMS-ABPM) device (TM-2441; A&D Company), which can also be used for home BP monitoring and is equipped with a high-sensitivity actigraph, a thermometer, and a barometer. This is the first study to evaluate three hemodynamic properties under resting home and active ambulatory conditions using the same device: (1) BP variability; (2) trigger-specific BP sensitivity to physical activity, temperature, and atmospheric pressure; and (3) central hemodynamics. A total of 2754 patients were enrolled, and 2731 patients with the required number of ambulatory BP readings (at least 6 daytime and 3 nighttime readings) were included in the final analysis. The overall patient group showed worse control of morning and nighttime BPs compared to office and daytime BPs, and the control rate was also poor among patients with a higher number of antihypertensive drugs. In conclusion, the baseline data of the HI-JAMP study demonstrated that morning home and nighttime BP remain difficult to control even among patients taking two or more hypertensive agents. By simultaneously considering office, home, and ambulatory BPs, the HI-JAMP study will contribute to the development of hypertension management strategies and new BP indices.

Peak home blood pressure as an earlier and strong novel risk factor for stroke: the practitioner-based nationwide J-HOP study extended.

While home blood pressure (BP) measurement is recommended for hypertension management, the clinical implications of peak home BP values have not been well studied. This study investigated the association between pathological threshold or frequency of peak home BP and cardiovascular events in patients with ≥1 cardiovascular risk factor. The Japan Morning Surge-Home Blood Pressure (J-HOP) study enrolled participants from 2005-2012 with extended follow-up from December 2017 to May 2018, which generated the dataset for this analysis. Average peak home systolic BP (SBP) was defined as average of the highest three BP values on 14-day measurement period. Patients were divided into quintiles of peak home BP, and the risk of stroke, coronary artery disease (CAD) and atherosclerotic cardiovascular disease (ASCVD; stroke+CAD) was determined. In 4231 patients (mean 65 years) followed for 6.2 years there were 94 strokes and 124 CAD events. The adjusted hazard ratio (HR) (95% CI) for the risk of stroke and ASCVD in patients with average peak home SBP in the highest versus lowest quintile was 4.39 (1.85-10.43) and 2.04 (1.24-3.36), respectively. Risk was greatest for stroke in the first 5 years: HR 22.66 (2.98-172.1). The pathological threshold of average peak home SBP for 5-year stroke risk was 176 mmHg. There was a linear association between the number of times peak home SBP > 175 mmHg and stroke risk. Peak home BP was a strong risk factor for stroke, especially within the first 5 years. We propose exaggerated peak home SBP > 175 mmHg as an early and strong novel risk factor for stroke.

Nighttime hemodynamic phenotype. A novel risk factor for cardiovascular disease, especially heart failure: the practitioner-based nationwide JAMP study.

BACKGROUND: Non-dipper and riser patterns of nocturnal blood pressure (BP) are risk factors for cardiovascular disease (CVD), including heart failure (HF). However, the risk associated with a disrupted nocturnal pattern of heart rate is not well known. OBJECTIVES: To investigate whether the nighttime heart rate is a risk factor for HF, alongside nighttime BP phenotype. METHODS: The practitioner-based, nationwide, prospective Japan Ambulatory Blood Pressure Monitoring Prospective (JAMP) study included patients with ≥ 1 CVD risk factor but without symptomatic CVD at baseline. All patients underwent 24-h ambulatory BP monitoring at baseline and were followed annually. Nocturnal heart rate dipping (%) was calculated as 100•[1 - nighttime/daytime heart rate]. RESULTS: During a mean 4.5 years' follow-up in 6,359 patients (mean age 68.6 years), there were 306 CVD events (119 stroke, 99 coronary artery disease, and 88 HF). A 10-beats/min increase in nighttime heart rate was significantly associated with a 36-47% increase in the risk of total CVD, stroke and HF events independently of office SBP and nighttime SBP (all p < 0.005). The CVD and HF risk associated with nocturnal heart rate dipping status was independent of office and 24-h systolic BP and nocturnal BP dipping status (p < 0.001). Performance of the final model for predicting HF including BP parameters was significantly improved by the addition of nocturnal heart rate dipping patterns (p = 0.038; C-statistic 0.852). CONCLUSION: Nighttime non-dipper and riser patterns of heart rate were associated with CVD especially HF, independently and additively of nocturnal BP dipping status, indicating the importance of antihypertensive strategies targeting nighttime hemodynamics. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000020377.

Different Home Blood Pressure Thresholds to Predict Perfect 24-Hour Ambulatory Blood Pressure Control in Treated Hypertension Based on an "All-in-One" Device.

BACKGROUND: Home blood pressure (BP) is an important component of digital strategies for hypertension management. However, no studies have used the same device to investigate 24-hour BP control status in relation to different home BP control thresholds. METHODS: Participants in the general practitioner-based, multicenter HI-JAMP study (Home-Activity Information and Communication Technology-Based Japan Ambulatory Blood Pressure Monitoring Prospective) underwent office BP measurement, then 24-hour ambulatory BP monitoring, then home BP monitoring for 5 days. A validated all-in-one BP monitoring device was used to measure office, home, and ambulatory BP. Baseline data were used to investigate ambulatory BP control status in individuals with well-controlled home BP based on the different guideline thresholds (125/75 mm Hg, 130/80 mm Hg, and 135/85 mm Hg). RESULTS: Data from 2269 patients were analyzed. For individuals with well-controlled home BP <135/85 mm Hg (59.5% of the total population), the prevalence of uncontrolled 24-hour (≥130/80 mm Hg), daytime (≥135/85 mm Hg), and nighttime ambulatory BP (≥120/70 mm Hg) was 19.9%, 18.5%, and 33.6%, respectively. Corresponding prevalence rates in the 42.7% of participants with well-controlled home BP <130/80 mm Hg were 13.4%, 12.9%, and 26.0%, and when well-controlled home BP was strictly defined as <125/75 mm Hg (23.9% of the population), prevalence of rates of uncontrolled 24-hour, daytime, and nighttime ambulatory BP were 7.0%, 9.0%, and 15.3%, respectively. CONCLUSIONS: Home BP control status defined using different thresholds could predict 24-hour ambulatory BP control status in treated hypertension. One-third of individuals still had uncontrolled nocturnal hypertension when home BP was controlled to <135/85 mm Hg, but ambulatory BP was quite well controlled when home BP was <125/75 mm Hg.

Inconsistent Control Status of Office, Home, and Ambulatory Blood Pressure All Taken Using the Same Device: The HI-JAMP Study Baseline Data.

BACKGROUND: Inconsistencies between the office and out-of-office blood pressure (BP) values (described as white-coat hypertension or masked hypertension) may be attributable in part to differences in the BP monitoring devices used. METHODS: We studied consistency in the classification of BP control (well-controlled BP vs. uncontrolled BP) among office, home, and ambulatory BPs by using a validated "all-in-one" BP monitoring device. In the nationwide, general practitioner-based multicenter HI-JAMP study, 2,322 hypertensive patients treated with antihypertensive drugs underwent office BP measurements and 24-hour ambulatory BP monitoring (ABPM), consecutively followed by 5-day home BP monitoring (HBPM), for a total of seven BP measurement days. RESULTS: Using the thresholds of the JSH2019 and ESC2018 guidelines, the patients with consistent classification of well-controlled status in the office (<140 mmHg) and home systolic BP (SBP) (<135 mmHg) (n = 970) also tended to have well-controlled 24-hour SBP (<130 mmHg) (n = 808, 83.3%). The patients with the consistent classification of uncontrolled status in office and home SBP (n = 579) also tended to have uncontrolled 24-hour SBP (n = 444, 80.9%). Among the patients with inconsistent classifications of office and home BP control (n = 803), 46.1% had inconsistent ABPM-vs.-HBPM out-of-office BP control status. When the 2017 ACC/AHA thresholds were applied as an alternative, the results were essentially the same. CONCLUSIONS: The combined assessment of the office and home BP is useful in clinical practice. Especially for patients whose office BP classification and home BP classification conflict, the complementary clinical use of both HBPM and ABPM might be recommended.