bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACHIEVED SYSTOLIC BLOOD PRESSURE BELOW 130 MMHG PRESERVES KIDNEY FUNCTION IN HIGH-RISK HYPERTENSIVE PATIENTS WITHOUT CARDIAC HYPERTROPHY BUT WITH PROTEINURIA
Authors: Olsen Eirik , Soraas Camilla , Schmieder Roland , Jamerson Kenneth , Macdonald Thomas , Mancia Giuseppe , Heimark Sondre , Mehlum Maria H. , Mariampullai Julian , Liestol Knut , Larstorp Anne C. , Hoieggen Aud , Kjeldsen Sverre E. , Rostrup Morten , Mo Rune , Julius Stevo , Weber Michael A. 
Published: May 2024

Objective:
Kidney function is preserved by achieving systolic blood pressure (SBP) primarily <140mmHg and possibly <130mmHg in hypertensive patients. We aimed to investigate kidney function when achieving SBP 130-139 and <130mmHg in high-risk hypertensive patients without cardiac hypertrophy who participated in a major prospective hypertension outcome trial with 4-6 years of follow-up.

Design and method:
Of the 15,245 study participants, 13,803 patients were without cardiovascular events during the first six months after randomization with roll-over from previous medications to blinded study drugs and had a minimum of 3 subsequent BP visits. Of these, 2,458 patients with cardiac left ventricular hypertrophy (LVH) by ECG were not included in the present analysis because, as previously reported, they had increased cardiac and all-cause mortality at achieved SBP <130mmHg. Of the remaining 11,345 patients, 2502 patients had proteinuria at baseline (measured twice) and 8843 patients had not. Cox analyzes adjusted for baseline covariates compared the pre-specified kidney endpoints 50% rise of se-creatinine (worsening kidney function, WKF) and end-stage renal disease (ESRD, dialysis and/or transplantation) for patients who achieved average SBP 130-139 and <130mmHg with those who remained with SBP >=140mmHg.

Results:
In all patients, WKF appeared in n=108/1072 patients with SBP >140mmHg, in n=35/984 (HR=0.394, CIs 0.265-0.587, p<0.001) with SBP 130-139mmHg and in n=8/444 (HR=0.215, CIs 0.102-0.451, p<0.001) with SBP <130mmHg. In patients without proteinuria at baseline corresponding p-values were p=0.016 and p=0.038, respectively, and thus weaker for the latter two SBP ranges. Quartile analyses confirmed these findings. There were similar findings for ESRD with p=0.026, p=0.006 and p=0.006 for quartiles 3, 4 and 5, respectively with quartile 4 patients (n=600) achieving mean SBP=126mmHg (SD=5). There were similar findings for lower achieved diastolic BP from >=90 to 80-89 to <80mmHg.

Conclusions:
In high-risk hypertensive patients above 50 years, but without cardiac hypertrophy, we found that when achieving lower average systolic BP from >=140 to 130-139 to <130mmHg, patients with proteinuria had markedly less worsening of kidney function and less end-stage renal disease. In parallel diastolic BP<80mmHg gave optimal renal protection.
EPLERENONE VS IRBESARTAN AS FIRST LINE THERAPY IN OBESE HYPERTENSIVE PATIENTS: PRELIMINARY RESULTS OF HEBRO TRIAL IN AMBULATORY BLOOD PRESSURE MEASUREMENTS
Authors: Iliakis Panagiotis , Drogkaris Sotirios , Kouremeti Maria , Siafi Eirini , Tatakis Fotis , Stathoulopoulou Maria , Manta Eleni , Kachrimanidis Ioannis , Sakalidis Athanasios , Tsioufis Panagiotis , Karaminas Nikolaos , Liatakis Ioannis , Dimitriadis Kyriakos , Thomopoulos Costas , Kasiakogias Alexandros , Konstantinidis Dimitrios , Tsioufis Konstantinos 
Published: May 2024

Objective:
Obesity is significantly associated with hypertension and cardiovascular outcomes. Little is known about the impact of aldosterone blockade using eplerenone on hypertensive obese patients as first line therapy. The aim of this study is to compare the efficacy between eplerenone-based strategy and irbesartan-based strategy in obese hypertensive individuals, regarding blood pressure reduction in office and out-of-office measurements.

Design and method:
HEBRO (antiHypertensive treatment with Eplerenone vs. irBesartan in hypeRtensive Obese patients) is a prospective, randomized, open-labeled, multicenter trial enrolled 112 obese hypertensive patients aged 30-75 years old, evaluated by home BP, office BP and ambulatory BP measurements. Patients were randomized to either 25 mg eplerenone twice (59) or 150 mg irbesartan (53) once daily. The primary endpoint is the difference in ambulatory BP measurements after 6 months follow-up period.

Results:
We enrolled 112 patients, 54.6 years old, 53% female, mean BMI 34.4 kg/m2 and mean eGFR 82.5 ml/min/1.73m2. At baseline, mean ABPM was 139.3/84.3 mmHg +/- 9.2/7.1 in the irbesartan arm vs. 140.7/84.8 mmHg +/- 9.8/9.0 in the eplerenone arm and mean OBP was 145.2/93.1 mmHg +/- 9.4/9.0 in the irbesartan arm vs. 147.9/92.8 mmHg +/- 8.3/10.2 in the eplerenone arm. At 2 months, mean ABPM drop since baseline was -13.5/-6.1 mmHg +/- 13.3/7.9 in the irbesartan arm vs. -8.1/-4.4 mmHg +/- 13.6/8.5 in the eplerenone arm, p=0.065 and p=0.319 for systolic and diastolic BP respectively. At 4 months, mean ABPM drop since baseline, was -17.1/-9.7 mmHg +/- 11.9/7.9 in the irbesartan arm vs. -16.1/-8.3 mmHg +/- 12.8/7.9 in the eplerenone arm, p=0.738 and p=0.456 respectively. At 6 months, mean ABPM drop since baseline, was -18.6/-10.2 mmHg +/- 11.9/6.5 in the irbesartan arm vs. -15.8/-8.6 mmHg +/- 13.8/9.3 in the eplerenone arm, p=0.358 and p=0.376.

Conclusions:
Mean ambulatory BP measurements were similar in both study arms at baseline and all follow-up time frames. Eplerenone-based strategy was non-inferior compared to irbesartan-based strategy, regarding ambulatory BP reduction in obese hypertensives, with no statistical significance. However, there was a trend towards irbesartan arm in the 2 months’ time frame. Patients are still enrolled and data on larger pool are anticipated.
POOLED, LONG-TERM ANALYSIS OF THE GLOBAL SYMPLICITY CLINICAL TRIAL PROGRAM OF RADIOFREQUENCY RENAL DENERVATION FOR THE TREATMENT OF UNCONTROLLED HYPERTENSION
Authors: Mahfoud Felix , Townsend Raymond R. , Mancia Giuseppe , Kandzari David E. , Whitbourn Robert , Bhatt Deepak L. , Bakris George , Kario Kazuomi , Fahy Martin , Böhm Michael 
Published: May 2024

Objective:
The Global Symplicity Clinical program is the largest investigation of radiofrequency renal denervation (RDN) to treat uncontrolled hypertension (HTN) to date. Collectively, over 4,000 patients enrolled into Spyral First-in-Man, the Global SYMPLICITY Registry (GSR) DEFINE, and multiple randomized controlled and sham controlled trials including HTN-Japan, Symplicity HTN-3, and the SPYRAL HTN-OFF and ON MED studies. We leveraged the entire Symplicity Global Clinical program patient dataset to develop a multivariate, patient-level, mixed model assessing (1) long-term BP reductions after RDN, and (2) whether specific patient characteristics correlate with future BP reductions after the procedure.

Design and method:
Repeated BP measurements from each patient in the Global Symplicity Clinical program were analyzed using linear mixed models fitted with 24-h ambulatory systolic (S)BP and office SBP as outcome variables. Baseline SBP, baseline number of antihypertensive (AH) medications, and AH medications over time were included as fixed effects. Additional patient characteristics were included as potential significant fixed effects. To account for multiple BP measurements per patient and multiple studies, nested random effects were included using an auto-regressive correlation structure.

Results:
The mixed model included data from 4156 patients treated with either the first-generation Symplicity Flex or the next-generation Symplicity Spyral catheter. Estimated, office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic with a steep reduction after RDN through the first 6 months (Figure), followed by a steady reduction in SBP afterward through 36 months. Higher baseline SBP was correlated with greater BP reductions. History of AF (-3.7 mmHg compared to no AF, p=0.0048) and increasing eGFR at baseline (-0.039 mmHg for every 1 ml/min increase in baseline eGFR, p=0.040) significantly correlated with lower 24-h ambulatory SBP.

Conclusions:
This is the most comprehensive analysis of radiofrequency RDN to date. Higher baseline SBP was strongly correlated with greater BP reductions. The results demonstrate the durability of RDN as an adjunctive therapy to treat HTN patients. Prospective studies need to validate whether certain patient characteristics are associated with improved response to RDN.
BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE INDICES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Authors: Zarifis Ippokratis , Triantafyllou Areti , Nikolaidou Barbara , Lazaridis Antonios , Malliora Anastasia , Papadopoulou Stella -LIDA , Kotsis Vasilios , Gkaliagkousi Eugenia 
Published: May 2024

Objective:
Blood pressure (BP) variability (BPV) has been identified as an independent predictor of cardiovascular risk and morbidity. Scarce information regarding the BPV in patients with diabetes mellitus (DM) exists, especially on short-term average real variability (ARV). In our study, we compared ARV indices and surrogate target organ damage markers in patients with Type 2 DM (T2DM) and in control individual.

Design and method:
In this cross sectional study, we identified individuals with T2DM and adequate controls. Patients were matched to controls on a 1:1 ratio using propensity score matching. Matching was based on age, gender, BMI, previous diagnosis of hypertension and office Systolic and Diastolic BP values. Office BP values were measured and Ambulatory BP Monitoring was performed, and central BP and Pulse Wave Velocity were calculated with validated devices. The BPV parameters of ARV and weighted Standard deviation (wSD) were calculated using standardized formulas based on the ABPM data.

Results:
A total of 190 individuals (95 with DM and 95 controls) were studied (mean age was 55.0±10.0 and 63% were males. Notably, the DM group had only slightly elevated HbA1c and preserved eGFR, indicating a cohort with adequate DM control. 24-hour SBP ARV correlated with age, Aortic SBP and PWV (r = 0.295, 0.287 &0.253 respectively, p for all<0.001). DM patients had significantly increased 24-hour SBP ARV (10.00±2.40 vs 9.40±1.76, p = 0.049) and significantly elevated PWV (8.93±1.89 vs. 8.30±1.69, p =0.017) compared to the control group.

Conclusions:
In a cohort of T2DM patients with adequate glycemic control, BPV indices are significantly increased compared to euglycemic controls. The correlation of BPV parameters with indices of TOD, could partly explain its prognostic significance regarding CV risk prediction. Diabetes triggers the dysregulation of the homeostasis of BP even in the early stages of the disease, possibly through impaired endothelial function. Further studies are necessary to confirm our findings and shed light on the pathophysiology of this effect.
COMPARISON OF CENTRAL SYSTOLIC BLOOD PRESSURE (CSBP) ESTIMATED BY DIRECT CENTRAL BLOOD PRESSURE (DCBP) FORMULA AND RADIAL TONOMETRY BY SPIGMOCOR: AN INVASIVE VALIDATION STUDY
Authors: Leone Dario , Vallelonga Fabrizio , Bruno Giulia , Fragapani Salvatore , Cesareo Marco , Airale Lorenzo , Mingrone Giulia , Milan Alberto 
Published: May 2024

Objective:
Background: Arterial hypertension (AH) is the main risk factor for cardiovascular events for western populations. Blood pressure (BP) is usually measured at brachial artery level, but current evidence suggest that central blood pressure (cBP) could have a greater prognostic role. Recent studies showed that central Systolic BP (cSBP) can be reliably estimated by Direct Central Blood Pressure formula (DCBP = MBP2/DBP) using mean (MBP) and diastolic (DBP) blood pressure measured at brachial level. Aim: this study seeks to compare cSBP calculated using DCBP with cSBP estimated by radial tonometry (cSBPpwa) in comparison to SBP invasively measured (invSBP).

Design and method:
Methods: Consecutive patients who underwent invasive catheterization of the aorta and coronary arteries for clinical reasons were included. Using applanation tonometry with SphygmoCor device, cSBP was estimated by a generalized transfer function derived from radial pressure waveform calibrated to brachial SBP and DBP evaluated by oscillometric approach.

Results:
Results: We included 50 patients (66 ± 9.1 years, 74% men). The mean invSBP, cSBPpwa and DCBP were 140 ± 19.6, 134 ± 17.8 and 131 ± 16.7 mmHg respectively. The (DCBP-cSBPpwa) and (DCBP-invSBP) errors were -3.0 ± 11.9 and -9.6 ± 14.3 mmHg respectively. There was a linear relationship between invSBP and cSBPpwa, and invSBP and DCBP (R2 = 0. 783 and 0.490 respectively, p < 0.001). 35 patients (70%) had invSBP values > 130 mmHg: a cSBPpwa value of 129 and a DCBP value of 125.6 mmHg exhibited a sensitivity and a specificity of 13.3 and 22.9%, and 26.7 and 25.6% respectively in discriminating this threshold (Youden index = -0.638 and – 0.47; AUC 0.048 and 0.170 respectively).

Conclusions:
Conclusions: The DCBP formula allows for the estimation of invSBP worse than radial tonometry generalized transfer function, but better describing the risk of high central blood pressure values.
TYG INDEX AS PREDICTOR OF METABOLIC SYNDROME IN YOUNG TO-MIDDLE AGE STAGE I HYPERTENSIVES, UNTREATED AT THE BASELINE
Authors: Saladini Francesca , Mos Lucio , Vriz Olga , Garavelli Guido , Mazzer Andrea , Rattazzi Marcello , Palatini Paolo 
Published: May 2024

Objective:
Tyg index, a surrogate marker of insulin resistance, was shown to be a predictor of development of metabolic syndrome (MS) among diabetes patients and general population while the predictive value among young hypertensives is less known. The aim of the present study was to investigate the predictive capacity of tyg index for incident MS among young untreated hypertensives.

Design and method:
we investigated 949 young-to-middle age stage I hypertensives from the HARVEST study, mean age 32.4±8.7 years, mean BMI 24.7±3.2 kg/m2, 69.2% males, without MS at baseline. Mean 24h blood pressure (BP) at entry 130.0±10.9/81.0±8.3 mmHg. Tyg index was calculated according to the usual formula. Patients were divided into tyg quintiles:7.008-7.895, 7.896-8.199, 8.200-8.423, 8.424-8.585, >=8.586 respectively. The risk of MS was calculated by means of survival Cox analyses adjusted for several confounders.

Results:
Patients in the highest quintiles were significantly older 35.3±8.1 years and heavier 25.3±3.3 kg/m2 than the bottom ones (p<0.001). Also baseline metabolic parameters were worse in top quintile (serum glucose 96.2±14.1, uric acid 5.3±1.2 mg/dl, total cholesterol 212.1±35.3 mg/dl, HDL 51.8±10.2 mg/dl) in comparison to the lower ones (p<0.001 for all comparisons). Baseline 24h BP values did not differ according to Tyg quintile, while heart rate was higher in the top quintile (74.3±8.4 bpm, p<0.001). During 8.1 years of follow-up, 76.3% of subjects developed new onset MS. Again, metabolic parameters were worst in the highest tyg quintile (serum glucose 97.9±15.4 mg/dl, total cholesterol 225.9±44.7 mg/dl, and HDL 52.1±15.2 mg/dl, as was final BMI (26.2±3.6Kg/m2, p<0.001 for all comparisons). Final 24h BP did not differ according to Tyg quintile while heart rate was higher in the highest quintile (p<0.001). In multivariate Cox analysis patients in the 4th and 5th quintiles presented the highest risk of new onset MS (HR 1.51 (1.11-2.06) p=0.009; HR 1.46 (1.09-1.46)p=0.011, respectively), in comparison to the bottom quintile.

Conclusions:
The risk of development of metabolic syndrome was significantly increased among patients in the top tyg quintiles, confirming its predictive capacity as a surrogate marker of insulin resistance among young stage I hypertensives.
INTENSIVE BP CONTROL FOR THE PREVENTION OF CARDIOVASCULAR EVENTS AMONG INDIVIDUALS WITH HYPERTENSION AT LOW CARDIOVASCULAR RISK: A TARGET TRIAL EMULATED USING OBSERVATIONAL DATA
Authors: Douros Antonios , Jiao Tianze , Platt Robert W. , Reynier Pauline , Filion Kristian B. 
Published: May 2024

Objective:
There is a lack of evidence on the optimal target blood pressure (BP) for patients with hypertension at low cardiovascular risk. Our population-based study aimed to determine whether following an intensive target BP control plan is associated with a decreased risk of major adverse cardiovascular events (MACE) compared with following a standard BP control plan in this population.

Design and method:
We conducted a population-based cohort study emulating a target trial. The study was based on electronic medical records from general practices in the United Kingdom. We initially created a base cohort of patients with incident hypertension at low cardiovascular risk (QRISK3-defined risk <10%). All treatment-naïve patients with systolic BP > 150 mmHg entered then the study cohort upon their first prescription for an antihypertensive drug (including combination therapy) between 1998 and 2018. The date of this prescription defined the study cohort entry date. To emulate a target trial of intensive (target BP: 130/80 mmHg), standard (140/90 mmHg), and modest (150/90 mmHg) BP control strategies, we used an active comparator, new-user cohort design with dynamic marginal structural models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE. We also estimated HRs and 95% CIs for serious adverse events (SAEs), a composite endpoint including electrolyte abnormality, acute kidney injury, and antihypertensive drug-related SAEs.

Results:
Among 77,934 patients included in the study, adjusted incidence rates of MACE were 2.8, 3.2, and 3.3 per 1,000 persons per year in the intensive, standard, and modest strategy groups, respectively. The adjusted HRs (95% CIs) for the intensive versus standard strategy were 0.96 (0.86 to 1.08) for MACE and 0.91 (0.84 to 0.99) for SAEs. The adjusted HRs (95% CIs) for the modest versus standard strategy were 1.06 (0.97 to 1.16) for MACE and 0.99 (0.94 to 1.05) for SAEs. Cumulative hazards for MACE for the three treatment strategies during the first five years of follow-up are shown in Figure

Conclusions:
Compared with a standard BP control strategy, an intensive strategy was not associated with a decreased risk of MACE among hypertensive patients at low cardiovascular risk.
CUMULATIVE DIASTOLIC BLOOD PRESSURE BURDEN IN NORMAL SYSTOLIC BLOOD PRESSURE AND CARDIOVASCULAR DISEASE
Authors: Cho So Mi Jemma , Lee Hokyou , Koyama Satoshi , Schuermans Art , Ganesh Shriienidhie , Hornsby Whitney , Honigberg Michael , Natarajan Pradeep 
Published: May 2024

Objective:
The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) Guideline remains controversial. Described cardiovascular effects are inconsistent due to BP variability, confounding by systolic BP, and effect modification by age. We examined whether long-term diastolic burden independently predicts the first major adverse cardiovascular event (MACE) in participants with sustained untreated normal systolic BP.

Design and method:
The Mass General Brigham Biobank is a volunteer cohort study of New England adults recruited between 2010 and 2021 across eight healthcare sites. A total of 18,181 participants aged 18 to 64 years and without prior cardiovascular disease, antihypertensives prescription, or high systolic BP were studied. Cumulative diastolic burden was determined as the area under curve for diastolic BP (DBP) 80 mmHg or higher over a 5-year period prior to enrollment. MACE was defined as a composite of first incident ischemic heart disease, stroke, heart failure, or all-cause death. Hazard ratio (HR) between cumulative diastolic burden and MACE was estimated using Cox proportional hazards regression.

Results:
Of the 18,181 participants, mean [SD] age at enrollment was 47.6 [14.3] years, 13,574 [74.7%] were female, and 2853 (15.7%) MACE occurred over a median [IQR] follow-up of 3.5 [1.9-5.3] years. Each SD increase in cumulative DBP was associated with HR (95% CI) of 1.07 (1.03-1.11), adjusting for age, sex, race, body mass index, systolic BP, lipids, renal function, diabetes, smoking, statin, and antihypertensives initiation during follow-up. In addition to traditional risk factors, cumulative DBP improved the discrimination C index (95% CI) from 0.73 (0.72-0.74) to 0.74 (0.73-0.75) (Likelihood ratio test P=0.019), whereas inclusion of enrollment DBP did not improve prognosis.

Conclusions:
Among individuals with normal systolic BP, cumulative DBP may augment risk stratification beyond a single DBP measure and other traditional risk factors.
PREVALENCE AND PROGNOSTIC VALUE OF T-WAVE INVERSION IN HYPERTENSIVE PATIENTS: A 5-YEAR FOLLOW-UP STUDY
Authors: Kasiakogias Alexandros , Stathoulopoulou Maria , Leontsinis Ioannis , Fragoulis Christos , Konstantinidis Dimitrios , Fillipou Christina , Karaminas Nikos , Nikolaou Andriani , Iliakis Panagiotis , Drogkaris Sotiris , Polyzos Dimitrios , Tsioufis Panagiotis , Mantzouranis Emmanouil , Aragiannis Dimitrios , Tsioufis Konstantinos 
Published: May 2024

Objective:
Data on prevalence and associated prognosis of repolarization abnormalities among hypertensive patients are limited. We investigated the presence and extent of ST-segment and T-wave changes in a hypertensive population and their predictive ability for cardiovascular disease.

Design and method:
We studied 1851 white Caucasian hypertensive patients (age 58±12years, 51% females) without a history of cardiovascular disease for a mean period of 5.3±3.4 years. At the baseline examination, all patients underwent standard 12-lead electrocardiography. T-wave inversion (TWI) was defined as T-wave deflection > -0.1 mV in > 2 contiguous leads, unless associated with bundle branch block. Anterior, lateral, or inferior TWI was defined as TWI in leads V2-V4 or V5, V6, I, AVL or II, aVF respectively. The depth in millimeters of TWI in each lead was recorded and the maximum depth per location was calculated. ST depression was defined as >1 mm in depth in two or more contiguous leads. During follow-up, patients underwent clinic visits at least yearly for management of hypertension and risk factors. The outcome studied was the incidence of cardiovascular morbidity set as the composite of non-fatal coronary artery disease and stroke.

Results:
In the entire population, prevalence of TWI was 3.8%, of which 39% presented with anterior TWI, 73% with lateral TWI and 11% with inferior TWI. ST depression was observed in 3.6% of patients (anterior in 0.8%, inferior in 0.9% and lateral in 2.6%). Incidence of the composite endpoint during follow-up was 4%. Cox regression analysis revealed that presence of TWI was associated with a significantly greater risk for cardiovascular events (HR: 2.6, 95% CI: 1.1-5.9, p=0.025). The association was stronger for lateral TWI (HR: 3.3, 95%: CI: 1.34-8.30, p=0.01) compared to other locations. In multivariate models controlling for standard confounders these associations were overall sustained. Depth of TWI and presence of ST depression were not associated with cardiovascular risk.

Conclusions:
Among hypertensive patients without cardiovascular disease, TWI is infrequent but significantly associated with future cardiovascular events. Lateral TWI carries the worse prognosis.