bluuebunny/crossref_metadata_2025 huggingface dataset:
DOCA-SALT DIMINISHES BRAIN RAS ACTIVITY IN PARALLEL WITH PLASMA AND RENAL RAS ACTIVITY – NO EVIDENCE FOR SELECTIVE BRAIN RAS ACTIVATION
Authors: Uijl Estrellita , Ren Liwei , Colafella Katrina M. Mirabito , Poglitsch Marko , Domenig Oliver , Zlatev Ivan , Kim Jae B. , Huang Stephen , Melton Lauren , Foster Don , Danser A.H. Jan
Published: April 2021

Objective:

Deoxycorticosterone acetate (DOCA)-salt is suggested to promote hypertension by selectively upregulating the brain renin-angiotensin system (RAS), while suppressing the circulating RAS. Yet, we previously observed parallel downregulation of plasma and brain renin in mice. Here, we quantified angiotensinogen (AGT) and angiotensin (Ang) in rat brainstems.

Design and method:

For 7 weeks, rats received DOCA (200 mg; 60-day release pellet) and saline as drinking water. The contribution of AGT (liver vs. kidney/brain), Ang II type 1 receptors (AT1R) and blood pressure to tissue Ang content was determined by treatment with vehicle, liver-targeted AGT siRNA (30 mg/kg fortnightly; s.c.), valsartan (31 mg/kg/day; s.c.) or spironolactone (80 mg/kg/day; s.c.) during the final 3 weeks (n = 7–8/group). Plasma renin and AGT were quantified by enzyme-kinetic assay, tissue AGT by western blotting, and Ang I and II by LC-MS/MS.

Results:

Plasma renin, AGT, Ang I and II in rats not exposed to DOCA-salt were 20 ± 4 ng Ang I/mL/h, 730 ± 37 nM, 140 ± 24 pM and 108 ± 24 pM. AGT was present in liver, kidney and brainstem. Kidney Ang I and II were 540 ± 135 and 510 ± 97 fmol/g, while brainstem Ang I and II were undetectable in all and 30% of the rats, respectively (LLOQ <6 fmol/g). DOCA-salt increased blood pressure by 19 ± 1 mmHg and lowered plasma and renal Ang I and II by ∼90%, while brainstem Ang II became undetectable in 70% of the rats. AGT siRNA lowered plasma AGT by 97 ± 0.3%, with similar reductions in the liver and kidney, while brain AGT was unaltered. Whereas spironolactone normalized blood pressure, it increased plasma renin, and plasma, renal and brain Ang I and II. siRNA and valsartan tended to further lower renal Ang, without affecting blood pressure, plasma renin or plasma and brain Ang I and II.

Conclusions:

DOCA-salt suppresses plasma, renal and brain Ang II in parallel. Renal Ang II depends on hepatic AGT and AT1R-mediated internalization. Brain AGT is liver-independent, but unaltered by DOCA-salt, thus not permitting selective brain RAS upregulation. The RAS upregulation during spironolactone, combined with its antihypertensive effect, argues against the (brain) RAS as a major blood pressure determinant in this model.
ESTABLISHMENT OF A NEW SPECIFIC HIGH SENSITIVITY MEASUREMENT SYSTEM FOR SOLUBLE ANGIOTENSIN IV RECEPTOR
Authors: Konoshita Tadashi , Azuma Shinichiro , Sugiyama Mitsutoshi , Furutani Machi , Kaeriyama Saori , Saito Rie , Sato Satsuki , Imagawa Michiko , Zenimaru Yasuo , Suzuki Jinya , Fujii Miki , Makino Yasukazu
Published: April 2021

Objective:

The renin angiotensin system plays a pivotal role in the development of cardiovascular and renal conditions. We had identified angiotensin IV receptor (AT4) as a hypertension/diabetes-specific gene through systemic transcriptome analysis followed by ontology based hierarchical clustering. Previously we have established a measurement system for soluble AT4 (sAT4) by polyclonal antibodies with 1 μg/ml sensitivity. Actual measurements for clinical subjects suggest the sAT4 measurement system would be useful for assessment of the pathophysiology of hypertension/obesity. Thus, we tried to establish a new specific high sensitivity measurement system for sAT4 with monoclonal antibodies.

Design and method:

As the antigen, we prepared a recombinant protein of AT4. Mice were immunized with the protein then spleen and lymph nodes were applied to make hybridomas with X63. We have screened the clones and selected candidate clones. Then we tested the best combination of the antibodies for the sandwich ELISA system and then optimized the reaction conditions. With this system, as a pilot study, we measured plasma concentrations of 114 subjects with life style related diseases and investigated relationships of sAT4 with various clinical and biochemical parameters by ANOVA.

Results:

Based on the standard curve for serial-step dilutions against reference molecules, the new measurement system for sAT4 showed 20 pg/ml sensitivity, 3–8 % intra-assay CV and about 10 % inter-assay CV without cross reactivities against 3 standard substrates. Actual measurements on clinical subjects revealed that the sAT4 values tended to be lower on hypertensive cases, obesity cases and dyslipidemic cases and that the sAT4 values were significantly low on CKD cases.

Conclusions:

Thus, we could establish a new specific high sensitivity measurement system for sAT4. The AT4 was originally identified from GLUT4 vesicles and thought to be involved in insulin sensitivity. It is also known to degrade angiotensin III to IV. Besides these findings, our data suggest the possibility that AT4 is involved in the pathophysiology of hypertension/obesity in a high sensitivity level for the first time. As perspectives we will assess the distribution of the concentrations and will measure the adequate numbers based on statistical power.
BLOOD PRESSURE LOWERING EFFECTS AND SAFETY OF ESEXERENONE, NEWLY AVAILABLE MINERALOCORTICOID RECEPTOR BLOCKER
Authors: Satoh Fumitoshi , Morimoto Ryo , Tezuka Yuta , Omata Kei , Yamanami Hiroaki , Ono Yoshikiyo , Ito Sadayoshi
Published: April 2021

Objective:

Esaxerenone (CS-3150) is a novel, highly potent, selective and long acting non-steroidal mineralocorticoid receptor (MR) blocker with MR blocking action of IC50 3.7 nM, other steroid hormone receptors blocking action of IC50 >5000 nM and half life loss of 18.6 hours. The authors aimed to investigate blood pressure (BP)-lowering ability and safety of esaxerenone in resistant hypertensive patients by add-on or by replacement from spironolactone or eplerenone.

Design and method:

This study was designed as a prospective observational study in 230 patients, approved by the local ethical committee and followed for 12 weeks. In add-on group, 52 resistant hypertensive patients, whose office BP was > 130/80 (<75 years old) or 140/90 (>75 years old) treated with at least three hypertensive agents (CCBs, RAS inhibitors and diuretics) according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019), were treated by the add-on use of esaxerenone. In replacement group, 208 resistant hypertensive patients, whose BP was controlled by at least 4 antihypertensive drugs including spironolactone or eplerenone, were medicated with esaxerenone by replacement from spironolactone or eplerenone.

Results:

In add-on group, both systolic and diastolic BP were significantly lowered from 139 ± 16 / 82 ± 14 mmHg (means ± SD) to 129 ± 16 / 79 ± 12 mmHg (p < 0.0001 and p = 0.0185, respectively) with mean esaxerenone dose of 1.44 mg. In replacement group, systolic BP was significantly lowered from 126 ± 16 mmHg (means ± SD) to 120 ± 14 mmHg (p < 0.0001), but diastolic BP was not, with mean esaxerenone dose of 1.58 mg once a day, which was changed from mean spironolactone and eplerenone doses of 34 and 58 mg, respectively. In add-on group, serum potassium concentration was significantly increased from 4.18 ± 0.46 to 4.40 ± 0.58 mmol/L and eGFR was decreased from 74.2 ± 23.9 to 66.9 ± 24.0, but those in replacement group were not significantly changed.

Conclusions:

This study suggested that esaxerenone has more potent BP lowering ability than spironolactone or eplerenone especially in systolic BP and has the equivalent safety.
RECEPTOR INTERACTING MOLECULE ATRAP AS MODULATOR OF RENAL SODIUM HANDLING AND PATHOLOGICAL BLOOD PRESSURE RESPONSE
Authors: Tamura Kouichi , Yamaji Takahiro , Kinguchi Sho , Kobayashi Ryu , Azushima Kengo , Uneda Kazushi , Haruhara Kotaro , Kanaoka Tomohiko , Urate Shingo , Abe Eriko , Tanaka Shohei , Ishii Takeo , Kumagai Tomohiko , Yamashita Akio , Wakui Hiromichi
Published: April 2021

Objective:

Pathological activation of renal angiotensin II (Ang II) type 1 receptor (AT1R) signaling exerts stimulates renal tubular Na+ transporters including epithelial Na+ channel to increase renal sodium reabsorption.

Design and method:

In the course of an investigational search for a means to functionally and selectively modulate AT1R signaling for that purpose, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified by employing yeast two-hybrid screening of a mouse kidney cDNA library and named AT1R-associated protein (ATRAP).

Results:

We showed that ATRAP promotes constitutive AT1R internalization so as to inhibit pathological AT1R activation in response to certain stimuli. In the kidney, ATRAP is abundantly distributed in epithelial cells along the renal tubules. The results employing genetic engineered mice with modified ATRAP expression showed that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli such as chronic Ang II infusion dietary high salt loading and 5/6 nephrectomy.

Conclusions:

Accumulating findings concerning functional and pathological roles of the novel receptor-interacting molecule ATRAP suggest that ATRAP would be a target of interest for hypertension in the cardiovascular and renal continuum.
ASSOCIATION BETWEEN THE DIFFERENCE OF BILATERAL BRACHIAL-ANKLE PULSE WAVE AND CARDIOVASCULAR EVENTS, ALL-CAUSE MORTALITY
Authors: Zheng Mengyi , Wu Shouling
Published: April 2021

Objective:

Aims: To assess whether an elevated bilateral pulse wave velocity difference (BPWVD) is associated with a higher risk of cardiovascular disease (CVD) and all-cause mortality.

Methods and

Design and method:

From the community-based longitudinal Kailuan Study, we included 38,512 participants (mean age:48.9 ± 12.8 years) who underwent measurements of the brachial-ankle pulse wave velocity (baPWV) from 2010 to 2017, and who were followed to 2018 for CVD outcome and to 2019 for the assessment of all-cause mortality. During a mean follow-up of 4.25 ± 2.39 years for assessment of CVD and 5.23 ± 2.39 years of all-cause mortality, 815 CVD cases (cerebral infarction, n = 566; intracerebral hemorrhage, n = 70; myocardial infarction, n = 179) and 952 mortalities were identified. The mean BPWVD was 63.0 cm/s (median:43 cm/s; inter-quartile range:19, 80 cm/s), and 9,708 (25.2%) participants were categorized as the high BPWVD group with a BPWVD in the highest quartile (?80 cm/s). In the multivariable Cox proportional hazard model, compared with the normal BPWVD group, the high BPWVD group had a significantly higher risk of myocardial infarction and all-cause mortality, with adjusted hazard ratios (HRs) (95% confidence interval (CI)) of 1.43 (95%CI: 1.04–1.96) and 1.18 (95%CI: 1.03–1.35), respectively. A higher BPWVD by one standard deviation was associated with HRs of 1.06 (95% CI: 1.02–1.10) for incident CVD, 1.10 (95% CI: 1.02–1.17) for incident myocardial infarction and of 1.07 (95% CI: 1.04–1.10) for all-cause mortality.

Conclusion:

Higher BPWVD was positively associated with the risks of CVD and all-cause mortality. Our findings emphasize the importance of assessing BPWVD to identify high-risk individuals for CVD and mortality.
VASCULAR AGING INDEPENDENTLY PREDICTS ALL-CAUSE MORTALITY IN THE HEINZ NIXDORF RECALL STUDY
Authors: Weber Thomas , Wassertheurer Siegfried , Hametner Bernhard , Mayer Christopher , Moebus Susanne , Schramm Sara , Roggenbuck Ulla , Lehmann Nils , Joeckel Karl -Heinz , Erbel Raimund
Published: April 2021

Objective:

Vascular aging is an attractive concept for simplified risk stratification. Longitudinal data regarding its predictive value, additive to traditional and new risk factors, are sparse.

Design and method:

We recently established population-based reference values for healthy (HVA), normal (NVA) and early (EVA) vascular aging in the Heinz Nixdorf Recall (HNR) study. HVA was the lowest, and EVA the highest age- and sex-specific decile of estimated aortic pulse wave velocity, derived from radial waveforms with a validated regression formula. The prognostic value of vascular aging was tested in HNR study participants without overt cardiovascular disease at baseline, using Kaplan Meier curves and Cox Regression models. The latter included age, sex, diastolic blood pressure, cholesterol, diabetes, smoking status and coronary calcium (Agatston score) as covariates.

Results:

We included 1810 participants (980 women), mean age was 68.1 years (range 55–85), mean blood pressure 129/76 mm Hg. 64.6% were hypertensives, 17.0% diabetics, 12.2% smokers. During a mean follow up of 4.7 years, 67 participants died. Mortality was 1.22% in 164 HVA participants, 3.59% in 1392 NVA participants, and 5.91% in 254 EVA participants (p = 0.038, log rank test) – Figure. In Cox regression analysis, vascular aging (HR for HVA: 0.18, CI 0.04–0.73, and HR for NVA: 0.48, CI 0.27–0.88; both compared to EVA) as well as age (directly related) and diastolic blood pressure (inversely related) were independently associated with all-cause mortality.

Conclusions:

Vascular aging, determined from estimated aortic pulse wave velocity, predicts all-cause mortality in a middle-aged and elderly population, independent from classic risk factors, and coronary calcium score.
THE EFFECTS OF ITI-214 (A NEW PHOSPHODIESTERASE 1 INHIBITOR) ON VASCULAR AGEING FEATURES ASSOCIATED TO DNA REPAIR RESPONSE IN MICE
Authors: Golshiri Keivan , Ataei Ehsan , De Vries Rene’ , Van Veghel Richard , Snyder Gretchen L. , Zhang Lei , Li Peng , Davis Robert E. , Danser A.H. Jan , Roks Anton J.M.
Published: April 2021

Objective:

DNA damage and repair responses have been linked to accelerated vascular aging. Accordingly, mice with a genetic deletion of ERCC1 (Ercc1d/- mice), a DNA repair protein, display a rapid onset of vascular aging. A hallmark hereof is disturbed NO-cGMP signalling, in which an increase of the cyclic nucleotide-metabolizing enzyme phosphodiesterase 1 (PDE1) is implicated. We hypothesized that specific PDE1 inhibition has beneficial effects in the aged vasculature. To test this, we evaluated the effects of chronic and acute PDE1 inhibition with ITI-214 in Ercc1d/- mice and WT littermates.

Design and method:

ITI-214 (treated), or no drug (control), was given in drinking water from the age of 6 to 14 weeks. Blood pressure (BP) and in vivo vasodilator responses (hindleg reactive hyperemia:RH) were measured in week 12 and 13. At 14 weeks aortic tissue was obtained for ex vivo wire myograph studies to analyse endothelium-dependent and endothelium-independent relaxations to acetylcholine (Ach) and nitric oxide donor (sodium nitroprusside: SNP) respectively.

Results:

There were significant reductions in systolic (93.39 ± 3.406 vs. 111.7 ± 5.238 mmHg, P = 0.009) and diastolic (64.47 ± 2.7 vs. 76.43 ± 4.699 mmHg, P = 0.038) BP in treated Ercc1d/- vs. controls. RH was 50% lower in control Ercc1d/- vs. WT (P = 0.025). ITI-214 treatment did not improve RH. In contrast, ITI-214 enhanced the aortic maximal Ach response from 70.24 ± 3.24 to 76.96 ± 4.76% (P = 0.002) and the SNP response from 64.83 ± 6.10 to 85.24 ± 7.58% (P = 0.0001) in WT but not in Ercc1d/-. In contrast to chronic treatment, acute administration of ITI-214 in organ baths enhanced the SNP response in both control WT (from 64.83 ± 6.10 to 79.32 ± 5.63%, P = 0.003) and control Ercc1d/- mice (from 45.61 ± 11.6 to 75.45 ± 3.61%, P = 0.0001).

Conclusions:

The acute effect of ITI-214 confirms the role of PDE1 in mediating decreased NO-cGMP signalling caused by defective DNA repair. Therefore, PDE1 inhibition is a strategy to acutely improve vasodilation in the aged vasculature.
DNA REPAIR DEFECT IN SMOOTH MUSCLE CELL REPRODUCES FEATURES OF AGE-RELATED VASCULAR DISEASE IN MICE
Authors: Ataabadi Ehsan Ataei , Golshiri Keivan , De Vries René , Snyder Gretchen L. , Zhang Lei , Li Peng , Davis Robert E. , Jan Danser A.H. , Roks Anton J.M.
Published: April 2021

Objective:

DNA damage and repair responses have been implicated in age-related vascular disease. Evidence in mice shows that deletion of the Ercc1 gene, encoding an endonuclease that participates in several DNA repair systems, leads to features of accelerated ageing. It is not known from which cell type the vascular aging effect of Ercc1 deletion originates. A possibility is local DNA damage in vascular smooth muscle cells (VSMC). We determined features of vascular aging in a mouse model with specific Ercc1 deletion in smooth muscle cells (SMC-KO).

Design and method:

12 SMC-KO and 13 Wild-type (WT) littermates were generated using alpha SM22-Cre driven cre-lox deletion of Ercc1. Blood pressure (BP) and in vivo vasodilation (reactive hyperemia: RH) were measured at the age of 22 and 23 weeks respectively. Mice were sacrificed at 24 weeks. Thoracic aorta and iliac artery endothelium-dependent (ED) and –independent (EI) relaxation were assessed (wire myograph).

Results:

There was no significant difference in BP between WT and SMC-KO. RH was decreased in SMC-KO vs. WT by 73% (P = 0.008). In SMC-KO mice maximal relaxation in iliac arteries to acetylcholine (ED) and sodium nitroprusside donor (EI) were decreased as compared to WT (ED: 48.04 ± 6.80 vs. 86.16 ± 3.68, P = 0.001; EI: 79.84 ± 4.04 vs. 93.78 ± 2.13, P = 0.022). In aorta similar observations were made (ED: 17.11 ± 2.29 vs. 73.42 ± 4.29, P = 0.0001; EI 55.87 ± 4.77 vs. 69.01 ± 5.17, p = 0.007). When added in the organ bath ITI-214 acutely increased aortic EI relaxation both in WT (from 69.01 ± 5.17 to 80.53 ± 2.05, P = 0.006) and SMC-KO (from 55.87 ± 4.77 to 67.17 ± 3.70, P = 0.084).

Conclusions:

Local DNA damage in SMC causes a decrease of vasodilator responses. This effect is blood pressure-independent. Given that responses to sodium nitroprusside, a nitric oxide (NO) donor, and PDE1, a cGMP-metabolising enzyme, were both involved, most probably a decline of NO-cGMP signalling is involved.
MACHINE LEARNING CLUSTERING FOR BLOOD PRESSURE VARIABILITY: VALIDATION FROM THE SPRINT TO THE HONG KONG COMMUNITY COHORT
Authors: Tsoi Kelvin , Chan Nicholas , Yiu Karen , Poon Simon , Ho Kendall , Lin Bryant
Published: April 2021

Objective:

Visit-to-visit BPV is associated with risks of cardiovascular diseases. Our aim is to investigate the classification methods of patients with varying levels of BPV using different machine learning algorithms.

Design and method:

Two sets of visit-to-visit blood pressure (BP) readings were extracted from (i) SPRINT in the United States and (ii) BP cohort in Hong Kong (HK). BPV were defined as the mean absolute residuals of regression trends on BP over time. Patients were clustered into low, medium and high levels of BPV with the traditional quantile clustering and five machine learning algorithms, including K-means clustering, Partitioning Around Medoids (PAM), Spectral clustering, Ward's method and Expectation Maximization. Clustering methods were assessed by the Stability Index, and similarities were assessed by the Davies-Bouldin Index (DBI) and the Silhouette Index. Regression models were fitted to compare the risk of stroke.

Results:

Results: A total of 8,133 participants were included from SPRINT with the mean BP measurement 14.7 times in 3.28 years of follow-up, and1,094 participants were recruited from HK cohort with the mean BP measurement 165.4 times in 1.37 years. Quantile clustering assigned one-third participants as the high level of BPV, but machine learning methods only assigned 10 to 27%. Quantile clustering is the most stable method (Stability Index: 0.982 in the SPRINT and 0.948 in the HK cohort) but shown to have certain levels of cluster similarities (DBI: 0.752 and 0.764, respectively) (Table 1). Across the machine learning algorithms, K-means clustering is the most stable method (Stability Index: 0.975 and 0.911, respectively) with lowest similarities on cluster classification (DBI: 0.653 and 0.680, respectively). Patients with high level of BPV under the machine learning models showed stronger association with stroke.

Conclusions:

Among the machine learning algorithms, K-means clustering shows the most stable and reliable results. One-seventh of the population with high level of BPV had elevated risk of stroke compared to conventional BPV classification. Machine learning can be potentially used in the electronic health system for better patient management.
MACHINE LEARNING BASED MODELS FOR PREDICTING WHITE-COAT AND MASKED PATTERNS OF BLOOD PRESSURE
Authors: Lip Stefanie , Mccallum Linsay , Reddy Sandeep , Chandrasekaran Nataraj , Tule Sanjana , Bhaskar Ravi Kiran , Padmanabhan Sandosh
Published: April 2021

Objective:

Blood pressure (BP) is inherently variable. White-coat (WC) and masked hypertension are manifestations of this variability making office BP (OBP) unreliable with direct implications on diagnosis and management. Whilst the causes for this phenomenon are not fully known, predicting whether an individual's BP has WC or masked pattern will improve efficiencies in overall BP management. In this study, we used machine learning (ML) methods which are powerful in finding generalisable predictive patterns to develop models for accurate prediction of different BP patterns.

Design and method:

Data from patients referred from primary care to the specialist Glasgow BP clinic, all of whom underwent ambulatory blood pressure monitoring (ABPM) were analysed. The independent variables included a range of conventional clinical parameters included in the referral letter along with OBP. Missing data were imputed using K nearest neighbours, an ML algorithm that approximates a point value based on the nearest available point values. Following this, four ML algorithms (support vector machine, decision tree, random forest (RF) and extreme gradient boosting (XGBoost)) were applied to the dataset, split into 70% training and 30% validation subsets. Performance of models was reported using area under the curve, accuracy, precision (fraction of relevant instances among the retrieved instances) and recall (fraction of the total amount of relevant instances that were actually retrieved) measures.

Results:

There were 926 patients – average age 51 ± 16 years, 43%-female, 49% were new presentation for investigation of hypertension, 38% were not on any BP lowering therapy, 1.1% had type 2 diabetes and 5.2% had eGFR < 60. The proportion of different BP patterns were – Normal BP:8.1%, Normal BP-masked:3.7%, Normal BP-whitecoat: 30.7%, Hypertension-whitecoat:23.3% and Hypertension:34%. Of the four predictor models, the highest classification accuracies were obtained for the XGBoost algorithm (accuracy:85%, precision:85%) followed by the RF classifier (accuracy:84%, precision:84%). Figure-1 demonstrates the multiclass AUC and leading predictors using the XGBoost model.

Conclusions:

ML models are able to predict WC and masked patterns in hypertensive patients and those suspected of having hypertension with relatively high accuracy and this warrants validation in larger cohorts.
DIPPING PATTERN AND SHORT-TERM BLOOD PRESSURE VARIABILITY ARE STRONGER PREDICTORS OF CARDIOVASCULAR EVENTS THAN AVERAGE 24-HOUR BLOOD PRESSURE IN HYPERTENSION OF THE YOUNG
Authors: Palatini Paolo , Reboldi Paolo , Saladini Francesca , Angeli Fabio , Mos Lucio , Fania Claudio , Mazzer Adriano , Vriz Olga , Verdecchia Paolo
Published: April 2021

Objective:

Ambulatory blood pressure (ABP) monitoring (ABPM) is currently performed for stratification of risk in hypertension. However, in clinical practice interest is focused on average ABP whereas little attention is paid to other ABPM parameters. Previous data have been obtained mainly from populations including elderly individuals, while little is known on the clinical significance of ABPM data in young individuals. Aim of the present study was to investigate whether and to what extent parameters other than average ABP are associated with CVE in individuals <= 45 years of age.

Design and method:

We performed ABPM in 2356 young-to-middle-age participants enrolled in 2 prospective studies in Italy (HARVEST and PIUMA). Mean age was 35.6 ± 7.6 years and mean BP was 143.3 ± 15.7/93.5 ± 10.6 mmHg. The ABPM parameters of interest were average 24 h systolic BP (SBP), 24 h systolic SD, and 24 h SBP diurnal rhythm. Participants were grouped according to whether they had high or low average 24 h SBP (cutoff, 130 mmHg), high or low systolic SD (cutoff, 12.8 mmHg), and were dippers or nondippers (cutoff 10% nocturnal decline). All parameters were included simultaneously in the same Cox models. Hazard ratios (HR) were adjusted for traditional risk factors.

Results:

During a median follow-up of 12.4 years, 164 CVE were observed. All ABPM parameters were independent predictors of the endpoints. However, a higher risk was observed for non dipping (HR,2.4; 95%CI,1.6–3.6; p < 0.0001) and for high SD (HR,2.0; 1.4–2.8; p = 0.0002) than for high average SBP (HR,1.5; 1.1–2.2; p = 0.019). Compared to dippers with low average SBP, nondippers with high average SBP had a HR of 3.2 (95%CI, 2.2–5.2). Compared to participants with low SD and low average SBP, participants with high average SBP and high SD had a HR of 2.8 (2.7–4.6). Similar results were obtained in the 1780 hypertensives and when the ABPM parameters were used as continuous variables.

Conclusions:

In young-to-middle-age subjects, dipping pattern and short-term BP variability are strong predictors of adverse outcome on top of average 24-hour BP. These two parameters should always be included in the stratification of risk when young hypertensive patients are assessed with ABPM.
SEASONAL VARIATION OF NIGHTIME HOME BLOOD PRESSURE AND ITS ASSOCIATION WITH TARGET ORGAN DAMAGE: THE J-HOP NOCTURNAL BLOOD PRESSURE STUDY
Authors: Narita Keisuke , Hoshide Satoshi , Kario Kazuomi
Published: April 2021

Objective:

Although seasonal variation of nighttime home blood pressure (BP) was reported as higher in summer than winter, seasonal differences in the association of nighttime home BP with target organ damage (TOD) remains unclear. Hence, we assessed the seasonal variation of nighttime home BP and its association with TOD using a dataset of the Japan Morning Home-Surge BP (J-HOP) Nocturnal BP study.

Design and method:

This is a cross-sectional, post-hoc analysis using the dataset of the J-HOP Nocturnal BP study, which recruited patients with a history of or risk factors of cardiovascular disease. Participants underwent consecutive 14-day home BP measurements (morning and evening) and nighttime home BP measurements (a.m. 2, 3, and 4). Urine albumin creatinine ratio (UACR) and serum-brain natriuretic peptide (BNP) were collected at enrollment.

Results:

Among 2545 participants (age, 63.3 ± 10.3 yrs; antihypertensive medication use 82.6%), 629, 596, 719, and 601 participants were enrolled in spring, summer, autumn, and winter, respectively. Nighttime home systolic/diastolic BP (SBP/DBP) were higher in summer than in winter (SBP/DBP in summer, 123.3 ± 14.6/70.4 ± 8.9 mmHg; vs. in winter, 119.3 ± 14.0/69.1 ± 8.4 mmHg, each p value < 0.05 after adjusted with Bonferroni collection in each season), and the prevalence of riser pattern was also higher in summer than in winter (in summer, 27.2%; vs. in winter, 10.1%, p < 0.05). When the interaction between BP parameters and each season for the association with TOD was assessed, an association between riser pattern and UACR and an association between nighttime home DBP and BNP were stronger in winter compared to those in other seasons (both p for interaction < 0.05).

Conclusions:

In the present study, we revealed the association of nighttime home BP and TOD was stronger in winter than in other seasons.
FIRST RESULTS OF THE NEW HUNGARIAN HYPERTENSION REGISTRY: SEASONAL CHANGES OF BLOOD PRESSURE VALUES
Authors: Páll Dénes , Nemcsik János , Habony Norbert , Farsang Csaba , Ábrahám György , Simon Attila , Benczúr Béla , Járai Zoltán
Published: April 2021

Objective:

It is well known that blood pressure (BP) changes continuously and there is a seasonal change of BP. Our aim was to examine how these changes are present among the Hungarian population.

Design and method:

Omron M3 IT devices were placed to physicians between October 2018 and November 2019. All of the measured BP values were transmitted online to an evaluating center using the Medistance system of Omron. 1.691 general practitioners and 235 internists have been involved in the study. Based on this database, we analyzed the seasonal changes of BP in our population.

Results:

At this moment we have more than a million (1.008.398) BP data in our new Hungarian Hypertension Registry. Separating these BP data by month, we found the highest systolic BP average in winter (in December 141.84 mmHg, January 142.00 mmHg, February 141.47 mmHg). On the other hand, the lowest systolic BP data were measured in summer (in June 136.74 mmHg, July 137.10 mmHg, August 135.86 mmHg). We observed the same trend comparing diastolic BP. The highest average values were in January (85.48 mmHg), December (85.02 mmHg), February (84.93 mmHg) and the lowest were measured in August (82.13 mmHg), June (82.82 mmHg), July (83.11 mmHg). During spring and autumn, the BP values were between our winter and summer data. The mean difference between the average of the highest and lowest month (January vs August) is 6.34 mmHg for systolic, and 3.35 mmHg for diastolic BP. In summer (June, July, August) the ratio of the well-controlled hypertensives was 51.37%, 51.05% and 53.51%, respectively, while it was only 42.1%, 41.76% and 42.53% in December, January and February. We observed grade III. hypertension in 5.09%, 6.11% and 5.75% in summer, while it was much higher in winter (7.44%, 7.79%, 7.3%).

Conclusions:

There is an important difference in the average values of our winter and summer BP data, and the ratio of the well-controlled as well as the severe hypertensives. Based on these data there can be need for seasonal change in the quantity of their antihypertensive drugs to reach the optimal BP values.
A NOVEL DEFINITION, EARLY EVENING ELEVATED BLOOD PRESSURE, HAS A HIGH PREVALENCE RATE ACCORDING TO AMBULATORY BLOOD PRESSURE MONITORING
Authors: Ma Zhiyi , Zhao Yixin , Lu Xining , Yang Fan , Chen Yuanyuan , Sun Ningling
Published: April 2021

Objective:

Early evening (from 6pm to 10pm) involves with many daily life activities and is just before sleep. A novel definition, Early Evening Elevated blood pressure (EEE), was made in this study. We investigated its prevalence rate based on ambulatory blood pressure monitoring (ABPM).

Design and method:

The ABPM data was collected in our hospital from October to December in 2018. The age of each subject should be at least 18 years old. The percentage of successful measurements for each subject should not be lower than 70%. Only the first ABPM of one subject during these three months was included. The ABPM devices were US Space Lab 90217 Dynamic Blood Pressure Monitors. The EEE was defined as high average blood pressure from 6pm to 10pm (detailed definition and classification seen in Table 1). The high blood pressure and morning blood pressure surge were diagnosed based on 2018 ESC/ESH Guidelines for the management of arterial hypertension.

Results:

1. The ABPM data of total 697 subjects were valid data. Among them, there were 438 subjects with high blood pressure according to their ABPM. There were 324 subjects with morning blood pressure surge according to their ABPM. 2. The prevalence rate of EEE (Definition A) was 43.62% among all valid data and the prevalence rates of definition B, C and X were higher than that of A, 51.65%, 62.41% and 81.35% respectively. 3. The prevalence rate of EEE (Definition A) was 65.98% among those diagnosed with high blood pressure and was 71.60% among those diagnosed with morning blood pressure surge. (Details seen in Table 2)

Conclusions:

In this study, there was a high prevalence rate of early evening elevated blood pressure at least among the subjects undergoing ABPM. This EEE phenomenon might influence medication, including multi-kinds, overlap-add, high dosage and so on. Further investigation is needed to find out its possible reasons and better corresponding solutions.
SODIUM CONSUMPTION QUESTIONNAIRE WITH PHOTOGRAPHIC MANUAL: DEVELOPMENT OF A NEW TOOL FOR EVALUATION OF HYPERTENSIVE OUTPATIENTS
Authors: Bortolotto Luiz , Cardoso Bruna , Duenhas Ana
Published: April 2021

Objective:

To develop and evaluate the reliability of the Sodium Consumption Questionnaire with Photographic Manual for routine use in outpatient clinical care of hypertensive patients in a tertiary hospital, using the gold standard 24-hour sodium urinary test as reference.

Design and method:

Prospective cohort study with 50 patients, for development of the Sodium Consumption Questionnaire with Photographic Manual from the consumption frequency of rich sodium foods, intake of addition and per capita sodium compared to 24-hour sodium urinary test performed at the same day of application of the questionnaire. After patients signed informed consent it were excluded those who were unable to answer the questions, whose urine collection procedure was performed improperly and/or had a glomerular filtration rate < 45 mL/min/1.73m2. The reliability of the rich sodium foods list was done with pre-established portions, which were assessed by Cronbach's Alpha, as well as Pearson's correlation coefficient to rich sodium foods frequency and sodium intake per capita from 24-hour sodium urinary. The photographs for the manual were obtained from a horizontal surface and 45 ° angles in a portable studio with illumination and infinite background for better accuracy.

Results:

The mean age was 54 ± 13 years and 62,0% female, with a mean BP 165 ± 28/90 ± 25 mmHg and a mean body mass index of 31 (27,85 – 36,99) kg/m2. The mean 24-h Urinary sodium was 177 mEq (equivalent 4,07 grs of sodium).

The value for Cronbach's Alpha was 0.542, assuming this result as satisfactory for the questionnaire. The consumption frequency by rich sodium foods list and sodium added per capita showed significant correlation with 24-hour sodium urine (r = 0.892; p < 0.01 and r = 0.501; p < 0.01, respectively). Thus, the development of the Sodium Consumption Questionnaire with Photographic Manual was done with consumption frequency and 34 pre-established standard photographs.

Conclusions:

The Sodium Consumption Questionnaire with Photographic Manual was developed with reliability and significant correlation with 24-hour urine sodium, allowing applicability in outpatient routine.
ASSESSING THE EFFICACY OF A 90 DAY GLUTEN-FREE DIET ON CHANGE IN WEIGHT AND ANTHROPOMETRY IN HYPERTENSIVE MALES
Authors: Patil Mansi , Patil Vishal
Published: April 2021

Objective:

To assess the efficacy of a gluten-free diet on change in weight, blood pressure and anthropometry [waist circumference (WC), Waist to hip ratio (WHR), Body mass Index (BMI)] after 90 days in hypertensive males.

Design and method:

A cross-sectional study on 200 male patients with uncontrolled hypertension was carried out to assess the effect of a 90 day gluten-free diet on blood pressure, weight and anthropometry. Patients (n = 200) were advised a 1800 kcals diet with 60% carbohydrates, 20% proteins and 20% fats. Patients (n = 100) were provided gluten-free dietary advice and 100 patients (control group) were advised to continue a gluten containing diet. Diet diary was maintained by patients and monitored weekly. Clinic blood pressure, height, Weight, Waist circumference and hip circumference measured using the NHANES standard procedures were obtained. BMI and WHR were calculated.

Results:

At the commencement of the trial 90% (180/200) of the patients had weight greater than their Ideal body weight, with 68% (136/200) being obese and 22% (44/200) overweight. Significant weight loss was observed in both gluten free diet (p < 0.0001) and control group (p < 0.05). Mean weight loss in control group was 7.66 ± 1.24 kgs and in gluten free group was 13.03 ± 2.42 kgs. The gluten-free diet was associated with significant weight loss and reduction in WC, WHR (p < 0.001) and both SBP and DBP (p < 0.0001). Significant reduction in SBP in gluten free group with reduction in WC and BMI (p < 0.001). Significant reduction in DBP associated with reduction in WHR, WC and BMI (p < 0.001) after 90 days.

Conclusions:

Gluten-free diet was found to be effective in weight loss and reduction of systolic and diastolic blood pressure in patients with uncontrolled hypertension when consistently followed. Weight loss, reduced WC and WHR on gluten free diet was positively correlated with a reduction in SBP and DBP.
REDUCTION OF ALCOHOL CONSUMPTION CAN DECREASE HOME MORNING BLOOD PRESSURE IN MALE HYPERTENSIVE PATIENTS-OSAKE STUDY
Authors: Akagi Yuya , Kabayama Mai , Tamatani Michio , Tomita Jun , Takiuchi Shin , Yamamoto Koichi , Sugimoto Ken , Rakugi Hiromi , Kamide Kei
Published: April 2021

Objective:

Excess alcohol consumption is supposed to be a strong risk of blood pressure (BP) elevation, therefore the reduction of number of heavy drinkers is an important issue for health promotion. In previous studies, few studies have examined the effectiveness of reduced alcohol intake on BP by improving drinking habits. The aim of this study is to investigate the association between reduced alcohol consumption and changes in home morning BP in male hypertensive patients.

Design and method:

This research was conducted as part of OSAKE Study. The OSAKE study (a randomized controlled trial of saving alcohol amount program for keeping optimal blood pressure control in patients with hypertension) provides outpatient health guidance intervention and verifies its effectiveness on BP reduction. The subjects were 51 men who completed a six-month health guidance intervention or control period. Detailed alcohol consumption per week was inquired and converted to pure alcohol (g). A home BP auto measuring apparatus with auto data communicating system by internet was distributed to patients. To investigate the relationship between changes in alcohol consumption and BP reduction (δSBP, δDBP), multiple regression analysis adjusted for changes in room temperature (δT), the correlation of baseline BP with alcohol consumption was performed.δ

Results:

Mean age in study participants was 64 ± 7.6 years old. After 6 months from baseline, the weekly alcohol consumption decreased significantly from 423.2 ± 288.8 g to 330.2 ± 243.9 g (p < 0.01). Regarding weekly and monthly BP average both systolic BP (SBP) and diastolic BP (DBP) significantly decreased (1week SBP: 142 ± 10.3 to 138.9 ± 13, DBP: 88.1 ± 8.3 to 85.1 ± 9.8, 1 month SBP: 141.3 ± 10.1 to 138.2 ± 12.2, DBP: 87.9 ± 8.4 to 84.8 ± 9.4, respectively p < 0.05). As a result of multiple regression analysis, δalcohol consumption was significantly associated with both δSBP and δDBP for one week and one month (p < 0.05). For covariates, δT and δγGTP were also significantly associated with BP reduction.

Conclusions:

It may be effective for lowering home morning BP to improve drinking habits in male hypertensive patients.
BLOOD PRESSURE LOWERING TREATMENT FOR PREVENTION OF CARDIOVASCULAR EVENTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN INDIVIDUAL-PARTICIPANT DATA META-ANALYSIS
Authors: Pinho-Gomes Ana Catarina Pin , Azevedo Luis , Copland Emma , Canoy Dexter , Nazarzadeh Milad , Ramakrishnan Rema , Berge Eivind , Sundstrom Johan , Kotecha Dipak , Woodward Mark , Rahimi Kazem
Published: April 2021

Objective:

Randomised evidence showing that pharmacological blood pressure (BP) lowering can reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effect of BP-lowering treatment on fatal and non-fatal cardiovascular outcomes in patients with and without AF.

Design and method:

We extracted individual participant data from all trials with over 1,000 person-years of follow-up that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs vs placebo, or to more vs less intensive BP-lowering regimens. We investigated the effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline using fixed-effect one-stage individual participant data meta-analyses based on Cox proportional hazards models stratified by trial.

Results:

Twenty-two trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Patients with AF had lower BP at baseline than patients without AF (143/84 mmHg, SD 21/12mmHg) versus 155/88 mmHg, SD 21/13 mmHg, respectively). Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering, both in patients with and without AF. The hazard ratio for major cardiovascular events was 0.91 in patients with AF (95% confidence interval [0.83 – 1.00]) and 0.91 without AF (95% confidence interval [0.88 – 0.93]) for each 5-mmHg reduction in systolic BP, with no difference between subgroups (p = 0.91) (Figure). Similar patterns were observed for individual components of the composite primary outcome. In patients with AF, there was no evidence that treatment effects varied according to baseline systolic BP or use of specific drug classes.

Conclusions:

BP-lowering treatment reduces the risk of major cardiovascular events in patients with AF to a similar extent to that of patients without AF, even when baseline BP is below recommended treatment thresholds. Owing to their higher absolute cardiovascular risk, treatment in patients with AF is likely to result in greater absolute risk reduction than in patients without AF. Guidelines should be updated to clearly recommend pharmacological BP lowering for prevention of cardiovascular events in patients with AF.
ASSESSMENT OF CARDIOVASCULAR EVENTS IN HYPERTENSIVE PATIENTS AT RISK FOR HEART FAILURE USING GERIATRIC NUTRITIONAL RISK INDEX
Authors: Hashizume Toshikazu , Arita Mikio
Published: April 2021

Objective:

The management of hypertension in heart failure (HF) stage classification A/B is important to prevent the development of symptomatic HF. In addition, malnutrition is commonly prevalent in patients with HF. On the other hand, the relationship between malnutrition and cardiovascular prognosis in hypertensive patients at risk for HF stage A / B has not yet been fully validated. This study aimed to evaluate the association between the Geriatric Nutritional Risk Index (GNRI), one of the most commonly used nutritional indicators, and long-term outcomes in hypertensive patients at risk for HF stage A/B.

Design and method:

We retrospectively investigated 418 hypertensive patients at risk of HF stage A/B. GNRI was calculated at baseline as follows: GNRI = [14.89 × serum albumin (g/dl) + [41.7 × (body weight/body weight at body mass index of 22)]]. Patients were then stratified into tertiles based on GNRI. The study endpoint was a composite of cardiovascular (CV) event, including CV death, non-fatal myocardial infarction, and non-fatal stroke.

Results:

Over a 6.0-year median follow-up, 49 CV events occurred. Using Kaplan-Meier analysis, patients with lower GNRI group (<103.2, n = 139) showed worse prognosis compared with those with middle GNRI group (103.2 to < 111.1, n = 139) and higher GNRI group (>111.1, n = 140) (Chi-square value 10.8; p = 0.005, log-rank test). In the multivariate Cox proportional hazards analysis, lower GNRI group was significantly associated with the incidence of CV events (hazard ratio 2.23, 95% confidence incidence interval 1.14–4.39, p = 0.02) compared with higher GNRI group after adjusting for confounding factors.

Conclusions:

GNRI was significantly associated with CV events in hypertensive patients at risk for heart failure stage A/B. The assessment of GNRI might be a useful index to predict CV events in hypertensive patients at risk for HF stage A/B.
CLINICAL CHARACTERISTICS AND BLOOD PRESSURE TIME-COURSE IN THE YOUNG ACCORDING TO HYPERTENSION SUBTYPE
Authors: Saladini Francesca , Mos Lucio , Vriz Olga , Mazzer Andrea , Fania Claudio , Rattazzi Marcello , Palatini Paolo
Published: April 2021

Objective:

The prognostic significance of different hypertension subtypes in youth is still debated. The aim of the study was to investigate baseline clinical and haemodynamic characteristics and blood pressure (BP) time-course in young subjects with systolic hypertension compared to other hypertension subtypes.

Design and method:

We investigated 1206, 18-to-45-year old subjects from the HARVEST: 81 normotensives (NT), 146 isolated systolic hypertensives (ISH), 281 isolated diastolic hypertensives (IDH) and 698 systolic-diastolic hypertensives (SDH). Baseline haemodynamic and metabolic characteristics, BP and heart rate (HR) changes during a 7-year follow-up were measured. Age-and-sex-adjusted ANCOVA analysis was used for group comparisons.

Results:

ISH were younger and more frequently males compared to others (25.6 ± 6.6 years, p < 0.001), were thinner compared to SDH (24.6 ± 2.6 vs 25.8 ± 3.6 kg/m2, p = 0.028). HR was higher among ISH (75.7 ± 9.4 bpm) and SDH (75.8 ± 9.7) compared to other categories (p < 0.001). ISH were more active in sports (55.5%) compared to others (p < 0.001). Metabolic characteristics were not significantly different among groups. Systolic white-coat effect was higher among ISH (17.6 ± 12.4 mmHg) compared to others (p < 0.001). Cardiac output was significantly higher among ISH (6.3 ± 1.2 ml/min) compared to NT and IDH (p < 0.001); ISH had similar peripheral resistances to NT and lower than IDH and SDH (p < 0.001). Small and large artery compliance was greater and central systolic BP and augmentation index were lower among NT and ISH than IDH and SDH, but differences were not statistically significant (N = 360). During follow-up systolic BP decreased (-7.6 ± 14.4 mmHg) among ISH, while it increased among NT and IDH (p < 0.001). HR decreased in all categories but to a higher extent among ISH (-3.8 ± 10.9 bpm) and SDH (-3.4 ± 10.8 bpm, p = 0.002 versus NT). The percent of patients who started pharmacological treatment during follow-up was: 70.6% among SDH, 54.1% among IDH, 41.1% among ISH, and 39.5% among NT (p < 0.001).

Conclusions:

Young ISH had greater white coat effect, hyperkinetic circulation and lower peripheral resistances compared to other hypertension categories, while arterial distensibility parameters did not differ significantly among groups. Subjects with ISH showed a favourable time-course of BP and HR with a lower percent of subjects needing antihypertensive treatment, suggesting a lower risk profile.