Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.

High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.

Blood Pressure Phenotypes Defined by Ambulatory Blood Pressure Monitoring and Carotid Artery Changes in Community-Dwelling Older Japanese Adults: The Ohasama Study.

White coat hypertension is defined as elevated blood pressure in the office, but a normal blood pressure out-of-office, whereas masked hypertension is defined as elevated blood pressure in the office, but normal out-of-office blood pressure. The objective was to investigate the associations between these blood pressure phenotypes and carotid artery changes. Conventional blood pressure, ambulatory blood pressure, and carotid ultrasonography were evaluated in 851 Ohasama residents (31.8% men; mean age 66.3 years). The blood pressure phenotypes were defined by the ordinary thresholds (140/90 mmHg for conventional blood pressure, 135/85 mmHg for daytime blood pressure) and then by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) thresholds for hypertension (130/80 mmHg for both conventional and daytime blood pressure), irrespective of antihypertensive medication treatment status. Blood pressure phenotypes were linearly associated with the mean intima-media thickness of the carotid artery in ascending order for sustained normal blood pressure, white coat hypertension, masked hypertension, and sustained hypertension according to the ordinary thresholds and the 2017 ACC/AHA thresholds (both linear trends P < 0.0001) after adjustments for possible confounding factors. The odds ratios for the presence of carotid plaques showed similar linear trends with the blood pressure phenotypes according to the 2017 ACC/AHA thresholds (linear trend P < 0.0191). In conclusion, there was a close relationship between blood pressure phenotypes and carotid artery changes, suggesting that blood pressure phenotypes as defined by ambulatory blood pressure are potentially useful for risk stratification of carotid artery changes in the Japanese general population.

Nocturnal blood pressure measured by home devices: evidence and perspective for clinical application.

: Studies using ambulatory blood pressure (BP) monitoring have shown that BP during night-time sleep is a stronger predictor of cardiovascular outcomes than daytime ambulatory or conventional office BP. However, night-time ambulatory BP recordings may interfere with sleep quality because of the device cuff inflation and frequency of measurements. Hence, there is an unmet need for obtaining high quality BP values during sleep. In the last two decades, technological development of home BP devices enabled automated BP measurements during night-time. Preliminary data suggest that nocturnal home BP measurements yield similar BP values and show good agreement in detecting nondippers when compared with ambulatory BP monitoring. Thus, nocturnal home BP measurements might be a reliable and practical alternative to ambulatory BP monitoring to evaluate BP during sleep. As the use of home BP devices is widespread, well accepted by users and has relatively low cost, it may prove to be more feasible and widely available for routine clinical assessment of nocturnal BP. At present, however, data on the prognostic relevance of nocturnal BP measured by home devices, the optimal measurement schedule, and other methodological issues are lacking and await further investigation. This article offers a systematic review of the current evidence on nocturnal home BP, highlights the remaining research questions, and provides preliminary recommendations for application of this novel approach in BP management.

N-Terminal Pro-B-Type Natriuretic Peptide Is Not a Significant Predictor of Stroke Incidence After 5 Years　- The Ohasama Study.

BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been used for risk stratification in heart failure or acute coronary syndrome, but the beyond 5-year predictive value of NT-proBNP for stroke remains an unsettled issue in Asian patients. The aim of the present study was to clarify this point.Methods and Results:We followed 1,198 participants (33.4% men; mean age, 60.5±11.1 years old) in the Japanese general population for a median of 13.0 years. A first stroke occurred in 93 participants. Referencing previous reports, we stratified participants according to NT-proBNP 30.0, 55.0, and 125.0 pg/mL. Using the NT-proBNP <30.0 pg/mL group as a reference, adjusted HR for stroke (95% CI) in the NT-proBNP 30.0-54.9-pg/mL, 55.0-124.9-pg/mL, and ≥125.0-pg/mL groups were 1.92 (0.94-3.94), 1.77 (0.85-3.66), and 1.99 (0.86-4.61), respectively. With the maximum follow-up period set at 5 years, the hazard ratio of the NT-proBNP≥125.0-pg/mL group compared with the <30.0-pg/mL group increased significantly (HR, 4.51; 95% CI: 1.03-19.85). On extension of the maximum follow-up period, however, the association between NT-proBNP and stroke risk weakened. CONCLUSIONS: NT-proBNP was significantly associated with an elevated stroke risk. Given, however, that the predictive power decreased with the number of years after NT-proBNP measurement, NT-proBNP should be re-evaluated periodically in Asian patients.

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore I Vessel Assessment Software Across the Human Age Range.

BACKGROUND: Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measures of arteriolar and venular geometry. Few studies addressed the reproducibility of SIVA measurements across a wide age range. METHODS: In the current study, 2 blinded graders read images obtained by nonmydriatic retinal photography twice in 20 11-year-old children, born prematurely (n = 10) or at term (n = 10) and in 60 adults (age range, 18.9-86.1 years). RESULTS: Former preterm compared with term children had lower microvessel diameter and disorganized vessel geometry with no differences in intraobserver and interobserver variability. Among adults, microvessel caliber decreased with age and blood pressure and arteriolar geometry was inversely correlated with female sex and age. Intraobserver differences estimated by the Bland-Altman method did not reach significance for any measurement. Across measurements, median reproducibility (RM) expressed as percent of the average trait value was 8.8% in children (median intraclass correlation coefficient [ICC], 0.94) and 8.0% (0.97) in adults. Likewise, interobserver differences did not reach significance with RM (ICC) of 10.6% (0.85) in children and 10.4% (0.93) in adults. Reproducibility was best for microvessel caliber (intraobserver/interobserver RM, 4.7%/6.0%; ICC, 0.98/0.96), worst for venular geometry (17.0%/18.8%; 0.93/0.84), and intermediate for arteriolar geometry (10.9%/14.9%; 0.95/0.86). CONCLUSIONS: SIVA produces repeatable measures of the retinal microvasculature in former preterm and term children and in adults, thereby proving its usability from childhood to old age.

Prevalence, Treatment, and Control Rates of Conventional and Ambulatory Hypertension Across 10 Populations in 3 Continents.

Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%-30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues.

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population.

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39-3.94) for a 10-year higher age, 1.92 (1.11-3.31) and 1.70 (1.14-2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08-8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62-2.01), 1.64 (1.45-1.87), 1.13 (1.05-1.22), and 2.84 (2.21-3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.

Salt intake and the validity of a salt intake assessment system based on a 24-h dietary recall method in pregnant Japanese women.

BACKGROUND: Information regarding salt intake in pregnant women in Japan is limited. An electronic system for the assessment of salt intake using a 24-h dietary recall method has been developed in Japan. The objectives of the present study were to investigate salt intake in pregnant women and to compare the salt intake estimated by the electronic salt intake assessment system with that measured by 24-h urinary salt excretion (24-hUNaCl). METHODS: Data were collected on 24-hUNaCl and salt intake estimated by the salt intake assessment system for 35 pregnant Japanese women at approximately 20 weeks of gestation. The adjusted 24-hUNaCl (24-hUNaCl/[the number of urinations during the examination day--the number of missing urine collections] × the number of urinations during the examination day, g/day) was used as a standard. RESULTS: The mean adjusted 24-hUNaCl was 7.7 ± 2.5 g/day, and mean systolic/diastolic blood pressure values were 106.1 ± 8.6/62.8 ± 6.5 mmHg. The adjusted 24-hUNaCl was significantly correlated with the salt intake estimated by the salt intake assessment system (r = 0.47, p = 0.004). Bland-Altman analysis showed no significant mean difference (adjusted 24-hUNaCl--salt intake estimated by the assessment system = -0.36 g/day, p = 0.4) and no significant proportional bias (p = 0.1). CONCLUSION: These results suggest that pregnant women in Japan restrict their salt intake, at least when they are being examined for salt intake. They also suggest that repeated use of the described system may be useful in estimating salt intake in pregnant women.

Individual assessment of inherent arterial stiffness using nomogram and pulse wave velocity index: the Ohasama study.

We measured the brachial-ankle pulse wave velocity (baPWV) in 491 normotensives and determined the "PWV index" (measured baPWV-theoretical baPWV) in 491 normotensives and 83 controlled hypertensives. Linear regression analysis revealed that the theoretical baPWV (cm/sec) was 0.21 × age(2) (years(2))-13.73 × age (years) + 0.05 × mean arterial pressure(2) (mmHg(2)) + 3.95 × heart rate (bpm) + 36.49 × gender (1 male; 0 female) + 733 (R(2) = 0.53). The calculated PWV index was significantly higher in 13 smokers than 70 nonsmokers among controlled hypertensives. The calculated PWV index might provide more precise information about inherent arterial stiffness.

[Cost effectiveness of hypertension treatment based on the measurement of ambulatory blood pressure].

In recent years soaring medical costs have become a major social problem in developed countries. Ambulatory blood pressure (ABP) measurements have a stronger predictive power for cardiovascular events than clinic blood pressure (CBP) measurements. Therefore the introduction of ABP measurement for the diagnosis and treatment of hypertension should lead to a decrease in medical expenditure. This study presents calculations of the cost saving and life years associated with changing from CBP to ABP measurement as diagnostic tool. We constructed a Markov model using data from the Ohasama study and a Japanese national database. Study population was 7.042 million individuals aged 40 years and above living in Japan. The introduction of ABP for hypertension would result in a reduction of about 9.48 trillion yen per 10 years. We conducted a sensitivity analysis and found that the introduction of ABP was associated with at least a cost reduction of 47500 billion yen. But it did not provide significant extension of average life years. However the introduction of ABP for hypertension treatment would be a very effective method in perspective of public health because it reduced about 59600 individuals of stroke and about 18900 individuals of death. Given its cost-effectiveness, extensive application of ABP measurement in clinical practice is expected.

Cost-effectiveness of the introduction of home blood pressure measurement in patients with office hypertension.

OBJECTIVE: Cost-effectiveness of hypertension treatment is an important social and medical issue in Western as well as in Eastern countries, including Japan. Home blood pressure (HBP) measurements have a stronger predictive power for cardiovascular events than casual clinic blood pressure (CBP) measurements. Therefore, the introduction of HBP measurement for the diagnosis and treatment of hypertension should lead to a decrease in medical expenditure. This study presents calculations of the cost savings likely to take place when HBP is implemented for newly detected hypertensive subjects in Japan. DESIGN AND METHODS: We estimate the cost savings from the perspective of a Japanese healthcare system. To estimate the costs associated with changing from CBP to HBP measurement as the diagnostic tool, we constructed a simulation model using data from the Ohasama study. These calculations are based on current estimates for cost of treatment, prevalence of white-coat hypertension at baseline, and varying the incidence of new hypertension after the initial screening. RESULTS: When HBP measurement is not incorporated into the diagnostic process, the medical cost is estimated at US$10.89 million per 1000 subjects per 5 years. When HBP measurement is incorporated, the medical cost is estimated at US$9.33 million per 1000 subjects per 5 years. The reductions in medical costs vary from US$674,000 to US$2.51 million per 1000 subjects per 5 years for treatment of hypertension, when sensitivity analysis is performed. CONCLUSIONS: The introduction of HBP measurement for the treatment of hypertension is very useful for reducing medical costs.

The economic impact of the introduction of home blood pressure measurement for the diagnosis and treatment of hypertension.

OBJECTIVES: To investigate the economic consequences resulting from introduction of home blood pressure measurement in diagnosis of hypertension instead of casual clinic blood pressure measurement. METHODS: We constructed a decision tree model using data from the Ohasama study and a Japanese national database. The Ohasama study provided the prognostic value of home blood pressure as compared with clinic blood pressure measurement. RESULTS: It is predicted that the use of home blood pressure for hypertension diagnosis results in a saving of 9.30 billion US dollars (1013.6 billion yen) in hypertension-related medical costs in Japan. Most of this was attributable to medical costs saved by avoiding the start of treatment for untreated individuals who were diagnosed as hypertensive by clinic blood pressure but whose blood pressures were in the normal range when based on home blood pressure; that is, the so called white-coat hypertension. Furthermore, it could be expected that adequate blood pressure control mediated by the change in the diagnostic method from clinic to home blood pressure measurement would improve the prognosis for hypertension. We estimated that the prevention of hypertensive complications resulted in a reduction of annual medical costs by 28 million US dollars (3.0 billion yen). In addition, stroke prevention due to adequate blood pressure control based on home blood pressure measurement reduced annual long-term care costs by 39 million US dollars (4.2 billion yen). A per-person break-even cost for introducing home blood pressure monitoring was calculated as 409 US dollars (44,580 yen). CONCLUSIONS: The introduction of home blood pressure measurement for the diagnosis and treatment of hypertension would be very effective to save costs.

Efficacy of combination antihypertensive therapy with low-dose indapamide: assessment by blood pressure self-monitoring at home.

We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes, as well as its duration of action, using blood pressure (BP) self-monitoring at home. Seventy-six patients undergoing monotherapy with a calcium channel blocker (CCB), angiotensin converting-enzyme inhibitor (ACEI), or angiotensin AT1-receptor blocker (ARB), but had an average morning home systolic BP (SBP) > or =135 mmHg or diastolic BP (DBP) > or =85 mmHg, were studied. Indapamide (1 mg) was added to their existing treatment once daily for 4 weeks. The additional hypotensive effects of indapamide were evaluated by casual and home BPs, and the results were compared among the three groups of subjects classified according to their initial drug treatment classes. The morning/evening (M/E) ratio of BP reduction was calculated to assess the duration of the effect. Overall, indapamide significantly (P < 0.001) lowered morning home BP (147 +/- 12/87 +/- 9 mmHg to 135 +/- 12/81 +/- 9 mmHg), evening home BP (138 +/- 15/79 +/- 10 mmHg to 126 +/- 12/73 +/- 9 mmHg), and casual BP (145 +/- 21/86 +/- 14 mmHg to 136 +/- 17/81 +/- 13 mmHg). All groups showed significant indapamide-induced home SBP/DBP decreases, whereas only the ACEI and ARB groups, but not the CCB group, showed a home pulse pressure (PP) reduction. Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group. The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP. Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs.

Control of blood pressure as measured at home and office, and comparison with physicians' assessment of control among treated hypertensive patients in Japan: First Report of the Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

The Japan Home versus Office Blood Pressure Measurement Evaluation (J-HOME) study was conducted to measure the control of blood pressure (BP) as evaluated by home BP measurement among 3,400 patients with essential hypertension (mean age: 66 years; females: 55%) receiving antihypertensive treatment in primary care settings in Japan. The purpose of this first report was to compare characteristics of BP control as measured at home and in the clinic (office) and define their association with BP control as evaluated by physicians. Mean systolic/diastolic BP (SBP/DBP) values were 140/82 mmHg for home BP and 143/81 mmHg for office BP. BP levels were not adequately controlled among approximately 60% of the patients, according to reference values described in the national guidelines (office BP: <140/90 mmHg; home BP: <135/85 mmHg). Even among patients evaluated by physicians as having excellent or fairly good BP control, office and home SBP values were insufficiently controlled in approximately 50%. Although the tendency was more remarkable among older patients, whose recommended target BP levels are higher than those of middle-aged patients in the Japanese Hypertension Society 2000 criteria, office and home BP values were not adequately controlled in approximately 50% of the middle-aged patients whose BP control was evaluated as good. Our findings suggest that an important reason why home and office BP values are not adequately controlled is that physicians approve relatively higher BP levels under treatment, even among middle-aged patients.