bluuebunny/crossref_metadata_2025_split huggingface dataset:
OBSTRUCTIVE SLEEP APNEA AND PRIMARY ALDOSTERONISM: A MULTICENTER CROSS-SECTIONAL STUDY
Authors: Buffolo Fabrizio , Li Qifu , Monticone Silvia , Heinrich Daniel A. , Mattei Alessio , Pieroni Jacopo , Mei Mei , Yang Shumin , Hu Ya -Hui , Yang Mei -Chen , Sabbadin Chiara , Pizzolo Francesca , Giacchetti Gilberta , Fallo Francesco , Veglio Franco , Reincke Martin , Wu Vin -Cent , Mulatero Paolo 
Published: April 2021

Objective:
2016 Endocrine Society guideline recommends screening for primary aldosteronism (PA) all patients with hypertension and obstructive sleep apnea (OSA), despite evidences supporting this recommendation are limited.
We designed a multi-ethnic, multicentre, cross-sectional study to assess the prevalence of PA in patients with OSA and the prevalence of OSA in unselected patients with PA.

Design and method:
203 patients with OSA (101 Chinese and 102 of Caucasian ethnicity) were screened for PA, followed by confirmatory test and subtyping diagnosis in case of confirmed PA. 207 patients with PA (104 Caucasians, 100 Chinese and 3 of African descent) were tested by cardio-respiratory polygraphy for OSA diagnosis.

Results:
The prevalence of PA in patients with OSA was 8.9% (11.8% in Caucasian and 5.9% in Chinese patients). Among patients without other indications for PA screening beyond OSA diagnosis, the prevalence of PA was very low (1.5%). The prevalence of OSA in patients with PA was 67.6% (64.4% in Caucasians, 70.0% in Chinese ethnicity). We observed a significant correlation between serum aldosterone levels and apnea/hypopnea index in Caucasian patients with PA (R2 = 0.360, p = 0.013), but not in the Chinese patients with PA. In the Caucasian group with PA, multinomial logistic regression confirmed a significant association between aldosterone levels and moderate-severe OSA (OR 1.002, p = 0.002), but no association was present in the Chinese group.

Conclusions:
Patients with OSA do not display a higher risk of PA, challenging the Endocrine Society guideline recommendation of screening all patients with OSA for PA, irrespective of the grade of hypertension. However, OSA is a frequent condition in patients with PA and aldosterone level can contribute to OSA severity in patients with PA of Caucasian ethnicity.
APPLYING WEIGHTED PULSE DECOMPOSITION ANALYSIS WITH SIGNAL QUALITY INDEX TO FINGER PHOTOPLETHYSMOGRAM FOR ESTIMATION OF BLOOD PRESSURES
Authors: Wang Tzung-Dau , Guo Jia-Wei , Tsai Pei-Yun , Lin Hung-Ju , Wu An-Yeu 
Published: April 2021

Objective:
Pulse decomposition analysis of photoplethysmography (PPG) signals can be used to estimate blood pressures. This study aimed to generate stable component waves by introducing weighting to the informative PPG portion and to ensure the reliability of the decomposed outputs assessed by signal quality index (SQI) and its relations to blood pressures.

Design and method:
We adopted weighted least squares criterion for the pulse decomposition analysis. Five Gaussian component waves were used. The systolic wave and diastolic wave were obtained by summing up the first three component waves and the last two component waves, respectively. The stiffness index (SI) was calculated by the time difference of the systolic wave peak (t_S) and the diastolic wave peak (t_D). The mean square error (MSE) between the synthesized PPG pulse and the normalized PPG pulse was adopted as SQI to evaluate decomposed results. The effect of weighting was investigated and compared by averaged variance of t_S and t_D. Proper SQI was examined to strike a good balance between the pass rate and the degradation of correlation coefficients of blood pressures to SI.

Results:
PPG data were collected from 20 subjects, with systolic blood pressures (SBP) and diastolic blood pressures (DBP) from 99 to 158 mmHg and 60 to 110 mmHg, respectively. A total of 2442 PPG pulses were analyzed. The averaged variances of t_S and t_D were reduced from 9.69 to 6.1 ms and 15.31 to 9.89 ms if weighting was adjusted from 1 to 80. The MSE for SQI was set around 2 × 10(-3), which could achieve pass rate of 98.7%. The degradation of correlation coefficients of body weight divided by SI, a parameter reflective of vascular stiffness, to SBP and DBP was less than 0.02, and was greater than that of body weight divided by SI obtained by conventional Gaussian decomposition (r for SBP, 0.51 vs 0.44; r for DBP, 0.49 vs 0.40).

Conclusions:
With the introduction of weighting, the decomposed PPG component waves became stabilized. SQI in terms of MSE for weighted pulse decomposition analysis ensured reliable outputs and enhancing its relations to blood pressures.
COMPARATIVE EFFECTIVENESS OF HYDROCHLOROTHIAZIDE VERSUS CHLORTHALIDONE ON CARDIAC, RENAL AND ELECTROLYTE EVENTS BY EGFR STAGE
Authors: Edwards Cedric , Petrcich William , Hundemer Gregory , Clark Edward , Knoll Greg , Ruzicka Marcel , Rhodes Emily , Burns Kevin , Sood Manish 
Published: April 2021

Objective:
Thiazide diuretics are recommended as first line blood pressure lowering therapy. Previously conducted trials demonstrating cardiovascular benefit (like ALLHAT and SHEP), used Chlorthalidone and not Hydrochlorothiazide as the diuretic. Despite this, Hydrochlorothiazide is commonly prescribed and is available in many combination preparations. Little is known about the comparative effectiveness of the 2 drugs, as estimated glomerular filtration rate (eGFR) declines. We set out to examine the association of hydrochlorothiazide and cardiac, kidney and electrolyte-related adverse events compared to chlorthalidone by eGFR level.

Design and method:
Population-based, retrospective cohort study of adults of advanced age (> or = 66 years) with a diagnosis of hypertension in Ontario, Canada (2009–2016). Fine and Grey sub-distribution hazards models examining the association of matched hydrochlorothiazide vs. chlorthalidone pairs and outcome events in an intention to treat analysis. Study outcomes were a cardiac event, kidney (egfr decline> 30%) event, electrolyte disorder (hypo- or hyperkalemia, hyponatremia) or all-cause mortality. We examined the effect of eGFR groups (> 60, 45–59, < 45 ml/min/1.73m2) on outcomes using an interaction term.

Results:
A total of 9,786 hydrochlorothiazide users were matched 4:1 to 2,936 chlorthalidone users (mean age 73.6, 55% female, 41.6% diabetes). Baseline eGFR distributions were 73.4, 17.4 and 9.2% for > 60, 45–59, and <45 ml/min, respectively. In individuals with an eGFR > 60 ml/min, hydrochlorothiazide was associated with a lower risk of eGFR decline (HR 0.78 95%CI 0.70–0.88), CV events (HR 0.83 95%CI 0.76–0.92), hypokalemia (HR 0.54 95CI 0.48–0.60) and all-cause mortality (HR 0.79 95%CI 0.63–0.98) compared to chlorthalidone. These effects attenuated with lower eGFR levels and no differences were observed in hyperkalemia or hyponatremia.

Conclusions:
Among individuals with an eGFR > 60 ml/min, hydrochlorothiazide use was associated with a lower risk of eGFR decline, CV events, hypokalemia and all-cause mortality. These differential effects were not observed at lower eGFR levels.
THIGH CIRCUMFERENCE AND RISK OF ALL-CAUSE, CARDIOVASCULAR AND CEREBROVASCULAR MORTALITY: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 1999–2006
Authors: Chen Chao-Lei , Huang Jia-Yi , Liu Lin , Yu Yu-Ling , Shen Geng , Lo Kenneth , Huang Yu-Qing , Feng Ying-Qing 
Published: April 2021

Objective:
Research gap exists regarding the relationship between thigh circumference and all-cause and cause-specific death, especially cardiovascular and cerebrovascular death. The objective of this study was to examine how thigh circumference associate with all-cause, cardiovascular and cerebrovascular mortality among US adults.

Design and method:
This cohort study included 19885 US adults who participated in the 1999–2006 National Health and Nutrition Examination Survey (NHANES), a national representative survey of the civilian, non-institutionalized U.S. population sponsored by the Centers for Disease Control and Prevention, with thigh circumference measurement at baseline and follow-up mortality assessment through 31 December 2015. In the 1999–2006 NHANES study, there were a total of 4,1474 participants. Adult subjects were enrolled. However, subjects missing mortality data and thigh circumference measurement were excluded. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for mortality according to thigh circumference in quartiles. Kaplan–Meier survival curve and restricted cubic spline regression were performed to examine the prospective association. Finally, subgroup analyses by age, gender, BMI, and baseline comorbid diseases were conducted.

Results:
During a median follow-up of 142.34 months, 3513 all-cause deaths occurred, with 432 cardiovascular disease deaths, and 143 cerebrovascular disease deaths. Multivariate Cox regression indicated that every 1 cm increase in thigh circumference was related to 4% and 6% decreased all-cause mortality and cardiovascular mortality, respectively. Compared to the reference group, the highest quartile of thigh circumference had a significantly negative relationship with all-cause mortality (HR 0.74, 95%CI 0.56–0.97, P < 0.05). However, the association of thigh circumference with cerebrovascular mortality was not significant. Subgroup analysis in lean participants (defined as BMI < 25 kg/m2) showed that thigh circumference had inverse correlations with all-cause mortality and cardiovascular mortality (P < 0.0001).

Conclusions:
A low thigh circumference seems to be associated with increased risk of all-cause and cardiovascular mortality, but not cerebrovascular mortality. The measure of thigh circumference might be a relevant anthropometric measure to help general practitioners in early identification of individuals at an increased risk of total and cardiovascular mortality.
THE ASSOCIATION OF CALF CIRCUMFERENCE AND ALL-CAUSE, CARDIOVASCULAR AND CEREBROVASCULAR MORTALITY: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS
Authors: Huang Jiayi , Liu Lin , Chen Chaolei , Huang Yuqing , Shen Geng , Yu Yuling , Feng Yingqing 
Published: April 2021

Objective:
Very limited data is available on the association of all-cause, cardiovascular and cerebrovascular mortality and calf circumference(CC). The objective of this study was to examine the association between CC and all-cause, cardiovascular as well as cerebrovascular mortality.

Design and method:
The data from the 1999–2006 National Health and Nutritional Examination Surveys (NHANES) was used. A total of 20,214 individuals aged >= 18 years who had measured CC were selected for this study. CC was defined as the widest point of calf. To investigate the association between CC and all-cause, cardiovascular and cerebrovascular mortality, Cox regression was used in different models. We further stratified the regression models into subgroups and tested for interaction to assess whether the association between CC and mortality was influenced by other covariates. The Kaplan-Meier analysis was conducted to compare the survival between CC and cause-specific mortality.

Results:
Current study included 20,214 participants (47.25% were men and the mean age was 45.8 years). In the fully adjusted model, for each 1 cm increment, CC was inversely associated with all-cause mortality (HR = 0.92, 95% CI = 0.90–0.94, P < 0.0001) and cardiovascular mortality (HR = 0.90, 95% CI = 0.84–0.97, P = 0.0056). Meanwhile, the highest quartile of CC had 50% (HR = 0.5, 95%CI = 0.40–0.64, P trend < 0.001) lower risk of all-cause mortality and 57% (HR = 0.43, 95%CI = 0.21–0.88, P trend = 0.045) lower risk of cardiovascular mortality, compared to the lowest quartile of CC. For cerebrovascular mortality, however, no significant association with CC was found. In the subgroup analysis, we found that CC had more potent protective effect on those who with body mass index (BMI) <25 kg/m2 (all-cause mortality: HR = 0.80, 95%CI = 0.79–0.82, P interaction < 0.0001; cardiovascular mortality: HR = 0.74, 95%CI = 0.70–0.78, P interaction = 0.0005).

Conclusions:
Our results suggested an independently inverse association between CC and all-cause and cardiovascular mortality. Besides, CC had more significant protective effect on those who with BMI <25 kg/m2. However, CC was not associated with cerebrovascular mortality.
HIGH SODIUM INTAKE INDUCES A CATABOLIC STATE VIA GLOMERULAR HYPERFILTRATION AND ENHANCED GLOMERULOTUBULAR BALANCE IN PATIENTS WITH ESSENTIAL HYPERTENSION
Authors: Rossitto Giacomo , Maiolino Giuseppe , Lerco Silvia , Ceolotto Giulio , Blackburn Gavin , Mary Sheon , Antonelli Giorgia , Berton Chiara , Bisogni Valeria , Cesari Maurizio , Seccia Teresa M. , Lenzini Livia , Montezano Augusto , Touyz Rhian , Petrie Mark C. , Daly Ronan , Welsh Paul , Plebani Mario , Rossi Gian Paolo , Delles Christian 
Published: April 2021

Objective:
A blood pressure (BP)-independent catabolic shift upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. This study sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures in patients with hypertension.

Design and method:
We analysed clinical and biochemical data collected at the time of screening for secondary causes from consecutive patients with a final diagnosis of essential hypertension. The systematic screening protocol included 24 h urine collection on usual diet and avoidance or washout from medications affecting the renin-angiotensin-aldosterone system. Classes of Na+ intake (Low < 2.3 g/d; Medium 2.3–5 g/d; High > 5 g/d) were defined based on urinary 24 h Na+ excretion. Tubular energy expenditure was estimated by measured Na+ reabsorption and Na+/ATP stoichiometry. Non-targeted liquid chromatography – mass spectrometry (LC-MS) metabolomics was conducted on plasma samples from an unselected subcohort.

Results:
We included 766 patients (428 males, 55.9%; age, 47 ± 13 years; BMI, 25.6 [23.0–29.0] kg/m2). Urinary 24h-Na+ excretion was an independent predictor of glomerular filtration rate (GFR, estimated by creatinine clearance; Low: 94.1 [69.9–118.8], Medium: 103.8 [86.9–126.0], High: 127.5 [108.3–147.8] ml/min/1.73m2; p < 0.001 for comparisons) after correction for age, sex, BP, body mass index, aldosterone and potassium excretion (p = 0.001). With increasing Na+ intake, the fractional excretion (FE) of free water decreased (Low: 1.13% [0.73–1.72] vs. High: 0.89% [0.69–1.12], p = 0.015), while FE of Na+ increased (Low: 0.39% [0.30–0.47] vs. High: 0.81% [0.73–0.98], p < 0.001); however, absolute 24 h tubular Na+ reabsorption and the associated energy expenditure similarly increased (δ High vs. Low = 18 [12–24] kcal/d, p < 0.001). At LC/MS metabolomics (n = 67), metabolites which were more abundant in High vs. Low Na+ intake (p < 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle.

Conclusions:
When exposed to high Na+ intake, kidneys effectively dissociate Na+ and water handling at the cost of higher GFR, increased tubular energy expenditure and, ultimately, protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and this metabolic shift may have broad implications on global cardiovascular risk.
EFFECT OF RENAL DENERVATION ON ATRIAL FIBRILLATION (ERDAF)
Authors: Papakonstantinou Panteleimon , Konstantinidis Dimitrios , Leontsinis Ioannis , Iliaki Panagiotis , Tsioufis Konstantinos 
Published: April 2021

Objective:
Renal sympathetic denervation (RDN) is a novel minimally invasive therapeutic option for patients with resistant arterial hypertension (AH). Recent data has shown that RDN with or without pulmonary vein isolation (PVI) may also have a positive impact on the management of patients with paroxysmal or persistent atrial fibrillation (AF). The purpose of the ERDAF study (Effect of Renal Denervation on Atrial Fibrillation) is to evaluate the renal sympathetic denervation in patients with resistant AH and symptomatic paroxysmal or persistent AF in order to show if there is a reduction in the AF-related symptoms, the AF recurrence rate, and the total burden (symptomatic and/or asymptomatic) of the arrhythmia.

Design and method:
This is a single-center, randomized study, in which thirty (30) consecutive patients > 18 years with resistant hypertension and symptomatic paroxysmal or persistent AF will be included after the restoration of the sinus rhythm. Patients will be randomized in a 1:1 ratio to either sympathetic transcatheter RDN on top of drug therapy (n = 15) or only conservative management with drug therapy (n = 15)(Figure). An implantable loop recorder (ILR) will be implanted subcutaneously in all patients after their study enrollment for long cardiac rhythm monitoring. Symptoms of arrhythmia will be evaluated based on the EHRA score. Patients will be monitored for a period of 18 months after the ILR implantation.

Results:
The first three months after RDN will be excluded from our final analysis (blanking period). Follow-up visits will be scheduled for the first month and every three months thereafter for a period of 18 months.

Conclusions:
The primary endpoint will be the change in the total AF burden (Total time in AF during the follow-up period). Secondary endpoints will include the change in the symptomatic and asymptomatic burden of AF, the time to detect the first AF recurrence (symptomatic and/or asymptomatic)-early recurrence of AF after RDN, and the change in blood pressure (systolic, diastolic and mean blood pressure) during the follow-up period.
BLOOD PRESSURE TRAJECTORIES FROM CHILDHOOD TO YOUTH AND ARTERIAL STIFFNESS IN ADULTHOOD: A 30-YEAR LONGITUDINAL FOLLOW-UP STUDY
Authors: Chu Chao , Wang Yang , Mu Jianjun 
Published: April 2021

Objective:
BP trajectories may be a stronger indicator of CVD compared with single BP assessment. This study aimed to identify the subgroups of individuals sharing similar blood pressure (BP) trajectories from childhood to youth and explore the associations of these trajectories with arterial stiffness in adulthood.

Design and method:
A group-based trajectory model was used to identify BP trajectories among 2082 individuals in the Hanzhong adolescent hypertension cohort by using BP values repeatedly measured at four visits from childhood (6–15 years) to youth (14–23 years). This cohort was again followed up and the brachial–ankle pulse wave velocity (baPWV) was examined 30 years after the baseline survey (36–45 years). Mixed linear regression models were used to examine the associations of BP trajectories from childhood to youth with adult baPWV.

Results:
Among the 2082 individuals with at least three BP measurements spanning an 8-year period, three trajectory groups of systolic BP were identified as follows: the low-level group (n = 889), medium-level group (n = 1021), and high-level group (n = 172). The age-, sex-, and BMI-adjusted baPWV in adulthood presented a gradient increase with the elevation of systolic BP trajectory levels (1198.2 ± 215.5 cm/s vs. 1265.3 ± 213.6 cm/s vs. 1349.3 ± 214.5 cm/s, all p < 0.001). After adjustment for potential confounding factors, the association between baPWV and systolic BP trajectories was statistically significant (adjusted β = 45.7 cm/s; p < 0.001 for the medium-level group and β = 106.7 cm/s; p < 0.001 for the high-level group compared with the low-level group). Similar results were obtained for the association of baPWV with the trajectories of diastolic BP and mean arterial pressure (MAP), except for pulse pressure.

Conclusions:
Our investigation demonstrates different BP trajectories from childhood to youth and shows the trajectories of systolic BP, DBP, and MAP are significant predictors of arterial stiffness in adulthood.
RELATIONSHIP BETWEEN THE HYPOTHALMIC-PITUITARY-ADRENOCORTICAL AXIS ACTIVITY AND THE CHARACTERISTICS OF ALDOSTERONE-PRODUCING ADENOMAS
Authors: Thuzar Moe , Lo Yu-Chin , Guo Zeng , Inder Warrick , Stowasser Michael 
Published: April 2021

Objective:
Aldosterone production can be regulated by adrenocorticotrophic hormone (ACTH) which normally controls cortisol secretion. Some cases of aldosterone-producing adenoma (APA) display features which may suggest increased sensitivity to the stimulatory effects of ACTH. The objective of this study is to investigate if there is any relationship between the hypothalamic-pituitary-adrenocortical (HPA) axis activity and the characteristics of APAs.

Design and method:
This is a retrospective review of the HPA axis activity of 41 histologically-confirmed APA cases which were characterised with regards to clinical, biochemical and somatic mutation status. HPA axis activity was assessed from morning plasma cortisol, ACTH and 1 mg overnight dexamethasone (DEX) suppression test. Correlation was analysed by Pearson's correlation coefficient, and the HPA axis activity between APAs with KCNJ5 mutation and those without was compared using Mann Whitney U-test.

Results:
Twelve out of 41 patients (29.3%) were women, median age was 49 years and 85.4% were overweight/obese. All except 2 had somatic mutations within APA. Fourteen (34.1%) were KCNJ5 mutation. Only one patient (APA not KCNJ5 mutated) had post-DEX cortisol > 50 nmol/L. Upright morning plasma aldosterone concentration (PAC) correlated with tumour size (r = 0.347, P = 0.026), plasma cortisol (r = 0.425, P = 0.006) and plasma ACTH (r = 0.446; P = 0.056). Plasma ACTH and cortisol were positively correlated (r = 0.511, P = 0.025). Higher PAC, cortisol and ACTH concentrations were in turn associated with the need for higher defined-daily-dose (DDD) of anti-hypertensive medications (r = 0.466, P = 0.002 for PAC; r = 0.315, P = 0.045 for cortisol; r = 0.449, P = 0.054 for ACTH). Higher PAC was also predictive of higher BMI (r = 0.348, P = 0.026). Plasma cortisol, ACTH, post-DEX cortisol, BMI and DDD of anti-hypertensives were not significantly different between those with KCNJ5 mutation compared to those without.

Conclusions:
HPA axis activity correlated with clinico-biochemical characteristics in patients with APAs, but the prevalence of autonomous hypercortisolism was low. The findings suggest a potential role of ACTH in the pathophysiology of APAs. There was no significant difference in HPA axis activity between those with somatic KCNJ5 mutation compared to those without.