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Objective: We aimed to evaluate the influences of cardiovascular disease (CVD) on the relationship between baseline systolic blood pressure (SBP) and outcomes in community populations with diabetes., Methods: This is an observational study of 16,431 community adults with diabetes. The relationship between SBP with major adverse cardiovascular event (MACE) and all-cause death were evaluated using multivariable-adjusted Cox proportional hazard models and restricted cubic spline., Results: After a median follow-up of 3.4 (IQR 2.6, 4.3) years, 2145 (13.1 %) MACE and 1025 (6.2 %) all-cause death occurred. In participants free of CVD, in reference to SBP < 120 mmHg group, the risks for MACE increased as SBP category (120-129, 130-139, and ≥ 140 mmHg) advanced (P-trend < 0.001), and there was a linear relationship (P-nonlinear = 0.75). The risks for all-cause death were lower in SBP of 120-139 mmHg and 140-159 mmHg groups but higher in SBP ≥ 160 mmHg group, and there was a U-shaped relationship (P-nonlinear < 0.001). In participants with existing CVD the relationship between baseline SBP with MACE and all-cause death did not show any specific pattern., Conclusion: Results of the current study suggest that the relationship between baseline SBP with MACE and all-cause death varied significantly by baseline CVD status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hyperuricemia is a common comorbidity of hypertension and probably has a causal relationship with hypertension. Alpha-mangostin (α-MG) has been reported to have uric acid lowering effect. This study aimed to investigate the dual effects of α-MG on blood pressure (BP) and uric acid levels in angiotensin II (Ang II)-infused hypertensive mice. Male C57BL/6 mice were randomized into five groups: control, Ang II infusion (500 ng/kg/min for 2 weeks), Ang II infusion with gavage administration of α-MG 4.0 and 8.0 mg/kg and benzbromarone (25 mg/kg) respectively. BP, uric acid levels, vascular structure and function, and renin-Ang II system expressions in the aorta were assessed. Treatment with α-MG reduced BP, improved endothelial relaxation, and reversed aortic wall thickening and collagen deposition in Ang II-induced hypertensive mice. It also downregulated Ang II receptor 1 (AT1R) and angiotensin converting enzyme (ACE) expression, while upregulating ACE2, Mas receptor (MasR), and angiotensin (1-7) in the aorta. Moreover, α-MG demonstrated a significant enhancement in uric acid clearance and reduction in serum uric acid levels. Conversely, benzbromarone did not result in a decrease in BP, indicating that the hypotensive effect of α-MG may not be necessarily dependent on its urate-lowering properties. α-MG can attenuate Ang II-induced hypertension and reverse vascular remodeling, potentially by balancing the ACE/Ang II/AT1R axis and the ACE2/Ang-(1-7)/MasR axis. Our findings provide insights into α-MG as a novel anti-hypertensive drug especially in patients with hyperuricemia., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white-coat hypertension (WCH), masked hypertension (MH), white-coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome-based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24-h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de-escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24-h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

None of the spironolactone trials in heart failure (HF) assessed the blood pressure (BP) responses to exercise, while conflicting results were reported for exercise capacity. In the HOMAGE trial, 527 patients at increased HF risk were randomized to usual treatment with or without spironolactone (25-50 mg/day). The current substudy included 113 controls and 114 patients assigned spironolactone, who all completed the incremental shuttle walk test at baseline and months 1 and 9. Quality of life (QoL) was assessed by EQ5D questionnaire. Between-group differences (spironolactone minus control [Δs]) were analyzed by repeated measures ANOVA with adjustment for baseline and, if appropriate, additionally for sex, age and body mass index. Δs in the pre-exercise systolic/diastolic BP were -8.00 mm Hg (95% CI, -11.6 to -4.43)/-0.85 mm Hg (-2.96 to 1.26) at month 1 and -9.58 mm Hg (-14.0 to -5.19)/-3.84 mm Hg (-6.22 to -1.47) at month 9. Δs in the post-exercise systolic/diastolic BP were -8.08 mm Hg (-14.2 to -2.01)/-2.07 mm Hg (-5.79 to 1.65) and -13.3 mm Hg (-19.9 to -6.75)/-4.62 mm Hg (-8.07 to -1.17), respectively. For completed shuttles, Δs at months 1 and 9 were 2.15 (-0.10 to 4.40) and 2.49 (-0.79 to 5.67), respectively. Δs in QoL were not significant. The correlations between the exercise-induced BP increases and the number of completed shuttles were similar in both groups. In conclusion, in patients at increased risk of developing HF, spironolactone reduced the pre- and post-exercise BP, but did not improve exercise capacity or QoL., (© 2024. The Author(s).)

Pulse pressure amplification (PPA) is the brachial-to-aortic pulse pressure ratio and decreases with age and cardiovascular risk factors. This individual-participant meta-analysis of population studies aimed to define an outcome-driven threshold for PPA. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n = 5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement. Age ranged from 30 to 96 years (median 53.6). Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA < 1.3 vs ≥1.3 were 1.54 (95% confidence interval [CI]: 1.00-2.36) and 2.45 (CI: 1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs ≥60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. The proportion of high-risk women (PPA < 1.3) was higher at younger age (<60 vs ≥60 years: 67.7% vs 61.5%; P < 0.001). In conclusion, over and beyond common risk factors, a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular coronary complications and is an underestimated risk factor in women aged 30-60 years. Our study supports pulse wave analysis for risk stratification., (© 2024. The Author(s).)

Objectives: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy., Methods: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses)., Results: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P  = 0.28; HBP: -0.2%, P  = 0.20; 24 h ABP: 1.1%, P  < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P  < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27)., Conclusion: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Previous studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated., Methods: miPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31 -/- ) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (T reg ) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell., Results: miPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and T reg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted T reg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31., Conclusion: miPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting T reg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs., (© 2024. The Author(s).)

To practice standardized office blood pressure (OBP) measurement guidelines pragmatically, we developed an intelligent assisted OBP (IOBP) measurement system in the Chinese community, which can automatically obtain two or three BP values after a 5-min rest before the patients visit the doctor and transfer values to the community medical network in real time. We conducted a comparative study to investigate the agreement among IOBP, awake ambulatory BP (ABP), and conventional auscultatory OBP at different BP levels. Participants were divided into three groups according to BP, with 120/80 mmHg and 160/100 mmHg as the cut-off points. Attended IOBP, unattended IOBP, and auscultatory OBP were randomly measured before ABP monitoring. In total, 245 participants were included in the analysis. The mean systolic attended/unattended IOBP, auscultatory OBP, and awake ABP were 135.0, 136.7, 135.6, and 136.2 mmHg, respectively. Bland-Altman analysis revealed a bias of -1.1 and 0.5 mmHg for systolic attended/unattended IOBP compared with awake ABP in the overall sample. For auscultatory OBP, the bias was -0.4 (attended) and 1.2 mmHg (unattended). The discrepancy between the systolic attended/unattended IOBP and awake ABP was inconsistent at different BP levels. In Group 1 the values were -8.4 and -6.9 mmHg, whereas in Group 3, the values were 9.4 and 10.0 mmHg. BP measured using the IOBP measurement system was in accordance with awake ABP and conventional OBP, and can be a good choice in the Chinese community., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Central (aortic) systolic blood pressure (cSBP) is the pressure seen by the heart, the brain, and the kidneys. If properly measured, cSBP is closer associated with hypertension-mediated organ damage and prognosis, as compared with brachial SBP (bSBP). We investigated 24-hour profiles of bSBP and cSBP, measured simultaneously using Mobilograph devices, in 2423 untreated adults (1275 women; age, 18-94 years), free from overt cardiovascular disease, aiming to develop reference values and to analyze daytime-nighttime variability. Central SBP was assessed, using brachial waveforms, calibrated with mean arterial pressure (MAP)/diastolic BP (cSBP MAP/DBPcal ), or bSBP/diastolic blood pressure (cSBP SBP/DBPcal ), and a validated transfer function, resulting in 144 509 valid brachial and 130 804 valid central measurements. Averaged 24-hour, daytime, and nighttime brachial BP across all individuals was 124/79, 126/81, and 116/72 mm Hg, respectively. Averaged 24-hour, daytime, and nighttime values for cSBP MAP/DBPcal were 128, 128, and 125 mm Hg and 115, 117, and 107 mm Hg for cSBP SBP/DBPcal , respectively. We pragmatically propose as upper normal limit for 24-hour cSBP MAP/DBPcal 135 mm Hg and for 24-hour cSBP SBP/DBPcal 120 mm Hg. bSBP dipping (nighttime-daytime/daytime SBP) was -10.6 % in young participants and decreased with increasing age. Central SBP SBP/DBPcal dipping was less pronounced (-8.7% in young participants). In contrast, cSBP MAP/DBPcal dipping was completely absent in the youngest age group and less pronounced in all other participants. These data may serve for comparison in various diseases and have potential implications for refining hypertension diagnosis and management. The different dipping behavior of bSBP versus cSBP requires further investigation.

Background: Current guideline recommends both surgery and drug treatment for primary aldosteronism. Treatment effects on the cardiac structure and function remain under investigation., Objective: We performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocardial deformation and LV pressure., Methods: Our study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed conventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up., Results: During follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass index and left atrial volume index. However, only in the surgery group did global wasted work significantly decrease (200.8 ± 86.7 at baseline vs. 142.1 ± 58.1 mmHg% at 6 months) and global work efficiency (91.5 ± 3.1 vs . 93.6 ± 2.3%) and global longitudinal strain (-18.3 ± 2.7 vs . -19.2 ± 1.9%) significantly ( p < 0.01) increase at 6 months of follow-up. The corresponding differences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), -1.64% (95% CI, -2.56, -0.71%), and -0.85% (95% CI, -1.51, -0.20%), respectively. In addition, the changes in global wasted work at 6 months of follow-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group ( r = 0.54) and two groups combined ( r = 0.55), but not the surgery group., Conclusion: In spite of similar serum potassium normalization and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Xu, Xu, Zhu, Li and Wang.)

[Figure: see text].

[Figure: see text].

Purpose: We investigated associations of blood pressure (BP) with albuminuria and left ventricular hypertrophy (LVH) in young, middle and older aged patients with hypertension and/or diabetes mellitus., Materials & Methods: Study participants were treated patients with hypertension or diabetes, enrolled in a China nationwide registry. The 2510 patients were classified into young (<45 years, n  = 345), middle (45-64 years, n  = 1383) and older (≥65 years, n  = 782) age groups. Clinic BP was measured three times consecutively on each of the two clinic visits. These six readings were averaged for analyses. Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram (ECG) Cornell product and voltage methods., Results: The prevalence of albuminuria and ECG-LVH was 17.8 and 6.5%, respectively. Mean (±SD) systolic/diastolic BP was 132.0 ± 16.5/85.2 ± 11.9 mmHg, 136.8 ± 17.9/81.7 ± 11.2 mmHg, and 139.8 ± 16.7/75.8 ± 10.4 mmHg in the young, middle and older age groups. In the young age group, the prevalence of albuminuria increased from 8.8% in systolic/diastolic BP <120/80 mmHg to 14.6, 16.0% and 16.5% in 120-129/80-84, 130-139/85-89 and ≥140/90 mmHg, respectively. The corresponding values were 8.9, 7.0, 18.1 and 22.2%, respectively, in the middle age group, and 21.2, 15.5, 16.4 and 24.4%, respectively, in the older age group. Adjusted analyses confirmed the J-shaped relation between BP and albuminuria in the older but not young age group. The prevalence of ECG-LVH was significantly ( p for trend ≤0.04) higher with increasing BP similarly in all age groups., Conclusions: The association between BP and organ damage seems to differ in young, middle and older aged patients for albuminuria but not ECG-LVH.

Purpose: In a randomised, double-blind trial, we investigated effects of lacidipine on clinic and ambulatory blood pressure (BP) and arterial stiffness in patients with mild-to-moderate hypertension, as compared with amlodipine., Materials and Methods: Previously untreated and treated patients ( n  = 269, 50-80 years of age) with clinic hypertension (a clinic systolic/diastolic BP 140-180/<110 mmHg and <160/100 mmHg, respectively) were randomly assigned to double-dummy treatment with lacidipine (4-6 mg/day) or amlodipine (5-7.5 mg/day) for 20 weeks. The primary efficacy variable was the change in 24-h ambulatory systolic BP at 20 weeks of treatment. Arterial stiffness was measured as brachial-ankle pulse wave velocity (PWV)., Results: After 20 weeks of treatment, 24-h systolic BP decreased from 141.3 ± 14.0 and 138.3 ± 12.8 mmHg at baseline, respectively, in the lacidipine ( n  = 134) and amlodipine groups ( n  = 135), by a least square mean (±SE) change of 15.2 ± 1.3 and 15.5 ± 1.3 mmHg, respectively, with a between-group difference (95% confidence interval [CI]) of 0.3 mmHg (-3.4 to 4.1, p  = 0.86). Similar results were observed for other ambulatory BP components and clinic BP. Clinic and ambulatory pulse rate did not significantly change in either group ( p  ≥ 0.21). PWV decreased significantly ( p  < 0.001) from baseline in both groups, with a non-significant between-group difference of 0.24 m/s ( p  = 0.45). The incidence rate of adverse events was 30.3% ( n  = 40) and 27.5% ( n  = 36) in the lacidipine and amlodipine groups, respectively ( p  = 0.61). No serious adverse event occurred in the trial., Conclusions: Lacidipine effectively lowers clinic and ambulatory BP in patients with mild-to-moderate hypertension and significantly improves arterial stiffness, similarly as amlodipine.

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II-induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets-induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II-induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.

This review portrays how ambulatory blood pressure (BP) monitoring was established and recommended as the method of choice for the assessment of BP and for the rational use of antihypertensive drugs. To establish much-needed diagnostic ambulatory BP thresholds, initial statistical approaches evolved into longitudinal studies of patients and populations, which demonstrated that cardiovascular complications are more closely associated with 24-hour and nighttime BP than with office BP. Studies cross-classifying individuals based on ambulatory and office BP thresholds identified white-coat hypertension, an elevated office BP in the presence of ambulatory normotension as a low-risk condition, whereas its counterpart, masked hypertension, carries a hazard almost as high as ambulatory combined with office hypertension. What clinically matters most is the level of the 24-hour and the nighttime BP, while other BP indexes derived from 24-hour ambulatory BP recordings, on top of the 24-hour and nighttime BP level, add little to risk stratification or hypertension management. Ambulatory BP monitoring is cost-effective. Ambulatory and home BP monitoring are complimentary approaches. Their interchangeability provides great versatility in the clinical implementation of out-of-office BP measurement. We are still waiting for evidence from randomized clinical trials to prove that out-of-office BP monitoring is superior to office BP in adjusting antihypertensive drug treatment and in the prevention of cardiovascular complications. A starting research line, the development of a standardized validation protocol for wearable BP monitoring devices, might facilitate the clinical applicability of ambulatory BP monitoring.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55-72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/<80 mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, -16.4 mm Hg [95% CI, -18.7 to -14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5-16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.

Purpose: We hypothesise that dietary sodium intake interacts with serum uric acid to influence blood pressure (BP) in children and adolescents. In the present study, we investigated ambulatory BP in relation to hyperuricaemia, dietary sodium intake and their interaction in children and adolescents with hypertension., Materials and Methods: A total of 616 study participants were 10-24 years old and had primary hypertension diagnosed after admission in a specialised inpatient ward. Ambulatory BP monitoring was performed during hospitalisation. 24-h urine was collected for measurements of electrolytes. Hyperuricaemia was defined as a serum uric acid of ≥327.25 μmol/L in patients <18 years old and of ≥420 and ≥360 μmol/L, respectively, in male and female patients ≥18 years old., Results: In adjusted analyses, patients with hyperuricaemia ( n  = 283), compared with those with normal serum uric acid, had similar 24-h systolic BP (131.7 mmHg, p  = 0.54) and a significantly ( p  ≤ 0.005) lower 24-h diastolic BP (77.5 vs . 80.9 mmHg) and higher 24-h pulse pressure (54.2 vs . 51.7 mmHg). In similar adjusted analyses, 24-h ambulatory pulse pressure, but not systolic/diastolic BP ( p  ≥ 0.12), significantly differed across the quartile distributions of urinary sodium excretion ( p for trend ≤ 0.04). Further adjusted analyses showed significant ( p  ≤ 0.04) interaction between serum uric acid and urinary sodium excretion in relation to 24-h systolic BP. In patients with hyperuricaemia ( p  = 0.04), but not those with normal serum uric acid ( p =  0.13), 24-h systolic BP was significantly associated with urinary sodium excretion, with a 6.5 ± 2.1 mmHg difference between quartiles 4 and 1. Similar results were observed for daytime and night-time BP and pulse pressure., Conclusions: Both hyperuricaemia and higher dietary sodium intake were associated with higher pulse pressure, and their interaction further heightened systolic BP.

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42015031227.

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension., Methods: Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP., Results: At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m 2 ; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg; P ≤0.025) and 24-hour BP (2.33/1.49 mm Hg; P ≤0.012), but not for the clinic and nighttime BPs ( P ≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred., Conclusions: BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02156024.

Objectives: Cardiovascular dysautonomia can be present at early, late and even prodromal stages of Parkinson's disease. This study aimed to describe the characteristics of 24-h ambulatory blood pressure (BP) monitoring and investigate the frequency of cardiovascular dysautonomia in Parkinson's disease without an abnormal BP history., Methods: Parkinson's disease patients without history of abnormal BP were consecutively enrolled from three Chinese centres, on whom office BP measurement, neurological evaluations and 24-h ambulatory BP monitoring were performed., Results: Totally, 101 Parkinson's disease patients (42.6% women) with an average age of 66.6 ± 8.2 years were included in our cohort, and data analysis revealed that 26 (25.74%) patients suffered from orthostatic hypotension, among whom 18 (69.23%) were symptomatic. Patients with orthostatic hypotension compared with those without had significantly higher nocturnal SBP level, and more severe nonmotor symptoms, autonomic dysfunction and cognitive impairment. Further, 54 out of 101 (53.47%) individuals had a reverse dipping pattern in SBP and/or DBP. Reverse dippers had more cases of orthostatic hypotension (P < 0.001), and more severe nonmotor symptoms. SBP dipping ratio of less than -2.98% generated 76.9% of sensitivity, 69.3% of specificity, 46.5% of positive predictive value (PPV), 89.7% of negative predictive value (NPV) and 77.4% of accuracy, while diastolic dipping ratio of less than -1.80% generated 76.9% of sensitivity, 70.7% specificity, 47.6% of PPV, 89.8% of NPV and 77.8% of accuracy for suspecting orthostatic hypotension., Conclusion: Orthostatic hypotension can occur in one-fourth Parkinson's disease patients without abnormal BP history, and reverse dipping was present in more than half of patients with Parkinson's disease. Reverse dipping pattern was helpful to suspect orthostatic hypotension.

We investigated blood pressure (BP) and heart rate variability and baroreflex sensitivity (BRS) in white-coat, masked and sustained hypertension in untreated patients (n = 645). Normotension and white-coat, masked, and sustained hypertension were defined according to the clinic (cutoff 140/90 mmHg) and 24-h ambulatory (130/80 mmHg) BPs. The Finometer device recorded beat-to-beat finger BP and electrocardiograms in the supine and standing positions for the computation of frequency-domain power-spectral BP and heart rate variability indexes and BRS. In multivariate analysis, BP variability indexes in the supine position differed significantly (P < 0.0001) for both low-frequency (LF) and high-frequency (HF) components and the LF/HF ratio, with the lowest LF and HF power and highest LF/HF ratio in white-coat hypertension (n = 28), the highest LF and HF power and lowest LF/HF ratio in sustained hypertension (n = 198), and intermediate values in normotension (n = 189) and masked hypertension (n = 230). These differences diminished in the standing position, being significant (P < 0.0001) only for the LF component variability. The LF/HF ratio in BP in the supine position decreased with advancing age in normotension and sustained hypertension (P ≤ 0.03) but not white-coat or masked hypertension (P ≥ 0.12). For heart rate variability, a significant difference was observed only for the LF component in the supine position (P = 0.0005), which was lowest in white-coat hypertension. BRS in masked and sustained hypertension was significantly (P ≤ 0.0001) lower than that in normotension in both supine and standing positions and decreased with advancing age (P ≤ 0.0001). In conclusion, masked, but not white-coat, hypertension showed similar patterns of, but slightly less severe, changes in BP and heart rate variability and BRS to sustained hypertension.

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33-1.70) for cSBP, 1.36 (95% CI, 1.19-1.54) for cPP, 1.49 (95% CI, 1.33-1.67) for pSBP, and 1.34 (95% CI, 1.19-1.51) for pPP ( P <0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit ( P <0.001) with generalized R increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.2 increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.

Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults (≥18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally, 3 blood pressure readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic blood pressure ≥140 mm Hg, or a diastolic blood pressure ≥90 mm Hg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1 508 130 screenees 482 273 (32.0%) had never had a blood pressure measurement before and 513 337 (34.0%) had hypertension, of whom 58.7% were aware, and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to <140/90 mm Hg, and 28.9% to <130/80 mm Hg. Of all those with hypertension, 31.7% were controlled to <140/90 mm Hg, and 350 825 (23.3%) participants had untreated or inadequately treated hypertension. Of those taking antihypertensive medication, half were taking only a single drug, and 25% reported using aspirin inappropriately. This survey is the largest ever synchronized and standardized contemporary compilation of global blood pressure data. This campaign is needed as a temporary substitute for systematic blood pressure screening in many countries worldwide.

: Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.

Background: The method of evaluating office blood pressure (OBP) varies greatly among different guidelines., Objectives: We performed a cohort study to compare the association of various directly transferred attended automated OBP (AOBP) estimations with all-cause and cardiovascular mortalities., Methods: Overall, 475 181 sets of OBPs from 35 622 participants aged 35 years or older were extracted from the electronic health record of the Xinzhuang town hospital in the Minhang District, Shanghai, China. Each set of OBPs contained three consecutive AOBPs that were transferred directly to the electronic health record. The mean of three OBPs, mean of the last two OBPs, and alternative average OBP were calculated., Results: The difference between the first and average OBPs changed along with the calendar month, and it was highest in December (5.3/2.1 mmHg) and lowest in July (3.8/2.0 mmHg). The subjects older than 80 years of age displayed the largest discrepancy in the blood pressure control rate according to the first OBP or average OBP (12.1%). During the 3.9-year follow-up, 1055 deaths occurred. The alternative average SBP was associated with both all-cause [hazard ratio: 1.07, 95% confidence interval (CI): 1.04-1.11] and cardiovascular (hazard ratio: 1.17, 95% CI: 1.11-1.23) mortalities. The uncontrolled alternative average OBP remained significantly associated with an increasing risk of all-cause (hazard ratio: 1.24, 95% CI: 1.09-1.40) and cardiovascular (hazard ratio: 1.53, 95% CI: 1.25-1.86) mortality, but not the average of the last two or mean of three readings., Conclusion: We observed an obvious discrepancy in the OBP level and OBP control rate according to different AOBP estimations. The alternative average OBP seemed to be more powerful in predicting both all-cause and cardiovascular mortalities than the average of the last two or mean of three readings.

We investigated the prevalence, awareness, treatment, and control of hypertension in a large opportunistic screening study in China. Our study participants had to be ≥18 years of age and had ideally not taken blood pressure (BP) for ≥1 year. BP was measured three times consecutively in the sitting position with a 1-minute interval, using a validated electronic BP monitor or mercury sphygmomanometer. Trained volunteer investigators administered a questionnaire to collect information on medical history, lifestyle, and use of medications. The 364 000 participants (52.6% women, and mean age 53.4 years) had a mean systolic/diastolic BP of 124.2/76.4 mm Hg. The proportion of hypertension was 24.7%. In all hypertensive subjects (n = 89 925), the awareness, treatment, and control rates of hypertension were 60.1%, 42.5%, and 25.4%, respectively. In multiple stepwise logistic regression analyses, the odds for unawareness vs awareness of hypertension was higher in men and lower with age advancing, current smoking, and the presence of diabetes mellitus, coronary heart disease, and stroke or transient ischemic attack (P < .0001). The odds for uncontrolled vs controlled hypertension was higher with age advancing and current smoking, and lower with the presence of diabetes mellitus and coronary heart disease (P ≤ .03) in 38 207 treated hypertensive patients, and it was also higher with the use of antihypertensive monotherapy (odds ratio 1.13, P = .0003) in 19 523 treated hypertensive patients with specific antihypertensive drugs. Our study identified several factors as barriers to BP control in China, such as male gender, younger age, current smoking, and the under-use of combination therapy., (© 2020 Wiley Periodicals, Inc.)

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP ( P <0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age ( P <0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age ( P <0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP.

We investigated association between blood pressure and glucose control and the prevalence of albuminuria and left ventricular hypertrophy (LVH) in patients with hypertension and diabetes. Our study participants were treated patients with both diseases, enrolled in a China nationwide registry. The 773 patients were classified into four groups according to the control status of hypertension (systolic/diastolic blood pressure [BP] ≤140/90 mm Hg) and diabetes (HbA1c <7.0%): both uncontrolled (n = 208), only diabetes (n = 175) or hypertension controlled (n = 172), and both controlled (n = 218). Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥30 mg/g. LVH was assessed by the electrocardiogram Cornell product method. Antihypertensive therapy was not different between the four groups (P ≥ .48). The use of insulin alone or insulin plus oral antidiabetic agents was significantly higher than those with both diseases controlled (P ≤ .02). Patients with controlled hypertension and diabetes had a significantly (P < .0001) lower prevalence of albuminuria (odds ratio 0.22, 95% confidence interval 0.11-0.43) than those with both diseases uncontrolled. Intensive BP control to <130/80 mm Hg was associated with lower risks of albuminuria in all patients (P = .001) and patients with HbA1c <7.0% (P = .048). Intensive glycemic control to HbA1c <6.5% was also associated with a significantly lower risk of albuminuria in all patients (P = .01), but not those with controlled BP (P = .43). Similar trends were observed for LVH, but statistical significance was not achieved on either intensive control condition (P ≥ .07). In patients with hypertension and diabetes, blood pressure and glucose control were associated with a lower prevalence of albuminuria and LVH, especially when achieving a more stringent target., (© 2020 Wiley Periodicals, Inc.)

Hypertension (HTN) is an important risk factor for cardiovascular disease (CVD) but the association between HTN and CVD cannot be explained by average blood pressure (BP) alone. BP variability (BPV) is another important factor, along with the effects of HTN on the vasculature. The concept of systemic hemodynamic atherothrombotic syndrome (SHATS) has been proposed, describing an age-related and synergistic vicious cycle of hemodynamic stress and vascular disease. The importance of SHATS is based on the assumption that the assessment of BPV and arterial disease is likely to provide an effective opportunity to intervene early to reduce progression to HTN in younger patients or to CVD events and organ damage in older patients. In addition to providing an overview of current evidence for the mechanisms and clinical data related to SHATS, this article proposes a new SHATS score for use to diagnose and assess the severity of SHATS. The score includes two components - a BP score and a vascular score - which are multiplied to generate the SHATS score. This reflects the synergistic, rather than additive, effects of BP and vascular disease on target organ damage and CVD events. Although it requires refinement and validation in future studies, early detection of SHATS using tools such as the proposed score, combined with population-based stratification and technology-based anticipation medicine incorporating real-time individual data, has the potential to contribute to meaningful reductions in rates of CVD events and target organ damage., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: Baroreflex emerges as a therapeutic target of hypertension. We investigated blood pressure (BP) lowering effect of the combined passive head-up and -down movement with device-guided slow breathing in untreated mild hypertension or high-normal BP. Methods: In a randomized, cross-over trial, untreated subjects with an ambulatory systolic/diastolic BP of 125-140/80-90 mmHg and a clinic BP of 130-150/80-90 mmHg were randomized to intervention treatment with head movement and slow breathing or sham control, and then crossed over. Both treatments consisted of 1-week preparation, 2-week treatment, and 1-week recovery. During the 2-week treatment, subjects were treated for a session of 20 min/day. BP, pulse rate and respiration were measured before and after each treatment session. Ambulatory BP monitoring was performed at baseline and the end of the 2-week treatments' period, and home BP monitoring in the morning and evening for the whole 8-week follow-up period. Results: 14 subjects completed the study. The intervention treatment, compared to control, reduced respiration rate by -2.1 breaths/min (95% CI -2.9 to -1.2, p  = .0001), but not clinic BP and pulse rate ( p  ≥ .67). The intervention treatment, compared to control, significantly reduced nighttime systolic/diastolic blood pressure by -5.63/-3.82 mm Hg ( p  ≤ .01) but not 24-h or daytime ambulatory blood pressure ( p  ≥ .69). Home BP decreased with the intervention treatment, but the between-treatment difference was not statistically significant ( p  ≥ .27). Conclusions: The combined head movement with slow breathing did not influence 24-h BP, but reduced nighttime BP in untreated mild hypertension or high-normal BP.

The new American College of Cardiology/American Heart Association guideline reclassified office blood pressure and proposed thresholds for ambulatory blood pressure (ABP). We derived outcome-driven ABP thresholds corresponding with the new office blood pressure categories. We performed 24-hour ABP monitoring in 11 152 participants (48.9% women; mean age, 53.0 years) representative of 13 populations. We determined ABP thresholds resulting in multivariable-adjusted 10-year risks similar to those associated with elevated office blood pressure (120/80 mm Hg) and stages 1 and 2 of office hypertension (130/80 and 140/90 mm Hg). Over 13.9 years (median), 2728 (rate per 1000 person-years, 17.9) people died, 1033 (6.8) from cardiovascular disease; furthermore, 1988 (13.8), 893 (6.0), and 795 (5.4) cardiovascular and coronary events and strokes occurred. Using a composite cardiovascular end point, systolic/diastolic outcome-driven thresholds indicating elevated 24-hour, daytime, and nighttime ABP were 117.9/75.2, 121.4/79.6, and 105.3/66.2 mm Hg. For stages 1 and 2 ambulatory hypertension, thresholds were 123.3/75.2 and 128.7/80.7 mm Hg for 24-hour ABP, 128.5/79.6 and 135.6/87.1 mm Hg for daytime ABP, and 111.7/66.2 and 118.1/72.5 mm Hg for nighttime ABP. ABP thresholds derived from other end points were similar. After rounding, approximate thresholds for elevated 24-hour, daytime, and nighttime ABP were 120/75, 120/80, and 105/65 mm Hg, and for stages 1 and 2, ambulatory hypertension 125/75 and 130/80 mm Hg, 130/80 and 135/85 mm Hg, and 110/65 and 120/70 mm Hg. Outcome-driven ABP thresholds corresponding to elevated blood pressure and stages 1 and 2 of hypertension are similar to those proposed by the current American College of Cardiology/American Heart Association guideline.

Approximately 365 million people in Asia were classified as elderly in 2017. This number is rising and expected to reach approximately 520 million by 2030. The risk of hypertension and cognitive impairment/dementia increases with age. Recent data also show that the prevalence of hypertension and age-related dementia are rising in Asian countries. Moreover, not many people in Asian countries are aware of the relationship between hypertension and cognitive impairment/dementia. Furthermore, hypertension control is poorer in Asia than in developed countries. Hypertension is known to be a major risk factor for damage to target organs, including the brain. Decreased cognitive function can indicate the presence of target organ damage in the brain. Twenty-four-hour blood pressure profiles and blood pressure variability have been associated with cognitive impairment and/or silent cerebral diseases, such as silent cerebral infarction or white matter lesions, which are predisposing conditions for cognitive impairment and dementia. Hypertension that occurs in midlife also affects the incidence of cognitive impairments in later life. Managing and controlling blood pressure could preserve cognitive functions, such as by reducing the risk of vascular dementia and by reducing the global burden of stroke, which also affects cognitive function., (©2019 Wiley Periodicals, Inc.)

In the last three decades protocols for the validation of blood pressure measuring devices have been developed by the US Association for the Advancement of Medical Instrumentation, the British Hypertension Society, the German Hypertension League, the European Society of Hypertension Working Group on blood pressure Monitoring and the International Organization for Standardization. The European Society of Hypertension International Protocol required much smaller sample size than the other protocols, aiming to reduce the time, resources and cost of validation studies and thereby increase the number of validated devices. Given its specifications, the European Society of Hypertension International Protocol was adequate for 'high- and low-accuracy' devices, yet assessment of 'moderate accuracy' devices had high uncertainty with resultant high rate of device failure. Thus, devices validated using the European Society of Hypertension International Protocol should be considered to be as accurate as those validated with the previous Association for the Advancement of Medical Instrumentation or British Hypertension Society protocols. However, the European Society of Hypertension International Protocol did not allow subgroup evaluation (arm sizes, special populations, etc). The mission of the European Society of Hypertension International Protocol to promote the concept of validation has been well achieved, as almost double studies have been published using it than all the other protocols together. However, the maintenance of different validation protocols is confusing and therefore experts from the Association for the Advancement of Medical Instrumentation, European Society of Hypertension International Protocol and International Organization for Standardization have now developed the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) as the recommended 21st-century procedure for worldwide application. The European Society of Hypertension Working Group has published a practical guide for using the Universal Standard. It is in the interests of all scientific bodies to propagate the Universal Standard and ensure its wide implementation.

Objective: Atrial fibrillation (AF) and hypertension are prevalent chronic disease conditions in the elderly population. In the present cross-sectional study, we investigated the association between blood pressure (BP) and AF in an elderly Chinese population., Method: Our elderly (≥65 years) subjects were residents recruited from 6 communities in Shanghai from 2006 to 2017. Atrial fibrillation was systematically screened by rest 12-lead electrocardiogram (ECG) or by a handheld single-lead ECG. BP status was defined according to the European hypertension guidelines as optimal, normal, or high-normal BP, and stage 1, 2, or 3 hypertension., Result: In the 6,966 participants (women 56.0%, mean age: 72.3 years), the prevalence of AF was 3.3%, and the prevalence of hypertension was 58.7% (83.7% treated). In all participants, the association with prevalent AF was negative for systolic BP (odds ratio [OR] per 10-mm Hg increase 0.79, 95% confidence interval [CI]: 0.71-0.88, P < 0.0001) but positive for diastolic BP (OR per 5-mm Hg increase 1.11, 95% CI: 1.02-1.22, P = 0.02). In untreated participants (n = 3,544), the association with prevalent AF was U-shaped for both systolic and diastolic BP, with the nadir at high-normal BP and a significantly higher risk of prevalent AF in optimal systolic BP (OR: 3.11, 95% CI: 1.65-5.85, P = 0.004) and stage 2 or 3 diastolic hypertension relative to the nadir (OR: 8.04, 95% CI: 2.28-28.3, P = 0.001)., Conclusion: In the elderly population, BP shows a complicated relationship with prevalent AF, with high-normal BP at the lowest risk and optimal systolic BP and stage 2 or 3 diastolic hypertension at increased risks., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: Hypertension is a leading global risk factor for death and disability. Seeking new ways to prevent and treat hypertension is a priority for scientists and healthcare professionals worldwide. In November 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) issued a new hypertension guideline shifting the definition of hypertension from 140/90 mm Hg to 130/80 mm Hg for systolic/diastolic blood pressure. This new diagnostic threshold of hypertension has sparked a lively discussion worldwide over whether it should be applied in clinical settings to diagnose and treat hypertension. China, the world's most populous country, is facing a hypertension crisis. According to the 140/90 mm Hg guideline, China has an estimated 244.5 million population aged ≥ 18 years with hypertension, and another 435.3 million with pre-hypertension. If the new guideline is adopted, the prevalence of hypertension in China would double. This change would significantly impact patients, healthcare professionals, scientists, and policy makers in terms of the delivery of care and needed resources., Aim: This study aims to investigate whether Chinese physicians will use the 130/80 mm Hg threshold to diagnose hypertension in clinical practice., Methods: In March 2018, we launched a mobile app-based survey to study 253 Chinese physicians' perspectives on the ACC/AHA Guideline., Results: A total of 253 physicians from 21 Chinese provinces completed the survey. Nearly 80% of the participants had already noticed the ACC/AHA guideline change. The proportion of participants who said they would use the new threshold to diagnoses hypertension was 41%, while 59% said they would not use the new threshold. The primary reason for those who said "yes" was that they believed early diagnosis of hypertension can trigger early actions to prevent the increasing blood pressure. For those who said "no", they argued that their decision was based on the fact that the Chinese Hypertension Prevention Guideline had not yet changed the diagnostic threshold from 140/90 to 130/80 mm Hg., Conclusions: Different understanding of hypertension prevention and treatment exists among Chinese physicians. It is an emergent need to form an evidence-based authoritative answer to guide Chinese physicians' future clinical practice.

In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140-179/90-109 mm Hg and 24-hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4-week treatment and for 48 hours at 8-week treatment with a dose of medication missed on the second day. After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine-GITS group, with a significant (P ≤ 0.04) between-group difference in 24-hour (-1.2 mm Hg) and daytime diastolic BP (-1.5 mm Hg). In conclusion, amlodipine and nifedipine-GITS were efficacious in reducing 24-hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine-GITS., (©2019 Wiley Periodicals, Inc.)

Background: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke., Methods: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616., Findings: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome., Interpretation: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group., Funding: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Guidelines on the required number of ambulatory blood pressure (ABP) readings focus on individual patients. Clinical researchers often face the dilemma of applying recommendations and discarding potentially valuable information or accepting fewer readings., Methods: Starting from ABP recordings with ≥30/≥10 awake/asleep readings in 4277 participants enrolled in eight population studies in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO), we randomly selected a certain number of readings (from 30 to 1 awake and 10 to 1 asleep readings) at a time over 1000 bootstraps at each step. We evaluated: (i) concordance of the ABP level; (ii) consistency of the cross-classification based on office blood pressure and ABP; and (iii) accuracy in predicting cardiovascular complications. For each criterion, we fitted a regression line joining data points relating outcome to the number of readings covering the ranges of 30-20/10-7 for awake/asleep readings., Results: Reducing readings widened the SD of the systolic/diastolic differences between full (reference) and selected recordings from 1.7/1.2 (30 readings) to 14.3/10.3 mm Hg (single reading) during wakefulness, and from 1.9/1.4 to 10.3/7.7 mm Hg during sleep; lowered the κ statistic from 0.94 to 0.63, and decreased the hazard ratio associated with 10/5 mm Hg increments in systolic/diastolic ABP from 1.21/1.14 to 1.06/1.04 during wakefulness and from 1.26/1.17 to 1.14/1.08 during sleep. The first data points falling off these regression lines during wakefulness/sleep corresponded to 8/3 and 8/4 readings for criteria (i) and (iii) and to 5 awake readings for criterion (ii)., Conclusions: 24-h ambulatory recordings with ≥8/≥4 awake/asleep readings yielded ABP levels similar to recordings including the guideline-recommended ≥20/≥7 readings. These criteria save valuable data in a research setting, but are not applicable to clinical practice.

Blood pressure (BP) is a vital sign and the essential measurement for the diagnosis of hypertension. Therefore, its accurate measurement is a key element for the evaluation of many medical conditions and for the reliable diagnosis and efficient treatment of hypertension. In the last 3 decades prestigious organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on BP Monitoring, and the International Organization for Standardization (ISO), have developed protocols for clinical validation of BP measuring devices. All these initiatives aim to standardize validation procedures and establish minimum accuracy standards for BP monitors. Unfortunately, only a few of the BP measuring devices available on the market have been subjected to independent validation using one of these protocols. Recently, the AAMI, ESH, and ISO experts agreed to develop a single universally acceptable standard (AAMI/ESH/ISO), which will replace all previous protocols. This major international initiative has been undertaken to best serve the needs of patients with hypertension, a public interested in cardiovascular health, practicing physicians, scientific researchers, regulatory bodies, and manufacturers. There is an urgent need to influence regulatory authorities throughout the world to make it mandatory for all BP measuring devices to have undergone independent validation before approval for marketing. Efforts need to be intensified to improve the accuracy of BP measuring devices, further optimize the validation procedure, and ensure that objective and unbiased validation data become available., (©2018 Wiley Periodicals, Inc.)

Cuff blood pressure (BP) is the reference standard for management of high BP, but the method is inaccurate and can lead to BP misclassification. The aims of this study were to determine whether distinctive BP phenotypes exist based on BP transmission (amplification) variability from central-to-peripheral arteries and whether applying one standard cuff BP measurement approach (eg, oscillometry) to all people could discriminate the BP phenotypes. Intra-arterial BP was measured at the ascending aorta and brachial and radial arteries in 126 participants (61±10 years; 69% male) after coronary angiography. Central-to-peripheral systolic BP (SBP) transmission (SBP amplification) was defined by ≥5 mm Hg SBP increase between the aorta-to-brachial or brachial-to-radial arteries. Standard cuff BP was measured 4 different times using 3 different devices. Three independent investigators also provided data (n=255 from 4 studies) using another 3 separate cuff BP devices. Four distinct BP phenotypes were discovered based on variability in SBP amplification: phenotype 1, both aortic-to-brachial and brachial-to-radial SBP amplification; phenotype 2, only aortic-to-brachial SBP amplification; phenotype 3, only brachial-to-radial SBP amplification; and phenotype 4, neither aortic-to-brachial nor brachial-to-radial SBP amplification. Aortic SBP was significantly higher among phenotypes 3 and 4 compared with phenotypes 1 and 2 ( P =0.00074), but this was not discriminated using any standard cuff BP measures ( P =0.31). Data from independent investigators confirmed the key findings. This is the first-in-human discovery of BP phenotypes that have significantly different BPs, but which are not discriminated by standard cuff BP devices used in daily clinical practice. Improved BP device accuracy may be achieved by considering individual phenotypic BP differences., (© 2018 American Heart Association, Inc.)

We investigated the relationship between ambulatory blood pressure (BP) and oxygen desaturation index (ODI), while accounting for pulse rate and age. ODI was assessed by overnight finger pulse oximetry in 2342 participants on the day of ambulatory BP monitoring, and calculated as the number of desaturation episodes per sleeping hour. Both BP and pulse rate increased significantly (P ≤ .006) from normal (< 5 events/h) to mildly (5-14), moderately (15-30), and severely (≥ 30 events/h) elevated ODI. The association for BP was substantially attenuated by accounting for pulse rate (partial r² from .003-.012 to .002-.006). In adjusted analysis, the associations of 24-hour diastolic BP and 24-hour pulse rate with ODI were dependent on age (P ≤ .0001) and only significant in younger subjects (< 60 years, P ≤ .0001). In conclusion, the association between ambulatory BP and ODI was partially mediated by pulse rate, a measure of sympathetic activity, and was more prominent in younger subjects., (©2018 Wiley Periodicals, Inc.)