bluuebunny/crossref_metadata_2025 huggingface dataset:
ASSOCIATION OF HYPERTENSION WITH ALL-CAUSE MORTALITY AMONG HOSPITALIZED PATIENTS WITH COVID-19
Authors: Rodilla Enrique , Saura Alberto , Jiménez Iratxe , Mendizábal Andrea , Pineda-Cantedo Araceli , Lorenzo-Hernández Elizabeth , Fidalgo-Montero Maria Del Pilar , López-Cuervo Joaquín Fernández , Gil-Sánchez Ricardo , Rabadán-Pejenaute Elisa , Abella-Vázquez Lucy , Giner-Galvañ Vicente , Solís-Marquínez Marta Nataya , Boixeda Ramon , Peña-Fernández Andrés De La , Carrasco-Sánchez Francisco Javier , González-Moraleja Julio , Torres-Peña José David , Guisado-Espartero María Esther , Escobar-Sevilla Joaquín , Guzmán-García Marcos , Martín-Escalante María Dolores , Martínez-González Ángel Luis , Casas-Rojo José Manuel , Gómez-Huelgas Ricardo
Published: April 2021

Objective:

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. The main objective of the study is to analyze whether HT represents an independent risk factor for death as a hard endpoint in patients hospitalized with SARS-CoV-2 in Spain.

Design and method:

Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors.

Results:

The mean age of the study population was 67.5 ± 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035).

Conclusions:

The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.
HYPERTENSION AND COVID-19: THE POSSIBLE ROLE OF METALLOPROTEINASE-9 IN COVID-19 PATHOPHYSIOLOGY
Authors: Mesquita Carolina Dávila , Do Couto Ariel Emiliano Souza , Campos Ligia Borges , Mora Bruno Cesar Petroski , Mestriner Fabiola , Vasconcelo Tauana Fernandes , Barbosa Jessyca Michelon , Corsi Carlos Curylofo , Ferro Denise , Ribeiro Mauricio Serra , Menegueti Mayra Gonçalves , Martins M. Auxiliadora , Becari Christiane
Published: April 2021

Objective:

The pathophysiological mechanism of acute lung injury in COVID-19 includes a cascade of local and systemic responses with activation of several pro-inflammatory cytokines, including metalloproteinases. The aim of this study is investigate the role of matrix metalloproteinase-9 (MMP-9) in plasma from patients with severe COVID-19 hospitalized in a Brazilian ICU.

Design and method:

The study was designed to analyze the MMP-9 plasmatic in COVID-19 severe infection. Epidemiological data and blood samples were obtained from 42 subjects hospitalized in the ICU with clinically SARS-CoV-2 infection confirmed by RT-PCR (COVID), and 15 healthy subjects (Control). Zymography methods obtained the MMP-9 plasma activity. Continuous variables are shown by mean ± STDV and analyzed by the Mann-Whitney test. Categorical variables were compared by the Chi-squared test. The MMMP-9 activity is shown in the log of normalized and analyzed by unpaired T-test. Two-way ANOVA was used to analyze subgroups divided by gender, age greater or less than the median 60.4-year-old, hypertensive or normotensive, non-obese or obese.

Results:

The COVID and Control groups did not differ significantly by age (62.6 ± 13vs.57.6 ± 12.2 years old, p = 0.097) and BMI (30.3 ± 6.1vs.29.33 ± 5.7 kg/m2, p = 0.338). The COVID group has fewer women than the Control group (28.6%vs.80%, p = 0.0008). The COVID subjects with hypertension were 42% vs.67% in the Control group (p = 0,2), and diabetes was similar in both groups. The hospital stay in the COVID group was 14.5 ± 11.5 days and the hospitalization death rate was 32.5%.

The COVID-19 group has shown an increase in MMP-9 activity compared with the Control group (0.38 ± 0.072 UA; 95%CI = 0.23–0.52,p < 0.0001). The MMP-9 activity increasing was independent of gender (p = 0.45), age (p = 0.93), BMI (p = 0.3) or hypertension (p = 0.6) and dependent of the COVID-19 infection (p < 0.0001). Therefore, our data are showing that the COVID-19 infection was responsible for MMP-9 improvement in plasma of severe COVID-19 infection (p < 0.0001) while all different analyses consistently showed a significant effect of COVID-19 infection (p < 0.0001).

Conclusions:

There is a significant increase in the MMP-9 plasmatic activity in severe COVID-19 patients independently of sex, age, obesity, and hypertension. Therefore, MMP-9 may be a potential new target for acute lung injury therapy in patients with COVID-19.
RNA-SEQ REVEALS HSP90 AS A REGULATOR FOR INTERLEUKIN 6-MEDIATED ACTIVATION OF NCC VIA THE MINERALOCORTICOID RECEPTOR
Authors: Moseley Auriel , Zhang Michelle , Tansey Malu , Ko Ben , Eaton Douglas , Wynne Brandi
Published: April 2021

Objective:

Hypertension (HTN) is characterized by increased Na+ reabsorption and systemic inflammation including increased cytokines such as IL6. Clinically, IL6 is increased in hypertensive patients. Previous data from our laboratory has revealed a mechanism for IL6-mediated activation of the mineralocorticoid receptor (MR), leading to increased Na+ transporter activation and HTN via reactive oxygen species (ROS) and Rac1. We hypothesized that IL6 induces a specific transcriptome in the late distal nephron (DCT2) and used RNA-seq to investigate.

Design and method:

Mouse DCT2 (mDCT15) cells were treated with IL6 (100ng/mL, 24hrs) or vehicle (n = 4, each), then total RNA isolated. Data from the Illumina-sequenced transcriptome underwent comparative analysis to identify significant differentially expressed transcripts between vehicle and IL6 treated cells.

Results:

Differential gene expressed revealed multiple targets, including HSP90 (3.03x10-6, p-adj) encoding for heat shock protein (HSP) 90. HSP90 has been previously shown as crucial for ligand binding, MR nuclear translocation and activation.

To investigate whether inhibition of HSP90 would affect IL6-mediated MR activation of distal Na+ transporters, such as the sodium chloride cotransporter (NCC), a thiazide-sensitive Na+ uptake was performed on transwells in vehicle, IL6 (100ng/mL) or IL6-Gel (geldanamycin, HSP90 inhibitor; 5uM) in mDCT15 cells (n = 3). IL6 treatment increased Na+ uptake compared (1666 ± 12 nmol/mg/20 min vs.1449 ± 7; p < 0.001). With HSP90 inhibition, Na+ uptake was reduced (1499 ± 12; p < 0.001).

Conclusions:

Using RNA-seq, we have uncovered specific transcripts activated within the late distal nephron (DCT2) following IL6, including HSP90, which we confirmed to be an important and novel player in IL6-mediated activation of NCC.
IMMUNE CELLS MEDIATED EFFECTS OF SODIUM CHLORIDE ON THE DEVELOPMENT OF VASCULAR INFLAMMATION AND ABDOMINAL AORTIC ANEURYSM IN ANGIOTENSIN II-TREATED APOE-KO MICE
Authors: Stegbauer Johannes , Yakoub Mina , Rahman Masudur , Hering Lydia , Potthoff Sebastian , Argov Doron , Flögel Ulrich , Rump Lars Christian , Temme Sebastian
Published: April 2021

Objective:

Chronic high salt (NaCl) intake is a major risk factor for cardiovascular diseases. Recent studies showed that excessive chronic NaCl intake affects immune response and thereby contributes to the pathogenesis of vascular injury. However, it remains unclear whether NaCl intake initially primes immune cell response by promoting memory T cells and sensitize the development of vascular injury in response to a subsequent stimulus.

Design and method:

Therefore, we investigate whether 14 days of NaCl treatment (1% NaCl) followed by a 7 day washout period affects the incidence and outcome of abdominal aortic aneurysms (AAA) in apolipoprotein E deficient (ApoE-KO) mice infused chronically with angiotensinII (AngII) (1000ng/kg/min) via osmotic minipumps for 10 days. Assessment of AAA was done by magnetic resonance imaging (MRI). To visualize vascular inflammation in vivo, perfluorocarbon nano-emulsions (PFC) injected intravenously before and 2, 4, 7 and 10 days after chronic AngII infusion were detected by combining 1H/19F MRI using a 19F RARE sequence. After 10 days of AngII infusion, aortas with perivascular fat were dissected. Aortic inflammation and immune cells infiltration were analyzed by flow cytometery, immunohistology and realtime PCR.

Results:

The survival rate of ApoE-KO mice pretreated with NaCl was significantly lower and the AAA incidence rate was significantly higher compared to sham-treated apoE-KO mice. The amount of 19F signal detected in areas of AAA was significantly increased in apoE-KO mice pretreated with NaCl. Histological analysis confirmed these results and showed that most of the immune cells were in the PVAT rather than dwelling in the vascular tissues. At day 10, proinflammatory cytokines like TNF-alpha, iNOS and TGF-ß as well as numbers of neutrophils, monocytes, effector memory CD4 and CD8 T cells were significantly higher in aortas of NaCl pretreated apoE-KO mice compared to sham-treated mice. Moreover, NaCl augmented the development of effector Th1 CD4 and effector CD8 cells from naïve T cells in vitro, respectively.

Conclusions:

In conclusion, these results suggest a significant role of NaCl in priming immune cell phenotype and thereby mediating vascular inflammation and damage in AngII infused apoE-KO mice.
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.
ADHERENCE TO THERAPY IN UNCONTROLLED MIDDLE-OLD HYPERTENSIVES – A PROBLEM TO SOLVE
Authors: Livia Popescu , Horia Balan
Published: April 2021

Objective:

Hypertension is worldwide spread, affects 40.41% of Romanians, and represents the leading cause of death. Epidemiological evidence suggests increasing proportion of elderly people. One half/two thirds of them have hypertension. Suboptimal adherence to treatment is considered to be the main impediment in controlling chronic diseases and the most common precipitating factors for hospitalization. Among the new concepts in 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension is a strong emphasis on evaluating treatment adherence as a major cause of poor BP control.

The aim of our study was to assess adherence to therapy in uncontrolled middle-old hypertensives admitted in an Internal Medicine Department

Design and method:

We enrolled 192 consecutive treated but uncontrolled patients with hypertension (BP>140/90mmHg) and age between 75 and 85 years old. All patients completed the Morisky questionnaire for adherence to treatment.

Results:

90 patients (53.57%) were females, and 78 (46.43%) males. Morisky score 0 (maximum adherence to therapy) was recorded in only 15.47% of the patients, 36.92 % had intermediate adherence (Morisky score 1–2) and 47.61% low adherence (Morisky score 3–4). Adherence to treatment was low in both sexes. Men had a sleight better maximum adherence than women (17.94% vs 13.33%). Women had a sleight lower low adherence to therapy than men (46.66% vs 50%).

Conclusions:

In-hospital middle-old uncontrolled patients with hypertension have a very poor adherence to therapy. Low adherence is present in both sexes. Since adherence to therapy is crucial in controlling chronic diseases, effective strategies to increase adherence to therapy are mandatory in uncontrolled middle-old hypertensives.
ASSOCIATION OF ARTERIAL HYPERTENSION AND BLOOD PRESSURE WITH MORTALITY AMONG POPULATION AGED 55 YEARS AND OLDER, ACCORDING TO ANTIHYPERTENSIVE TREATMENT
Authors: Imaeva Asiia , Shalnova Svetlana , Balanova Yulia , Kapustina Anna , Shkolnikov Vladimir
Published: April 2021

Objective:

Objective: to evaluate relationship of arterial hypertension (AH), elevated blood pressure (BP) and all-cause and cardiovascular disease (CVD) mortality among Muscovites aged 55 years and older according to antihypertensive therapy.

Design and method:

Methods: data of 1876 Muscovites 55 years and older (47.9% males) from the prospective population-based cohort study named the Stress, Aging and Health in Russia (SAHR) was used. The elevated BP was defined as BP > = 140/90 mmHg. AH was diagnosed according to European Society of Cardiology Guidelines. The treatment of hypertension was defined as the current use of a prescribed medication intended to lower BP, the effective treatment – as the presence of SBP < 140 mmHg and DBP <90 mmHg among treated participants. During the follow-up period (mean – 8,5 years) 547 deaths, including 330 from CVD, were identified. Hazard proportional risk model (Cox) was applied for hazard risks (HR) evaluation with 95%CI.

Results:

Results: the prevalence of AH and elevated blood pressure was 73,9% and 53,4%, respectively. After adjusting for age and sex AH had no significant associations with all-cause and CVD mortality (HR = 1,2; 95% CI: 0,98–1,5; p = 0,07; HR = 1,24; 95% CI: 0,94–1,64; p = 0,1). Whereas elevated BP was significantly associated with all-cause and CVD mortality (HR = 1,31; 95% CI: 1,10–1,55; p = 0,003, HR = 1,40; 95% CI: 1,12–1,75; p = 0,004). Moreover there was the strong contribution of elevated BP to all-cause mortality (HR = 1,39; 95% CI: 1,10–1,77; p = 0,006) and CVD mortality (HR = 1,55; 95% CI: 1,14–2,10; p = 0,005) among those who received antihypertensive therapy after adjustment to sex and age. Receiving antihypertensive therapy had no associations with all-cause and CVD mortality (p > 0,05). At the same time, the effective antihypertensive therapy reduced risk of all-cause and CVD mortality by 28% and 35%, respectively (HR = 0,72; 95% CI: 0,57–0,91; p = 0,006; HR = 0,65; 95% CI: 0,48–0,88; p = 0,005).

Conclusions:

Although AH is an important risk factor of CVD, among population aged 55 years and older only the elevated levels of BP and antihypertensive therapy efficacy were associated with all-cause and CVD mortality.
ANTIHYPERTENSIVE DRUG THERAPY BETWEEN ELDERLY PATIENTS IN A RURAL AREA OF PORTUGAL
Authors: Iashchuk Mykhailo , Galvez Juan Manuel Urbano , Real Lorena Lozano , Araujo Paula Sofia
Published: April 2021

Objective:

The aim of this study is to evaluate the antihypertensive therapy among > 65 years old in a rural area of Portugal.

Design and method:

The study includes 400 patients 65–93 years old. Average age was 76.2 ± 6.8 years old (76.4% women). The 40.3% of individual have complete basic education and 4% still continued to work. Study was conducted in several internal medicine external offices of a Hospital in a rural area of Portugal from October 2017 to May 2019. The presence of High Blood Pressure (HBP), cardiovascular diseases (CVD) and antihypertensive therapy was evaluated in 2 groups of patients: 65–79 years old (n = 336) and > 80 years old (n = 64).

Results:

Antihypertensive therapy was reported by 93% (n = 372) patients. The 45,46% of the patients (n = 171) received monotherapy. Combination of two-drugs were taken by 31.98% (n = 119) of the patients. Three and four drugs combination were taken by 16,12 % (n = 60) and 5,91% (n = 22) of the patients, respectively. The study revealed ACE inhibitors and like thiazides diuretics as most frequent drugs (52.8% and 49.6% of patients, respectively). The distribution of another groups of antihypertensive pills is following: calcium channel blocker - 39.6%, angiotensin receptor blocker - 24.7%, beta blocker - 14% patients and central action blockers 6,5 %. In patients taking 2 anti-hypertensive drugs, the most frequent association was ACE inhibitors and like thiazides diuretics (42,3 %) followed by ACE inhibitor plus calcium channel blocker (28,5 %). In patients taking 3 drugs, the most frequent association was ACE inhibitor plus like thiazide diuretic plus calcium channel blocker.

Conclusions:

Most hypertensive patients > 65 years old receive combination antihypertensive therapy. Combinations of ACE inhibitors + like thiazides diuretics or ACE inhibitors + calcium channel blocker are among the most common.
THE IMPACT OF ADIPOKINES IN THE ONSET OF ATRIAL FIBRILLATION
Authors: Papadopoulos Dimitrios , Sanidas Elias , Velliou Maria , Tsakalis Konstantinos , Zerva Kanella , Kyrana Panagiota , Iliopoulos Dimitrios , Mantzourani Marina , Toutouzas Konstantinos , Barbetseas John
Published: April 2021

Objective:

Several adipose tissue bioactive factors (adipokines) have been linked to cardiovascular (CV) diseases. Apelin and omentin-1 have cardioprotective effects whereas visfatin and chemerin have negative effects on CV function. The aim of this study was to calculate apelin, omentin-1, visfatin and chemerin plasma levels in patients with a first episode of atrial fibrillation (AF) investigating any potential association of these factors with the presence of the arrhythmia.

Design and method:

Overall, 60 patients without a previous history of AF were studied. Of them, 30 had a first documented episode of AF on ECG or 24-hour Holter monitoring during the last month and 30 did not. Apelin, omentin-1, visfatin and chemerin plasma levels were measured by the Elisa method.

Results:

Compared to non-AF patients, visfatin and chemerin levels were higher in patients with a first episode of AF while apelin and omentin-1 levels were lower. However, statistically significant differences were observed only for apelin and visfatin. No statistically significant differences in demographic characteristics and CV risk factors were noted between the two groups (Table).

Conclusions:

Visfatin as a non-cardioprotective adipokine was increased in patients having AF for the first time while apelin as a cardioprotective adipokine was decreased indicating a potential correlation of these hormones with the presence of the arrhythmia.
THE RELATIONSHIP BETWEEN ATRIAL FIBRILLATION AND RENAL DYSFUNCTION
Authors: Tatar Maria Cristina , Husariu Madalina , German-Sallo Marta , Tilea Ioan
Published: April 2021

Objective:

Lately, interrelation between atrial fibrillation (AF) and chronic kidney disease (CKD) has received increasing attention, owing to the collective risk factors. The aim of this study, was to appreciate the severity of the renal dysfunction depending on the temporal pattern of atrial fibrillation in patients presenting both conditions.

Design and method:

We retrospectively analyzed 258 atrial fibrillation patients, mean age 73.48 yr (SD= 10.4), 51.6% females, presenting different stages of chronic kidney disease. The study population was divided in three groups based on the presentation and duration of AF: paroxysmal, persistent and permanent. In order to quantify the severeness of the CKD, we estimated the glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation.

Results:

Related to the type of atrial fibrillation, 38% of patients had paroxysmal AF, 3.9% persistent AF, respectively 58.1% had permanent AF. Regarding the mean value of the eGFR, in the paroxysmal AF group we obtained a mean value of 69.06 ml/min/1.73 (median= 67.5, SD= 33.54) while in the persistent AF group the mean eGFR value was 70.9 ml/min/1.73 (median= 67.5, SD= 31.2) and in the group of permanent AF, the mean value was 61.2 ml/min/1.73 (median= 55.5, SD= 30.26). Therefore, no statistically significant difference (p = 0.6262) was obtained in terms of the severity of renal dysfunction compared to the type of atrial fibrillation.

Conclusions:

Our findings demonstrate that neither type of AF is predisposing to more severe outcome of chronic kidney disease. On the other hand, independent of atrial fibrillation type, the eGFR is an important monitoring tool of CKD progression in atrial fibrillation patients. Overall, due to increasingly occurrence of atrial fibrillation with chronic kidney disease, further studies are required in order to streamline their management, taking into account renal function in determining cardioembolic risk as well.
ESTIMATED PULSE WAVE VELOCITY (EPWV) DISTRIBUTION IN A COHORT STUDY – EH-UH STUDY (CROATIAN SCIENTIFIC FOUNDATION)
Authors: Bosnjak Vito , Blagus Luka , Frkanec Stjepan , Katic Luka , Domislovic Viktor , Matasin Marija , Glavic Mihaela Marinovic , Kos Jelena , Vrkic Tajana Zeljkovic , Pecin Ivan , Jelakovic Ana , Premuzic Vedran , Dika Zivka , Karanovic Sandra , Jelakovic Bojan
Published: April 2021

Objective:

Carotid-femoral pulse wave velocity (cfPWV) was recommended by guidelines as a biomarker of arterial stiffness and an independent predictor of future cardiovascular (CV) events. However, due to practical and logistic reasons it was not become a routine in clinical work. Recently, it was shown that estimated PWV (ePWV) which is much more convenient for everyday work correlates excellent with cfPWV and had predictive role in hypertensive patients with various degrees of CV risk. Our aim was to determine the distribution of ePWV values in general Croatian population.

Design and method:

In a stratified random sample of 1087 subjects from the general Croatian adult population which was enrolled in a nationwide survey (EH-UH 1) from 2000–2005 analyses on ePWV were done and subjects were followed-up for 17 years. ePWV was calculated from age and mean BP (MBP): ePWV = 9.587 - 0.402 × age + 4.560 × 10-3 × age2 - 2.621 × 10-5 × age2 × MBP + 3.176 × 10-3 × age × MBP - 1.832 × 10-2 × MBP. MBP = diastolic BP (DBP) + 0.4(SBP - DBP).

Results:

Mean values of ePWV according to the age and BP categories are shown in Figure 1. Distribution of PWV according to the age category in the normal values European population (European Heart Journal 2010; 31: 2338) and ePWV in general Croatian population are presented in Table 1. Concordance between cfPWV and ePWV was found in younger subjects with less stiffed arteries. Discrepancies between cfPWV and ePWV increased with levels of cfPWV

Conclusions:

According to our knowledge this is the first study presenting the distribution of ePWV by age category in a population-based survey. Observed differences between cfPWV and ePWV in older subjects could be explained with differences between groups (normal population vs. general population) but also by the fact that our participants were not classified according to levels of BP what is in line with the results of other authors (J of Hypertension 2016, 34:1279)
URINARY UROMODULIN IS POSITIVELY ASSOCIATED WITH TOTAL CARDIOVASCULAR RISK IN MIDDLE-AGED NON-TREATED SUBJECTS WITH HIGH-NORMAL BLOOD PRESSURE
Authors: Josipovic Josipa , Simicevic Livija , Milicic Borna , Domislovic Viktor , Jelakovic Bojan
Published: April 2021

Objective:

Recent studies found bidirectional association of urinary uromodulin (UM) with total cardiovascular (CV) risk. Our aim was to analyse association of urinary UM with total CV risk in a group of middle-aged non-treated subjects with high-normal blood pressure (BP).

Design and method:

We included 326 apparently healthy subjects (mean age 37). Fasting blood and urine samples were obtained and office and ambulatory BP were measured in all subjects. UM (morning spot urine sample) was determined by ELISA (Cobas Roche).

Results:

According to the JNC-7 classification, 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. Based on the general cardiovascular risk algorithm 257 (78.8 %), 42 (12.9 %) and 19 (5.8%) participants were classified into the low/medium risk, high risk and very high risk groups, respectively. There were 12.9% high risk and 5% very high risk subjects in PHT, and 21% high and 16% very high risk participants in HT groups, while there weren’t high/very high risk subjects in OBP group. Nonindexed UM (nUM) was significantly lower in low/medium vs. high/very high risk groups (48.2 vs. 69/73; P = 0.003). Nonsignificant trend to the higher nUM values (mg/ml) were found in HT/PHT compared to OBP (52/56.1 vs 49.8 mg/ml). Opposite trend (43/42.9 vs. 40.6 mg/g creatinine) was observed for indexed UM (iUM). In PHT group, there were significant difference in nUM between low/medium and high/very high risk groups (50 vs. 75/77; P = 0.006). In the whole group, nUM correlated positively with total CV risk (Rho = 0.169; P = 0.003). In the PHT group, both nUM (Rho 0.32; P < 0.001) and iUM (Rho 0.236; P = 0.007) correlated positively with total CV risk.

Conclusions:

Urinary uromodulin is positively associated with total cardiovascular risk in middle-aged non-treated prehypertensives.