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

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

Concept, study design, and baseline nighttime blood pressure control status of the WISDOM-Night Study using a wrist-type oscillometric home blood pressure monitoring device.

There is growing evidence that nocturnal hypertension is an independent risk factor for cardiovascular diseases, including heart failure. However, brachial blood pressure (BP) measurements during sleep might themselves disturb sleep quality. We initiated a nationwide, multicenter observational prospective study using a wrist-type oscillometric nighttime BP monitoring device with new algorithms to measure supine BP accurately without sleep disturbance. This study, named the Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Night BP Study (WISDOM-Night Study), was designed to clarify the impact of wrist-measured daily nighttime BPs on cardiovascular prognosis (stroke, coronary artery disease, heart failure, etc.) using 7 days of BP measurements at 2:00 a.m., 3:00 a.m., 4:00 a.m., and 4 h after bedtime. A total of 2751 patients with one or more cardiovascular risk factors were recruited between March 2021 and March 2024 and are currently being followed up for 7 years. Additionally, 1416 of the WISDOM-Night Study-enrolled patients who also agreed to participate in the WISDOM-Hypertension-Mediated Organ Damage (HMOD) Study underwent echocardiography to evaluate the association between wrist-measured BP and left ventricular structure. Data from this WISDOM-Night Study should provide the prospective association between nighttime BP and cardiovascular disease and reveal the indexes of nighttime BP with clinical pathological relevance. This first report of the WISDOM-Night Study describes the study design, baseline characteristics, and BP control status.

Home blood pressure-lowering effect of esaxerenone versus trichlormethiazide for uncontrolled hypertension: a predefined subanalysis of the EXCITE-HT randomized controlled trial by basal calcium channel blocker versus angiotensin receptor blocker.

This prespecified subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to examine the non-inferiority of esaxerenone to trichlormethiazide as a second-line antihypertensive agent according to the basal antihypertensive agent used (angiotensin receptor blocker [ARB] or calcium channel blocker [CCB]). The primary endpoint, change in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to end of treatment was similar between the two groups (intergroup difference in least squares mean change [95% confidence interval]: -1.3 [-3.8, 1.3]/-0.2 [-1.6, 1.3] mmHg for ARB; -2.7 [-4.2, -1.2]/-0.8 [-1.7, 0.1] mmHg for CCB). The respective incidences of serum potassium levels <3.5 mEq/L and ≥5.5 mEq/L in the ARB subgroup were 3.4% and 4.2% for esaxerenone and 7.9% and 0% for trichlormethiazide; in the CCB subgroup, they were 2.8% and 0.6% for esaxerenone and 13.9% and 1.2% for trichlormethiazide, respectively. The incidence of uric acid level ≥7.0 mg/dL was numerically higher in the trichlormethiazide group than the esaxerenone group in both the ARB and CCB subgroups. The non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP was demonstrated regardless of whether the basal antihypertensive agent was an ARB or CCB. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns. Serum potassium levels tended to be higher when esaxerenone was combined with an ARB than with a CCB, but this can be mitigated if administered according to the package insert. A subgroup analysis of the EXCITE-HT study according to basal antihypertensive agent demonstrated the non-inferiority of esaxerenone to trichlormethiazide in lowering morning home BP regardless irrespective of the basal antihypertensive agent. Esaxerenone with a CCB showed superiority to trichlormethiazide in lowering SBP, without any new safety concerns.

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

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

Relationship between the number of drugs used during percutaneous coronary intervention and adverse events in patients with chronic coronary syndrome: Analysis of CLIDAS database.

Background: Polypharmacy is associated with an increased risk of adverse events due to the higher number of drugs used. This is particularly notable in patients with chronic coronary syndrome (CCS), who are known to use a large number of drugs. Therefore, we investigated polypharmacy in patients with CCS, using CLIDAS, a multicenter database of patients who underwent percutaneous coronary intervention. Method and results: Between 2017 and 2020, 1411 CCS patients (71.5 ± 10.5 years old; 77.3 % male) were enrolled. The relationship between cardiovascular events occurring during the median follow-up of 514 days and the number of drugs at the time of PCI was investigated. The median number of drugs prescribed was nine. Major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke, heart failure, transient ischemic attack, or unstable angina, occurred in 123 patients, and all-cause mortality occurred in 68 patients. For each additional drug, the adjusted hazard ratios for MACE and all-cause mortality increased by 2.069 (p = 0.003) and 1.102 (p = 0.010). The adjusted hazard ratios for MACE and all-cause mortality were significantly higher in the group using nine or more drugs compared to the group using eight or fewer drugs (1.646 and 2.253, both p < 0.001). Conclusion: This study showed that an increase in the number of drugs used for CCS may be associated with MACE and all-cause mortality. In patients with CCS, it might be beneficial to minimize the number of medications as much as possible, while managing comorbidities and using guideline-recommended drugs.

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

Clinical implications of high peak nighttime home blood pressure (BP) are currently unknown. This study investigated the association between peak nighttime home systolic BP (SBP) and cardiovascular events in individuals with at least one cardiovascular risk factor. In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, nighttime home BP was automatically measured three times each night for 14 days at baseline using a nighttime home BP monitoring device (HEM-5001, Omron Healthcare). Peak nighttime home SBP was defined as average of the highest three values over the 14-night measurement period. Cardiovascular events (stroke, coronary artery disease, heart failure, aortic dissection) were tracked over a mean follow-up period of 7.1 years. This analysis included 2545 individuals (mean age 63.3 ± 10.3 years, 49% male). After adjusting for covariates (including age, sex, and average office, morning, evening, and nighttime home SBP), stroke risk was significantly higher in individuals with peak nighttime home SBP in the highest quintile (≥149.0 mmHg) compared to the lowest quintile (<119.3 mmHg) (hazard ratio [HR] 4.24, 95% confidence interval [CI] 1.07-16.77; p = 0.039 overall and 8.92, 1.49-53.43; p = 0.017 in the subgroup with ≥6 nighttime home SBP measurements). This increased stroke risk remained significant after controlling for day-by-day average real variability of nighttime BP. The average peak nighttime home SBP cut-off value for predicting an increased risk of incident stroke was 136 mmHg. We propose that exaggerated peak nighttime home SBP, determined from ≥6 measurements, is a novel risk factor for stroke, independent of conventional office and home BP values. The exaggerated peak nighttime home systolic blood pressure (HSBP) determined from six or more measurements as a novel risk factor for stroke, independent of conventional office and home blood pressure (BP) values.

Innovations in blood pressure measurement and reporting technology: International Society of Hypertension position paper endorsed by the World Hypertension League, European Society of Hypertension, Asian Pacific Society of Hypertension, and Latin American Society of Hypertension.

Blood pressure (BP) is a key contributor to the lifetime risk of preclinical organ damage and cardiovascular disease. Traditional clinic-based BP readings are typically measured infrequently and under standardized/resting conditions and therefore do not capture BP values during normal everyday activity. Therefore, current hypertension guidelines emphasize the importance of incorporating out-of-office BP measurement into strategies for hypertension diagnosis and management. However, conventional home and ambulatory BP monitoring devices use the upper-arm cuff oscillometric method and only provide intermittent BP readings under static conditions or in a limited number of situations. New innovations include technologies for BP estimation based on processing of sensor signals supported by artificial intelligence tools, technologies for remote monitoring, reporting and storage of BP data, and technologies for BP data interpretation and patient interaction designed to improve hypertension management ("digital therapeutics"). The number and volume of data relating to new devices/technologies is increasing rapidly and will continue to grow. This International Society of Hypertension position paper describes the new devices/technologies, presents evidence relating to new BP measurement techniques and related indices, highlights standard for the validation of new devices/technologies, discusses the reliability and utility of novel BP monitoring devices, the association of these metrics with clinical outcomes, and the use of digital therapeutics. It also highlights the challenges and evidence gaps that need to be overcome before these new technologies can be considered as a user-friendly and accurate source of novel BP data to inform clinical hypertension management strategies.

Change in pulse pressure and cardiovascular outcomes after percutaneous coronary intervention: The CLIDAS study.

Background: Limited data exist on the prognostic value of changes in pulse pressure (PP, the difference between systolic and diastolic blood pressure) during hospitalization for patients with coronary artery disease who have undergone percutaneous coronary intervention (PCI). Methods: In the Clinical Deep Data Accumulation System (CLIDAS), we studied 8,708 patients who underwent PCI. We aimed to examine the association between discharge PP and cardiovascular outcomes. PP was measured before PCI and at discharge. Patients were divided into five groups (quintiles) based on the change in PPQ1 (-18.0 ± 9.9 mmHg), Q2 (-3.8 ± 2.6), Q3 (reference; 3.7 ± 2.0), Q4 (11.3 ± 2.6), and Q5 (27.5 ± 11.2). We then analyzed the relationship between PP change and outcomes. Results: The mean patient age was 70 ± 11 years, with 6,851 (78 %) men and 3,786 (43 %) having acute coronary syndrome. U-shaped relationships were observed for the incidence rates of major adverse cardiac or cerebrovascular events (MACCE, a composite endpoint of cardiovascular death, myocardial infarction, and stroke), revascularization, and hospitalization for heart failure (HF). After adjusting for confounding factors, higher PP at discharge was associated with an increased risk of MACCE (adjusted hazard ratio 1.41; 95 %CI, 1.06-1.87 in Q5 [73.9 ± 9.3 mmHg]). Evaluating PP change revealed a U-shaped association with MACCE (1.50; 1.11-2.02 in Q1 and 1.47; 0.98-2.20 in Q5). Additionally, Q5 had a higher risk for hospitalization for HF (1.37; 1.00-1.88). Conclusions: Our findings demonstrate a U-shaped association between changes in PP and cardiovascular outcomes. This data suggests the significance of blood pressure control during hospitalization for patients who have undergone PCI.

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

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

Differences in ambulatory versus home blood pressure levels by ethnicity: data from the United Kingdom and Japan.

This study tested the hypothesis that differences in ethnicity impact the level of agreement between ambulatory blood pressure (ABP) and home BP (HBP) levels. A retrospective analysis of cross-sectional data from the UK and Japan was performed. Participants underwent office BP, daytime ABP, and HBP measurements. The ABP-HBP difference was compared between ethnic groups by multiple linear regression analysis. Diagnostic disagreement was defined as a disparity between the hypertension diagnoses obtained using ABP and HBP, since both measures share common thresholds of 135/85 mmHg for hypertension. Definite diagnostic disagreement was assigned where such a difference exceeded ±5 mmHg for either systolic BP (SBP) or diastolic BP (DBP). A total of 1 408 participants (age 62.1 ± 11.1 years, 48.6% males, 78.9% known hypertensive, White British 18.9%, South Asian 11.2%, African Caribbean 12.0%, Japanese 58.0%) were eligible. More Japanese participants showed higher ABP than HBP compared to White British: SBP + 3.09 mmHg, 95% confidence interval (CI) + 1.14, +5.04 mmHg; DBP + 5.67 mmHg, 95%CI + 4.51, +6.84 mmHg. More Japanese participants than African Caribbean participants exhibited diagnostic disagreement in SBP (33.2% vs. 20.7%, p = 0.006). Furthermore, Japanese participants had a higher percentage of definite diagnostic disagreement in SBP compared to White British (9.3% vs. 4.5%, p = 0.040) and African Caribbean participants (9.3% vs. 3.0%, p = 0.018). In conclusion, Japanese participants showed greater disparity between ABP and HBP compared to White British participants. Complementary use of ABP and HBP monitoring may be more beneficial for assessing cardiovascular disease risk in Japanese participants compared to other ethnic groups.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial.

BACKGROUND: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is the first sham-controlled trial investigating the safety and efficacy of RDN in China. METHODS: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; AngioCare, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months. RESULTS: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P<0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P<0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P=0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P=0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up. CONCLUSIONS: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02901704.

Corrigendum to "Impact of heart failure severity and major bleeding events after percutaneous coronary intervention on subsequent major adverse cardiac events" [Int. J. Cardiol. Cardiovasc. Risk and Prev. 2023 Jun 25:18:200193].

[This corrects the article DOI: 10.1016/j.ijcrp.2023.200193.].

Achievement of guideline-recommended target blood pressure is associated with reducing the risk of hemorrhagic and ischemic stroke in Japanese coronary artery disease patients -the CLIDAS study.

The Japanese Society of Hypertension have established a blood pressure (BP) target of 130/80 mmHg for patients with coronary artery disease (CAD). We evaluated the data of 8793 CAD patients in the Clinical Deep Data Accumulation System database who underwent cardiac catheterization at six university hospitals and the National Cerebral and Cardiovascular Center (average age 70 ± 11 years, 78% male, 43% with acute coronary syndrome [ACS]). Patients were divided into two groups based on whether or not they achieved the guideline-recommended BP of <130/80 mmHg. We analyzed the relationship between BP classification and major adverse cardiac and cerebral event (MACCE) separately in two groups: those with ACS and those with chronic coronary syndrome (CCS). During an average follow-up period of 33 months, 710 MACCEs occurred. A BP below 130/80 mmHg was associated with fewer MACCEs in both the overall (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70-1.00, p = 0.048) and the ACS group (HR 0.67, 95%CI 0.51-0.88, p = 0.003). In particular, stroke events were also lower among those with a BP below 130/80 mmHg in both the overall (HR 0.69, 95%CI 0.53-0.90, p = 0.006) and ACS groups (HR 0.44, 95%CI 0.30-0.67, p < 0.001). In conclusion, the achievement of BP guidelines was associated with improved outcomes in CAD patients, particularly in reducing stroke risk among those with ACS.

Effects of renal denervation on the incidence and severity of cardiovascular diseases.

Renal denervation (RDN) is a neuromodulation therapy performed in patients with hypertension using an intraarterial catheter. Recent randomized sham-controlled trials have shown that RDN has significant antihypertensive effects that last for more than 3 years. Based on this evidence, the US Food and Drug Administration has approved two devices, the ultrasound-based ReCor ParadiseTM RDN system and the radiofrequency-based Medtronic Symplicity SpyralTM RDN system, as adjunctive therapy for patients with refractory and uncontrolled hypertension. On the other hand, there have been no randomized sham-controlled prospective outcome trials on RDN, and the effects of RDN on cardiovascular events such as myocardial infarction, heart failure, and stroke have not been elucidated. This mini-review summarizes the latest findings focusing on the effects of RDN on organ protection and physiological function and symptoms in both preclinical and clinical studies. Furthermore, the feasibility of using blood pressure as surrogate marker for cardiovascular outcomes is discussed in the context of relevant clinical studies on RDN. A comprehensive understanding of the beneficial effects of RDN on the incidence and severity of cardiovascular diseases with their underlying mechanisms will enhance physicians' ability to incorporate RDN into clinical strategies to prevent cardiovascular events including myocardial infarction, heart failure, and stroke. This mini-review focuses on the effects of RDN on organ protection and physiological function and symptoms in preclinical and clinical studies. RDN is expected to reduce the onset and progression of cardiovascular diseases including myocardial infarction, heart failure, and stroke in clinical practice. LV left ventricular, LVEF left ventricular ejection fraction, VO2max maximal oxygen uptake, VT ventricular tachycardia, VF ventricular fibrillation, 6MWD 6-min walk distance, NT-proBNP N-terminal pro-B-type natriuretic peptide, NYHA New York Heart Association, BBB blood-brain barrier, BP blood pressure.