2023 update and perspectives.

Total 276 manuscripts were published in Hypertension Research in 2022. Here our editorial members picked up the excellent papers, summarized the current topics from the published papers and discussed future perspectives in the sixteen fields. We hope you enjoy our special feature, 2023 update and perspectives in Hypertension Research.

Polypill Therapy for Cardiovascular Disease Prevention and Combination Medication Therapy for Hypertension Management.

Although various guidelines for cardiovascular disease prevention have been established, the optimal drug therapy is often not implemented due to poor medication adherence and the clinical inertia of healthcare practitioners. Polypill strategies are one solution to this problem. Previous studies have established the usefulness of polypills, i.e., combination tablets including three or more medications, for the prevention of cardiovascular disease. For this purpose, the polypills generally contain an antiplatelet medication, an antihypertensive medication, and a statin. For the specific management of hypertension, combination therapy including more than two classes of antihypertensive medications is recommended by most international guidelines. Combination tablets including two classes of antihypertensive medications, such as renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) and Ca-channel blockers or thiazide diuretics, have been reported to be useful for cardiovascular disease prevention and lowering blood pressure (BP) levels. The use of RAS inhibitors is recommended for a wide range of complications, including diabetes, chronic heart failure, and chronic kidney disease. The combination of an RAS inhibitor and diuretic or Ca-channel blocker is thus recommended for the management of hypertension. Finally, we expect that novel medications such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2i), which have a more diverse range of effects in hypertension, heart failure, or diabetes, may be a solution to the problem of polypharmacy. Evidence is accumulating on the benefits of polypill strategies in cardiovascular disease prevention. Combination tablets are also effective for the treatment of hypertension.

Comparison of Ambulatory and Home Blood Pressure Variability for Cardiovascular Prognosis and Biomarkers.

BACKGROUND: Although blood pressure variability (BPV) is reported to be associated with cardiovascular prognoses, it has not been established whether ambulatory BPV (ABPV; ie, short-term 24-hour BPV) or home BPV (HBPV; day-to-day BPV) is a superior clinical marker. METHODS: We analyzed the associations of ABPV and HBPV with cardiovascular prognoses and biomarkers in 1314 hypertensive outpatients who underwent both home and ambulatory BP measurements in the J-HOP study (Japan Morning-Surge Home Blood Pressure). BPV was evaluated by the SD, coefficient of variation, and average real variability of the patients' 24-hour ambulatory and home systolic BP values. RESULTS: During the median 7.0-year follow-up, 109 cardiovascular events occurred. All SD, coefficient of variation, and average real variability values of the HBPV were significantly associated with cardiovascular risk even after adjusting by average 24-hour ambulatory systolic BP and each ABPV value: 1 SD of hazard ratio (95% CI) for the SD, 1.36 (1.14-1.63); coefficient of variation, 1.38 (1.16-1.66); and average real variability 1.29 (1.10-1.51) of HBPV. The ABPV parameters did not exhibit comparable relationships. The cardiovascular risk spline curves showed a trend toward increased risks with increasing HBPV parameters. There were no differences between ABPV and HBPV in the relationships with B-type natriuretic peptide and the urine albumin-creatine ratio. CONCLUSIONS: In this comparative analysis of ambulatory and home BP monitoring values in individuals with hypertension, ABPV was not significantly associated with cardiovascular prognosis adjusted by average BP level, and HBPV was suggested to have modest superiority in predicting cardiovascular prognosis compared with ABPV.

Short- to long-term blood pressure variability: Current evidence and new evaluations.

Increased blood pressure (BP) variability and the BP surge have been reported to be associated with increased cardiovascular risk independently of BP levels and can also be a trigger of cardiovascular events. There are multiple types of BP variation: beat-to-beat variations related to breathing and the autonomic nervous system, diurnal BP variation and nocturnal dipping related to sleep and physical activity over a 24-hr period, day-to-day BP variability with anomalous readings within a several-day period, visit-to-visit BP variability between outpatient visits, and seasonal variations. BP variability is also associated with the progression to hypertension from prehypertension and the progression of chronic kidney disease and cognitive impairments. Our research group proposed the "resonance hypothesis of blood pressure surge" as a new etiological hypothesis of BP variability and surges; i.e., the concept that when the time phases of surges and hypertension-inducing environmental influences coincide, resonance occurs and is amplified into a larger "dynamic surge" that triggers the onset of cardiovascular disease. New devices to assess BP variability as well as new therapeutic interventions to reduce BP variability are being developed. Although there are still issues to be addressed (including measurement accuracy), cuffless devices and information and communication technology (ICT)-based BP monitoring devices have been developed and validated. These new devices will be useful for the individualized optimal management of BP. However, evidence regarding the usefulness of therapeutic interventions to control BP variability is still lacking.

Association of Home and Ambulatory Blood Pressure With Cardiovascular Prognosis in Practice Hypertensive Outpatients.

BACKGROUND: Although international guidelines for hypertension management recommend home and ambulatory blood pressure (BP) monitoring, few studies have assessed which is more useful in predicting cardiovascular incidence in hypertensive outpatients. METHODS: We analyzed the association of home and ambulatory BP with cardiovascular prognosis in 1336 practice outpatients with hypertension who underwent both home and ambulatory BP measurements in the J-HOP study (Japan Morning Surge-Home Blood Pressure). RESULTS: During the median 6.9 years of follow-up, 111 cardiovascular events occurred. Both home and ambulatory systolic BP (SBP) were associated with cardiovascular risk independent of office SBP (hazard ratio [95% CI] per 20 mm Hg of average morning and evening home SBP, 1.46 [1.11-1.93]; 24-hour ambulatory SBP, 1.41 [1.02-1.94]). Moreover, average morning and evening home SBP was also associated with cardiovascular risk even adjusted by 24-hour ambulatory SBP (hazard ratio [95%CI] per 20 mm Hg, 1.38 [1.01-1.87]), but 24-hour ambulatory SBP was not associated with cardiovascular risk adjusted by average morning and evening home SBP. Regarding this relationship, the model-fit was significantly improved by using the analysis of likelihood ratio, but that was not significant in the analysis using C statistics. Additionally, even in patients with well-controlled 24-hour ambulatory BP, uncontrolled morning home BP was associated with cardiovascular risks (hazard ratio [95% CI], 2.15 [1.02-4.50]). In patients with well-controlled average morning and evening home BP, uncontrolled ambulatory BP was not associated with cardiovascular risks. CONCLUSIONS: This study demonstrated the prognostic values of home and ambulatory BP in practice hypertensive outpatients. Our findings indicated the modest superiority of home BP compared to ambulatory BP to predict cardiovascular prognosis.

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.

The role of blood pressure management in stroke prevention: current status and future prospects.

INTRODUCTION: Stroke is the second-leading cause of death worldwide and the second-leading cause of disability-adjusted life-years. It is well known that hypertension is a significant risk factor for cardiovascular events, including stroke. AREAS COVERED: Recent interventional trials have demonstrated the superiority of intensive blood pressure (BP) control for prevention of cardiovascular events compared to standard BP control. Notably, in the Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients (STEP) trial, intensive BP control showed superiority in the prevention of stroke events in elderly hypertensive patients. Novel medications such as angiotensin receptor-neprilysin inhibitors and sodium glucose cotransporter 2 inhibitors have the potential to suppress various CVD events including stroke. Non-pharmacological antihypertensive therapies such as renal denervation have demonstrated BP-lowering effects and may be useful for stroke prevention. Additionally, new methods and systems of BP monitoring including various kinds of nighttime BP measurement devices, wearable devices, and methods using information and communication technology can be used to assess the pathophysiology of BP variability as a risk factor and an event trigger of stroke incidence. EXPERT OPINION: Novel therapies and new technologies for BP evaluation strongly support the development of individualized anticipatory medicine, which should be useful for the prevention of stroke.

Infective Endocarditis Revealed after Resolution of COVID-19 Infection.

A 34-year-old previously healthy Japanese woman was diagnosed with COVID-19 and treated with remdesivir and dexamethasone. She was discharge but returned the next day due to acute myocardial infarction. Conservative treatment was selected because of an embolic occlusion in the distal portion. Contrast-enhanced computed tomography and brain magnetic resonance imaging revealed a right renal infarction and multiple cerebral embolisms, respectively; she had a fever of 38.9°C that night. Blood culture was positive for methicillin-susceptible Staphylococcus aureus. Transthoracic echocardiography revealed an 11-mm vegetation on the posterior mitral valve leaflet. Native mitral valve infective endocarditis causing multiple embolizations was diagnosed. She underwent surgical mitral valve replacement.

Update on Hypertension Research in 2021.

In 2021, 217 excellent manuscripts were published in Hypertension Research. Editorial teams greatly appreciate the authors' contribution to hypertension research progress. Here, our editorial members have summarized twelve topics from published work and discussed current topics in depth. We hope you enjoy our special feature, "Update on Hypertension Research in 2021".

Simple predictive score for nocturnal hypertension and masked nocturnal hypertension using home blood pressure monitoring in clinical practice.

OBJECTIVE: The decision whether to measure night-time blood pressure (BP) is challenging as these values cannot be easily evaluated because of problems with measurement devices and related stress. Using the nationwide, practice-based Japan Morning Surge-Home BP Nocturnal BP study data, we developed a simple predictive score that physicians can use to diagnose nocturnal hypertension. METHODS: We divided 2765 outpatients (mean age 63 years; hypertensive patients 92%) with cardiovascular risks who underwent morning, evening, and night-time home BP (HBP) measurements (0200, 0300, and 0400 h) into a calibration group ( n  = 2212) and validation group ( n  = 553). We used logistic-regression models in the calibration group to identify the predictive score for nocturnal hypertension (night-time HBP ≥120/70 mmHg) and then evaluated the score's predictive ability in the validation group. RESULTS: In the logistic-regression model, male sex, increased BMI) (≥25 kg/m 2 ), diabetes, elevated urine-albumin creatinine ratio (UACR) (≥30 mg/g Cr), elevated office BP (≥140/90 mmHg) and home (average of morning and evening) BP (≥135/85 mmHg) had positive relationships with nocturnal hypertension. The predictive scores for nocturnal hypertension were 1 point (male, BMI, and UACR); 2 points (diabetes); 3 points (office BP ≥140/90 mmHg); 6 points (home BP ≥135/85 mmHg); total 14 points. Over 75% of the nocturnal hypertension cases in the validation group showed at least 10 points [AUC 0.691, 95% CI (0.647-0.735)]. We also developed a score for masked nocturnal hypertension, that is, nocturnal hypertension despite controlled daytime HBP. CONCLUSION: We developed a simple predictive score for nocturnal hypertension that can be used in clinical settings and for diagnoses.

Seasonal Variation in Day-by-Day Home Blood Pressure Variability and Effect on Cardiovascular Disease Incidence.

BACKGROUND: Although day-by-day home blood pressure (BP) variability (BPV) has been associated with cardiovascular disease (CVD) risk, it remains unclear whether this association differs from season to season. The present study aimed to assess seasonal variation in day-by-day home BP variability and its association with CVD risk. METHODS: We analyzed the data from a nationwide, prospective observational study, the J-HOP study (Japan Morning Surge-Home Blood Pressure), in which 14 consecutive days of home BP monitoring were conducted. The values of SD (SDsystolic BP [SBP]), coefficient of variationSBP, and average real variabilitySBP of home SBP were used as indices of day-by-day home BPV. RESULTS: Among 4231 participants (mean age, 64.9±10.9 years, 46.7% male, 91.5% hypertensives), all 3 day-by-day home BPV indices were lower in summer than winter after adjusting for confounding factors. In winter, SDSBP, coefficient of variationSBP, and average real variabilitySBP were significantly associated with increased risk of CVD events (coronary artery disease, stroke, heart failure, and aortic dissection; adjusted hazard ratio [95%CI] per 1-SD of SDSBP, 1.26 [1.02-1.54]; coefficient of variationSBP, 1.24 [1.02-1.52]; average real variabilitySBP, 1.44 [1.17-1.77]). These relationships were also observed in the analysis of quartiles of BPV parameters (adjusted hazard ratio [95%CI] compared to the first quartile, fourth quartile of SDSBP 2.26 [1.06-4.85]; coefficient of variationSBP 2.96 [1.43-6.15]; average real variabilitySBP 2.73 [1.25-5.93]). In other seasons, however, there were no significant associations between day-by-day home BPV and CVD event risk. CONCLUSIONS: Our findings indicate that day-by-day home BPV measured in winter is more strongly associated with future CVD incidence than that measured in other seasons.

Association of treatment-resistant hypertension defined by home blood pressure monitoring with cardiovascular outcome.

In diagnosis of treatment-resistant hypertension (TRH), guidelines recommend out-of-office blood pressure (BP) measurements, ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM). Although evidence of an association between ABPM-evaluated TRH and cardiovascular disease (CVD) prognosis has accumulated, data are sparse regarding HBPM-evaluated TRH. We investigated this issue using data from the nationwide practice-based J-HOP (Japan Morning-Surge Home BP) study, which recruited 4,261 outpatients (mean age 64.9 years; 46.8% men; 91.5% hypertensives) who underwent morning and evening HBPM for 14 days. During 6.2 ± 3.8 years (26,418 person-years) follow-up, 270 total CVDs (stroke, coronary artery disease, aortic dissection, and heart failure) occurred. The adjusted hazard ratio (HR) (95% CIs) of uncontrolled TRH, i.e., uncontrolled BP using 3 classes of medications including diuretics or ≥4 classes of medications, for total CVD risk compared to controlled BP using <3 classes were 2.02 (1.38-2.94) and 1.81 (1.23-2.65) in home BP of 135/85 mmHg and 130/80 mmHg, respectively. Additionally, patients with TRH defined by guidelines, i.e., uncontrolled BP using 3 classes of medications including diuretics or controlled/uncontrolled BP using ≥4 classes of medications, also had higher total CVD risk compared to non-TRH under all home BP criteria. Moreover, in patients with uncontrolled apparent-TRH, i.e., TRH defined by office BP, uncontrolled home BP (≥135/85 mmHg) was still associated with atherosclerotic CVD (CVDs except heart failure) risk (adjusted HR [95% CI], 2.38 [1.09-5.19]). This is the first study to demonstrate an independent association between TRH evaluated by HBPM and CVD outcomes.

Cardiovascular Prognosis in Drug-Resistant Hypertension Stratified by 24-Hour Ambulatory Blood Pressure: The JAMP Study.

[Figure: see text].