bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-16-1: RESISTANT HYPERTENISION: CLINICAL CHARACTERISTICS AND BLOOD PRESSURE CONTROL
Authors: Carcel Cheryl , Neal Bruce , Rogers Kris , Oparil Suzanne , Narkiewicz Krzysztof , Wang Jiguang , Schiffrin Ernesto L. , Azizi Michel , Poulter Neil , Chalmers John 
Published: January 2023

Objectives:
We quantified the characteristics of patients with treatment resistant hypertension (TRH) in a large multi-country sample of specialist tertiary centres and estimated incidence and prevalence in participating regions.

Methods:
The Survey of Patients with treatment Resistant hyperTension (SPIRIT) study was a retrospective review of medical records of patients seen at tertiary centres located in Western Europe, Eastern Europe, North America, South America, Australia and Asia. Data on demographics, medical history and medication use were extracted from medical records. Prevalence and incidence of TRH were estimated based upon reported catchment populations.

Results:
1555 patients from 76 centres in 15 countries were included from May-August 2017. Mean age was 64 (SD, 12.7), 60% were males and 62% were Caucasian, 36% had CKD (eGFR < 60 ml/min), 41% had diabetes, 12% were smokers and 27% had a previous CV event. Daytime ambulatory BP was the most frequently used measurement (46%) with a mean systolic BP of 144 mmHg (SD, 19.2) and diastolic BP 81 mmHg (SD, 13.8). 95% patients were prescribed diuretics (thiazides 75%), 93% an inhibitor of the renin-angiotensin aldosterone system, 86% a calcium antagonist, 75% a beta-blocker and 35% an aldosterone antagonist. There were moderate differences in participant characteristics and management patterns between regions. The overall estimated mean incidence of TRH was 5.8 per 100,000 per year (ranging between 2.3 and 14.0 across regions) and the corresponding estimated mean prevalence of TRH was 23.9 per 100,000, ranging between 7.6 and 90.5 across regions.

Conclusion:
TRH remains a common health issue. Observed variation between regions likely reflects some real differences in patient characteristics and physician management practices, but may also be due to inconsistent patient recruitment methods across participating centres.
S-16-4: PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY RESULTS FROM A PHASE 1 MULTIPLE ASCENDING DOSE STUDY OF THE SELECTIVE ALDOSTERONE SYNTHASE INHIBITOR CIN-107
Authors: Freeman Mason W , Bond Mary , Murphy Brian , Hui James , Isaacson Jonathan 
Published: January 2023

Objective:
To evaluate the safety, pharmacokinetics, and pharmacodynamics of multiple ascending doses of the highly potent, selective small-molecule inhibitor of aldosterone synthase (CIN-107) in a randomized, double-blind, placebo-controlled phase 1 study in healthy volunteers.

Design and methods:
Subjects were randomized into 5 cohorts to receive CIN-107 or placebo once daily for 10 days. Cohorts 1 and 2 were placed on a low salt diet to stimulate aldosterone production and were administered 2.5 or 5.0 mg oral CIN-107, respectively. They also underwent an adrenocorticotropic hormone challenge to increase aldosterone and cortisol levels to evaluate the specificity of CIN-107 for aldosterone synthase. Cohorts 3, 4, and 5 were placed on a normal salt diet and were administered 1.5, 2.5, or 0.5 mg oral CIN-107, respectively. Blood samples were collected prior to and after dosing on days 1 and 10 for measurement of plasma CIN-107 concentrations to characterize single-dose and steady-state pharmacokinetics. Pharmacodynamic measurements included aldosterone, cortisol, and electrolytes. Safety assessments included physical examination, electrocardiograms, orthostatic vital signs, and clinical laboratory evaluations, including renal function.

Results:
Fifty-four subjects completed the study. There were no deaths, serious adverse events, or discontinuations due to treatment-emergent adverse events (TEAEs). All TEAEs in subjects receiving CIN-107 were mild in severity. Plasma concentrations of CIN-107 increased proportionally with ascending doses. CIN-107 was rapidly absorbed, with peak concentrations observed within 4 hours after dosing. Mean half-life was 26–31 hours. A dose-dependent reduction of plasma aldosterone occurred with CIN-107 doses ≧1.5 mg, regardless of normal or low salt diet. Decreases in plasma aldosterone started on Day 1 and were sustained, with levels reduced by approximately 51–73% on Day 10 (Figure 1). CIN-107 had no meaningful impact on plasma cortisol levels. The urine sodium:potassium ratio increased on Day 1 and diminished by Day 10, an effect mediated by greater elimination of sodium on Day 1 compared to Day 10. A mild increase in the blood urea nitrogen:creatinine ratio and a mild reduction in the glomerular filtration rate (<15%) suggest that CIN-107 produced a mild diuretic effect.

Conclusions:
CIN-107 was safe and well tolerated and resulted in dose-dependent increases in plasma CIN-107 with a half-life that supports once-daily dosing. The dose-dependent decrease in plasma aldosterone, transient increase in sodium excretion, and mild diuretic effect support continued study in ongoing phase 2 clinical trials evaluating the efficacy and safety of CIN-107 for treatment-resistant or uncontrolled hypertension and primary aldosteronism.
S-17-1: URIC ACID AND CARDIOVASCULAR DISEASES
Authors: Borghi Claudio 
Published: January 2023

Uric acid (UA) is the final product of purine metabolism and its increase in the circulating blood defines the presence of hyperuricaemia commonly considered as a concentration of uric acid in serum above the threshold level of 7 mg/dL (416 mol/L) in men and > 6 mg/dL in women. The typical consequence of elevated UA levels is the development of gout, a condition affecting 2–3% of the general population but beside the effects on gout, the elevated levels of UA have been associated with a significant increase in the risk of hypertension, metabolic syndrome, and cardiovascular disease (CVD) regardless of the presence of serum urate deposition. All this evidence clearly supports a primary cardiovascular role for elevated serum UA probably based on multiple and interactive mechanisms of action not necessarily involving the articular and tissue deposition.
The interaction between elevated UA and cardiovascular diseases has been extensively investigated in the last 10 years providing interesting results in terms of patients identification, threshold of risk, pathophysiology, results of clinical trials and effects of drugs not primary involved in the management of uric acid levels. In particular, the evidence supports an increase of CV mortality and morbidity in patients with levels of SUA between 4.5 and 5.5 that are common in a large proportion of subjects and patients with overt cardiovascular diseases. This observation along with the differences in the mechanism leading to elevated UA (hyperproduction vs. underexcretion) will allow a more functional identification of patients suitable for pharmacological treatment with urate lowering drugs (ULT). Furthermore, the dynamic analysis of time-dependent trajectories of UA levels is a new approach to the interpretation and clinical management of cardiovascular disease. The overall representativity of a pattern of modification seems to better define the prognostic role of elevated UA and could be probably improved by an integrated interpretation of the different patterns beyond the role of risk cards and algorithms. Very recently, the management of elevated UA has also included the effects of non-ULT drugs as Losartan, SGLT-2 inhibitors, vericiguat whose administration in randomized clinical trials has improved uric acid levels with a linear proportion with the amount of UA reduction.
The interaction between hyperuricemia and CVD is a very dynamic issue that has been recently enriched with several additional information that have allowed a more effective identification of those subsets of patients that can successfully treated in daily clinical practice
S-17-4: EFFECTIVENESS OF STATIN INTENSIVE THERAPY IN TYPE 2 DIABETES WITH HIGH VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY
Authors: Ikeda Shota , Shinohara Keisuke , Enzan Nobuyuki , Matsushima Shouji , Tohyama Takeshi , Funakoshi Kouta , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki 
Published: January 2023

Objective:
Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. Thus, we hypothesized that the benefit of intensive lipid-lowering therapy is larger in T2DM patients with high visit-to-visit SBP variability who are considered at higher risk. This study aimed to investigate the effectiveness of intensive versus standard statin therapy in primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability.

Design and method:
The EMPATHY study was the first randomized trial comparing statin intensive therapy targeting low- density lipoprotein cholesterol (LDL-C) < 70 mg/dL and standard therapy targeting LDLC ®100 to < 120 mg/dL in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within initial 6 months. The outcome was the composite incidence of cardiovascular events, including cardiac, cerebral, renal, and vascular events or death associated with cardiovascular events.

Results:
In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. The number of blood pressure measurements was 6.6 ± 1.6. The median value of SD and ARV of SBP was 9.78 mmHg and 10.29 mmHg, respectively. These median values were used as cutoffs. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95% CI 0.45–0.90, p = 0.012) and 1.21 (95% CI 0.82–1.80, p = 0.34) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (p = 0.018). The analysis using ARV of SBP showed similar results (high ARV: hazard ratio 0.62, 95% CI 0.44–0.88, p = 0.008; low ARV: hazard ratio 1.15, 95% CI 0.78–1.70, p = 0.48; p for interaction = 0.022.).

Conclusion:
Statin intensive therapy targeting LDL-C < 70 mg/dL had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit to visit SBP variability. Stratification based on visit-to-visit SBP variability might be a novel and useful strategy to determine the target LDL-C levels in statin lipid-lowering therapy among T2DM patients with microvascular complications.
S-20-3: PLASMA ATRIAL AND BRAIN NATRIURETIC PEPTIDES LEVELS AND THE RISK OF INCIDENT ATRIAL FIBRILLATION: THE SUITA STUDY
Authors: Kokubo Yoshihiro , Kashima Rena , Teramoto Masayuki , Arafa Ahmed , Shimamoto Keiko , Gao Qi , Higashiyama Aya , Kohmo Kyoko Honda , Watanabe Makoto , Dohi Tomoharu , Matsumoto Chisa , Kusano Kengo 
Published: January 2023

Background:
Atrial fibrillation (AF), a common cardiac rhythm abnormality, is associated with significantly increased morbidity and mortality risk. We developed the risk prediction of incident AF using traditional risk factors. It is essential to consider the residual risk to increase risk predictions. Heart failure is not a factor that appeared in the Suita AF score but others. There is no prospective study on the relationship between plasma atrial and brain natriuretic peptide (ANP and BNP) levels and incident AF in non-Western residents.

Objectives:
We hypothesized the association between ANP, BNP, and incident AF in the Suita Study.

Methods:
A total of 2,828 participants (mean age 66.7 ± 10.4 years without AF at the baseline) have been prospectively followed-up for incident AF since November 2005. AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination or when AF was indicated as a current illness or was in the medical records during follow-up. ANP and BNP were measured by the CLEIA methods at the baseline survey examination. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were analysed after adjusting for the risk components of the recently published Suita AF risk score. Statistical analyses were performed using Cox proportional hazards regression methods and evaluated using C statistics and net reclassification improvement.

Results:
The baseline prevalence of hypertension according to the BNP levels were 34.5%, 50.1%, and 78.8% in BNP < 18.5 pg/dL, 18.5–99 pg/dL, and P ≧ 4100 pg/dL, respectively. During the 16,584 person-years of follow-up, we observed 65 incidents of AF. Compared to the subjects with ANP< 42 pg/dL and BNP< 18.4 pg/dL, the adjusted HRs (95% confidence intervals) of incident AF were 2.70 (1.53–4.78) for the subjects with ANP ≧ 42 pg/dL and 2.09 (1.09–4.01) and 9.75 (3.82–24.87) for the subjects with BNP = 18.5–99 pg/dL and BNPP ≧ 4100 pg/dL, respectively. The addition of ANP and BNP to variables recently combined in the Suita AF risk score showed an integrated discrimination improvement of 0.061 (0.035–0.087) and 0.068 (0.036–0.100), with 13.3% and 19.1% relative improvement in reclassification analysis, respectively. Furthermore, the addition of ANP to the Suita AF score with BNP showed a significant but slight integrated discrimination improvement of 0.007 (0.001–0.012) (P = 0.01).

Conclusions:
Each elevated ANP and BNP contributed significantly to the predictive for incident AF to calculate the Suita Risk Score, but adding ANP to the Suita AF score with BNP improved the risk prediction slightly.
S-27-2: RENAL WATER LOSS-INDUCED SKIN WATER CONSERVATION LEADS TO HIGH BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Ogura Takahiro , Kitada Kento , Morisawa Norihiko , Kidoguchi Satoshi , Nakano Daisuke , Titze Jens , Nishiyama Akira 
Published: January 2023

Objective:
Although previous studies have demonstrated the pathophysiological basis of hypertension in basic and clinical sciences, the decisive mechanism of essential hypertension remains to be clarified. We recently reported that 5/6 nephrectomized rats exhibited renal water loss due to impaired renal concentration ability and that the renal water loss triggered suppression of transepidermal water loss (TEWL). This skin water conservation was achieved by skin vasoconstriction-mediated reduction in skin vascular mass, which increased blood pressure in 5/6 nephrectomized rats. In this study, we examined the effect of renal and skin water handling on high blood pressure in spontaneously hypertensive rats (SHR).

Design and method:
We used male 9 weeks old SHR and its control normotensive Wistar Kyoto rats (WKY) in this study. The rats were kept in metabolic cages to collect urine for 24 hours. We also collected urine under water deprivation. After the urine collection, the rats were sacrificed and their plasma and tissues were collected. Skin sodium and potassium content were measured by the ashing-flame photometer method. In a separate experiment, we compared blood pressure and TEWL in anesthetized SHR and WKY. Body temperature was raised by elevating room temperature.

Results:
Compared with WKY, SHR exhibited a significant increase in urine volume and a decrease in urine osmolality. There were no significant differences in plasma osmole concentrations, urinary sodium, potassium, and urea excretion between the groups. SHR showed significantly higher urine volume and lower urine osmolarity than WKY even in water deprivation, suggesting that SHR has renal water loss. SHR exhibited significantly lower TEWL and higher blood pressure and skin sodium and potassium content compared with WKY. Skin vasodilation induced by elevating body temperature significantly reduced blood pressure in SHR but not WKY.

Conclusions:
These findings suggest that renal water loss due to the impaired renal concentration ability induces suppression of TEWL and skin osmole accumulation in SHR. This skin water conservation leads to high blood pressure via skin vasoconstriction to reduce skin vascular mass and TEWL. Skin water conservation as a compensatory mechanism for renal water loss may be a key mechanism and novel therapeutic target for essential hypertension.
S-29-5: EARLY CHANGES IN LEFT ATRIAL STRAIN AND GLOBAL VENTRICULAR FUNCTION IN HYPERTENSIVE PATIENTS WITH HEART FAILURE WITH PRESERVED EF
Authors: Hristova Krasimira , Tselov Nikolay , Tsonev Svetrlin , Marinov Rumen , Zlatancheva Galina , Slavchev Boris 
Published: January 2023

Background:
Hypertension is one of leading causes in heart failure with preserved ejection fraction (HFpEF).Left atrial (LA) maximal volume and index (LAVI) had a prognostic value in patients with heart failure and incidence of atrial fibrilation (AF). Recently, LA mechanical function and LA strain have been introduced as alternative methods to assess LA performance more accuratly.

Aim:
To evaluate the relation between early changes in LA function and strain (PALS) and correlate the association with global left ventricular (LV) function and longitudinal strain (GLS) in patients with HFpEF.and arterial hypertension.

Methods:
We evaluated 152 subjects in sinus rhythm: 22 normals (31y ± 5), and 70 pts with HFpEF (65y ± 12), 60 pts HFrEF (64 y ± 10). Echocardiography was performed in all patients and follow up after 12 monts and analyzed offline in order to extract the global and segmental strain values of the LV and LA and LA volume and LAVI.

Results:
The two groups of patients were comparable for most of clinical variables. LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. The LA diameter and maximal volume were higher in HFrEF group. The GLS is significantly reduced in HFrEF group. LV GLS is the main parameter for myocardial dysfunction, which changed significantly in the HFrEF (p < 0,001) at 12mFU. Reduced PALS in HFrEF was associated with impairment of all measures of LV systolic and diastolic function and events of atrial fibrilation / 33 % in HFrEF and 12 % in HFpEF/ and the correlation between global longitudinal strain and PALS was highly significant (p < 0.001; r = 0.71). At 12mFU, PALS was significantly associated with lower global longitudinal strain in group with HFrEF (p < 0.001, r = 0.61), LAVI > 28 ml/m2 (p < 0.01,r = 0.57) and slightly decreased in HFpEF /p < 0.5, r = 0.34/. ROC analysis shows the cut of value of 29 % for PALS which correlated with AF events.

Conclusions:
PALS and GLS are significantly reduced in HFpEF patients and decreased in HFpEF. PALS provides additional,prognostic value beyond LA volume and LAVI. Severe LV myocardial dysfunction and reduced GLS and decreased PALS, even still normal LAVI is a prognostic index for AF.
S-30-2: ASIAN MANAGEMENT OF HYPERTENSION: CURRENT STATUS, HOME BP MONITORING, AND SPECIFIC CONCERNS IN PHILIPPINES
Authors: Sison Jorge Admiral 
Published: January 2023

Introduction:
Cardiovascular disease (CVD) in the Philippines showed hypertension as the highest (38.6%), followed by stroke (30%), coronary artery disease (17.5 %), heart failure (10.4%). Risk factor were: diabetes at 3.9%, dyslipidemia at 72%, smoking at 31%, obesity at 4.9% (BMI). Latest hypertension prevalence is 37%. Aware hypertensives were 19%, unaware was 18%. Treatment rate was 68%, compliance was 86%, blood pressure (BP) control rate was 37%. Mortality from CVD were stroke, mostly infarct (22.6%), MI (6.5%), Heart Failure (6.5%). Drugs used were angiotensin receptor blockers (64%), calcium channel blockers (42%), beta-blockers (6%), ACE inhibitors (4%) and diuretics (1%).
Current status of home BP monitoring (HBPM): HBPM is performed by 23% of hypertensive population in the Philippine. Barriers to its use include cost, availability and lack of trust regarding the accuracy of digital BP devices. Currently, physicians encourage patients to monitor BP at home to better assess their treatment to rule out white coat, masked hypertension and other parameters.
Philippine sub-analysis of AsiaBP@Home study: Data on HBPM offer solution to problems encountered particularly in Asia. Based on AsiaBP@Home study as a multi-national Asian specialty center performance regarding home and clinic BP control, majority of uncontrolled hypertension simulated by the new lower ACC/AHA guideline threshold gave additional 18% increase in sustained uncontrolled hypertension (SUCH) and to additional 5% increase in white-coat uncontrolled hypertension (WUCH). In a sub-group analysis of the Philippines in this study (Fig.1), using conventional threshold values, well-controlled clinic SBP was only 69% and well controlled morning home SBP was 79%. Using the new threshold levels, the well-controlled clinic SBP decreased to 43% and well controlled morning home SBP was lower at 67%. Comparing the conventional to the new thresholds, controlled hypertension decreased from 62% to 37%, masked morning hypertension decreased from 8% to 6%, Sustained hypertension increased from 13% to 27%, and white-coat hypertension increased from 18% to 31%.

Summary:
Hypertension still remains a major problem in the Philippines. Office BP measurement remains to be our standard for hypertension assessment and it appears to be insufficient in guiding us in our management approach. With the availability of newer and practical tools such as the HBPM, it will certainly improve hypertension evaluation, patient awareness, physician alertness in achieving better BP control and hence, better outcomes.
S-34-4: HYPERTENSION AND SOME RELATED RISK FACTORS FROM MAY MEASUREMENT MONTH SCREENING PROGRAMME IN VIETNAM FROM 2017 TO 2019
Authors: Minh Huynh Van , Viet Nguyen Lan , Sinh Cao Thuc , Hung Phan Nam , MNgoc Nguyen Thi , Hung Ngo Van , Son Tran Kim , Thang Doan Chi , Thuan Nguyen Duc , Tuan To Anh 
Published: January 2023

Aim:
The May Measurement Month (MMM) programme is a global cross-sectional blood pressure (BP) screening programme. Here we present the combined data for the years 2017, 2018 and 2019 from Vietnam.

Study methods:
BP was measured at various screening sites, according to MMM standard protocol and hypertension was diagnosed if the BP was equal or over 140/90 mmHg or if the individual was already on antihypertensive medication.

Results:
A total of 44,786 individuals (mean age 47.70 ± 17.65 years, range 18 to 89 years; 58,8 % female) were screened over the 3 year period. The mean of the last two BP readings was 121.60 ± 18.64 mmHg; 13,972 (31,2%) readings were in the hypertensive range; 20,033 (44,7%) were in prehypertension; 5,910 (57,7%) were undiagnosed hypertension. A further 5,576 individuals were on antihypertensive medications but only 2,578 (46,2%) patients on BP controlled, 8.1% of those with previous myocardial infarction, 2.2% of those with previous stroke and 11.7% of the diabetic patients. SBP and DBP correlated with body mass index (BMI) (r = 0,228 and r = 0,235, p < 0,01) and age [OR, 95% CI: 3.22 (3.22–4,52)], with a large proportion of individuals having overweight/obese [OR, 95% CI: 2.70 (2.56–2.85)].

Conclusion:
Community screening MMM programmes help identify the prevalence of hypertension especially also help to identify those at high cardiometabolic risk. More emphasis should be given to monitoring those in high cardiometabolic risk categories and older age groups./.