bluuebunny/crossref_metadata_2025_split huggingface dataset:
VASCULAR AGEING MANIFESTATIONS AND RISK OF HYPERTENSION IN THE COMMUNITY. A CLUSTERING ANALYSIS OF CAROTID ECHO-TRACKING DATA ON 10,157 PARTICIPANTS
Authors: Alanis Guillermo Adrian , Boutouyrie Pierre , Bruno Rosa Maria , Abouqateb Mouad , Climie Rachel , Van Sloten Thomas , Danchin Nicolas , Laurent Stéphane , Jouven Xavier , Empana Jean -Philippe 
Published: May 2024

Objective:
To investigate the association between patterns of vascular ageing (VA) manifestations, and risk of hypertension in the community.

Design and method:
We used baseline (2008-2012) and follow-up data (up to 2020) from the Paris Prospective Study III, a French community-based prospective cohort including 10,157 volunteers. Baseline hypertension was defined as blood pressure equal or >140/90 mmHg or antihypertensive treatment use. Incident hypertension was defined as self-reported antihypertensive treatment at 2, 4, 6, 8, 10 years of follow-up. VA manifestations were assessed at baseline via echo-tracking in the right common carotid artery. Patterns of VA manifestations were identified using hierarchical clustering analysis. Associations between clusters of VA manifestations (main exposure) and prevalent and incident hypertension (outcomes) were assessed on separate logistic regression analysis.

Results:
The cross-sectional analysis included 8,839 study participants (mean age of 59±6 years, 39% female) without cardiovascular disease, among whom 3,129 (35.3%) were diagnosed with hypertension (74.8% with blood pressure equal or >140/90 mmHg and 40.8% under treatment). Three clusters of VA manifestations were identified. Cluster 1 (n=4,216;47.7%) was characterized by healthy vascular ageing (HVA) (low arterial stiffness and low prevalence of atherosclerosis). Cluster 2 (n=2,218;25.0%) was characterized by arterial stiffness (high local pulse wave velocity, beta stiffness index, pulse pressure, Young’s elastic modulus, and low distensibility coefficient). Cluster 3 (n=2,405;27.2%) was characterized by atherosclerosis (relative high prevalence of carotid plaques and high IMT). Compared to the HVA cluster, arterial stiffness (adjusted odds ratio [aOR]: 4.02; 95% CI 3.56;2.70) and atherosclerosis clusters (aOR 2.70; 95% CI 2.39;3.05) were associated with baseline hypertension independently of traditional risk factors. The longitudinal analysis included 5,384 normotensive participants (untreated blood pressure <140/90 mmHg) among whom 588 (10.9%) reported being under treatment after a median follow-up of 8.0 years (range: 7.9-9.4). In multivariate analysis, both arterial stiffness (aOR 1.45; 95% CI 1.15-1.82) and atherosclerosis (aOR 1.61; 95% CI 1.29-1.99) clusters were associated with anti-hypertensive treatment initiation.

Conclusions:
Vascular ageing manifestations reflecting carotid stiffness and carotid atherosclerosis are related to both prevalent and incident hypertension in the community.
DEFICIENCY OF THE COMPLEMENT RECEPTOR C5AR2 HAS NO EFFECT ON BLOOD PRESSURE AND END ORGAN DAMAGE IN ANGIOTENSIN II INDUCED HYPERTENSION
Authors: Dreher Leonie , Bode Marlies , Ehnert Nicolas , Herrnstadt Georg R. , Meyer-schwesinger Catherine , Köhl Jörg , Huber Tobias B. , Wenzel Ulrich O. 
Published: May 2024

Objective:
Complement activation plays an important role in development of hypertension and hypertensive end organ damage by affecting immunity and tissue integrity. The anaphylatoxin C5a, a key inflammatory mediator of the complement system, binds to the anaphylatoxin receptors C5aR1 and C5aR2. Recently we and others could demonstrate that C5aR1 knockout mice show reduced hypertensive renal end organ damage. However, the role of C5aR2 in hypertension remains unclear.

Design and method:
First, we investigated the expression of C5aR2 on infiltrating and resident renal and cardiac cells, using a tandem dye (td) tomato-C5aR2 knock-in reporter mouse. Flow cytometry analysis of leukocytes isolated from the kidneys of td tomato-C5aR2 reporter mice showed that dendritic cells were the major population expressing C5aR2 (34%), followed by monocytes/macrophages (30%) and neutrophils (14%). Confocal microscopy did not detect expression of C5aR2 in resident renal or cardiac cells.

Results:
Next, we examined the influence of C5aR2 deficiency on Ang II-induced hypertension and hypertensive end organ damage. To assess the role of C5aR2 deficiency in hypertensive injury, we used an aggravated model of hypertension including unilateral nephrectomy followed by infusion of Angiotensin (Ang) II (0.75 ng/g/min) and a high salt diet in both wildtype (n=12) and C5aR2 knockout mice (n=18). 9 normotensive mice served as controls.
No significant differences were observed regarding blood pressure, renal injury (albuminuria, glomerular filtration rate, glomerular and tubulointerstitial injury, inflammation), or cardiac injury (cardiac fibrosis, heart weight, gene expression) between hypertensive wildtype and hypertensive C5aR2-deficient mice.

Conclusions:
In summary, our findings showed that while C5aR2 is predominantly expressed on myeloid cells in the kidney, its deficiency does not appear to have an impact on Ang II-induced hypertensive injury.
THE INTERACTION BETWEEN GLOMERULAR FILTRATION RATE (GFR)-ADJUSTED URICEMIA AND INSULIN RESISTANCE IN PREDICTING MORTALITY: THE URRAH PROJECT
Authors: Russo Elisa , Viazzi Francesca , Pontremoli Roberto , Casiglia Edoardo , Desideri Giovambattista , D’Elia Lanfranco , Ferri Claudio , Galletti Ferruccio , Masulli Maria , Muiesan Maria Lorenza , Tikhonoff Valerie , Virdis Agostino , Grassi Guido , Borghi Claudio , Group Siia Working 
Published: May 2024

Objective:
Uric acid (UA) and insulin resistance (IR) are interlinked: UA contributes to adversely affect the insulin signaling pathway, while IR predicts the development of hyperuricemia. Both UA and IR are related to metabolic syndrome, which is nowadays one of the most prevalent risk factors for mortality. In the clinical scenario, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been proved to have a high correlation with IR. The aim of the research was to explore the interplay between IR and GFR-adjusted uricemia (UA/GFR) in determining mortality risk in a large study cohort.

Design and method:
Data from 18,694 subjects were included from Uric acid Right foR heArt Healt (URRAH) database. Differences between TG/HDL-C quintiles were evaluated by t-test or chi-square test. We evaluated the association between TG/HDL-C and UA/GFR, and the development of outcomes during the follow-up study period. The primary endpoint was all-cause mortality. The Kaplan-Meier method and Cox proportional hazard regression models were used to analyze the prognosis.

Results:
After a mean follow-up of 124±64 months, there were 2,665 (14.2%) deaths for all causes. The incidence of fatal, non-fatal cardiovascular events, and all-cause mortality increased in parallel with the increase of TG/HDL-C quintiles. In both diabetic and non-diabetic patients, TG/HDL-C showed a positive association with UA/GFR, and TG/HDL-C and UA/GFR significantly interact in determining all-cause mortality. Along with the increase of TG/HDL-C quintiles, we observed a statistically significant increase in the rate of mortality (P <0.0001), independently by uricemia, GFR, body mass index (BMI) and the presence of diabetes (Figure 1).
Multivariate analysis showed that the TG/HDL-C increases the risk for mortality even after adjustment for potential confounding factors included age, diabetes, UA/GFR, BMI and statins treatment (Table 1).

Conclusions:
TG/HDL-C and UA/GFR interact in the prediction of death. Both IR and UA/GFR impact on all-cause mortality, independently of age, gender, diabetes, hypertension and statins. These findings provide evidence of the interactive relationship between hyperuricemia and the impairment in insulin sensitivity in their contribution to the mortality risk, independently by renal function.
RESTING HEART RATE AND MORTALITY RISK IN HYPERTENSIVE PATIENTS WITH NO ATRIAL FIBRILLATION
Authors: Pittaras Andreas , Kokkinos Peter , Faselis Charles , Grassos Charalampos , Doumas Michael , Kallistratos Emmanouil , Manolis Athanasios , Samuel Immanuel Babu 
Published: May 2024

Objective:
The recent ESH Guidelines include elevated resting heart rate (RHR) as an independent risk factor among the established and suggested novel risk factors that influence cardiovascular risk in patients with hypertension, indicating sympathetic overdrive. Increased fitness affects both mortality and RHR. However, the association between RHR and mortality risk, adjusted for cardiorespiratory fitness, age, comorbidities and medication has not been fully explored.

Design and method:
We evaluated the association between RHR and mortality in 422,702 hypertensive patients (mean age 62.5 ± 8.6 years) with no evidence of atrial fibrillation during the entire follow-up. All completed a standardized exercise treadmill test (ETT), with no evidence of overt heart disease prior to and at the time of the ETT. To assess the risk in a wide and clinically relevant spectrum, we established 6 RHR categories per 10 heartbeat intervals ranging from <=60 to >100 beats. We used multivariable Cox regression to assess the RHR-mortality association. We adjusted the models for age, body mass index, cardiac risk factors, exercise capacity, and medications (including b-blockers).

Results:
During the median follow-up of 10.6 years, providing 4,551,327 person-years, there were 107,863 deaths with an average annual rate of 23.7 events per 1,000 person-years. We noted approximately 7% increase in risk for each 10 heart beats. Mortality risk was significantly elevated at a RHR of >80 beats/min (HR; 1.15, CI; 1.12 - 1.17; p <0.006) and increased progressively to 41% (HR; 1.41, CI; 1.36 - 1.45; p <0.001) for those with a RHR of >100 beats/min. Similar trends were noted for subjects aged <60; 60-69; and >=70 years and those treated with b blockers. In all assessments, mortality risk was consistently overestimated when fitness was not considered.

Conclusions:
We noted a progressive increase in mortality risk with increased RHR at >80 bpm in hypertensive patients with no AF. The association was independent of comorbidities, and medications.
LONG-TERM CLINICAL OUTCOME OF PHYSIOLOGY-GUIDED RENAL ARTERY STENTING WITH ZETAROLIMUS ELUTING STENTS IN PATIENTS WITH UNCONTROLLED RENOVASCULAR HYPERTENSION
Authors: Galli Verdiana , Trento Laura , Salfa Federica , Fezzi Simone , Trevisanello Aurora , Galuppi Enrico , Casal Matteo , Piscopo Matteo , Scarsini Roberto , Pesarini Gabriele , Gambaro Alessia , Ferrero Valeria , Tavella Domenico , Ribichini Flavio Luciano 
Published: May 2024

Objective:
Randomized clinical trials (RCTs) failed to demonstrate the superiority of renal artery stenting (RAS) on optimal medical therapy (OMT) alone in terms of blood pressure (BP) control, renal function stabilization and cardiovascular events in patients with renal arteries stenosis (SRA). Main limitations of these trials are the lack of clear diagnostic criteria to identify hemodynamically significant SRA and the use of bare metal stents. Aim of the study was to assess safety and efficacy of RAS with new-generation zotarolimus-eluting stents in uncontrolled renovascular hypertension, after hemodynamic flow-limitation assessment by invasive pressure-wire (PW).

Design and method:
From 2012 to 2022, patients with suspected renovascular uncontrolled hypertension despite OMT and rapid renal function decline were enrolled. Lesions of at least intermediate angiographical significance were analyzed with PW measurements. A pressure ratio between the distality of the diseased vessel and the aortic pressure without hyperemia (Pd/Pa) below 0.9 was considered as potentially responsible of renal ischemia. In 21 patients out of 40 interrogated, 25 SRA yielded a Pd/Pa<0.9 and therefore treated with ZES implantation. Primary endpoint of the study was systolic and diastolic office blood pressure (OBP) variation at 2 years. Secondary endpoints included the impact of RAS on renal function and cardiovascular events.

Results:
Baseline average OBP was 160.0±22.4/84.7±9.8mmHg. At a median follow-up of 17 months, a significant OBP reduction was observed, respectively by -16,7±23.7mmHg (systolic, p=0.006) and -9,7±14.7mmHg (diastolic, p=0.01). Glomerular filtration rate confirmed to be stable with a trend towards improvement by +2.87±10.44 ml/min/1.73m2. No procedure-related complications were reported. During the follow-up period, two episodes of hypertensive crisis, two myocardial infarction and three admissions for acute renal impairment were reported.

Conclusions:
SRA is one of the most frequent causes of secondary hypertension, with high rates of clinical events. Previous RCTs yielded negative results in demonstrating benefits either on BP control or renal function. Our experience suggests that functional guidance to identify appropriate candidates for RAS can be effective. Moreover, this is the first cohort of RAS implanted with new-generation ZES, that may have further improved clinical results because of the reduced risk of restenosis.
CAROTID-FEMORAL PULSE WAVE VELOCITY PROGRESSION IN HYPERTENSIVE PATIENTS IS ASSOCIATED WITH SUBSEQUENT CV OUTCOMES
Authors: Maloberti Alessandro , Rebora Paola , Occhino Giuseppe , Andreano Anita , Intravaia Rita Cristina My , Tognola Chiara , Toscani Giorgio , Morelli Martina , Pezzoli Stefano , D’Oro Luca Cavalieri , Russo Antonio , Giannattasio Cristina 
Published: May 2024

Objective:
Arterial stiffness (Pulse Wave Velocity-PWV) is associated with CV events and mortality. However, little is known on the relationship of its progression (δ PWV) over time with CV outcomes. The aim of our study was to evaluate the relationship between PWV progression and all-cause mortality and CV events in hypertensive subjects.

Design and method:
We enrolled 402 consecutive hypertensive outpatients. At baseline anamnestic, clinical, BP, laboratory data and PWV were assessed. We performed a PWV follow-up examination at a median time of 3.7±0.5 years. Patients were subsequently followed for a median time of 10.1 (IQR 9.5-10.5) years recording all-cause mortality and CV events.

Results:
At baseline the mean age was 53.2±13.0 years, SBP and DBP were 141.8±17.5 and 86.8±10.5 mmHg and PWV was 8.5±1.9 m/s. Despite an improvement in BP control (-9.2±19.5 and -8.0±12.3 for SBP and DBP respectively), at follow-up the population showed a PWV increase (δPWV +0.6±1.9 m/s). Progressors (δ PWW > 0.5 m/s, 204 patients, 50.7%) had a significantly lower survival probability and higher cumulative incidence of composite events, while no differences were seen for CV events (unadjusted analysis). At cox multivariable analysis neither δ PWV > 0.5 m/s (progressors) nor δ PWV (as a spline function) were associated with CV events and with all-cause mortality. However, the association with survival probability and cumulative incidence of CV events, as a composite outcome, was significant (HR = 2.32, 95% CI: 1.33 – 4.04, p=0.003).

Conclusions:
In conclusion, our study shows that PWV progression of at least 0.5 m/s is frequent in hypertensive patients and that it is associated with a significantly higher risk of developing CV events or dying (composite outcome).
ASSOCIATION OF HYSTERECTOMY WITH HYPERTENSION INCIDENCE IN KOREAN WOMEN: A NATIONWIDE COHORT STUDY
Authors: Kim Byung -GYU , Yuk Jin -Sung , Kim Gwang Sil , Byun Young Sup , Kim Myoung -Hwan , Yoon Sang -Hee 
Published: May 2024

Objective:
Although several observational studies have reported a higher risk of cardiovascular events in women who underwent hysterectomy, the underlying mechanism is unclear, and limited data exist regarding the effect of hysterectomy on the incidence of hypertension. We sought to evaluate the association between hysterectomy and the development of hypertension in Korean women aged 40–59 years.

Design and method:
In this Korean nationwide cohort study, 803,255 women aged 40-59 years were selected for analysis from January 1, 2002, to December 31, 2011. In total, 13,650 pairs were included in the hysterectomy and non-hysterectomy groups after 1:1 propensity score matching for age at 5-year intervals, year of inclusion, socioeconomic status, body mass index, residential region, Charlson comorbidity index, menarcheal age, menopause, diabetes, dyslipidemia, physical activity, smoking history, alcohol consumption, menopausal hormone therapy before inclusion, adnexal surgery history, uterine leiomyoma, and endometriosis. The primary outcome was the development of hypertension during follow-up. The participants were followed-up until December 31, 2020. Data analysis was performed from July 16, 2022 to January 07, 2023.

Results:
During median follow-up periods (10.6 years [IQR 9.2-12.6]; 10.9 years [IQR 9.2-12.7]), the incidence of hypertension was 22/1,000 person-years and 20/1,000 person-years for the hysterectomy and non-hysterectomy groups, respectively. The hysterectomy group had a significantly higher rate of development of hypertension than that of the non-hysterectomy group (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.05-1.17). The risk was prominent in women whose hemoglobin level increased by >2g/dL post-hysterectomy. In women who had an adnexa-sparing hysterectomy, the incidence of hypertension was higher (HR, 1.15; 95% CI 1.08-1.23, P <0.001) than that in the non-hysterectomy group.

Conclusions:
In this nationwide cohort study of Korean women revealed that hysterectomy was independently associated with an increased risk of hypertension among women aged 40 to 59. In particular, this risk elevation was prominent when the hemoglobin level increased by >2g/dL after hysterectomy, suggesting that hemorheologic changes following hysterectomy may have an impact on the occurrence of hypertension.
USING A MULTI-OMICS LANDSCAPE OF THE MATERNAL-FETAL INTERFACE TO MODEL THE LONGITUDINAL PATHOGENESIS OF EARLY-ONSET PRE-ECLAMPSIA
Authors: Nonn Olivia , Debnath Olivia , Valdes Daniela , Frolova Alina , Haider Sandra , Verlohren Stefan , Thilaganathan Basky , Kaituu-lino Tuuhevaha J , Tong Stephen , Staff Anne Cathrine , Coscia Fabian , Müller Dominik N. , Dechend Ralf , Gauster Martin , Ishaque Naveed , Herse Florian 
Published: May 2024

Objective:
Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications. We currently lack efficient screening tools and early therapies to address PE.

Design and method:
To identify candidate biomarkers and operative pathways in early onset PE (eoPE, severe PE with onset before week 34), we performed spatio-temporal multi-omics profiling of human eoPE placentae and healthy controls, and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-sequencing combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms.

Results:
We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts in eoPE. We found a significant increase in the senescence markers in preeclamptic maternal serum in early gestation and late gestation, before the development of clinical symptoms, indicating that the placental syndrome drives systemic maternal syndrome, even before clinical manifestation of eoPE.

Conclusions:
Our work describes a new disease progression model, starting with dysregulated transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.
POSTERIOR REVERSIBILE LEUKOENCEPHALOPATHY SYNDROME AND HYPERTENSIVE CRISIS DUE TO OBSTRUCTIVE SLEEP APNEA:SEARCHING FOR A LINK
Authors: Torin Gioia , Schiavon Laura , Molinari Leonardo , Pontesilli Giulia Maria , Napoli Ettore , Milan Marta , Rizzati Silvia , Moroldo Alessandro , Cerbo Anna , Roversi Rossella , Martire Giuseppe , Cuppini Stefano , Mazza Alberto 
Published: May 2024

Objective:
Posterior Reversible Encephalopathy Syndrome(PRES) is a clinic-radiological syndrome characterized by headache, nausea/vomiting, confusion, cognitive changes, seizures,cortical blindness. MRI shows bilateral hyper-intense lesions at the parieto-occipital sub-cortical level on T2 and FLAIR sequences. PRES is associated with severe hypertension, while obsstructive sleep apnesa(OSA) is a common cause of secondary hypertension but rarely causes hypertensive encephalopathy. We present a case of a 42-year-old woman who suffered of hypertensive emergency during hospitalization for dyspnea.

Design and method:
Clinical history revealed obesity, COPD, OSA in treatment with CPAP, HF with depressed EF (44%), adrenal hyperplasia and retroduodenal lesion under investigation. She was active smoker and BP was uncontrolled by valsartan 160 mg, furosemide 25 mg,bisoprolol 2,5 mg.
During the hospitalization in November 2023, patient presented headache, seizures, respiratory distress with high BP values (220/120 mmHg, HR 78 bpm).

Results:
Laboratory tests revealed only a mild increase of plasma cortisol levels (27.5 mcg/dL, range 0-24); low-dose overnight dexamethasone suppression test was normal (1.5 mcg/dl). Despite anti-hypertensive therapy with B-blocker urinary metanephrine levels were normal (184 mcg/24 h, range 0-320) and 18f-FDG PET-TAC for retroduodenal lesion was normal.
Cerebral CT did not show ischemic or hemorrhagic lesions while MRI documented radiological characteristics compatible with PRES (Figure 1). Electroencephalogram showed no epileptic abnormalities.
Antihypertensive intravenous treatment with urapidil (25 mg as bolus injection followed by 25 mg/h as continuous infusion) was performed for 36h and followed by oral treatment with canrenoate 25 mg, amlodipine 5 mg and doxazosin 4 mg, added to the above therapy. At discharge, BP was normalized (120/84 mmHg).
Checking the electronic card of CPAP, the patient used the device for more than four hours only in 35% of the nights.

Conclusions:
OSA is a risk factor for acute cardiovascular and cerebrovascular diseases like PRES.
CPAP application has been shown to induce small reductions (about 3 mmHg) in BP, but in clinical practice the adherence of treatment is very low (30-60%). On the other hand, the improvement of BP values during hospitalization, raises the suspicion that adherence to pharmacological treatment at home was in the same way poor.