bluuebunny/crossref_metadata_2025_split huggingface dataset:
DOES ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR EXACERBATE RENAL FUNCTION IN PATIENTS WITH CHRONIC KIDNEY DISEASE?
Authors: Suehiro Yohei , Sugano Naoki , Kidoguchi Satoshi , Yokoo Takashi 
Published: May 2024

Objective:
Angiotensin receptor neprilysin inhibitor (ARNI) is a new drug with potent antihypertensive effect and has been reported to exert cardiovascular protection in the patients with heart failure. On the other hand, recent meta-analyses revealed that the use of ARNI may increase urinary protein excretion in those with chronic kidney disease (CKD). Thus, whether ARNI has renal protective effect in CKD patients remains unclear. Therefore, we examine the change of renal function and proteinuria before and after the treatment with ARNI.

Design and method:
A total of 88 patients who were started to receive sacubitril/valsartan at our hospitals between September 2021 and March 2023 were included. We evaluated the change of estimated glomerular filtration rate (eGFR), urinary protein excretion, and blood pressure before and six months after the administration of sacubitril/valsartan among the following three groups; 1) those without CKD (non-CKD), 2) those with mild kidney impairment (CKDG3), and 3) those with advanced kidney impairment (CKDG4/5).

Results:
Regarding eGFR and urinary protein, no significant changes were observed during six months in all the groups. The rates of changes in eGFR during the study period were equivalent among three groups (non-CKD, CKDG3, CKDG4/5; -7.3% ±15.4, -2.5% ±15.3, 0.3% ±3.1, P=0.48), which were not different from the rates of changes in the preceding six months. The changes in urinary protein were also similar among three groups (non-CKD, CKDG3, CKDG4/5; 0.01 g/gCr Interquartile Range {IQR} -0.01 to 0.04, -0.015 g/gCr IQR -0.17 to 0.04, 0.01 g/gCr IQR -0.77 to 0.70, P=0.53). In contrast, the treatment with sacubitril/valsartan equally exerts antihypertensive effect for all the groups (non-CKD, CKDG3, CKDG4/5; -9.7 mmHg ±15.4 P<0.05, -11.0 mmHg ±14.7 P<0.05, -8.0 mmHg ±14.7 P<0.05).

Conclusions:
The present study could not reveal renal protective effects of sacubitril/valsartan, whereas could show a potent antihypertensive effect without worsening renal function in the patients with CKD.
INCREASE IN ARTERIAL STIFFNESS IN LIVING KIDNEY DONORS AFTER RENAL DONATION
Authors: Kannenkeril Dennis , Günes-altan Merve , Bosch Agnes , Striepe Kristina , Heller Katharina , Schiffer Mario , Janka Rolf , Amann Kerstin , Schmieder Roland E. 
Published: May 2024

Objective:
Low glomerular filtration rate (GFR) is associated with high cardiovascular mortality and morbidity. Living kidney donor’s vascular characteristics have been poorly investigated till now. In this analysis, living kidney donors were followed up with respect to vascular parameters for one year after renal donation.

Design and method:
Blood pressure (BP) and different arterial stiffness parameters were assessed before, 6 months and 1 year after renal donation using a 24-hour blood pressure device (Mobil-o-graph®). Cortical, medullary and total renal perfusion of the donors were assessed using Arterial Spin Labeling MRI before and 6 months after donation. Preimplantation biopsy of the donor kidney was obtained. Biopsies were scored for glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis, which was combined to a total renal chronicity score. Living donors with and without chronic renal histological changes were compared.

Results:
Twenty five living kidney donors with mean age of 54±9.4 were followed up for one year. The estimated GFR and urinary albumin creatinine ratio (UACR) were 87.7±15.9ml/min/1.73m2 and 19.5±18.4mg/g creatinine respectively at baseline. 12months after renal donation the eGFR was 55.6±10.9 ml/min/1.73 m2 and the UACR was 19.5±12.2mg/g creatinine. Pulse wave velocity (7.5±1.4 vs. 7.8±1.4;p=0.001), peripheral resistance (1.1±0.19 vs. 1.23±0.19;p=0.003), and augmentation index (heart rate corrected) (24.4±5.5 vs. 26.7±6.1;p=0.025) over 24 hours increased significantly 12months after donation, while no change has been noticed in systolic and diastolic BP. A relationship has been found between eGFR at baseline and mean 24-hour pulse wave velocity at 12months (r=-594, p=0.002). An increase in cortex perfusion was found 6 months after donation (351±53.4 vs. 88±40.7;p=0.013). The 24-hour systolic BP (116.6±6.8 vs. 129.1±10.7;p=0.011), -diastolic BP (73.2±4.4 vs. 81.3±5.6;p=0.006) and -central BP (118.6± 8.9 vs. 128.9±7.7;p=0.013) at 12 months post donation was significantly higher in donors with renal histological changes compared to donors without renal histological changes, while no difference in BP was noticed at baseline between thesegroups.

Conclusions:
Our data indicates that arterial stiffness increases after living kidney donation. This can be interpreted as an early change before increase in BP. Living donors with chronic renal histological changes tend to develop high BP after donation.
ASSOCIATION BETWEEN ORTHOSTATIC HYPERTENSION AND FRAILTY AMONG OLDER PATIENTS WITH HYPERTENSION
Authors: Kim Kwang Il , Choi Jung -Yeon , Ryu Dong Ryeol , Lee Hae -Young , Cho Myeong -Chan , Kim Cheol -Ho 
Published: May 2024

Objective:
Frailty frequently co-exists with hypertension in older patients. We aimed to evaluate the association between frailty and positional change in blood pressure, especially orthostatic hypertension.

Design and method:
Participants were recruited from 12 University hospitals in South Korea. Using a digital device, trained research nurses measured blood pressure in the supine and standing positions. Physical frailty was evaluated using the Korean version of the FRAIL questionnaire, gait speed, and hand-grip strength. Orthostatic hypertension was defined as a >= 20-mmHg increase in systolic blood pressure within 3 min of standing and upright systolic blood pressure of >= 140 mmHg.

Results:
We analyzed the data of 2,065 participants who had been enrolled until December 31, 2022. The mean age was 73.2 ± 5.6 years and 52.0% were female. The mean blood pressure was 137.1 ± 14.9 / 75.1 ± 9.7 mmHg. Among the participants, 1,886 (91.3%) showed normal response after standing, but 94 (4.6%) had orthostatic hypertension, and 85 (4.1%) had orthostatic hypotension. Orthostatic hypertension was associated with female sex, obesity, cognitive function, physical frailty, and lower quality of life (QOL). In the multivariable analysis, body mass index and frailty status were independently associated with orthostatic hypertension.

Conclusions:
Orthostatic hypertension is associated with physical frailty, cognitive impairment, and low QOL in older patients with hypertension. Therefore, evaluation of orthostatic blood pressure changes to confirm orthostatic hypertension or hypotension in frail older adults will serve as an important diagnostic procedure in vulnerable patients. Further studies are required to identify the underlying mechanisms of this association.
ASSOCIATION OF BLOOD PRESSURE WITH MORTALITY IN OLDEST OLD PEOPLE WITH FRAILTY IN CHINA: RESULTS FROM CHINESE LONGITUDINAL HEALTHY LONGEVITY SURVEY (CLHLS)
Authors: Liu Lu , Ruan Haiyan , He Sen , Chen Xiaoping 
Published: May 2024

Objective:
To determine the target blood pressure in old people (80+ years) with frailty.

Design and method:
In this community based, longitudinal prospective study, we enrolled 3,134 oldest old people with frailty. The exposure-response associations between blood pressure and all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality were assessed by the penalized cubic splines fitted in Cox models.

Results:
During 5 years follow-up, 2,532 deaths were documented. An approximate L-shaped association between systolic blood pressure (SBP) and 5-year all-cause mortality was identified. Compared with 140 mmHg (inflection point), the risk of all-cause mortality significantly increased for SBP below 127 mmHg, which varied from HR of 1.050 (95% CI: 1.003-1.100) to 1.576 (95% CI: 1.128-2.203). After 140 mmHg, mortality risk gradually fell with increasing SBP, although not reaching statistical significance. Diastolic blood pressure (DBP) suggested a significant U-shaped association with 5-year all-cause mortality with 90 mmHg conferred the lowest risk. Before that, the risk of all-cause mortality rose with decreasing DBP, which varied from HR of 1.041 (95% CI: 1.001-1.082) to 1.304 (95% CI: 1.005-1.692). After 90 mmHg, although the observed differences were not statistically significant, mortality risk tended to rise with increasing DBP. Among the 2,037 participants with a confirmed cause of death, 346 died from CVDs and 1,691 died from non-CVDs. In comparison with 120 mmHg, SBP above 134 mm Hg exhibited a significantly elevated CVD mortality risk; when SBP below 121 mmHg, significantly increased non-CVD mortality risk could be found in comparison with SBP at 140 mmHg. As for DBP, it could not predict CVD mortality risk; there was an approximate U-shaped association between DBP and non-CVD mortality that DBP below 69 mmHg was associated with a higher risk with 85 mmHg as the reference. Stratified and sensitivity analyses showed robustness of main findings.

Conclusions:
In the oldest old people with frailty, in addition to all-cause mortality, blood pressure management should balance CVDs risk and non-CVD risk. Maintaining blood pressure at 120-140/80-100 mmHg can reduce all-cause mortality risk and meanwhile may prevent the adverse events due to excessively higher or lower blood pressure.
BLOOD PRESSURE EFFECTS OF TRAZODONE IN HYPERTENSIVE OLDER ADULTS
Authors: Capacci Marco , Rivasi Giulia , Ceolin Ludovica , Turrin Giada , Rossi Lorenza , Menale Silvia , Bisignano Maria Francesca , Liccardo Alessandra , Mossello Enrico , Ungar Andrea 
Published: May 2024

Objective:
Trazodone is commonly prescribed in older adults and may have hypotensive effects due to the inhibition of alpha-adrenergic receptors.
The present study aimed to investigate the effects of trazodone on blood pressure (BP) and its related risk of syncope and falls in hypertensive older adults.

Design and method:
A longitudinal observational study involving patients aged 75 or older was conducted at the Hypertension Clinic and Memory Clinic of the Division of Geriatric and Intensive Care Medicine, Careggi Hospital, Florence. Participants underwent multidimensional geriatric assessment including office BP measurement, 3-minute active stand test (BP measurement immediately after standing [T0] and at 1 [T1] and 3 minutes [T3]), home and ambulatory BP monitoring. The composite outcome of syncope and falls was assessed at 12 months and its association with trazodone was analysed using multivariate Cox regression analysis.

Results:
Among 123 participants (mean age 81 years, 59% female), 12 (10%) reported regular trazodone use. Participants receiving trazodone showed lower office diastolic BP (71.8 mmHg vs. 80.1 mmHg, p=0.042) and a greater systolic and diastolic BP reduction immediately after standing (δsystolicT0 16.2 mmHg vs. 9.7 mmHg, p=0.038; δdiastolicT0 11 mmHg vs. 1.7 mmHg, p=0.003). No differences were reported as regards home and ambulatory BP. Incidence of syncope and falls at 12 months was 25%, with a significantly higher rate in patients receiving trazodone (58.3% vs. 21.2%, p=0.005). Trazodone was associated with an increased risk of syncope or falls independently of physical performance (HR 2.654, 95% CI 1.104 - 6.378). This association was not confirmed when multivariate Cox analysis was adjusted for dementia diagnosis (HR for trazodone 1.874, 95% CI 0.736 – 4.773; HR for dementia 2.556, 95% CI 1.018 – 6.419).

Conclusions:
In older adults with hypertension, trazodone is associated with a greater orthostatic BP drop and might increase the risk of syncope and falls.
PROGNOSIS OF RESISTANT HYPERTENSION IN KOREAN HYPERTENSIVE PATIENTS: A NATIONWIDE OBSERVATIONAL COHORT STUDY
Authors: Lee Chan Joo , Lee Ho Kyu , Seo Jiwon , Kang Dayoung , Hwang Jinseub , Park Sungha , Pyun Wook Bum 
Published: May 2024

Objective:
The prognosis of resistant hypertension is known to be worse than that of non-resistant hypertension, but studies on the prevalence and outcomes of resistant hypertension in Korean hypertensive patients are scarce.

Design and method:
A total of 2,086,208 patients, a 25% sample of hypertensive patients, were extracted from the Korean National Health Insurance Service Database from 2013 to 2018. Among them, excluding patients with missing values and those with a history of cardiovascular disease, a total of 935,169 patients were divided into resistant hypertension and non-resistant hypertension with a target blood pressure of 140/90 mm Hg. The primary outcome was a composite of all-cause death, myocardial infarction, stroke, and heart failure events during follow-up. Secondary outcomes were individual events of the primary outcome, end-stage renal disease (ESRD), and atrial fibrillation.

Results:
The average age of all subjects was 62.3 ± 11.4 years, and 50.1% were men. The prevalence of resistant hypertension was 7.4%. Compared with non-resistant hypertensive patients, resistant hypertensive patients were older, more likely to be male, smokers, non-exercisers, and obese, and had a higher prevalence of diabetes, dyslipidemia, and chronic kidney disease. The median follow-up duration was 6.0 years. The incidence of the primary outcome was 32.7 and 21.5/1000 person-years in the resistant and non-resistant hypertension, respectively. In a multivariable Cox proportional hazards analysis adjusting for age, sex, BMI, alcohol consumption, exercise, income, and comorbidities, the hazard ratio for the primary outcome was 1.32 (95% CI, 1.29-1.35, p<0.001) for resistant hypertension compared with non-resistant hypertension. The risk of all-cause death, myocardial infarction, stroke, heart failure, and atrial fibrillation were each significantly higher in patients with resistant hypertension, and the risk of ESRD was three times higher.

Conclusions:
This large-scale nationwide observational study showed that Korean patients with resistant hypertension have a significantly higher risk of clinical events compared with non-resistant hypertensive patients, with results like those of the previous studies from other countries. This study emphasizes the need to pay more attention to managing resistant hypertension.
TREAT TRIAL: MULTI-CENTER CROSS-SECTIONAL TREATMENT EVALUATION OF APPARENT RESISTANT HYPERTENSION IN BELGIUM
Authors: Brouwers Sofie , Huart Justine , Chabot Mathilde , Van Nieuwenhuyse Bregt , Munhoz Daniel 
Published: May 2024

Objective:
The goal of the TREAT study is to evaluate the prevalence of apparent treatment-resistant hypertension (aRHT) in a Belgian setting and to evaluate which determining factor of pseudo-resistant hypertension contributes the most to this prevalence: white coat hypertension (WCH), underdosing of adequate drugs or poor adherence to prescribed medicines.

Design and method:
TREAT is a single-visit, multicentric, non-interventional, cross-sectional survey. Inclusion criteria were the following: patients over 18 years old receiving 3 or more antihypertensive molecules and referred to specialized hospital centres for aRHT. The data were collected according to the patient’s medical records. Self-reported adherence to antihypertensive treatment was collected and a Hill-bone medication adherence scale was also proposed.

Results:
A total of 232 patients were included. Mean anti-hypertensive treatment duration was 10.6(±9.1) years. Patients were treated with a mean of 3.8(±1.1) antihypertensive molecules and 2.8(±1.1) antihypertensive pills. Only 48.5% of the aRHT patients were treated with the triple therapy recommended by the 2023 ESH hypertension guidelines (i.e. renin-angiotensin-aldosterone system inhibitor (RAASi), calcium channel blocker (CCB) and diuretic), and only 29.1% of patients were treated with the maximal recommended dose. Inadequate dosing was mostly present with diuretics, only 60% of patients was treated with at least half the maximum dose of a diuretic. WCH was present in 11% of patients in whose ambulatory BP measurements were available in records (n=136). Therapeutic adherence was self-reported as poor or moderate in 17.6% of patients (n=41). The Hill-bone medication adherence scale (n=140, 60.4%) showed a mean score of 12(±4.2) (good adherence). In this cohort, 31.8% of patients seemed to have true resistant hypertension.

Conclusions:
Among patients referred to specialized centres for aRHT, about 2/3 of patients have in reality pseudo-resistant hypertension. Whereas WCH and poor adherence seems to be limited in our dataset, many patients were polymedicated with non-recommended combinations of antihypertensive molecules in 1 out of 2 patients, with inadequate dosing in 2 out of 3 patients. Pseudo-resistant hypertension seems in our cohort to be mainly related to under-use of triple combination therapy and most likely also due to underdosing.
EFFECT OF SEQUENTIAL NEPHRON BLOCKADE X DUAL RENIN-ANGIOTENSIN SYSTEM BLOCKADE + BISOPROLOL IN THE TREATMENT OF RESISTANT HYPERTENSION, A RANDOMIZED CONTROLLED TRIAL (RESHYPOT)
Authors: Cestario Elizabeth Do Esp , Vilela-martin José Fernando , Cosenso-martin Luciana Neves , Rubio Tatiane Azevedo , Uyemura Jessica Rodrigue Roma , Da Silva Lopes Valquiria , Fernandes Letícia Aparecid Barufi , Tacito Lucia Helena Bonalume , Junior Heitor Moreno , Yugar-toledo Juan Carlos 
Published: May 2024

Objective:
The primary aim was to compare sequential nephron blockade (SNB) versus dual renin-angiotensin system blockade (DRASB) plus bisoprolol in patients with resistant hypertension to observe reductions in systolic and diastolic blood pressure (SBP and DBP) levels after 20 weeks of treatment.

Design and method:
This trial was an open-label, prospective, randomized, parallel-group, clinical study with optional drug uptitration. Participants were evaluated during five visits at 28-day intervals.

Results:
The mean age was 55.5 years in the SNB and 58.4 years in the DRASB + bisoprolol group (p=NS). Significant office BP reductions were observed in both groups. SNB group, SBP decreased from 174.5±21.0 to 127.0±14.74 mmHg (p<0.0001), and DBP decreased from 105.3±15.5 to 78.11±9.28 mmHg (p<0.0001). DRASB group, SBP decreased from 178.4±21.08 to 134.4 ± 23.25 mmHg (p<0.0001) and DBP decreased from 102.7±11.07 to 77.33±13.75 mmHg (p<0.0001). Ambulatory blood pressure monitoring
(ABPM) showed also significant SBP and DBP reductions in both groups (p<0.0001). Central systolic blood pressure had a greater reduction in the SNB group pre x post-intervention (128.8± 22.1 x 117.4± 17.9) (p = 0.03).

Conclusions:
In patients with RHTN adherent to treatment, SNB and DRASB plus bisoprolol showed excellent therapeutic efficacy, although SNB was associated with earlier SBP reduction and a greater reduction in Central systolic blood pressure.
LONG-TERM FOLLOW-UP OF PATIENTS WITH HIGH ALDOSTERONE-TO-RENIN RATIO BUT NEGATIVE CONFIRMATORY TEST FOR PRIMARY ALDOSTERONISM
Authors: Buffolo Fabrizio , Pecori Alessio , Reincke Martin , Outland Merve , Veglio Franco , Schwarzlmüller Paul , Bidlingmaier Martin , Kunz Sonja , Stremmel Christopher , Mengozzi Giulio , Priolo Gabriella , Mulatero Paolo , Adolf Christian , Monticone Silvia 
Published: May 2024

Objective:
About 10% of patients with hypertension has elevated aldosterone-to-renin ratio and 50-70% of them have a negative confirmatory test for primary aldosteronism (PA). However, the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing for PA, with a follow-up comprised between 2 and 8 years.

Design and method:
A total of 184 patients with a previously positive screening test for PA followed by a negative confirmatory test were enrolled in two hypertension centres: Torino and München. We repeated the screening test for PA and, if positive, the confirmatory test: either seated saline infusion test or captopril challenge test.

Results:
About 20% of patients had confirmed PA diagnosis after a mean follow-up of 5 years: 16% in Torino and 24% in München. When subtype diagnosis was offered systematically, 31% of patients displayed a unilateral form of PA. Patients with new onset of PA showed higher systolic blood pressure (142±17 versus 133±12 mmHg, P=0.005), diastolic blood pressure (89±8 versus 85±9 mmHg, P=0.007) and a higher rate of cardiac organ damage (60.9% versus 35.8%, P=0.031) than patients without PA, despite similar implementation of anti-hypertensive therapy. A mild progression of autonomous aldosterone secretion was present even in patients without confirmed PA, with increase of aldosterone post-saline infusion test (3.3 [2.3-4.3] versus 4.5 [3.5-5.4] ng/dL; P<0.001), but with relatively stable blood pressure levels. Among patients without PA, aldosterone post-saline infusion test at follow-up was positively associated with the follow-up time (β 0.262 [0.005; 0.520]; P=0.046).

Conclusions:
One fifth of patients with a negative confirmatory test for PA develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, especially in patients with worsening of blood pressure control.
MYOCARDIAL MECHANO-ENERGETIC EFFICIENCY CHANGES IN PRIMARY ALDOSTERONISM PATIENTS
Authors: Muiesan Maria Lorenza , Stassaldi Deborah , Capellini Sara , Rosei Claudia Agabiti , Bertacchini Fabio , Aggiusti Carlo , Salvetti Massimo , Paini Anna , De Ciuceis Carolina , Dusi Margherita , Camossi Roberto , Ghignatti Simone , Buso Giacomo 
Published: May 2024

Objective:
Cardiac organ damage has been found to be highly prevalent in primary aldosteronism (PA), possibly contributing to the increased risk of cardiovascular events. We reported a lower myocardial mechanoenergetic efficiency index (MEEi) in patients with PA as compared with essential hypertensive patients, possibly reflecting an impairment of production and utilization of energy in the myocardium. We analyze changes of echocardiographic parameters of cardiac anatomy and function, including MEEi, in a group of PA patients with a long-term follow-up (FU).

Design and method:
One-hundred-sixty-six patients (age 49 ± 10 years, 42% women) with PA underwent echocardiography and clinical evaluation at time of diagnosis and during FU (mean 85 ± 54 months) of treatment (23% adrenalectomy, 77% medical treatment). MEEi was obtained as the ratio between stroke volume and heart rate (HR) and normalized per grams of LV mass and δMEEi was calculated as difference between follow-up and baseline MEEi.

Results:
In the whole group a significant decrease in Blood Pressure (from 147/91mmHg to 132/81 mmHg p=0.0001) was observed, while body mass index (BMI) was increased (p=0.05) during FU. A decrease in LV mass index was observed (from 46.0 ± 16.7 to 36.9 ± 8.6 g/m2.7, p < 0.001), without significant changes in relative wall thickness (RWT). A decrease in left atrial volume was also observed, while E/e’ did not change. Midwall fractional shortening was reduced, while MEEi did not change (from 0.453 ± 0.15 to 0.445 ± 0.16 mL/s/g, ns from baseline to FU). A significant correlation was observed between changes in MEEi and changes in LVMi; patients with higher improvement in MEEi (>0.07 mL/s/g) had a higher LVMi at baseline and a greater decrease of LVMi and of RWT, in addition to greater reduction in HR and lower values of total cholesterol and LDL cholesterol at FU. No differences were observed between medically or surgically treated patients.

Conclusions:
In both medical and surgical treatment groups a reduction in LVH was observed. The improvement in MEEi seems to be related to a decrease in LVH, independently of medical or surgical treatment.