bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHANGES IN AMBULATORY BLOOD PRESSURE DURING THE TRANSITION TO RETIREMENT
Authors: Karelius Saana , Vahtera Jussi , Suorsa Kristin , Heinonen Olli Juhani , Pentti Jaana , Niiranen Teemu Juhani , Stenholm Sari 
Published: June 2023

Objective:
Retirement is a major life event characterized by removal of work-related stressors and changes in health behaviours. The association between retirement and changes in blood pressure (BP), and particularly in ambulatory BP, has been scarcely studied. We aimed to examine changes in ambulatory BP during retirement transition.

Design and method:
Two hundred and fifty ageing workers (mean age 63.2 years, 84% women) from the Finnish Retirement and Aging study participated in annual office BP measurements and 114 (mean age 63.1, 90% women) of them underwent annual ambulatory BP measurements before and after retirement. On average, the participants provided data on ambulatory BP at 2.7 (range 2 - 4) measurements. We used generalized linear models to examine BP changes at retirement. The FIREA study was conducted in accordance with the Helsinki declaration and was approved by the Ethics Committee of Hospital District of Southwest Finland (ETMK: 84/1801/2014). All participants gave written informed consent.

Results:
Most marked changes in BP during the follow-up were observed for asleep SBP, which decreased before retirement, increased during retirement transition and plateaued after retirement (before retirement vs. retirement transition P = 0.07 and after retirement vs. retirement transition P = 0.02). Awake SBP and 24-h SBP declined with most apparent decrease before retirement (before retirement vs. retirement transition P = 0.07 and P = 0.07). Awake DBP and 24-h DBP showed relatively consistent decline throughout the follow-up with no differences between the time periods. SBP and DBP dipping reduced before and during retirement transition, but not after retirement. Among shift workers, asleep BP increased and BP dipping decreased more than in regular day workers.

Conclusions:
Retirement was found to associate with beneficial changes in awake BP but unfavourable changes in asleep BP, especially in shift workers.
CUMULATIVE BLOOD PRESSURE LOAD AND INCIDENT DEMENTIA, COGNITIVE FUNCTION, AND ALL-CAUSE AND CARDIOVASCULAR DEATHS IN ADULTS AGED 70 YEARS AND OLDER
Authors: Xu Xiaoyue , Catts Vibeke , Harris Katie , Wang Nelson , Numbers Katya , Trollor Julian , Brodaty Henry , Rodger Anthony , Sachdev Perminder , Schutte Aletta 
Published: June 2023

Objective:
Few studies have focused on the contribution of long-term exposure to elevated BP to dementia and deaths, particularly among older adults. We examined the prognostic value of cumulative BP (cBP) and cBP load in relation to incident dementia, cognitive decline, all-cause and cardiovascular deaths among adults aged 70 years and above, followed over 15 years. We also explored whether seated vs standing BP has more predictive value for these outcomes.

Design and method:
The Sydney Memory and Aging Study (N = 1,037) comprised a cohort of community-dwelling individuals aged 70 - 90 years without dementia, recruited from two areas of Sydney, Australia. Baseline data collection was performed in 2005-2007 and the cohort was followed every two years for 7 waves until 2021. Sitting and standing systolic, diastolic BP and pulse pressure (PP) were measured from wave 1 to 3. Cumulative sitting and standing BP and its load were calculated from the area under the curve. We assessed the association of BP parameters with incident dementia, cognitive function, all-cause and cardiovascular deaths between wave 4 and 7, in Cox proportional hazards models.

Results:
A total of 520 participants with three waves of BP data were included (47.7% men, median age at baseline, 77 [IQR: 74 - 81] years). In the multivariable-adjusted Cox model, cumulative pulse pressure (cPP) load was associated with a higher risk of dementia (sitting p for trend = 0.004; standing p for trend = 0.023), and lower global cognitive scores (sitting p for trend = 0.005; standing p for trend = 0.022). However, no significant associations were found upon additional age adjustment (p for tend>0.05). Sitting and standing cPP and cPP load were also associated with higher risk of all-cause deaths (all p for trend < 0.006). No associations were found for cumulative systolic or diastolic sitting or standing BP and dementia and cognition, as well as all-cause and cardiovascular deaths in both crude and adjusted models.

Conclusions:
Long-term cPP load predicted a significant age-dependent increase in risk for dementia, cognitive decline, and deaths in adults older than 70 years.
ONGOING ANTI-HYPERTENSIVE TREATMENT DOESN’T IMPACT ON OUTCOME ON MEDIUM-LONG TERM SEQUELAE OF PATIENTS WITH MODERATE TO SEVERE COVID-19 PNEUMONIA
Authors: Cattaneo Chiara , Salvotti Francesca , Leidi Francesca , Pellegrinelli Riccardo , Geroldi Veronica , Loro Giorgia , Reale Scilla , Vaccarello Paola , Cherubini Fabio , Borghi Erika , Napoli Federico , Malerba Paolo , Ciuceis Carolina De , Rosei Claudia Agabiti , Rizzoni Damiano , Boari Gianluca E.M. 
Published: June 2023

Objective:
One “hot” topic that remains to be elucidated is the possible role of anti-hypertensive drugs on middle and long term outcome of COVID-19 pneumonia.
Namely, ACE2 receptor is highly expressed on the surface of cardiac and pulmonary cells, and it is used by coronaviruses, to enter host cells; specifically, the interaction between the “spike” protein of coronaviruses and ACE2 has been identified as a key factor for the virus transmission.
This makes the role of ACE-inhibitors and Angiotensin Receptor Blockers (ARBs) drugs extremely controversial and their role – if any – is still to be elucidated. Moreover, it is still unclear whether these drugs may have any impact on SARS-CoV-2 sequelae.

Design and method:
In this retrospective study, we analysed a group of 70 hypertensive unvaccinated patients treated in our Medicine ward for moderate to severe COVID-19 pneumonia during pandemic who survived and accepted to undergo a follow-up visit after a mean of 260 days including phone interview, standard laboratory tests, chest x-ray and/or chest computed tomography, spirometry with evaluation of DLCO. Patients were divided in three groups according to hypertensive treatment: ACE-inhibitors (n. 27) or ARBs (n. 21) or other anti-hypertensive medication.
The considered groups where homogeneous (see table)

Results:
As shown in the table, biochemical, radiological and respiratory data were not significantly different.
Again, we did not find any significant difference in terms of number of non-specific radiological alterations (i.e. ground-glass opacities, irregular linear/reticular opacities), lung fibrosis, spirometry data, DLCO diffusion, persisting effort dyspnoea.
Biochemical data were, once more, substantially super-imposable in the two groups

Conclusions:
In conclusion, in our study, we could not detect any difference in middle-long term outcome nor in complication type or number in the groups of hypertensive patients undergoing different treatments.
This result seems to support and to strengthen the idea that ACE-inhibitors and ARBs do not play a significant role on onset, evolution and middle-long term outcome of moderate to severe COVID-19 pneumoniae: although the number of follow-up patients is very small, we did not find any difference in sequelae in both groups.
COVID-19 AND ARTERIAL STIFFNESS IN VACCINATED YOUNG ADULTS WITHOUT PRIOR CO-MORBIDITIES. A CROSS-SECTIONAL ANALYSIS OF THE FIT@4COVID COHORT STUDY
Authors: Pereira Telmo , Lira Fábio , Caseiro Armando , Castanheira Joaquim , Coelho-e-Silva Manuel 
Published: June 2023

Objective:
The long-term consequences of COVID-19 amongst survivors of acute infection are unknown, particularly on the cardiovascular system. Given the ability of the virus to affect the arterial wall, the question emerges to whether COVID-19 has a negative modulating effect of the vascular aging trajectory, conveying accelerated arterial stiffening and endothelial dysfunction, and thus, contributing to an increased CV risk over the life course.

Objective:
The main aim of this study was to ascertain the consequences of COVID-19 on arterial stiffness, by measuring PWV and thereby evaluating the presence of EVA. Secondary objectives of the study include investigating the effect of the SARS-CoV-2 infection on haemodynamic parameters measured by PWA.

Design and method:
A cross-sectional analysis of the initial data from the Fit@4COVID cohort was made. Carotid-femoral pulse wave velocity (PWV) and carotid pulse wave analysis (PWA) were evaluated in participants with (Covid19 group) and without (Control group) prior infection with SARS-CoV-2. Groups were matched for age and gender. Blood samples were taken for confirmation of prior exposition to the virus and to study the immune and inflammatory profile.

Results:
A total of 60 participants, equally divided in two groups, were enrolled, with a mean age of 20 ± 1.0 years. No significant differences were observed between groups concerning anthropometric, sociodemographic and clinical characteristics. Significant differences between-groups were observed for PWV (control: 5.84 ± 0.33 m/s, Covid19: 6.19 ± 0,47 m/s; p < 0.01), even after adjusting for mean arterial pressure (p = 0.019). Significant differences were also depicted for central systolic blood pressure, with 106.40 ± 9.27 mmHg in the control group and 115.00 ± 11.23 mmHg in the Covid19 group (p = .012). Similar results were found when observing brachial systolic blood pressure, central pulse pressure and brachial pulse pressure, all of which showed higher values in the Covid19 group.

Conclusions:
The cross-sectional analysis of the initial Fit@4COVID data buttresses a relevant impact of the SARS-CoV-2 virus over the arterial wall, even in healthy young adults with mild forms of COVID-19. The long-term effects of COVID-19 over the cardiovascular system remains to be demonstrated.
COVID-19 AND MORTALITY IN HYPERTENSIVE PATIENTS ACCORDING TO CARDIORESPIRATORY FITNESS
Authors: Faselis Charles , Doumas Michael , Pittaras Andreas , Samuel Immanuel Babu , Gorsuch Belinda , Ladas Alexandros , Lavie Carl , Myers Jonathan , Kokkinos Peter 
Published: June 2023

Objective:
COVID-19 mortality risk increases with the presence of underlying comorbidities, including hypertension. Epidemiologic evidence also suggests an inverse association between self-reported physical activity and COVID-19 cases and deaths. However, no information exists regarding the association between cardiorespiratory fitness (CRF) assessed objectively by a standardized exercise treadmill test (ETT) and mortality in hypertensive patients.
We assessed the hypothesis that CRF is inversely and independently associated with COVID-19 mortality risk in non-vaccinated hypertensive patients

Design and method:
From 2020 to 2021, we identified 17,358 hypertensive patients (mean age: 60.3 ± 8.2 years) with a normal response to an exercise tolerance test (ETT), prior to COVID-19. We established five CRF categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.7 ± 1.2 METs; n = 3,486); Low-Fit (7.1 ± 1.3; n = 4,616); Moderate-Fit (8.4 ± 1.3 METs; n = 3,320); Fit (10.3 ± 0.9 METs; n = 4,084); and High-Fit (12.8 ± 1.6 METs; n = 1,852). Multivariable Cox proportional hazard models were constructed to estimate hazard ratios (HR) and 95% confidence intervals [CI] for mortality across CRF categories. The models were adjusted for age, gender, race, comorbidities, medications, hospitalization, intubation, and time elapsed between ETT and COVID-19. The Least-Fit category was used as the reference group.

Results:
Results: During the follow-up of 100 days, 1,853 individuals died (10.7%). The risk for death was 7% lower for each 1-MET increase in exercise capacity (HR = 0.93, CI: 0.92-0.95; p < 0.001). The risk across fitness categories declined progressively with increased CRF and was 26% lower for the Least-Fit individuals (HR = 0.74; CI: 0.66 - 0.84), approximately 30% to 40% lower for Moderate-Fit and Fit, and 50% lower (HR = 0.50; CI: 0.41 - 0.62; p < 0.001) for High-Fit patients.

Conclusions:
Increased CRF was inversely related to COVID-19 mortality risk in hypertensive patients. The association was graded and independent of comorbidities.
IMPACT IN RENAL PARAMETERS OF ACHIEVED BP DURING ANTIHYPERTENSIVE TREATMENT IN DIABETIC SUBJECTS. REAL WORLD DATA
Authors: Martinez Fernando , Calderon Jose Miguel , Diaz Javier , Sauri Inma , Fernandez Antonio , Lidón Laura , Forner Maria Jose , Redon Josep 
Published: June 2023

Objective:
The controversy to use an intensive or standard antihypertensive treatment in diabetic subjects is still not solved. The objective of the present study was to assess the impact of BP levels in renal parameters (progression of KDIGO stage and decrease of 20% GFR in two years) during treatment in Type 2 diabetic subjects.

Design and method:
T2DM patients were included. During the study, SBP, DBP, eGFR, UAE, HbA1, lipid levels were measured and average of values in each six months periods was calculated. Cox proportional hazard models time-derived was applied to assess the impact of BP levels in progression of one stage in KDIGO (stages I to IV) and a 20% reduction in the eGFR in 2 year-period. Covariates of age, sex, smoking, previous cardiovascular events, HbA1c, lipid levels and drug treatments for hypertension, diabetes, anticoagulant or antiaggregant were included in the analysis.

Results:
52553 patients (age 66+/-11 yr, gender 51.2% females) with eGFR and 47558 with UAE measured during the study were included. 3851, 74 per 104/patients/year decline eGFR and 3568, 67 per 104/patients/year progress at least one KDIGO level. Overall, the increment or reduction of risk for the achieved SBP and DBP adjusted for all the other variables, as well as the risk for each of the covariates are in the figure for progression of KDIGO. SBP below 120 mmHg increases the risk of both eGFR and KDIGO whatever the DBP. DBP <70 mmHg does not increase the risk unless SBP >150 mmHg.

Conclusions:
In diabetic patients’ intensive reduction of SBP <120mmHg but not DBP<70mmHg increases the risk of renal damage.
A SYSTEMATIC REVIEW AND META-ANALYSIS ABOUT THE PREVALENCE OF FUNCTIONING ADRENAL INCIDENTALOMAS
Authors: Sconfienza Elisa , Tetti Martina , Forestiero Vittorio , Veglio Franco , Mulatero Paolo , Monticone Silvia 
Published: June 2023

Objective:
Adrenal hyperfunction is associated with an increased risk of cardio-metabolic complications in subjects with adrenal incidentaloma. The aim of our study was to assess the prevalence of autonomous/possible autonomous cortisol secretion, primary aldosteronism, pheochromocytoma and Cushing syndrome in patients with adrenal incidentaloma.

Design and method:
We performed a comprehensive search of multiple databases (PubMed, Ovid MEDLINE, Web of Science) for potentially relevant studies without language restriction, up to February 2022. Studies were excluded if the diagnostic criteria used for diagnosing the hormonal alteration were not available or not in agreement with the available guidelines; in case of duplicate reports or if the studies were performed on selected cohorts of patients/specific populations.

Results:
We included 36 studies in the final analysis. The overall prevalence of functioning adrenal incidentalomas was 27.5%. Autonomous cortisol secretion/possible autonomous cortisol secretion, with a prevalence of 11.7% (95% C.I. 8.6, 15.7), was the most frequent hormonal alteration, while primary aldosteronism occurred in 4.4% of the patients (95% C.I. 3.1, 6.2). Subgroup analysis showed that primary aldosteronism was more prevalent in patients from Asia compared with patients from Europe/America, on the contrary, autonomous cortisol secretion/possible autonomous cortisol secretion had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of autonomous cortisol secretion/possible autonomous cortisol secretion was influenced by the proportion of female patients, while the prevalence of primary aldosteronism was positively associated with the proportion of patients with hypertension and the publication year. Finally, pheochromocytoma and Cushing syndrome prevalence were 3.8% (95% C.I. 2.8, 5.0) and 3.1% (95% C.I. 2.3, 4.3), respectively.

Conclusions:
We confirmed a wide heterogeneity among studies, that was partially explained by the differences in the populations included, such as the female gender and the geographical regions where patients were recruited; moreover, the year of the study publication plays a potential role in the observed effect, thus underlying an increasing awareness of these hormonal alterations in the latest years.
CXCR4-DIRECTED [68GA]GA-PENTIXAFOR PET/CT AS A NOVEL DIAGNOSTIC MODALITY IN PRIMARY ALDOSTERONISM
Authors: Baz Amir Hossein Chaman , Gotthardt Martin , Deinum Jaap , Langenhuijsen Johan 
Published: June 2023

Objective:
Primary aldosteronism (PA) is caused by autonomous production of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction (‘subtyping’) is crucial, PA is cured by adrenalectomy in unilateral PA and is treated by medication in bilateral PA. Subtyping is currently done by adrenal vein sampling (AVS). We propose a new diagnostic imaging modality employing the PET-tracer [68Ga] Ga-PentixaFor. This tracer reportedly has high uptake in APAs, whereas uptake is low in BAH or normal adrenals. The goal of this study is to determine concordance of [68Ga] Ga-PentixaFor PET/CT and AVS. Secondary outcomes are optimal timepoint for scanning and quantitative criteria for lateralization at the optimal timepoint.

Design and method:
This study is step 1 of a two-step randomized controlled diagnostic trial. We included patients with PA from Radboudumc Nijmegen and UMC Utrecht, confirmed by an intravenous salt-loading test. Patients underwent AVS and [68Ga]Ga-PentixaFor PET/CT. A dynamic scan was performed to determine optimal timepoint for scanning in the first 6 patients. The main outcome was the concordance of AVS and [68Ga]Ga-PentixaFor PET/CT. The SUVmax was used to determine lateralization in [68Ga]Ga-PentixaFor PET/CT.

Results:
Nineteen patients underwent adrenal vein sampling and a [68Ga]Ga-PentixaFor PET/CT. The optimal timepoint of scanning was 1h post injection. AVS showed lateralization in 13/19 patients. Using a cut-off of SUV¬max-ratio of 1.4, concordance was 68%. (figure 1) Using a Bayesian prediction model, the predicted concordance is: 67% (CI80% = 53 - 79).
Figure 1: Scatter dot plot of the SUVmax Ratio in patients who had lateralization or no lateralization on AVS with a cut-off value of 1.4.

Conclusions:
[68Ga]Ga-PentixaFor PET/CT is a new imaging modality with high concordance with AVS. It is safe, readily available and as an out-patient procedure has the potential to improve subtyping in PA. With these preliminary results we have sufficient evidence of concordance to proceed to step 2 of the two-step trial: A pragmatic randomized controlled diagnostic trial, in which patients will be randomized in either [68Ga]Ga-PentixaFor PET/CT or AVS.
SALT RESTRICTION COMBINED WITH RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM BLOCKADE IS A POTENT ANTIHYPERTENSIVE STRATEGY IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Schneider Holger , Sarkis Anna -Lina , Sturm Lisa , Britz Vera , Lechner Andreas , Potzel Anne L , Müller Lisa Marie , Heinrich Daniel A , Künzel Heike , Nowotny Hanna F , Seiter Thomas Marchant , Kunz Sonja , Bidlingmaier Martin , Reincke Martin , Adolf Christian 
Published: June 2023

Objective:
The relationship between high dietary salt intake and high blood pressure is well established. Recommendations for salt restriction have found their way into major guidelines for essential hypertension. Patients with primary aldosteronism (PA), the most common endocrine cause of arterial hypertension, are believed to be exquisitely salt sensitive, i.e., respond particularly well to salt restriction. However, surprisingly little efforts have been made to determine the precise impact of salt restriction in patients with PA.
We, therefore, set out to implement a moderate salt restriction in patients with PA to assess its impact on blood pressure and secondary health outcomes.

Design and method:
We used nutritional education and continuous self-monitoring via a smartphone app to reduce salt intake in 41 patients with PA for a time span of 12 weeks. All patients were on mineralocorticoid receptor antagonist therapy and had stable blood pressure. Patients were monitored every 4 weeks with blood pressure and urine sampling and detailed blood work at weeks 0 and 12. Mental well-being was addressed by validated scoring systems.

Results:
Patients achieved a significant reduction of dietary salt intake (from 9.1 to 5.2 g/d) and of blood pressure (from 130/84 to 121/81 mmHg). We also registered a significant loss of body weight (-1.4 kg). While subjects initially featured PHQD scores compatible with depression, scores normalized at the end of the study. Multivariate regression analysis revealed that cumulative intake of drugs targeting the renin-angiotensin-aldosterone system was an independent predictor of blood pressure reduction.

Conclusions:
Salt restriction is an effective treatment in patients with PA. Patient empowerment by education and self-monitoring promotes salt restriction. Effects are facilitated by concomitant RAAS blockade. Salt restriction, despite being moderate, also improves mental well-being.
GENETIC DELETION OF AT1A RECEPTORS SELECTIVELY IN THE RENOMEDULLARY INTERSTITIAL CELLS OF THE KIDNEY MEDULLA ATTENUATES ANGIOTENSIN II-INDUCED HYPERTENSION
Authors: Li Xiao , Hassan Romana , Zhuo Jia 
Published: June 2023

Objective:
The present study tested the hypothesis that genetic deletion of angiotensin II (Ang II) AT1 (AT1a) receptors selectively in the renomemdullary interstitial cells (RMICs) of the kidney medulla attenuates the development of Ang II-induced hypertension in mice.

Design and method:
To test the hypothesis, we used inducible Tenascin-C-CreER2 and Agtr1a-floxed recombination approach to generate a novel mouse model with deletion of AT1a receptors selectively in the RMICs of the kidney (RMIC-Agtr1a-/-). Adult male wildtype (WT) and RMIC-Agtr1a-/- mice (n = 10 per group) were implanted with a telemetry probe and infused with or without Ang II via an osmotic minipump (∼500 μg/kg/day, i.p.) for 2 weeks.

Results:
Mice with deletion of AT1a receptors selectively in RMICs of the kidney medulla were fertile and grew normally without apparent structural or histological abnormality in the kidney medulla. However, telemetry systolic, diastolic, and mean blood pressure were significantly lower in adult male RMIC-Agtr1a-/- than WT mice (WT: 122 ± 4 mmHg vs. RMIC-Agtr1a-/-: 102 ± 3 mmHg, P < 0.01). Interestingly, this hypotensive phenotype in RMIC-Agtr1a-/- mice was associated with significant decreases in 24 h urine output (WT: 1.56 ± 0.15 mL/24 h vs. RMIC-Agtr1a-/-: 0.98 ± 0.13 mL/24 h, P < 0.01), urinary sodium (WT: 207.9 ± 7.3 μmol/24 h vs. RMIC-Agtr1a-/-: 145.2 ± 5.4 μmol/24 h, P < 0.01), and potassium excretion (WT: 221.0 ± 6.7 μmol/24 h vs. RMIC-Agtr1a-/-: 160.8 ± 10.6 μmol/24 h, P < 0.01), respectively. Moreover, urine osmolality was markedly decreased in RMIC-Agtr1a-/-mice (WT: 1724 ± 335 mOsm/Kg H2O vs. RMIC-Agtr1a-/-: 1128 ± 102 mOsm/Kg H2O, P < 0.01). Ang II infusion significantly increased telemetry systolic blood pressure to 148 ± 5 mmHg in WT mice, but it increased systolic blood pressure only to 129 ± 8 mmHg in RMIC-Agtr1a-/- mice (P < 0.01). Furthermore, infusion of Ang II for 2 weeks failed to restore urine osmolality in RMIC-Agtr1a-/- mice (1226 ± 110 mOsm/Kg H2O, n.s.).

Conclusions:
In conclusion, the results of the present study support the hypothesis that AT1a receptors in the RMICs of the kidney medulla plays a critical role in maintaining basal blood pressure homeostasis and the development of Ang II-induced hypertension.