bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONG-TERM EVENT RATES, RISK FACTORS, AND TREATMENT PATTERN IN PATIENTS QUALIFYING FOR DUAL BLOOD PRESSURE-LOWERING THERAPY: AN OBSERVATIONAL STUDY IN 1.4 MILLION INDIVIDUALS
Authors: Coca Antonio , Borghi Claudio , Stergiou George S. , Blacher Jacques , Lee Christopher , Tricotel Aurore , Castelo-Branco Anna , Khan Irfan , Abdel-Moneim Mohamed 
Published: June 2023

Objective:
Elevated blood pressure (BP) is a major risk factor for cardiovascular (CV) morbidity and mortality. This study assessed CV event rates, their predictive factors, and treatment patterns for BP-lowering therapy in a population qualifying for dual BP-lowering therapy, over a long-term follow-up.

Design and method:
This study utilized the Clinical Practice Research Datalink, Hospital Episode Statistics, and Office for National Statistics databases in England. Individuals aged > = 18 years with hypertension, qualifying for dual BP-lowering therapy as per the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines were identified during a 15-year period (2005 to 2019). Primary endpoint was composite of non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for heart failure, and CV death. Secondary endpoint was all-cause death. Main subgroups of interest were atherosclerotic cardiovascular disease (ASCVD) and diabetes. Event rates and association of risk factors with primary endpoint and all-cause death were evaluated using Kaplan-Meier method and Cox-proportional hazards model, respectively. Treatment patterns were summarized via percent of patient-time on a given therapy during each year of follow-up.

Results:
Overall, 1,426,079 patients were included. The mean (SD) age was 62.9 (14.1) years and ∼50% were male. The 15-year event rates for the primary composite endpoint and all-cause death were 27.1% and 32.6%, respectively (Table 1) with CV event rates being ∼2.5-fold and ∼1.5-fold in those with ASCVD and diabetes, respectively (unadjusted analyses). Risk factors strongly associated with primary composite endpoint (hazard ratio >1.50) were age > = 65 years, heart failure, atrial fibrillation, chronic kidney disease 4 – 5, chronic obstructive pulmonary disease, coronary heart disease, stroke, and peripheral arterial disease (P < 0.0001 for all). At variance with guidelines, BP-lowering monotherapy was the most common treatment pattern (42.6% – 56.7% of patient-time) over 5–year follow-up period.

Conclusions:
Patients with hypertension qualifying for dual BP-lowering therapy are at high risk of major CV events and death, with the risk being substantially elevated in those with ASCVD or diabetes. These findings highlight an opportunity for further risk reduction in this population via timely initiation of dual BP-lowering therapy, especially in patients with comorbidities.
SERUM ACID URIC AND HYPERTRIGLYCERIDEMIA AND CAROTID PLAQUES: A SUB-ANALYSIS OF THE URIC ACID RIGHT FOR HEART HEALTH (URRAH) STUDY
Authors: Muiesan Maria Lorenza , Paini Anna , Rosei Claudia Agabiti , Maloberti Alessandro , Giannattasio Cristina , Salvetti Massimo , Cirillo Massimo , Ferri Claudio , Galletti Ferruccio , Grassi Guido , Iaccarino Guido , Palatini Paolo , Parati Gianfranco , Pontremoli Roberto , Tikhonoff Valerie , Verdecchia Paolo , Volpe Massimo , Casiglia Edoardo , Virdis Agostino , Borghi Claudio 
Published: June 2023

Objective:
High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular risk phenotypes, including subclinical atherosclerosis. An interaction between plaques Xanthine Oxidase (XO) expression, SUA, and HDL-C has been recently postulated

Design and method:
N = 6211 patients from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG > = 150 mg/dL. Higher levels of SUA (hSUA) were defined as > = 5.6 mg/dL in men and 5.1 mg/dl in women

Results:
A carotid plaque was identified in 1742 subjects (28 %). SUA and TG predicted carotid plaque (HR 1.09 [1.04 - 1.27], p < 0.001 and HR 1.25 [1.09 - 1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment.
Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), hSUA and hTG (38%) chisquare 0,0001) Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1,341); P = 0.001], normal SUA and hTG [HR 1. 305 (1.057 to 1.611); P = 0.001], and the combination of hUA and hTG [HR 1. 539 (1.274 to 1.859); P = 0.001], were associated with a higher risk of plaque

Conclusions:
Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single wisk factors. The association between SUA and CVD events may be explained in part because of a direct association of UA with carotid plaqu
SHOULD MIDDLE-AGED AND OLDER HIGH-RISK HYPERTENSIVE PATIENTS WITH DIABETES BE TREATED TO TARGET BT <130/80 MMHG?
Authors: Olsen Eirik , Søraas Camilla Lund , Mancia Giuseppe , Heimark Sondre , Mehlum Maria H. , Liestöl Knut , Kjeldsen Sverre E. , Høieggen Aud , Rostrup Morten , Mo Rune , Julius Stevo , Weber Michael 
Published: June 2023

Objective:
Diabetes Mellitus Type-2 (DM2) is common in hypertensive patients, increasing the risk of cardiovascular disease. Current guidelines recommend targeting systolic BP (SBP) to 130 - 139 mmHg in diabetic patients >65 years. We investigated whether the middle-aged and elderly hypertensive DM2 patients in the VALUE Trial had reduced risk of cardiovascular disease and death if SBP was lowered to <130 mmHg.

Design and method:
Of the 15,245 participants, there were 13,803 patients without cardiovascular events during the first six months after randomization, roll-over from previous medication and up-titration of study drugs. Of these 2,458 patients had left ventricular hypertrophy by electrocardiogram. These patients were excluded from analyses due to increased mortality when SBP is lowered to <130 mmHg (submitted).
Of the remaining 11,345 patients, 3,932 had DM2. Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other pre-specified endpoints for patients achieving average SBP 130 - 139 mmHg (DM2 group 1,605, non-DM2 group 3,260) and SBP <130 mmHg (DM2 group 600, non-DM2 group 1,546). Reference groups were patients achieving average SBP > = 140 mmHg.

Results:
Mean age in DM2 patients was 66.9 years. The DM2 group achieving average SBP <130 mmHg did not have significant changes in primary cardiac endpoint, all-cause mortality, or stroke (Table). However, DM2 had lower incidence of reduced kidney function (increase in serum creatinine of 50% compared to baseline, HR = 0.43, p = 0.008). In the DM2 group achieving average SBP 130 - 139 mmHg there were significant reductions in cardiovascular events and kidney function.

Conclusions:
Our findings suggest that lowering systolic BP <130 mmHg in DM2 has little effect on reducing cardiovascular events compared to systolic BP 130 - 139 mmHg. However, we did find an effect on kidney function. In conclusion, our data suggest that treating middle-aged and elderly DM2 patients <130/80 mmHg can prevent reduction of renal function which is an endpoint of high importance in DM2 patients.
NEW SCREENING CUTOFF VALUES FOR DETECTION OF ALDOSTERONOMA EXAMINED BY LC-MS/MS AND NEWLY DEVELOPED NON-COMPETITIVE CLEIA
Authors: Satoh Fumitoshi , Ono Yoshikiyo , Tezuka Yuta , Omata Kei , Takase Kei , Sato Akihiro , Suzuki Takashi , Sasano Hironobu 
Published: June 2023

Objective:
Thinking of the poor accuracy of conventional CLEIA measurements of aldosterone, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method but it is costly, labor intensive and time consuming. A novel non-competitive chemiluminescent enzyme immunoassay (sandwich assay) (NC-CLEIA) for measuring aldosterone was recently developed. We validated the accuracy and diagnostic ability of the NC-CLEIA and compared the results obtained with those by LC-MS/MS and also determined the new screen cutoffs by both measurements, respectively, detecting aldosterone-prodcuing adenoma (APA) in hypertensive patients.

Design and method:
We measured plasma renin activity by enzyme assay and plasma aldosterone concentrations (PAC) using LC-MS/MS and NC-CLEIA in 133 APA, 100 bilateral hyperaldosteronism and 111 essential hypertension patients to examine the accuracy of the values of PAC measured by this new NC--CLEIA as compared with those by LC-MS/MS, and determine the new screen cutoff values by both measurements to detect APA, respectively.

Results:
Passing-Bablok analysis revealed that NC-CLEIA (regression slope, intercept and correlation coefficient were 0.962, -0.043, and 0.994, respectively), was significantly correlated and equivalent to LC-MS/MS than RIA. Bland-Altman plot analysis of NC-CLEIA by LC-MS/MS also demonstrated much smaller systemic errors (a bias of -0.348 ng/dL with limits of agreement of -4.390 and 3.694 and 95% confidence interval). The receiver-operating characteristics analysis demonstrated that cut-off values of aldosterone/renin activity ratio obtained by LC-MS/MS and NC-CLEIA were 31.2 and 31.5 (ng/dL per ng/mL/hr) with a sensitivity of 91.0% and 90.2%, and a specificity of 75.4% and 76.8%, respectively, in terms of discriminating APA from non-APA. Therefore, we can recommend an ARR > 30.0 ng/dL per ng/mL/hr as a screening cut-off by both LC-MS/MS and NC-CLEIA, which would discriminate APA with a sensitivity of 91.7% in both assays, and with a specificity of 73.0% and 73.9 %, respectively.

Conclusions:
This novel NC-CLEIA assay for PAC could serve as a clinically reliable alternative to LC-MS/MS to detect APA among hypertensive patients with more accuracy than the conventional methods.
ASSESSMENT OF LEFT ATRIAL FUNCTION IN INDIVIDUALS WITH RESISTANT HYPERTENSION BY ADVANCED ECHOCARDIOGRAPHY
Authors: Laurinavicius Antonio Gabriele , Souza Jonathan Batista , Sousa Marcio Gonçalves , Colombo Fernanda Consolim , Assef Jorge Eduardo 
Published: June 2023

Objective:
Resistant hypertension is a challenging phenotype within the hypertension (HTN) spectrum, requiring careful assessment and follow-up. Evaluation of left atrial function may be clinically informative, but is commonly neglected. Strain and three-dimensional echocardiography (3D ECHO) may be useful complementary tools for assessing atrial function among hypertensive patients.

Design and method:
96 eligible adult patients were categorized into three groups: resistant hypertensive (RH), controlled hypertensive (CH), and normotensive (N), and underwent advanced echocardiography techniques to identify specific morphofunctional changes in the left atrium (LA) throughout different HTN phenotypes.

Results:
As shown in Figure 1, LA reservoir strain was significantly lower among RH than N and CH patients (p < 0.001). Accordingly, LA conduit strain showed a gradient through the groups: higher among N, followed by CH and RH (p = 0.015). LA contraction strain was higher among CH than N and RH (p = 0.02). Maximum indexed, pre-A, and minimum atrial volumes obtained by 3D ECHO showed differences between N and the others (p < 0.001), but not between CH and RH. N showed higher fraction of passive emptying of the LA than the others (p = 0.02), with no difference between CH and RH. Total emptying of the LA only differed between the extreme groups N and RH, being lower in the latter, while active emptying of the LA showed no difference between the groups (p = 0.82).

Conclusions:
Advanced echocardiography measures, especially LA strain, proved to be early markers of atrial myocardial damage in both RH and CH. We demonstrated for the first time that morphofunctional changes in the LA due to resistant hypertension may occur concomitantly and even independently from those observed in the left ventricle.
POOLED, 6-MONTH SAFETY AND EFFICACY RESULTS USING THE SYMPLICITY SPYRAL RADIOFREQUENCY RENAL DENERVATION CATHETER
Authors: Mahfoud Felix , Mancia Giuseppe , Townsend Raymond , Kandzari David , Whitbourn Robert , Böhm Michael 
Published: June 2023

Objective:
Over 1,200 patients received renal denervation (RDN) to reduce high blood pressure using the current generation, multi-electrode, radiofrequency Symplicity SpyralTM catheter as part of the SPYRAL HTN Global Clinical Program. The Spyral FIM was a prospective, single-arm study to assess feasibility. The SPYRAL HTN-OFF MED and -ON MED studies were randomized, sham controlled, blinded trials assessing the safety and efficacy of RDN in the absence and presence of antihypertensive medications, respectively. The Global SYMPLICITY Registry is an all-comer, global, single-arm study assessing safety and efficacy of RDN in a real-world setting with patients on various medication regimens. Here, we present the pooled, 6-month efficacy and safety results of RDN using the Spyral catheter.

Design and method:
At each follow-up, including at 6 months, office systolic and diastolic blood pressures and 24-h ambulatory systolic and diastolic were collected. Adverse safety events and other indicators including estimated glomerular filtration rate (eGFR) and incidence of renal artery stenosis were recorded. GSR was an all-comer registry for patients with uncontrolled hypertension, whereas patients in the SPYRAL HTN-OFF and ON MED trials were required to have an OSBP > = 150 and <180 mmHg and ODBP > = 90 mmHg.

Results:
As of December 19, 2022, 1,298 patients have received RDN therapy using the Spyral catheter, including eligible control patients from the randomized trials who elected to cross over to receive RDN after unblinding. Mean, 6-month reductions in office and 24-h ambulatory BP from baseline are shown in the Figure. Patients had similar, significant reductions in diastolic blood pressure from baseline through 6 months. Including crossover patients, eGFR decreased by 1.5 mL/min/1.73 m2 through 6 months in RDN patients using the SPYRAL catheter (n = 962; 95% CI: -2.27,-0.74; p < 0.001). There have been no recorded instances of renal artery stenosis >70% through 6 months.

Conclusions:
Patients receiving RDN had significant and consistent 6-month reductions in BP compared to baseline measures. There have been no incidences of renal artery stenosis, and reductions in eGFR are consistent with natural progression with age. These results highlight the efficacy and safety of RDN using the current generation Spyral catheter.
TRANSLUMINAL ANGIOPLASTY OF THE RENAL ARTERIES IN PATIENTS WITH FIBROMUSCULAR DYSPLASIA
Authors: Azancot Sarah , Amar Laurence , Lorthioir Aurelien , Azizi Michel 
Published: June 2023

Objective:
FMD is the second most frequent cause of renal artery stenosis (RAS) after atherosclerosis and can lead to hypertension. To cure or improve this renovascular hypertension, patient with fibromuscular dysplasia and renal artery stenosis undergo renal artery revascularization by percutaneous renal transluminal angioplasty (PTRA). Although this method has been performed for many years, there have been only few small size trials published. This retrospective single center study aimed to evaluate the rate of cured hypertension after PTRA.

Design and method:
We included all adult patients diagnosed with FMD who were seen in our referral center for hypertension management (Hôpital Européen Georges Pompidou, Paris) from January 2010 to March 2020. Blood pressure response was assessed at 3 month and one year. Primary outcome was one year cured hypertension rate in ambulatory measurement, secondary outcomes were improvement and complication rate.

Results:
Overall, 76 adult patients (87% female, mean age at enrollment 35.5 years) were included. FDM was multifocal in 74% and unisite in 68% of patients. AT baseline, mean day ambulatory blood pressure (dABP) was 141 ± 17/89 ± 14 mmHg under a mean of 2.3 ± 1.37 antihypertensive treatments. All patient underwent PTRA. Stent were inserted in 8 patients (10.5%) with residual stenosis after PTRA and in 8 patients (10.5%) with renal artery dissection, total complication rate was 18.4%. At one-year follow-up, mean dABP was 128 ± 12/78 ± 9 mmHg (p < 0.0001) with 1.1 ± 1.3 treatments (p < 0.0001). In total, 75% beneficiated from renal angioplasty: 31% were cured and 44% were improved. Cured hypertension was associated with low body mass index (BMI) (p = 0.017) and unisite FDM (p = 0.017) on a multivariable analysis.

Conclusions:
In patients with FMD, PTRA is associated with cured hypertension 31% of patients with renal artery FMD undergoing PRTA. Hypertension is more likely to be cured in patient with low BMI and multisite FMD. These results are to be put in perspective with a complication rate of 18.4%.
THE PROGNOSTIC ROLE OF CLINICAL FEATURES AND BIOMARKERS IN PATIENTS HOSPITALIZED WITH CARDIORENAL SYNDROMES
Authors: Theofilis Panagiotis , Vordoni Aikaterini , Volis Nikolaos , Doumani-Korka Georgia , Kampourelli Aikaterini , Xanthopoulou Eleni , Kalaitzidis Rigas 
Published: June 2023

Objective:
Cardiorenal syndromes (CRS), involving the heart-kidney cross-talk and the activation of neurohumoral and inflammatory pathways, is an entity characterized by high morbidity and mortality.
The aim of this study was to evaluate the prognostic role of risk factors and biomarkers in patients hospitalized for CRS.

Design and method:
In this prospective, observational cohort study, 113 consecutive patients hospitalized for CRS were enrolled. Socio-demographic characteristics, personal medical history, and prior medication use were recorded upon admission, and echocardiography was performed. Moreover, an array of blood markers were measured. The endpoint of interest was a composite of death or dialysis dependence at discharge.

Results:
Patients were classified into two groups; Group 1 (N = 59): discharged being dialysis-independent, Group 2 (N = 54): death/dialysis dependence at discharge. No major differences were detected in baseline characteristics between the two groups. Group 2 patients used renin-angiotensin-aldosterone system blockers (RAASb) less often (Group 1: 69.5% vs. Group 2: 46.3%, p = 0.01) and more frequently presented with oliguria/anuria (Group 1: 28.8% vs. Group 2: 70.4%, p < 0.001) and any infection (Group 1: 33.9% vs. Group 2: 55.6%, p = 0.02). No dissimilarities were noted in echocardiographic markers. Group 2 patients had significantly lower hemoglobin, serum albumin, bicarbonate, and 25-hydroxy-vitamin D (25OHD). At the same time, N-terminal prohormone brain natriuretic peptide, serum potassium, and parathyroid hormone (PTH) were significantly higher in Group 2 patients (Figure 1). In a multivariate regression analysis, lack of RAASb was independently associated with a 17.7-fold increased risk of death or dialysis dependence at discharge, while the decreasing 25OHD/PTH ratio (beta coefficient -0.01, p = 0.007) and increasing admission serum potassium levels (beta coefficient 0.82, p = 0.03) increased the possibility of facing the composite endpoint. Following a receiver operating characteristic curve analysis, 25OHD/PTH ratio emerged as the most accurate predictor of facing the composite endpoint, with an ideal cutoff of 103.7 (sensitivity 81%, specificity 74%) (Figure 2).

Conclusions:
Lack of prior RAASb use, high admission serum potassium, and a low 25OHD/PTH ratio are associated with poor prognosis in patients hospitalized for CRS.
CHANGES ON LEFT VENTRICULAR FUNCTION AND CHARACTERISTICS ACCORDING TO THE DEGREE OF INTERDIALYTIC WEIGHT GAIN IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Anastasiou Vasileios , Alexandrou Maria Eleni , Kamperidis Vasileios , Daios Stylianos , Tsilonis Konstantinos , Theodorakopoulou Marieta , Moysidis Dimitrios , Iatridi Fotini , Giannakoulas George , Ziakas Antonios , Sarafidis Pantelis 
Published: June 2023

Objective:
Pronounced pulmonary circulation overloading has been observed in hemodialysis patients with higher fluid intake over the long interdialytic interval. This study aimed to evaluate the impact of the degree of fluid accumulation on left ventricular (LV) systolic and diastolic function and sizing characteristics.

Design and method:
For the present analysis, 41 patients receiving maintenance hemodialysis thrice-weekly were divided by the recommended threshold of interdialytic-weight- gain corrected for dry weight (IDWG%) into a higher (>4.5%) and a lower ( < 4.5%) IDWG% group. All participants underwent 4 echocardiographic assessments at the start and the end of the 3-day and the 2-day interdialytic interval in a crossover design.

Results:
Over the 3-day interval, significant increments in stroke volume (SV) were observed for both groups, but were more prominent in the higher IDWG% group (>4.5% 18.63 ± 22.84vs. <4.5%12.6 ± 14.48mmHg, p = 0.04). Similarly, a greater increase in cardiac output was evidenced in patients with higher IDWG% over the 2- day interval (>4.5%1.31 ± 1.38 vs.<4.5%0.36 ± 2.08L/m 2, p = 0.012). With regards to diastolic function, a significant increase in E/A and E/E’m ratios was observed over the 3-day interval, but significant between-group differences in interdialytic changes were detected only for the E/A ratio (IDWG>4.5% 0.35 ± 0.29 vs. <4.5% 0.06 ± 0.44, p = 0.035). Left atrial dimensions and LV mass were enlarged to a similar extent in both study-groups during both intervals.

Conclusions:
Patients exceeding the recommended threshold of interdialytic fluid accumulation experience higher increases in SV and deterioration of preload- dependent indexes of diastolic function, particularly during the 3-day interval.