Effectiveness of digital health interventions for telemedicine/telehealth for managing blood pressure in adults: a systematic review and meta-analysis.

This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.

Achievement rate of target blood pressure in patients with hypertension treated by hypertension specialists and non-specialists in a real-world setting.

Hypertension remains a major global healthcare issue. Considering that most Japanese patients with hypertension are managed by general practitioners, hypertension specialists should be involved in actual clinical practice. We investigated the blood pressure (BP), guidelines recommended for achievement rate of the target BP, and clinical variables of patients with hypertension treated by hypertension specialists and those treated by non-specialists in a real-world setting. Factors associated with the target BP achievement in this population were also investigated. Outpatients with hypertension from 12 medical facilities in Okinawa Prefecture were enrolled (n = 1469 [specialist group, 794; non-specialist group, 675]; mean age, 64.2 years; females, 45.8%). For all patients, BP and rate of the target BP achievement were 129.0 ± 15.5/74.6 ± 10.6 mmHg, and 51.8%, respectively. BP and the rate of target of BP achievement were 128.0 ± 15.1/73.4 ± 10.4 mmHg and 56.7% in the specialist group, and they were 130.1 ± 15.9/76.0 ± 10.8 mmHg and 46.1% in the non-specialist group. The urinary salt excretion and obesity rates were comparable between the specialist and non-specialist groups. Multivariable logistic analyses indicated that hypertension specialists and good medication adherence were positive factors, whereas obesity, chronic kidney disease, diabetes mellitus, and urinary salt excretion were inverse factors associated with target BP achievement in this population. Initiatives for salt reduction, medication adherence, and proper obesity management are crucial to improving BP management in patients with hypertension. Hypertension specialists are expected to play an essential role in them. For all patients, the target blood pressure (BP) achievement rate were 51.8%. Hypertension specialists and good medication adherence were positive factors in achieving target BP; conversely, obesity, diabetes mellitus, chronic kidney disease, and high urinary salt excretion were inverse factors in achieving target BP among patients with hypertension.

Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial.

INTRODUCTION: Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia. METHODS: This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat ( n  = 47; febuxostat group) or benzbromarone ( n  = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity. RESULTS: Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m 2 ) between the febuxostat [-0.23, 95% confidence interval (CI), -2.00 to 1.55] and benzbromarone (-2.18, 95% CI, -3.84 to -0.52) groups (difference, 1.95; 95% CI, -0.48 to 4.38; P  = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity ( P  = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug. CONCLUSIONS: No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.

Strategies for improving the treatment and control of hypertension in Japan.

Despite the significant advancements in the diagnosis and treatment of hypertension, the burden of hypertension remains a major global health care concern. In Japan, estimates show that more than two-thirds of the population have uncontrolled hypertension, regardless of whether they were taking antihypertensive medication. To improve hypertension management, hypertension guidelines have been developed and updated regularly by hypertension societies across various countries and regions. The Japanese Society of Hypertension (JSH) updated the Guidelines for the Management of Hypertension in 2019 (JSH 2019). The JSH 2019 aims to establish a standard management strategy for hypertension and provide evidence to all health care providers. One of its updated main features is its proposal for multidisciplinary team-based care (TBC) involving physicians, pharmacists, nurses, dietitians, and other health care providers. The TBC will help initiate and intensify the management of hypertension, as well as combat clinical inertia, which is expected to contribute to uncontrolled blood pressure and subsequent development of cardiovascular diseases. This is consistent with the recommendations from recent major guidelines on hypertension management. Moreover, to reduce the evidence-practice gap in hypertension management, it is essential to disseminate the essence of the guidelines and provide hypertension education programs for all health care providers and patients. This review summarizes the points of the JSH 2019-based strategy for improving hypertension management and discusses guidelines for its implementation into actual clinical practice.

Effect of Nutrition Education on the Vegetable Intake of Residents in Okinawa.

Background: Increasing vegetable intake is recommended for promoting health in communities. This study investigated the effects of nutrition education on vegetable intake and the factors associated with changes in vegetable intake among residents of Okinawa. Methods and Results: Subjects (n=1,345; mean [±SD] age 56.8±14.6 years; 40.5% male) were recruited from among local residents participating in the Yui Kenko Project. Subjects completed the brief-type self-administered diet history questionnaire (BDHQ) and questionnaires on socioeconomic demographics and social capital. Subjects were divided into 2 groups according to residential area, namely south Okinawa (n=679), where local health promotion activities have been undertaken since the early 2000s, and central Okinawa (n=666). Survey results were fed back to each subject, and health lectures were then conducted at local community centers. After 1 year, the BDHQ was repeated to investigate changes in vegetable and nutritional parameters. After the intervention, residents of south Okinawa increased their crude and energy-adjusted vegetable intake (P<0.05), whereas residents of central Okinawa showed decreased vegetable intake (P<0.05). Univariable and multivariable regression models indicated that, in south Okinawa, participation in local health promotion activities and agreement with general trust were positively correlated with changes in energy-adjusted vegetable intake, whereas in central Okinawa no correlations were observed. Conclusions: The status of social capital should be taken into account when implementing initiatives to increase vegetable intake in communities.

Factors Associated with Nonachievement of Target Blood Pressure in Patients on Antithrombotic Therapy: A Real-World Study.

INTRODUCTION: The current guidelines for managing hypertension recommend strict blood pressure (BP) control to prevent bleeding complications in patients with hypertension on antithrombotic therapy. However, the target BP value of <130/80 mmHg is achieved in a small proportion of these patients. This study aimed to examine the factors associated with nonachievement of target BP value (≥130/80 mmHg) in patients on antithrombotic therapy. METHODS: This retrospective study was conducted at an outpatient clinic in 2018. Clinical parameters were obtained from the center's electronic medical database. Office BP was measured once in the sitting position. A target BP value of <130/80 mmHg was defined according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2019. RESULTS: Of the 26,803 outpatients who had scheduled visits during this time, 2,427 received antithrombotic therapy. Patients with chronic kidney disease stage 5 or on hemodialysis and those with missing data on body mass index were excluded from the study; eventually, 2,201 outpatients met the inclusion criteria. BP values of <140/90 mmHg were observed in 59.2% of these outpatients; however, only 30.6% displayed the target BP value of <130/80 mmHg. Univariate and multivariate logistic regression analyses indicated that male gender and obesity significantly correlated with nonachievement of the target BP (≥130/80 mmHg). However, heart failure and ischemic heart disease were negatively but significantly related to nonachievement of the target BP. CONCLUSIONS: The target BP value was achieved in only a small proportion of the patients treated with antithrombotic drugs. In patients on antithrombotic therapy, obesity appeared to be a modifiable risk factor, whereas cardiovascular comorbidities, such as heart failure, were negative factors contributing to nonachievement of the target BP.

Optimal blood pressure target to prevent severe hypertension in pregnancy: A systematic review and meta-analysis.

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there is still a conflict of opinion on the recommendations of antihypertensive therapy. This study aimed to identify the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension. Ovid MEDLINE and the Cochrane Library were searched, and only randomized controlled trials (RCTs) were included if they compared the effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments in nonsevere hypertensive pregnant patients. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) for the outcomes. Forty RCTs with 6355 patients were included in the study. BP-lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37-0.56), preeclampsia (RR, 0.82; 95% CI, 0.69-0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17-0.84), placental abruption (RR, 0.52; 95% CI, 0.32-0.86), and preterm birth (< 37 weeks; RR, 0.81; 95% CI, 0.71-0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02-1.54). An achieved systolic blood pressure (SBP) of < 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an SBP of ≥ 140 mmHg, with a significant interaction of the BP levels achieved with BP-lowering therapy. There was no significant interaction between the subtypes of hypertensive disorders of pregnancy and BP-lowering treatment, except for placental abruption. BP-lowering treatment aimed at an SBP < 130 mmHg and accompanied by the careful monitoring of fetal growth might be recommended to prevent severe hypertension.

Salt and potassium intake evaluated with spot urine and brief questionnaires in combination with blood pressure control status in hypertensive outpatients in a real-world setting.

Reducing salt and increasing potassium intake are recommended lifestyle modifications for patients with hypertension. The estimated 24-h urinary salt excretion value from spot urine using Tanaka's formula and the salt check-sheet scores, questionnaire-based scores of salt intake, are practical indices of daily salt intake. However, few studies have evaluated salt intake with these methods in hypertensive outpatients. We examined salt and potassium intake with the spot urine method and the salt check-sheet scores of hypertensive outpatients in a multi-facility, real-world setting and examined whether the salt or potassium intake evaluated with these methods related to inadequate blood pressure control. Hypertensive outpatients from 12 medical facilities in the Okinawa prefecture were enrolled from November 2011 to April 2014 (n = 1559, mean age 63.9 years, 46% women). The mean blood pressure, urinary salt excretion value, urinary potassium excretion value, and total score on the salt check-sheet were 129/75 mmHg, 8.7 g/day, 1.6 g/day, and 10.4 points, respectively. The urinary salt excretion value and total score on the salt check-sheet but not urinary potassium excretion value were associated with inadequate blood pressure control (≥140/90 mmHg). Higher body mass index, estimated glomerular filtration rate, urinary potassium excretion value, total score on the salt check-sheet, and presence of inadequate blood pressure control were associated with high urinary salt excretion (≥10.2 g/day). In conclusion, hypertensive outpatients with high urinary salt excretion values estimated using Tanaka's formula or with high scores on the salt check sheet may be candidates for more intensive salt reduction guidance.

Effect of Mineralocorticoid Receptor Blockade on Arterial Stiffness and Endothelial Function: A Meta-Analysis of Randomized Trials.

Although numerous studies have confirmed the beneficial effects of pharmacological therapy for arterial stiffness and endothelial dysfunction, which are predictors/therapeutic targets for cardiovascular diseases, only a few overall quantitative evaluations of MRAs (mineralocorticoid receptor antagonists) exist. We searched PubMed and Cochrane CENTRAL (Cochrane Central Register of Controlled Trials) for randomized trials evaluating MRA effects on arterial stiffness measured by pulse wave velocity (PWV) or augmentation index and endothelial function measured by flow-mediated dilation. Data from the included trials were pooled by using random-effects meta-analysis of the weighted mean difference (MD) between the comparator groups. The primary outcome was the MD of PWV. In 11 trials including 515 patients, the MRA treatment reduced the PWV when compared with control (MD, -0.75 m/s [95% CI, -1.12 to -0.39], P<0.00001), without heterogeneity. There were comparable effects of MRA on carotid-femoral PWV and those on other forms of PWV (P=0.705 for heterogeneity). The effects of MRA on PWV were independent of blood pressure reduction related to the treatment according to meta-regression analysis. The MRA treatment reduced the augmentation index compared with control in 5 trials including 283 patients (MD, -6.74% [95% CI, -10.26 to -3.21], P=0.0002) and increased the flow-mediated dilation in 11 trials including 570 patients (MD, 1.18% [95% CI, 0.14 to 2.23], P=0.03). In conclusion, the current meta-analysis demonstrates the beneficial effects of MRA on PWV, augmentation index, and flow-mediated dilation.

Investigation of Blood Pressure Control in Hypertensive Patients with and without Antithrombotic Therapy in a Real-World Setting.

Background Although numerous studies have demonstrated a strong association between blood pressure (BP) and hemorrhagic complications of antithrombotic therapy, there is still a paucity of information regarding the status of BP control in hypertensive patients on antithrombotic therapy. Methods This cross-sectional, retrospective study was conducted at an outpatient clinic to examine BP control and its associated factors in hypertensive patients receiving or not receiving antithrombotic therapy. Results Of 26,803 outpatients who had scheduled visits in 2018, 7,800 hypertensive patients met the inclusion criteria, of whom 1,727 cases were on oral antithrombotic drugs. Then, target BP values were defined according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2019. While BP values <140/90 mmHg were observed in 63.0% and 61.6% of patients with and without antithrombotic therapy, respectively, only 31.1% and 23.4% of them displayed BP values <130/80 mmHg. Multivariable logistic analysis indicated that comorbidity with obesity was a significant correlate of insufficient BP control (target BP <130/80 mmHg) in hypertensive patients, irrespective of antithrombotic therapy (patients with antithrombotic therapy, odds ratio (OR) = 1.690, 95% confidence interval (CI) = 1.351-2.113; patients without antithrombotic therapy, OR = 1.475, 95% CI = 1.290-1.687). Conclusion The majority of patients exhibited BP values <140/90 mmHg, whereas BP values <130/80 mmHg were achieved only in a small proportion of the patients. Furthermore, obesity appeared to be one of the factors contributing to insufficient BP control in a real-world setting.

Validation of preferred salt concentration in soup based on a randomized blinded experiment in multiple regions in Japan-influence of umami (L-glutamate) on saltiness and palatability of low-salt solutions.

Sodium reduction is an important public health goal. Individual and population approaches are necessary for reducing the sodium content of processed foods and meals. The aim of the present study is to affirm the effect of monosodium L-glutamate (MSG), an umami substance, on the saltiness or palatability of low-salt solutions and to explore the preferred salt concentration in soup. Five hundred and eighty-four healthy participants from nineteen regions in Japan tasted 0.3, 0.6, and 0.9% NaCl solutions with or without 0.3% MSG. Evaluations of saltiness and palatability for each solution were conducted using a visual analog scale in a double-blinded randomized manner. Saltiness gradually increased depending on the concentration of NaCl. The saltiness of the 0.3% NaCl solution with MSG was rated significantly higher than that without MSG. The palatability ratings were higher for the solutions with MSG than for those without MSG for all NaCl concentrations. In particular, the palatability rating of the 0.3% NaCl solution with MSG was twice as high as that without MSG and was significantly higher than that of the other five test solutions. Furthermore, these results were observed to be approximately the same, irrespective of sex, age, region, etc. Salt reduction is believed to result in a loss of palatability. However, our results suggest that umami can compensate for the loss of palatability caused by salt reduction and that the addition of an appropriate amount of an umami substance can facilitate salt reduction from 0.9 to 0.3% without sacrificing palatability.

Optimal blood pressure targets for patients with hypertension: a systematic review and meta-analysis.

Optimal blood pressure (BP) targets for hypertension have been an important clinical issue but have been elusive. The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant benefits of intensive BP-lowering treatment with a target systolic BP level of < 120 mm Hg on major cardiovascular (CV) events and mortality, whereas there was a modest increase in renal events related to BP-lowering treatment. We searched the PubMed, Cochrane CENTRAL, and ICHUSHI databases for randomized trials that assigned participants to intensive versus usual BP-lowering treatment with different BP targets. The outcomes were major CV events, all-cause death, myocardial infarction, stroke, heart failure, renal events, and adverse events. Nineteen trials that enrolled a total of 55,529 participants with a mean follow-up duration ranging from 1.6 to 12.2 years were included in the present analysis. There was a significant reduction in major CV events, myocardial infarction, and stroke and a trend toward a reduction in heart failure associated with intensive BP-lowering treatment, but no differences in the risks of all-cause death, renal events, or adverse events were observed between the randomized groups. Subgroup analyses indicated that intensive BP-lowering treatment with a target of < 130/80 mm Hg and/or achievement of BP < 130/80 mm Hg were associated with a significant reduction in major CV events compared with the usual group. In conclusion, intensive BP-lowering treatment reduces the risk of CV events. A target BP level of < 130/80 mm Hg appears to be optimal for CV protection in patients with hypertension.

Target blood pressure level for the treatment of elderly hypertensive patients: a systematic review and meta-analysis of randomized trials.

Although recent systematic reviews (SRs) of randomized clinical trials (RCTs) support the benefit of blood pressure (BP) treatment in the elderly, the optimized target BP level remains controversial. We performed a SR to determine the clinical benefit of antihypertensive treatments with a target systolic BP (SBP) of <140 mmHg in the elderly. We searched for RCTs comparing intensive and less intensive treatments or placebo and active treatments reported until May 2017 and identified 11 RCTs in which the target or on-treatment SBP in the intensive or active treatment was less than 140 mmHg. Among the RCTs, 6 RCTs with primary or subanalysis results for patients aged 70 years or older were finally chosen for the meta-analysis. We found that intensive lowering of BP did not reduce the risk ratio (RR) of composite cardiovascular outcomes (95% CI: 0.67-1.05, p = 0.13). By contrast, intensive lowering of BP achieved RR reductions of 24% for all-cause death (0.63-0.92) and of 39% for cardiovascular death (0.48-0.77). Intensive lowering of BP did not alter the incidence of stroke (0.63-1.23) and serious adverse events (SAEs) (0.93-1.09). In conclusion, intensive antihypertensive regimens targeting SBP < 140 mmHg did not significantly reduce the risk of cardiovascular diseases compared to that of less intensive treatments, but did reduce the risk of death without increasing adverse events in patients aged 70 years or older. These findings support the benefit of intensive treatment targeting SBP to ≤140 mmHg in the elderly.

Responsiveness of α2-adrenoceptor/I1-imidazoline receptor in the rostral ventrolateral medulla to cardiovascular regulation is enhanced in conscious spontaneously hypertensive rat.

Stimulation of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla decreases the blood pressure via sympathoinhibition. However, alteration of receptor responses in genetically hypertensive rats remains unclear. We examined cardiovascular responses of α2-adrenoceptor/I1-imidazoline receptor agonist and antagonists microinjected into the rostral ventrolateral medulla of conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Injection of 2-nmol clonidine-an α2-adrenoceptor/I1-imidazoline receptor agonist-unilaterally into the rostral ventrolateral medulla decreased the blood pressure, heart rate, and renal sympathetic nerve activity; the responses were significantly enhanced in spontaneously hypertensive rats than in Wistar Kyoto rats. Co-injection of 2-nmol 2-methoxyidazoxan (a selective α2-adrenoceptor antagonist) or 2-nmol efaroxan (an I1-receptor antagonist) with 2 nmol of clonidine attenuated the hypotensive and bradycardic effects of clonidine-only injection. Injection of 2-methoxyidazoxan alone increased the blood pressure and heart rate in spontaneously hypertensive rats, but not in Wistar Kyoto rats. These results suggest enhanced responsiveness of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats.

Effects of xanthine oxidase inhibitors on renal function and blood pressure in hypertensive patients with hyperuricemia.

Hyperuricemia may promote the progression of hypertension and renal dysfunction. However, the effects of hyperuricemia treatment on blood pressure and renal function in adult hypertensive patients with hyperuricemia remain unclear. A total of 137 hypertensive patients with hyperuricemia (96 men and 41 women; mean age of 67 years) who recently started taking xanthine oxidase inhibitors (allopurinol or febuxostat) as outpatients were recruited. Serum uric acid level, estimated glomerular filtration rate (eGFR, ml min(-1) per 1.73 m(2)) and blood pressure (mm Hg) were retrospectively compared immediately before and shortly after starting treatment with xanthine oxidase inhibitors. The mean blood pressure and the eGFR immediately before starting treatment were 128/71 mm Hg and 44.6 ml min(-1) per 1.73 m(2), respectively. Although the eGFR decreased from 46.6 to 44.6 ml min(-1) per 1.73 m(2) before starting treatment with xanthine oxidase inhibitors, it increased to 46.2 ml min(-1) per 1.73 m(2) (P=0.001, compared with immediately before treatment) without any significant changes in blood pressure after the administration of xanthine oxidase inhibitors. Multiple regression analysis revealed that the increase in eGFR after starting xanthine oxidase inhibitor treatment positively correlated with the changes in systolic blood pressure and negatively correlated with the changes in uric acid levels and the use of renin-angiotensin system inhibitors. These results suggest that xanthine oxidase inhibitors may delay the progression of renal dysfunction in adult hypertensive patients with hyperuricemia.