bluuebunny/crossref_metadata_2025 huggingface dataset:
ANGIOTENSIN AT2 RECEPTORS IN THE NUCLEUS OF THE SOLITARY TRACT REDUCE BLOOD PRESSURE VIA INHIBITION OF GABA SIGNALING
Authors: Mohammed Mazher , Sumners Colin , Johnson Dominique , Scott Karen , Krause Eric , De Kloet Annette , Elsaafien Khalid
Published: April 2021

Objective:

Sustained CNS administration of angiotensin AT2 receptor (AT2R) agonists lowers blood pressure (BP) in normal and hypertensive rodents, but the location(s) and mechanism(s) of action are unknown. One locus may be the intermediate solitary tract nucleus (intNTS), which contains a high density of AT2R located on GABA neurons, and it is well-known that increased GABA signaling in the intNTS contributes to increased BP and hypertension. Our studies have revealed that reductions in BP (∼8 mmHg) induced by 2-week intracerebroventricular (icv) infusion of the AT2R agonist C21 (7.5 ng/kg/h) in normotensive mice is associated with significant decreases in gene expression of GABA synthetic enzymes (GAD-1 & GAD-2) in the intNTS. From this, we developed the hypothesis that the depressor action of C21 is mediated through AT2R located on intNTS GABA neurons and a reduction of GABA signaling.

Design and method:

To test this, we engineered a novel mouse line that has Cre-recombinase expression directed to the AT2R gene (AT2R-Cre), and demonstrated that Cre recombinase activity mirrors AT2R mRNA expression within the NTS. Next, we used the Cre-LoxP system and virally (AAV)-mediated gene transfer to direct expression of the light-sensitive excitatory opsin channelrhodopsin-2 (ChR2) and/or eYFP specifically to neurons in the NTS that synthesize AT2R. Using these mice, we performed cardiovascular recordings during optogenetic manipulations (blue light) that selectively excite AT2R-expressing neurons in the intNTS.

Results:

These studies revealed that: (i) Optogenetic stimulation of the AT2R intNTS neurons expressing ChR2 in isoflurane anesthetized mice elicited significant increases in BP compared with control mice that express only eYFP; (ii) The AT2R-containing neurons that were activated by blue light stimulation are GABAergic, as indicated by increased expression and co-localization of c-Fos mRNA with GAD-1 mRNA and eYFP; (iii) Chronic icv infusion of C21 as above significantly blunted the light-induced increases in BP, an effect that was present across all patterns of optical stimulation.

Conclusions:

Collectively, these data indicate that AT2R-mediated decreases in BP involve a blunting of GABA signaling in the intNTS, and suggest that neurons expressing AT2R at this site may be an access point for cardiovascular control.
PREVALENCE AND PREDICTORS OF HYPOTENSION IN NURSING HOME RESIDENTS UNDERGOING AMBULATORY BLOOD PRESSURE MONITORING
Authors: Rivasi Giulia , Tortu’ Virginia , D’Andria Maria Flora , Turrin Giada , Giuliani Evelina , Ceolin Ludovica , Rafanelli Martina , Mossello Enrico , Ungar Andrea
Published: April 2021

Objective:

In nursing home (NH) residents, hypotension may predispose to adverse events including falls, fractures and mortality. Yet, evidence on hypotension detected by ambulatory blood pressure monitoring (ABPM) is scarce in this setting. This study aimed to determine the prevalence and the clinical predictors of ambulatory hypotension in NH residents and to analyze its related ABPM profile.

Design and method:

We retrospectively analysed data from a sample of 100 NH residents undergoing a comprehensive geriatric assessment and ABPM. Ambulatory hypotension was defined as a systolic blood pressure (SBP) drop of 20 mmHg or greater between two consecutive measurements to a minimum SBP < 100 mmHg. Participants with nocturnal hypotension were excluded from the analysis. Predictors of ambulatory hypotension were investigated using multivariate logistic regression adjusted for comorbidities, functional status and hypotensive medications.

Results:

Among 91 residents (mean age 83, 56% female), 50 showed ambulatory hypotension. They had a higher prevalence of heart failure (p = 0.02) and atrial fibrillation (p = 0.007) and more commonly received digoxin (p = 0.001) and benzodiazepines (p = 0.015). At ABPM they had lower 24 h, daytime and nighttime SBP (p < 0.001) and more frequently showed a white coat effect (p < 0.001) and a reverse-dipping profile (p = 0.013). At multivariate analysis, benzodiazepines (OR 4.040), digoxin (OR 19.987) and creatinine  < 1 mg/dl (OR 3.939) were independently associated with ambulatory hypotension.

Conclusions:

Hypotension is common in NH residents undergoing ABPM and more frequently occurs in subjects with lower ambulatory SBP, a reverse dipping profile and a white coat effect. Benzodiazepines, digoxin and low creatinine are predictors of ambulatory hypotension in NH residents.
DYNAMIC CHANGES IN CHILD-TO-ADULT BODY MASS INDEX AND METABOLIC SYNDROME IN MIDDLE AGE: 30-YEAR HANZHONG ADOLESCENT HYPERTENSION STUDY
Authors: Yuan Yue , Mu Ian-Jun , Chu Chao , Zheng Wen-Ling , Wang Yang , Ma Qiong , Hu Jia-Wen , Yan Yu , Liao Yue-Yuan , Chen Chen
Published: April 2021

Objective:

It is well known that body mass index (BMI) developmental patterns from childhood to adulthood are diverse, but few studies have focused on the association between BMI patterns and adult metabolic syndrome. The aim of this study was to identify distinct BMI trajectories and their relationship with metabolic syndrome in the Chinese population.

Design and method:

This study included 4623 participants, aged 6–18 years, from the prospective Hanzhong Adolescent Hypertension Cohort Study, which was established in 1987 and followed up for over 30 years. To address BMI heterogeneity, we used latent mixture modeling to identify developmental patterns related to BMI. Poisson regression models with robust error variance were used to analyze BMI association with adult metabolic syndrome outcomes. After excluding only the first three BMI measurements and the last three BMI measurements, 2679 participants were included in the final analysis, including 1524 males and 1155 females.

Results:

Five distinct developmental BMI patterns were identified in this study: slightly increasing normal (25.9%), moderately increasing normal/overweight (49.9%), progressively overweight/obese (19.8%), resolving (1.8%) and rapidly overweight/obese (2.6%). Compared with the slightly increasing normal group, those who had relatively higher BMI levels had a higher risk of MetS [all risk ratios (RRs) > 4.0, P < 0.05]. Compared with those in the ‘progressively overweight/obese’ group, participants who resolved youth adiposity had lower risks of central obesity, triglycerides and high-density lipoprotein cholesterol [RR = 0.84 (0.68–1.04); RR = 0.86 (0.47–1.57); RR = 0.88 (0.63–1.24), respectively].

Conclusions:

Our study indicated that the developmental patterns of BMI from childhood to adulthood are diverse and that adult BMI lacks stability. Obese subjects have an overall higher risk of MetS than that of subjects with normal BMI. The resolution of youth obesity may have a positive impact on lipid profiles. Early prevention and control of obesity at different stages of life is of utmost importance.
INTENSIVE TREATMENT IS SUITABLE FOR PATIENTS WITH LOW LEVEL OF BLOOD PRESSURE VARIABILITY: A SECONDARY ANALYSIS OF SPRINT
Authors: Tsoi Kelvin , Yiu Karen , Sit Ken , Lee Eric , Wong Samuel
Published: April 2021

Objective:

Visit-to-visit blood pressure variability (BPV) is a predictor of cardiovascular diseases (CVD). The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive hypertensive treatment (targeted at a systolic BP of less than 120 mmHg) can further reduce the risk of CVD and related mortality without additional risk of serious adverse events (SAE). However, the benefit of intensive treatment for patients with different BPV remained controversial.

Design and method:

This study re-analyzed the data from SPRINT through the NHLBI data repository from National Institute of Health. Primary outcomes were cardiovascular related events and mortality. Life-threatening events and hospitalization were reported as the SAE. BPV is defined by the mean absolute residuals of individual linear regression of 18-month BP readings. The k-means clustering, a machine learning algorithm, was applied to stratify subjects into low, medium and high levels of BPV. Patients with primary outcomes in the first 18 months were excluded in this study. Univariate and multivariate analyses were performed to investigate the association between BPV groups and benefits of intensive treatment. Patient's characteristics including age, gender, history of CVD, were treated as confounding factors. Hazard ratios (HR) with 95% confidence intervals (CI) were reported.

Results:

A total of 7,863 subjects were included, in which 1,018 (12.9%), 3,181 (40.5%) and 3,664 (46.6%) were classified into low, medium and high levels of BPV, respectively (Figure 1). In the multivariate analyses, intensive treatment showed to have a significant reduction on primary outcomes for those with low level of BPV (HR 0.59; 95% CI, 0.40–0.89), but not for those with medium and high levels of BPV (Table 1). SPRINT reported that intensive treatment did not increase risk of SAE, but this study found an increased risk of SAE among patients with high level of BPV (HR 1.24; 95% CI, 1.02–1.52).

Conclusions:

Intensive treatment only shows the cardiovascular benefit on the patients with low level of BPV, but it increases risk of SAE for those with high level of BPV. Personalized recommendation on the use of intensive treatment should be recommended.
DIURNAL RHYTHM AND SALT RESPONSIVE RESHAPING OF GUT MICROBIOTA CORRELATES WITH HYPERTENSION
Authors: Chakraborty Juthika Mandal Saroj , Cheng Xi , Galla Sarah , Hindupur Anay , Saha Piu , Yeoh Bang San , Mell Blair , Yeo Ji -Youn , Vijay-Kumar Matam , Yang Tao , Joe Bina
Published: April 2021

Objective:

Aberrant diurnal rhythms of Blood Pressure (BP) are well known to be associated with hypertension, however, whether rhythmicity of microbiotal composition is associated with salt sensitive hypertension remains unknown. We hypothesized that BP and gut microbiotal composition follow synchronous rhythms in high salt fed Dahl Salt Salt-Sensitive (S) rats and contribute to the progression of hypertension.

Design and method:

To test this hypothesis, we examined groups of Dahl S rats for their diurnal rhythms of both the gut microbiota and blood pressure in low salt (0.3%) and high salt (2%) conditions.

Results:

In high salt fed animals, Firmicutes/Bacteroidetes (F/B) ratio significantly changed between the dark (active) and light (rest) phases, which correlated with the diurnal rhythmicity of BP suggesting salt mediated rhythmic regulation of microbiota. Diurnal rhythms of Firmicutes, Bacteroidetes and Actinobacteria were independently associated with BP and significant in high salt fed animals. Discrete genera were observed to correlate independently or interactively with one or more of the following 3 factors- 1) BP rhythm, 2) dietary salt, 3) amplitude of BP. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUST) analysis revealed diurnal rhythmicity of microbiotal pathways. During the active phase of the host, microbiota upregulated biosynthetic processes whereas during the resting phase of the host, microbiota upregulated degradation pathways of metabolites. These diurnal changes in microbiota, their functional pathways and BP response were prominently associated with a concerted rhythmicity of renal Lipocalin 2 and Endothelin1.

Conclusions:

Collectively, these data demonstrated the existence of synchronous diurnal rhythms of BP and renal inflammation with diurnal reshaping of gut microbiota in salt-sensitive hypertension. Such a concerted rhythmicity with peaks observed at the mid-active phase suggests that targeting this timepoint to reshape microbiota and/or intervene with medication could benefit hypertensives.
BENEFICIAL EFFECTS OF WEEKLY WALKING ACTIVITY ON HYPERTENSIVE MEDIATED ORGAN DAMAGE IN THE COMMUNITY-DWELLING ELDERLY CHINESE: THE NORTHERN SHANGHAI STUDY
Authors: Lyu Yuyan , Zhang Yi , Chi Chen , Yu Shikai , Xu Yawei
Published: April 2021

Objective:

To investigate the effects of weekly walking activity on the asymptomatic hypertensive mediated organ damage (HMOD) remains unclear.

Design and method:

2830 community-dwelling elderly subjects (over 65 years) in northern Shanghai were recruited from June 2014 to June 2018. Weekly walking activity was evaluated by standard questionnaire based on the International Physical Activity Questionnaires-short form (including walking duration per time and walking days per week). Within the framework of comprehensive cardiovascular examinations, HMOD, including left ventricular mass index (LVMI), peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima-media thickness (CIMT), arterial plaque, creatinine clearance rate (CCR), urinary albumin-creatinine ratio (UACR), carotid-femoral pulse wave velocity (cf-PWV) and ankle-brachial index (ABI), were all evaluated.

Results:

There were 1862 (65.8%) participants enrolled in weekly walking activity, with 56.8 ± 36.8 min/day and a median of 6.71 days/week walking. Young elderly, fewer smokers, lower CIMT, lower cf-PWV, fewer abnormal ABI, lower prevalence of hypertension and coronary heart disease were observed in walking activity group (P < 0.05). Similarly, Pearson's correlation analysis revealed that weekly walking activity was significantly correlated with elderly (age 70 years or more) and smoker (both P < 0.05). To further investigate the association of weekly walking activity with HMOD, logistic regression analysis was conducted. Interestingly, weekly walking activity was only significantly associated with peripheral artery diseases (P < 0.05), together with cardiovascular risk factors. Subsequently, subgroup analysis about weekly walking activity was performed and the results revealed that only walking duration more than 30 min per time was related to arterial plaque (OR: 1.048, 95% CI: 1.002–1.095, P = 0.038).

Conclusions:

Taken together, in the community-dwelling elderly Chinese, weekly walking activity played a protective role in HMOD, especially vascular HMOD, regardless of walking duration per time and walking days per week.
GENETIC SUSCEPTIBILITY, ELEVATED BLOOD PRESSURE AND RISK OF ATRIAL FIBRILLATION
Authors: Nazarzadeh Milad , Pinho-Gomes Ana-Catarina , Bidel Zeinab , Canoy Dexter , Dehghan Abbas , Byrne Karl Smith , Bennett Derrick A. , Smith George Davey , Rahimi Kazem
Published: April 2021

Objective:

Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual's genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk.

Design and method:

First, causality of association was assessed through two-sample Mendelian Randomization (MR), using data from two independent genome-wide association studies that included a total of one million European population. Second, UK Biobank individual participant data of 329 237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with BP-lowering drug classes on AF risk was predicted through genetic variants in druggable genes that code proteins related to the function of each drug class. Estimated drug effects were compared with effects on incident coronary artery disease, for which direct trial evidence exists.

Results:

The two-sample MR analysis indicated that on average each 10-mmHg increment in systolic BP increased the risk of AF (odds ratio [OR]: 1.23 [1.11 to 1.36]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF (Figure). The indirect comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin converting enzyme inhibitors, beta-blockers and calcium channel blockers) suggested similar average effects for prevention of atrial fibrillation and coronary heart disease.

Conclusions:

The association between elevated BP and higher risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility.
COMBINATION OF SYSTOLIC BLOOD PRESSURE AND NON-HIGH-DENSITY LIPOPROTEIN CHOLESTEROL IS A MAJOR COMPONENT OF THE RISK SCORE FOR LATENT HEART FAILURE: THE SUITA STUDY
Authors: Kokubo Yoshihiro , Higashiyama Aya , Watanabe Makoto , Honda-Kohmo Kyoko , Miyamoto Yoshihiro
Published: April 2021

Objective:

There are few population-based prospective studies on heart failure (HF) in non-Western populations. We developed a novel risk score for incident latent HF (LHF) in a general Japanese population.

Design and method:

We prospectively followed-up 2,809 Suita Study subjects for incident LHF (age 66.7 ± 10.4 years, initially free of LHF). We calculated the non-HDL cholesterol levels by subtracting the HDL cholesterol from the total cholesterol. B-type natriuretic peptide (BNP) was measured by the CLEIA method. LHF was defined as BNP > = 100 pg/mL or HF medication from medical records. Each subject's health status and BNP were checked in biannual medical examinations, and all subjects completed annual questionnaires. We conducted a Cox proportional hazard model for incident LHF after adjusting for cardiovascular risk factors. The model discrimination was evaluated by the area under the receiver operating characteristic curve.

Results:

In 18,134 person-years of follow-up, 335 incident LHF events occurred. Compared to SBP < 120mmHg with non-HDLC > = 140 mg/dL, the adjusted hazard ratios (95%CI) for LHF were 1.6 (1.1–2.3), 1.9 (1.1–3.1), and 2.4 (1.6–3.6) for systolic hypertensives (sHT > = 140 mmHg) with non-HDLC > = 140 mg/dL and systolic prehypertensives (120–139 mmHg) and sHT with low non-HDLC (<140 mg/dL). We developed a scoring system for each risk factor as follows: 0, 3, 6, and 9 points for subjects in their 40–50 s, 60 s, 70 s, and 80 s, respectively; 3 points for atrial fibrillation; 2 points for cardiac murmur, coronary heart disease, or cerebral infarction; 2 points for sHT with non-HDLC > = 140 mg/dL and for systolic prehypertensives with low non-HDLC; 3 points for sHT with low non-HDLC; and 1 point for a glomerular filtration rate < 45 mL/min/1.73m2 and excessive drinker (> = 4 units/day) (C-statistic 0.727, 95% CI: 0.699–0.755). For example, individuals scoring 3 and 13 points had 2%, and 39% predicted the probability of developing LHF in 5 years, respectively.

Conclusions:

We developed a risk score to predict the 5-year incident LHF risk using variables that are conveniently available in a health examination. This risk score can be used to identify individuals at higher risk of LHF and to consult a doctor and encourage lifestyle improvements before the onset of HF.
EFFECT OF BLOOD PRESSURE OPTIMISATION ON ENDOTHELIAL FUNCTION IN PATIENTS WITH ATRIAL FIBRILLATION AND HYPERTENSION
Authors: Khan Ahsan Aftab , Thomas Graham Neil , Lip Gregory
Published: April 2021

Objective:

Hypertension accounts for more cases of atrial fibrillation (AF) than any other risk factors. AF and hypertension commonly co-exist and both are associated with endothelial dysfunction. FMD measurement using a high-resolution ultrasound has become a reliable and reproducible technique for assessment of endothelial dysfunction. To investigate whether optimising of blood pressure (BP) in patients with hypertension and AF leads to improvement in FMD.

Design and method:

In a longitudinal comparison, we recruited 30 participants with hypertension and permanent AF. Each participant had 3 serial BP readings and an echocardiogram. Their drug history was noted. High-resolution ultrasound was used to measure brachial artery diameter at rest and during reactive hyperaemia (endothelium-dependent FMD). Participant's BP medication was optimised according to their BP. Participants were then followed them up after 8 weeks for repeat FMD measurements. Data analysis was carried out using paired t-test on SPSS.

Results:

Following optimisation of BP medication, patients with permanent AF and hypertension were followed up after 8 weeks and FMD repeated. There was significant improvement in mean heart rate (77 ± 18 (baseline) vs 72 ± 17 (follow up), p = 0.01), systolic BP (140 mmHg [128 – 148] (baseline) vs 131 mmHg [122 – 146] (follow up), p = 0.03), diastolic BP (81 mmHg ± 13 (baseline) vs 77 mmHg ± 12 (follow up), p = 0.02) and mean arterial pressure (MAP) (100 mmHg ± 9 (baseline) vs 97 mmHg ± 13 (follow up), p = 0.01). Both groups had a similar baseline brachial artery diameter (p = 0.34). Endothelium-dependent FMD response was better following 8 weeks of BP optimisation but this was not significant (3.1%, 95% CI [2.3 – 4.8] (baseline) vs 5.2%, 95% CI [3.9 – 6.5] (follow up), p = 0.09). No variables were identified on univariate or multivariate analysis as independent predictors of FMD.

Conclusions:

Endothelial dysfunction can be improved following optimisation of BP medication suggesting modulation of endothelial function is possible in patients with permanent AF and hypertension. Longer-term improvement in FMD may have a prognostic implication.
NATIONWIDE SPATIOTEMPORAL TRENDS IN BLOOD PRESSURE AND THE ATTRIBUTABLE CARDIOVASCULAR BURDEN FROM 2005 TO 2018: A POOLED ANALYSIS OF 13.1 MILLION PARTICIPANTS IN CHINA
Authors: Kang Yuting , Wang Xin , Yin Peng , Chen Zuo , Jiang Linlin , Dong Wenlan , Zhang Linfeng , Zheng Congyi , Zhou Maigeng , Wang Zengwu , Gao Runlin
Published: April 2021

Objective:

The current study was performed to estimate the temporal trend and geographic disparities in blood pressure and thus to provide accurate population attributable fraction (PAF) of cardiovascular disease (CVD) burden attributable to raised blood pressure at national and provincial in China, which is crucial to inform and improve BP control measures.

Design and method:

For this analysis, we pooled three national large population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 2005 to 2018 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 2877 counties of 31 provinces in China. Data from a prospective cohort from 2002–2019 selected randomly from China Hypertension Survey, enrolling more than 30 000 individuals aged 35 years or over without CVD at baseline, was used to calculate the multivariable-adjusted HRs by Cox regression. HRs along with the blood pressure levels, were used to calculate the attributable burden of CVD.

Results:

We pooled 13.1 million adults to estimate blood pressure. The national systolic and diastolic BP was 136.7 and 83.8 mmHg. The systolic and diastolic BP slightly decreased from 2005 to 2018 in national level, while increased in several provinces with lower socioeconomic levels. As for PAF, the national PAFs for CVD associated with hypertension was 17.85% and 24.66% for male and female, respectively. At provincial level, the PAFs ranged from 24.17% in Beijing to 12.13 % in Hunan for male, 31.49% in Beijing to 19.05% in Jiangxi for female, there were 3 provinces (Beijing, Tianjin and Shanghai) with PAFs over 29.00%, while in another three provinces (Hunan, Jiangxi, and Guangxi), the PAF was lower than 15.00%. The PAF was higher among those younger than 65 years compared with those 65 years or older.

Conclusions:

The highest blood pressure levels have shifted from high-income provinces to low-income provinces, with remarkable provincial-level disparity in CVD burden attributable to hypertension. Regional targeted considerations may help to further tailor BP control strategies for reducing the burden of CVD and disparity.
BIOCHEMICAL, HISTOPATHOLOGICAL, AND GENETIC CHARACTERIZATION OF POSTURE RESPONSIVE AND UNRESPONSIVE ALDOSTERONE-PRODUCING ADENOMAS
Authors: Guo Zeng , Nanba Kazutaka , Mcwhinney Brett C. , Ungerer Jacobus P. , Wolley Martin , Gordon Richard D. , Rainey William E. , Stowasser Michael
Published: April 2021

Objective:

Aldosterone-producing adenoma (APA) accounts for ∼30% of primary aldosteronism. Based on responses of aldosterone to upright posture, APA can be divided into posture-responsive and –unresponsive forms. Somatic gene mutations in KCNJ5, CACNA1D, ATP1A1, or ATP2B3 have been reported to exist in more than 90% of APAs. We sought to compare the biochemical, histopathological, and genetic characterization between these two types of APAs.

Design and method:

Posture-responsive was defined as showing a rise in plasma aldosterone concentration of at least 50% 2 - 3 h after the assumption of upright posture (10 AM) above the basal level (7 AM) following overnight recumbency. Plasma levels of aldosterone and hybrid steroids (18-oxocortisol and 18-hydroxycortisol) were measured by LC-MS/MS. Histologic analysis and immunohistochemistry for CYP11B2 (aldosterone synthase) and CYP17A1 (17aplha-hydroxylase) were performed on APA tissue sections collected from 24 posture-unresponsive and 17 posture-responsive APA patients. Sanger sequencing of KCNJ5 and gene targeted next-generation sequencing were performed to detect somatic gene mutations.

Results:

Compared to patients with posture-responsive APA (of which 48.7% were composed of zona glomerulosa (ZG)-like cells and 35.3% showed ZG-zona fasciculata (ZF) mixed appearance), posture-unresponsive APA patients displayed higher (P < 0.01) levels of hybrid steroids, recumbent aldosterone and cortisol, greater (P < 0.05) suppression of aldosterone secretion from the contralateral unaffected adrenal, and larger (P < 0.01) tumors mostly composed of ZF-like cells that had higher (P < 0.01) expression of CYP17A1 (but not of CYP11B2). Of 41 studied APAs, 37 (90.2%) harboured aldosterone-driving somatic mutations (KCNJ5 = 14, 34.1%; CACNA1D = 13, 31.7%; ATP1A1 = 8, 19.5%; and ATP2B3 = 2, 4.9%), including 5 that were previously unreported (3 in CACNA1D and 2 in ATP1A1). Interestingly, 64.7% (11/17) of posture-responsive APAs carried CACNA1D mutations, whereas 54.2% (13/24) of posture-unresponsive APAs harboured KCNJ5 mutations.

Conclusions:

The excessive production of hybrid steroids by posture-unresponsive APAs may relate to their ZF-like tumor cell composition, resulting in strong expression of CYP17A1 (in addition to somatic gene mutation-driven CYP11B2 expression), thereby allowing production of cortisol which acts as the substrate for CYP11B2-generated hybrid steroids.
IIMAGING OF PRIMARY ALDOSTERONISM IN YOUNG PATIENTS FROM A LARGE INTERNATIONAL STUDY (AVIS-2-YOUNG)
Authors: Rossi Gian Paolo , Crimi’ Filippo
Published: April 2021

Objective:

Purpose The Endocrine Society guidelines suggested skipping adrenal vein sampling (AVS) when referring for surgery young PA patients with a unilateral adrenal nodule and a contralateral normally appearing gland at imaging, but this was based on a limited set of cases. Hence, we sought to determining if imaging provided an accurate identification of unilateral PA.

Materials and Methods:

We examined the large cohort of patients ?45 years-old recruited in the AVIS-2-Young study. Biochemical cure of PA after unilateral adrenalectomy was used as the final diagnosis to assess imaging diagnostic accuracy.

Results:

Among the 1625 AVIS-2 patients those ?45, 40 and 35 years-old were 29.0%, 15.5% and 6.1%, respectively. In the same age cohorts, a unilateral adrenal nodule was found in 53.2%, 57.3% and 47.3%; 42.6%, 38.5% and 50.9%, respectively, showed no nodules and 4.2%, 4.2% and 1.8% bilateral nodules. In those with a unilateral nodule, the culprit adrenal was identified in 81.4%, 84.1%, and 92.3% of the patients. Youden index analysis identified ? 38 years as the best cut-off for unilateral PA identification; by restricting the analysis to those with a nodule size to > 10 mm, the overall concordance was 94.0%. However, bilateral or no nodules were detected at imaging in > 37% of the patients with a final diagnosis of unilateral PA in all age cohorts.

Conclusion:

Referring PA patients ?45, 40 and 35 years-old based on a unilateral nodule at imaging carried a likelihood of wrong/inappropriate surgery in 18.6%, 15.8% and 7.7%, respectively. This error rate can be minimized to 6.0% by selecting patients ?38 years with a nodule > 10 mm. However, in these age cohorts up to 1/3 of the patients, who had unilateral surgically curable PA were not detected with imaging.
ATRIAL SEPTAL ANEURYSM IN ADULTS – IS IT A DEGENERATIVE HEART DISEASE?
Authors: Ejim Emmanuel , Ubani-Ukoma Chidi , Ugwu Collins , Njoku Paschal
Published: April 2021

Objective:

Atrial septal aneurysm (ASA) is a localised “saccular” deformity of the interatrial septum, generally at the level of the fossa ovalis, which protrudes to the right or the left atrium or on both sides. It is a well recognised cardiac abnormality that was previously diagnosed on autopsy only, but it is now frequently picked up on routine echocardiography or during evaluation of ischemic stroke. There is a dearth of data on atrial septal aneurysm in our environment, and the authors set out to find the common cardiac abnormalities associated with atrial septal aneurysm in adults who had transthoracic echocardiographic examination in Enugu, South-East Nigeria

Design and method:

Conquest Medical Imaging is a private medical diagnostic centre in Enugu, South-East Nigeria. The centre offers radiologic and ultrasonography diagnostic services. The echocardiographic records of 1390 patients done over a 4-year period were retrospectively reviewed. The examinations were done with a Logic 500MD Echocardiographic machine made by General Electric. Data obtained from the echocardiography register included presence of atrial septal aneurysm, age, gender, other cardiac abnormalities present.

Results:

A total of 1174 adults had echocardiographic examination during the period under review, and consisted of 667 males and 507 females. The mean age of the males was 43.1 ± 6.2 years, while the mean age of the females was 45.9 ± 7.1 years.

Atrial septal aneurysm was present in 28 patients representing 0.2% of the total adult population, and made up of 11 males and 17 females. 25 patients had one or more additional cardiac abnormalities, representing 89.3% of all patients with atrial septal aneurysm. Degenerative aortic valve disease, degenerative mitral valve disease, and left ventricular diastolic dysfunction were the cardiac abnormalities noted in addition.

Conclusions:

The frequent association of degenerative valvular heart diseases with atrial septal aneurysm in adults may suggest that atrial septal aneurysm has a degenerative aetiology in adults.
OBESITY PARADOX AND HYPERTENSION: NEW INSIGHTS IN HEART FAILURE PATIENTS
Authors: Imprialos Konstantinos , Koutsampasopoulos Konstantinos , Stavropoulos Konstantinos , Katsimardou Alexandra , Patoulias Dimitrios , Toumpourleka Maria , Bakogiannis Konstantinos , Bouloukou Sofia , Manafis Alexandros , Ziakas Antonios , Papadopoulos Christodoulos , Vassilikos Vassilios , Karagiannis Asterios , Doumas Michael
Published: April 2021

Objective:

Heart failure (HF) is more prevalent among obese and overweight individuals than among normal weight people, although there is a survival advantage for obese and overweight patients compared with normal weight or low weight patients, the so-called obesity paradox in HF. On the other hand, obesity increases the risk of hypertension and the relationship between HF and hypertension is well-established; however, the prognostic role of obesity has not been investigated sufficiently in hypertensive HF patients.

Design and method:

Patients with HF were evaluated in a cross sectional study. Office blood pressure (BP), both systolic (SBP) and diastolic (DBP), the duration in years from the first diagnosis of hypertension and body mass index (BMI) were recorded as well. The prognostic role of obesity was evaluated according to the number of hospitalizations for HF in the last six months and in the last year.

Results:

A total of 306 consecutive male patients with HF participated in the study. Overweight were 45,8%, obese 37,2% and normal weight 16,9% of patients according to BMI. Both SBP and DBP had a negative correlation with the number of hospitalizations for HF in the last six months and in the last year (r = -0.174, p = 0.008, r = -0.190, p = 0.004 for systolic, and r = -0,130, p = 0.049, r = -0.155 and p = 0.018 for diastolic, respectively). Overweight, obese and lean participants did not differ in BP, both SBP and DBP, and in their HF morbidity according to hospitalizations (p = 0.075, p = 0.271, and p = 0.407, respectively). Patients with hypertension had higher values of BMI (p = 0.032), but office SBP and DBP did not have any correlation with BMI. Also, BMI did not differ among patients with or without hypertension, and although BMI had a negative correlation with the number of hospitalization for HF, that was not significant (r = -0.062, p = 0.346).

Conclusions:

Our study provides some new insights regarding to the relationship between obesity and office BP in HF patients. Obese is highly prevalent in HF patients with or without hypertension, but the association between BMI and morbidity according to the number of hospitalizations has not been found to be significant in hypertensive patients.
META-ANALYSIS EVALUATING THE RISK OF ATRIAL FIBRILLATION WITH NEWER ANTIDIABETICS ACROSS THE CARDIOVASCULAR AND RENAL OUTCOME TRIALS
Authors: Patoulias Dimitrios , Toumpourleka Maria , Katsimardou Alexandra , Imprialos Konstantinos , Stavropoulos Konstantinos , Koutsampasopoulos Konstantinos , Mavridou Maria , Siskos Fotios , Papadopoulos Christodoulos , Doumas Michael
Published: April 2021

Objective:

Patients with type 2 diabetes mellitus (T2DM) experience a significantly increased risk for atrial fibrillation (AF) compared to unaffected subjects. The latter confers to increased risk for heart failure, all-cause and cardiovascular mortality. Notably, even patients with sufficient glycemic control feature an increased risk for AF. Thus, it seems to be of interest whether antidiabetic treatment can affect the risk for AF among patients with T2DM.

Design and method:

We searched PubMed from its inception to 2 October 2020. We sought to determine the risk of AF with the use of newer antidiabetics, namely dipeptidyl-peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, extracting corresponding data from the published cardiovascular and renal outcome trials. We assessed the risk for AF with each drug class separately.

Results:

We pooled data from 4 trials with DPP-4 inhibitors versus placebo or active comparator in a total of 34,884 patients, from 7 trials with GLP-1RAs versus placebo in a total of 55,943 patients and from 7 trials with SGLT-2 inhibitors versus placebo in a total of 55,966 patients. Risk of bias is considered as low across all selected studies. DPP-4 inhibitor treatment resulted in a non-significant decrease in the risk for AF, equal to 7% (RR = 0.93, 95% CI; 0.75 to 1.16, I2 = 1%). Similarly, GLP-1RA treatment produced a non-significant decrease in the risk for AF, equal to 12% (RR = 0.88, 95% CI; 0.76 to 1.03, I2 = 29%). Notably, SGLT-2 inhibitor treatment significantly decreased the risk for AF 19% (RR = 0.81, 95% CI; 0.69 to 0.95, I2 = 0%).

Conclusions:

Collectively, newer antidiabetics do not confer an increased risk for AF among patients with T2DM, while, SGLT-2 inhibitors seem to be protective, providing an additional cardiovascular benefit, besides the well-established ones.
PREDICTION OF LEFT VENTRICULAR REMODELING IN PATIENTS WITHOUT CARDIOVASCULAR DISEASE THROUGH MACHINE LEARNING: AN ECG-BASED APPROACH
Authors: Angelaki Eleni , Marketou Maria , Barbaris George , Patrianakos Alexandros , Parthenakis Fragiskos , Tsironis George
Published: April 2021

Objective:

Cardiac remodeling -even at early stages-is considered an important aspect of cardiovascular disease progression and is therefore emerging as a significant therapeutic target. We used machine learning (ML) techniques and investigated several ML classifiers built on basic clinical parameters and ECG features for detecting left ventricular remodeling (LVR), even at the early stages before the onset of LVH in a population without cardiovascular disease

Design and method:

We enrolled 475 subjects with and without essential hypertension and no other indications of cardiovascular disease. Based on left ventricular mass index (LVMi) and relative wall thickness (RWT), calculated using echocardiography, the subjects were classified into 3 groups; those with normal geometry, concentric remodelling, concentric and eccentric left ventricular hypertrophy (LVH). We trained a Random Forest, i.e. a nonlinear predictive ML model suitable for panel data, to classify subjects either in the normal group, or in the other three combined (LVH and both types of left ventricular hypertrophy-LVH). We also perform feature importance and feature interaction analysis by calculating SHAP values, a game theoretic tool that helps in interpreting the model's predictions.

Results:

Hypertension, age, and body mass index (BMI) were the most significant features, as expected. Additionally, a combination of BMI and Sokolow criteria as well as the areas under the QRS complex and the QTc duration, among others, were also important. The age of 65 marked a sharp change in the risk of being classified with LV remodelling and LVH. The random forest model was able to distinguish normal subjects from the ones with LVR and LVH with accuracy 80%, specificity 65% and sensitivity 91%.

Conclusions:

We found promising clinical and ECG features in the direction of machine based assistance in the detection of LVR even at early stages before the onset of LVH. Strategic and innovative solutions are needed to improve hypertension management, especially in primary care settings and our data indicate that ML may improve risk stratification of hypertensive population with simple clinical approaches.
UROCORTIN 2 LEVEL AND BLOOD PRESSURE VALUES IN PATIENTS WITH NEWLY DIAGNOSED HYPERTENSION
Authors: Walczewska Jolanta , Dzieza-Grudnik Anna , Siga Olga , Wizner Barbara , Wolkow Pawel , Gryglewska Barbara , Grodzicki Tomasz
Published: April 2021

Objective:

Urocortin 2 (Ucn2)is a peptide hormone having favorable hemodynamic actions. Lowering in blood pressure and in peripheral vascular resistance as well as vasodilating effect of ucn2 are considered to be important and interesting.

The aim of the study was to assess serum concentration of Ucn2 in patients with newly detected hypertension without pharmacotherapy.

Design and method:

We examined 71 participants (group I – healthy, group II newly diagnosed hypertension without treatment). All patients underwent 24-hour ambulatory blood pressure monitoring (SpaceLabs90207), anthropometric measurements, biochemical test, ucn2 blood level assessment.

Results:

Conclusions:

Subjects with higher level of UCN 2 have lower values of night DBP in ABPM, however other parameters of ABPM monitoring were not associated with levels of serum Ucn2.

Higher Ucn2 level may play a role in lowering blood pressure in patients with essential hypertension.

Not showing such a relation to daily BP values may suggest the disturbing effect of many environmental and life style factors on daily BP values.
ALPHA-GST AS A TUBULAR BIOMARKER IN EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN CARDIAC SURGERY
Authors: Santos Ana Carolina Casinhas Dos , Matos Andreia , Raimundo Mário , Madureira Ana Isabel , Malcato Ester , Côrte-Real Hugo , Gameiro Joana , Nobre Ângelo , Bicho Manuel , Almeida Edgar
Published: April 2021

Objective:

Acute Kidney Injury(AKI) is a frequent complication in cardiac surgery, leading to an increase in morbility/mortality. The monitorization of the creatinine after the procedure is recommended, however, new tubular biomarkers may allow earlier diagnosis of AKI(a few hours after the procedure, against the 24/48 hours standard). Glutathione S-transferase(GST), cytoplasmic enzymes involved in detoxification of free radicals, are presented in the proximal contoured tube. The aim of this study is to evaluate the use of a single alpha-GST determination at 3 h after surgery, to early diagnosis of AKI.

Design and method:

Cohort, prospective and observational study, with adults submitted to elective cardiac surgery (valvular/coronary), without chronic kidney disease. Blood and urine samples were collected simultaneously before(T0) and within 3 hours after surgery(T1). The levels of alpha-GST were determined in the urine samples by ELISA and normalized to urinary creatinine(UCr). The variation of alpha-GST was calculated using the difference between T1 and T0(T1-T0). Demographic, clinical and surgical-related data was collected. For statistical analysis, Chi-square and Mann-Whitney test were used. The ROC curve was generated in order to evaluate the discriminative power of the biomarker. P < 0.05 was statistically significant.

Results:

This study included 17 patients(11 male and 6 female), with 88.2% submitted to valvular surgery, with a mean age of 63.4 ± 14.3 years. Before the procedure, 82.4% of the patients had hypertension. After 48 hours surgery, using as gold standard the KDIGO classification, 6 patients presented AKI stage 1(75%) and 2(25%) stage 2. The mean arterial blood pressure was higher before surgery(T0: 90.0[74.5–103.3] vs T1: 64.5[57.2–80.7], p = 0.05). The increase of alpha-GST levels were associated to presence of AKI(p = 0.05). This increase remains when associated with the variation of alpha-GST(T1-T0) without and with AKI (- 0,002[-0.02–0.004]vs -0.02[0.009–0.04], respectively, p = 0.003). In the ROC curve, this variation had a AUC = 0.958(p = 0.05) and AUC = 0.854(p = 0.028) for the cut-off of the alpha-GST variation. These biomarkers present 78%-specificity and 75%-sensibility.

Conclusions:

alpha-GST is a promising biomarker to the early diagnosis of AKI after cardiac surgery with only one determination, contributing to this diagnosis before an increase of serum creatinine. Preventing costs and therapeutic options.
URINARY UROMODULIN DIRECTLY AND INDIRECTLY CONTRIBUTE TO LEFT VENTRICULAR HYPERTROPHY IN MIDDLE-AGED PREHYPERTENSIVES
Authors: Josipovic Josipa , Simicevic Livija , Milicic Borna , Domislovic Viktor , Vrsalovic Mislav , Jelakovic Bojan
Published: April 2021

Objective:

Recent GWAS studies found uromodulin gene polymorphisms to be associated with hypertension and atrial remodeling. This study analysed urinary uromodulin (UM), sodium excretion, blood pressure (BP) and echocardiogram in a group of middle-aged non-treated subjects.

Design and method:

We included 326 apparently healthy subjects (mean age 37). According to JNC-7 optimal BP (OBP), prehypertension (PHT) and hypertension (HT) were diagnosed in 103 subjects (72% m), 143 subjects (43% m), and 80 subjects (38% m), respectively. Fasting blood and urine samples were obtained and office and ambulatory BP were measured in all subjects. Sodium excretion was determined from the 24h-urine specimens in a subgroup of 175 subjects. All echocardiograms were performed by the same co-author. UM an alpha1 microglobulin (A1 M) from the morning spot urine sample were determined by ELISA (Cobas Roche, BioVendor) and Siemens Dade Behring BN II Nephelometer (Siemens, Germany), and were corrected to urine creatinine, respectively.

Results:

Nonsignificant trend to higher nonindexed UM (nUM, mg/ml) were found in HT/PHT compared to OBP, and opposite trend was observed for indexed UM (iUM, mg/g creatinine). nUM and iUM correlated positively with ABPM parameters in OBP group, but negatively in HT. In OBP and PHT groups iUM correlated positively with fractional sodium excretion (FENa) (Rho 0.272; P = 0.01) and FENa (Rho 0.208; P = 0.02), respectively, as well as with A1mCR (Rho 0.317; P < 0.001) and (Rho 0.347; P < 0.001), respectively. There were significant differences in interventricular septum diameter (IVSd) between first and second/ third terciles of nUM in the OBP group (P = 0.02) and first and third terciles in the PHT group (P = 0.04). nUM correlated positively with left ventricule mass (LVM) (Rho 0.221; P = 0.01) and IVSd (Rho 0.191; P = 0.03) in the whole group. In the PHT group nUM correlated positively with IVSd (Rho 0.399; P < 0.001).

Conclusions:

Positive association of UM with LVM suggests effect of uromodulin on left ventricule remodeling in middle-aged non-treated subjects.
EFFECT OF CUFF-INFLATION ON BLOOD PRESSURE, SLEEP EFFICIENCY AND AROUSAL: A SUBANALYSIS OF THE VAST STUDY
Authors: Socrates Thenral , Krisai Philipp , Meienberg Andrea , Mayr Michael , Burkard Thilo , Vischer Annina
Published: April 2021

Objective:

Standard cuff-based devices (RefBP) are the gold standard for 24 hour blood pressure (BP) measurement, however the repeated inflations may be distressing for patients especially at night. A cuffless blood pressure measurement device (TestBP) using pulse transit time for beat-to-beat calculation of BP is in clinical use. We investigated the effect of RefBP cuff-inflations on asleep measurements taken simultaneously with the TestBP including BP, sleep efficiency and arousal.

Design and method:

Cuffless and standard cuff-based 24 h BP measurements were simultaneously performed on both arms. TestBP was calibrated with the initial cuff-based measurement. A subgroup analysis was carried out on 21 participants who 1–4 days later had measurements repeated only with the TestBP device. Comparisons were made between the asleep simultaneous measurements RefBP/TestBP and the TestBP alone for systolic and diastolic asleep BP, sleep efficiency, total arousals during sleep and arousal during sleep per hour. Asleep was defined as time in bed as protocolled by the participant. According to current guidelines, asleep hypertension was defined as >=120/70 mmHg.

Results:

21 individuals were prospectively enrolled. Mean (±standard deviation (SD)) age was 49(±15) years and 57% were female. Mean (± SD) systolic asleep BP for the RefBP/TestBP and TestBP were 131(±21.7) and 131.2(±26) respectively. Mean diastolic asleep BP values for RefBP/TestBP and Test BP were 80(±14) and 83.7(±14.2). Wilcoxon signed rank test showed no significant difference when comparing mean systolic or diastolic asleep BP of RefBP/TestBP and TestBP (p = 0.86, p = 0.11 respectively). However when classifying the two groups into hypertensive or normotensive, there were significantly more systolic hypertensive classifications with RefBP/TestBP simultaneous measurements than with TestBP alone (p = 0.025, Fig1). There was no significant difference seen in sleep efficiency between the two groups (p = 0.117). There were significantly less total arousals with the TestBP alone (p = 0.040).

Conclusions:

We showed that simultaneous measurements with RefBP/TestBP may lead to more patients being labelled as having nocturnal systolic hypertension, potentially caused by more arousals from the cuff inflations of the RefBP. However, further studies are needed to identify the effects of cuff inflations on arousals and nocturnal hypertension.