bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.