bluuebunny/crossref_metadata_2025 huggingface dataset:
S-43-5: A PROSPECTIVE OBSERVATION FOR ORTHOSTATIC DYSREGULATION AND INTOLERANCE IN ADOLESCENCE: STUDY PROTOCOL OF THE SUITA OFFSPRING STUDY
Authors: Kashima Rena , Kokubo Yoshihiro , Arafa Ahmed , Teramoto Masayuki , Nakai Akane , Sakai Yukie , Nosaka Saya , Yasui Yuka , Kogirima Miho , Kato Yoshiaki , Sakata Yasuhiko
Published: January 2023

Background:

In recent years, the number of adolescents who do not attend school due to orthostatic dysregulation (OD) has increased rapidly in Japan, and countermeasures are urgently needed. In contrast, orthostatic intolerance (OI) is used as its counterpart in Western countries, and no internationally unified disease concept exists. Therefore, it is necessary to compare a population-based prospective study of OD and OI in adolescent urban communities.

Objective:

This study aims to show the clinical characteristics and prognosis of OD and OI in adolescent urban communities.

Methods:

We will launch the offspring cohort in 2022 in two school districts of Suita City, where we encourage medical examinations for all 11-, 14-, and 17-year-old adolescents. Approximately 200 adolescents of each age group will be undergoing medical examinations as research participants. We will perform a medical check-up to detect the constituents of metabolic syndrome, OD, and OI. We will implement questionnaires for the participants based on the Japanese OD Diagnostic and Treatment Guideline (OD symptoms) and diagnostic criteria in Western countries (OI symptoms). If any of the OD or OI symptoms (at least 3 points, 1 point or more) are positive, they will continue with a 10-minute standing test and their parents will fulfill the checklist for diagnosis of OD with psychosomatic disorder based on the aforementioned OD Guideline. Participants who are positive in the standing test will undergo echocardiography, Holter electrocardiography, and Parent-child home blood pressure measurements. We will refer to the Maternal and Child Health Handbook, Infant Health Examination, School Health Examination, and Lifestyle Related Disease Prevention Health Examination to explore OD and OI risk factors (for example, rapid change in growth curve and circadian rhythm formation). We will compare the prevalence of OD and OI by category using the respective diagnostic criteria in Japan and Western countries and reveal the relationship with classical risk, the diurnal variation in HBP of participants and their parents, cardiac function, and autonomic function. We will conduct follow-up studies every 3-year until 20 years old to examine morbidity and prognosis. In addition, we will perform a selected lifestyle questionnaire focusing on diet and physical activity for adolescents and then use metabolomic analysis to compare plasma metabolite profiles of with and without OD and OI participants to detect modifiable risk factors targeted in future interventions.
S-44-3: GENDER DIFFERENCE IN THE ASSOCIATION OF DIETARY CALCIUM INTAKE WITH BLOOD PRESSURE: ANALYSIS OF THE NHANES 2017 - 2020
Authors: Tantisattamo Ekamol , Wannaphut Chalothorn , Wattanachayakul Phuuwadith , Chaisrimaneepan Nattanicha , Lalitnithi Pakin , Lopimpisuth Chawin , Pangkanon Watsachon , Thimphitthaya Chanattha , Naunsilp Piengpitch
Published: January 2023

Background:

Higher dietary calcium intake is associated with lower blood pressure. This association among different genders is unclear.

Methods:

A cross sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 included participants ≧18 years old. The Association between the quartile of the dietary calcium intake and systolic and diastolic hypertension defined as three average measured systolic blood pressure ≧130 and diastolic blood pressure ≧80 mmHg, respectively was examined by multiple logistic regression.

Results:

Of 11,137 study participants, the mean ± SD age was 50 ± 19 years old and 51% were female. Up to 35% were White followed by Black, Asian, and other races. Median (interquartile range; IQR) dietary calcium intake of quartile 1 to quartile 4 were 21 (13, 33), 120 (83, 183), 233 (220, 293), and 625 (500, 959) mg/day, respectively. Average systolic blood pressure and diastolic blood pressure were 124 ± 19 and 74 ± 12 mmHg, respectively. Systolic and diastolic blood pressure were significantly lower in women compared to men for every quartile 1 and 2 of dietary calcium intake, higher in quartile 3, and not different in quartile 4 (Figure 1A and 1B). Dietary calcium intake in quartiles 3 and 4 were significantly associated with 38% and 55% greater odds of systolic hypertension (odds ratio (OR) Q3 1.375, P 0.006, 95% confidence interval (CI) 1.095, 1.728 and OR Q4 1.550, P < 0.0001, 95%CI 1.249, 1.923), but not with diastolic hypertension. After adjusting for age, gender, race, body mass index, serum creatinine, urine albumin:creatinine ratio, dietary sodium and potassium intakes, and the interaction term between gender and dietary calcium intake, only dietary calcium intake in quartile 3 was significantly associated with 82% lower odds of systolic hypertension (adjusted OR Q3 0.164, P 0.005, 95%CI 0.047, 0.578), while the association was greater and in the same direction for quartile 4, but it was not statistically significant (adjusted OR Q4 0.341, P 0.120, 95%CI 0.087, 1.326). Although there was an inverse association between dietary calcium intake and diastolic hypertension, it was not statistically significant. Gender was identified as an effect modifier, with a stronger positive association between the dietary calcium intake and systolic hypertension observed in female participants (Pinteraction 0.028).

Conclusions:

Dietary calcium intake and systolic hypertension, but not diastolic hypertension is inversely associated with a different magnitude between women and men. Additional longitudinal studies are required to further evaluate this relationship.
S-44-6: ASSESSING THE EFFECT OF SIMPLE CARBOHYDRATE RESTRICTED DIET ON BLOOD PRESSURE LEVELS OF HYPERTENSIVE
Authors: Patil Mansi V , Patil Vishal S
Published: January 2023

Objective:

In the recent past, various functional foods have been proposed to be effective tools for alleviating hypertension. There is a paucity of evidence on the efficacy of restricted sugar intake in an Indian setting and most evidence comes from non-validated studies. Studies have proposed that sugar acts by decreasing nitric oxide, increasing low-grade inflammation, increasing insulin resistance and promoting obesity.

The objective of the study is to assess the efficacy of restriction of simple carbohydrate intake on change in body weight, blood pressure and anthropometry [waist circumference (WC), waist to hip ratio(WHR) and body mass index (BMI)] after 30 days in males with pre-dominant hypertension.

Design and Methods:

A Case-Control Study with a sample size of 200 urban patients with clinical blood pressure > 140/90 were selected and divided into 2 groups.

A 1800kcal/day diet restricted in simple carbohydrates was given and Blood pressure, body weight, anthropometry (height, WC, HC, BMI, WHR, BSL (F, PP) were measured after 30 days. The participants had been following a structured 1800 kcal/day 3 months prior to the carbohydrate-restricted intervention. Complex carbohydrates were allowed. No change in physical activity was initiated.

Results:

A significant reduction was observed in the intervention group consuming a restricted carbohydrate diet along with a structured diet. Diet recall was taken using food frequency questionnaires and daily pictures of the plate that the participants consumed.

Conclusion:

A restricted simple carbohydrate diet was found to be effective in weight loss and reduction of systolic and diastolic blood pressure in patients with hypertension. The intervention group has a higher odds ratio and is positively associated with SBP, Weight loss and WC as compared to the control group. The source of simple carbohydrates in the majority of the participants was noted as bakery products, sauces and other hidden sources of carbohydrates. Participants were regularly counselled towards healthy eating and dietary sources of various nutrients.
S-44-7: CALORIC RESTRICTION AND BLOOD PRESSURE REGULATION DURING METABOLIC SYNDROME
Authors: Ortiz Rudy M
Published: January 2023

Poor dietary practices such as excessive glucose, sodium, and saturated fat intake are well-established contributing factors to promoting hypertension. Additionally, the obesity associated with the metabolic syndrome (MetS) is considered a significant contributing factor to the develop of the MetS-associated hypertension. Conversely, behavioral modifications of diet such as caloric restriction (CR) and intermittent fasting contribute to significant loss of body mass through reduced adiposity, which can lead to a decrease in arterial pressure. CR in combination with other behavioral modifications such as physical activity is necessary to significantly reduce the hypertension. As with the mechanisms by which increased adiposity (obesity) promote hypertension, the mechanisms by which CR reduce arterial pressure are not established. The relevant data suggest that a multitude of mechanisms may contribute simultaneously to reduce arterial pressure including improvements in nitric oxide (NO) and AMPK signaling, redox balance, renin-angiotensin system, and glucose tolerance. However, CR in animals does not consistently produce similar results with respect to improvements in arterial pressure. We have shown that perturbed dietary intake of nutrients (excessive cholesterol, glucose, and saturated fat) does not consistently exacerbate the MetS-associated hypertension while acute CR does not significantly reduce the hypertension despite improvements in other aspects of MetS. While partial recovery of the lost adiposity/body mass did not exacerbate the MetS-associated hypertension in OLETF rats, other detriments on cellular metabolism were identified suggesting that, at least during acute, metabolic perturbations, the mechanisms regulating arterial pressure are resistant to these cellular mechanisms. The complexity of the metabolic syndrome presents many challenges to the ability to dissect the mechanisms by which MetS risk factors promote the associated hypertension. Conversely, dissecting the mechanism by which CR ameliorates the MetS-associated hypertension remains equally challenging. Nonetheless, much more research on the mechanisms by which CR improves the MetS-associated hypertension is needed to gain a better understanding of the complex relationships among diet, hypertension, and MetS-related risk factors.
S-45-5: ONCO-HYPERTENSION; HYPERTENSION, ANTIHYPERTENSIVES AND THE CANCER
Authors: Pyun Wook Bum
Published: January 2023

Hypertension is known as most prevalent and powerful risk factor for the cardiovascular diseases such as death, myocardial infarction, stroke and heart failure. During the long period of hypertension, the cancer also occurred in patients with hypertension and hypertension is the most prevalent comorbidity in patients with cancer. Several issues raise the suspicious association between antihypertensive medications and cancer. First, the FDAs withdrawal of some losartan, valsartan and irbesartan because of carcinogenic byproduct during pharmaceutical process. Second, the theoretical mechanisms which may have role in cancer initiation such as apoptosis, angiogenesis, cell proliferation, tissue invasion. Third, some observation studies reported the association of cancer occurrence with antihypertensive medications. But the theoretical dose of carcinogenic byproduct is too high to have role for cancer development. And the other reports failed to prove the association of cancer occurrence with antihypertensive medications. We have to make it clear and keep having attention because this issue will be a big hurdle to improve the hypertension control rate and reduce the cardiovascular mortality.
S-46-1: WHITE-COAT HYPERTENSION AND MASKED HYPERTENSION: OVERALL EVIDENCE AND PERSPECTIVE FROM USA
Authors: Shimbo Daichi
Published: January 2023

The diagnosis and management of hypertension has been predominantly based on the measurement of blood pressure (BP) in the office. Extensive data has demonstrated that BP may greatly differ when measured in office than when measured outside the office setting, and higher out-of-office BP is associated with increased cardiovascular risk independent of office BP. White coat hypertension is defined as having high office BP without high out-of-office BP. Masked hypertension is defined as having high out-of-office BP without high office BP. Ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) are validated approaches for out-of-office BP measurement, and both methods can be used for detecting white coat hypertension and masked hypertension. This talk focuses on the evidence for conducting ABPM and HBPM for detecting white coat hypertension and masked hypertension, and the perspective from the USA about which approach for out-of-office BP measurement should be used for the diagnosis and management of hypertension among adults.
S-46-3: ANTIHYPERTENSIVE TREATMENT IN MASKED HYPERTENSION FOR TARGET ORGAN PROTECTION (ANTI-MASK): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
Authors: Huang Jianfeng , Zhang Dongyan , An Dewei , Li Mingxuan , Chen Xin , Feng Yingqing , Zheng Qidong , Li Yan , Wang Jiguang
Published: January 2023

Objective:

Masked hypertension is associated with target organ damage and adverse outcomes. However, up to now there is no interventional evidence that antihypertensive therapy will be beneficial to the patients.

Design and methods:

The ANTIhypertensive treatment in MASKed hypertension for target organ protection (ANTI-MASK) trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial (NCT02893358). Eligible patients were 30 to 70 years old, had untreated masked hypertension and at least one sign of target organ damage (TOD). Masked hypertension was defined as a normal office blood pressure (BP, < 140/90 mmHg) and an elevated 24-hour (> = 130/80 mmHg), daytime (> = 135/85 mmHg) or nighttime BP (> = 120/70 mmHg) at both screening visits. TOD included electrocardiogram diagnosed left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (ba-PWV) > = 1400 cm/s, or a random urinary albumin-to-creatinine ratio (ACR) > = 2.5 mg/mmol in men and > = 3.5 mg/mmol in women. Randomized patients were treated with alisartan 80 mg per day or placebo. If ambulatory BP was uncontrolled, drug dosage was doubled at the 2-month visit, and amlodipine 2.5 mg or matching placebo was added at the 4-month visit. The primary endpoint was the improvement rate of TOD after 12 months treatment, defined as the reverse (yes to no) of TOD or a significant decrease of ba-PWV or ACR by > = 20% of the baseline level.

Results:

From Feb 2017 to Oct 2020, 317 patients with masked hypertension (43.2% women, mean age 54 years) were randomized in 13 hospitals in China. Overall, baseline office, 24-h, daytime and nighttime BPs averaged 130/81,137/85, 141/87, and 126/77 mmHg, respectively. At baseline, 98% had an elevated ba-PWV, 12% microalbuminuria, and 8% LVH. 252 patients completed the 12-month treatment and 65 (20.5%) withdrew from the trial. In the intention-to-treat analyses, the improvement rate of TOD was significantly higher in the antihypertensive treatment group than the placebo group (47.4% vs 26.1%, P < 0.0001), as well as the decrease of the 24-h systolic/diastolic BPs (-9.1/-5.7 vs -1.5/-1.0 mmHg, P < 0.0001).

Conclusions:

Antihypertensive treatment was beneficial for patients with masked hypertension in terms of TOD protection.
S-47-2: DIAGNOSIS OF PRIMARY ALDOSTERONISM USING ARTIFICIAL INTELLIGENCE
Authors: Eisenhofer Graeme
Published: January 2023

Testing for primary aldosteronism (PA) involves an arduous multistep process culminating in either resection of an adrenal in patients identified with unilateral disease after adrenal venous sampling (AVS) or mineralocorticoid receptor blockade in patients without AVS-based evidence of lateralized aldosterone secretion. Multiple difficulties plague each step, including the confirmatory step where immunoassay interferences lead to many false-positive results (1). Mass spectrometry-based steroidomics provides an alternative approach that combined with artificial intelligence might be used for both screening and stratification of patients for therapeutic intervention. The approach may be particularly useful for identification of patients with unilateral disease due to somatic KCNJ5 mutations, who after imaging studies may proceed directly to adrenalectomy without need for confirmatory studies or AVS. To establish this approach, we developed machine learning (ML) models using a retrospective cohort of 462 patients tested for PA, including 139 with unilateral disease of whom 58 had KCNJ5 mutations (2) ML models are now undergoing external validation in a prospective multicenter study (PROSALDO), which has to date enrolled 542 eligible patients. Among these 186 have received follow-up, which has enabled exclusion of disease in 73 and confirmation of unilateral disease in 38 others according to post-surgical biochemical cure. Among the latter, genotyping in 19 patients identified KCNJ5 mutations in nine, all of whom showed post-operative cure and were correctly predicted by ML to have PA with KCNJ5 mutations. Among these nine and four others who were not part of the PROSALDO trial (3) 10 had their adrenals removed without AVS evidence of lateralization. In an interim analysis (with recognition that ML models were likely compromised by incorrect classifications due to immunoassay inaccuracy), among the 542 PROSALDO patients, 138 and 404 were respectively classified with and without PA. According to areas under receiving-operating characteristic curves (AUC), our ML model for screening performed equally poorly (AUC = 0.927) compared to aldosterone:renin ratios (ARR) determined by mass spectrometry (AUC = 0.909) and immunoassay (AUC = 0.895) measurements of aldosterone. Significantly improved performance was achieved by incorporation of plasma potassium and renin with steroidomics-based models (AUC = 0.9511). Results to date indicate promise for ML approaches to both more accurately screen for PA than possible with the ARR and also identify patients with unilateral disease due to KCNJ5 mutations who may directly proceed to surgery without need for confirmation studies or AVS.
S-47-4: THE BURDEN OF CARDIOVASCULAR DISEASE ATTRIBUTABLE TO HIGH SYSTOLIC BLOOD PRESSURE ACROSS CHINA AND ITS PROVINCES FROM 2005 TO 2018
Authors: Cao Xue , Zhao Zhenping , Kang Yuting , Tian Yixin , Song Yuxin , Wang Liming , He Yuna , Zhang Linfeng , Chen Zuo , Zheng Congyi , Chen Lu , Hu Zhen , Zhou Haoqi , Zhou Maigeng , Wang Zengwu
Published: January 2023

Background:

The temporal trends and geographical disparity in the burden of cardiovascular diseases (CVD) attributable to high systolic blood pressure (SBP) have not been fully discussed before in Chinese population. The current study was performed to quantify the CVD burden attributable to high SBP in China, which is crucial to inform and improve blood pressure control measures.

Methods:

We evaluated death numbers, age-standardized mortality rate and years of life lost (YLLs) and corresponding estimated annual percentage changes (EAPC) for CVD and its subcategories attributable to high SBP from 2005 to 2018. We polled data from China Chronic Disease and Risk Factor Surveillance, the China Health and Nutrition Survey and China Hypertension Survey to estimate the BP level between 2005 and 2018. A comparative risk assessment method was applied to compute the deaths and health burden attributable to high SBP for CVD and its subtypes by age, sex, year and provinces.

Findings:

We estimated that 2·67 million (95%UI 2·61 to 2·73) CVD deaths in China were attributable to elevated SBP in 2018. Age-standardized CVD mortality rate associated with high SBP decreased by 17·89% for China overall between 2005 and 2018, and the EAPC was -1·50 (95% UI -1·55 to -1·45). The death numbers for ischemic heart disease, ischemic stroke due to high SBP showed a relative growth in most provinces, while age standardized mortality rates declined in 2018 compared with 2005 in most provinces, which were in line with the national trend. YLLs for total CVD attributable to high SBP increased from 40·13 million (95%UI, 39·70 to 40·52) in 2005 to 48·16 million (95%UI, 47·44 to 48·90) in 2018 for China overall. YLL rates varied considerably across provinces, ranging from 3217·15 per 100 000 (95%UI 2947·43 to 3441·83) in Fujian to 7196·20 per 100 000 (95%UI 6864·28 to 7498·94) in Heilongjiang in 2018. Age-standardized YLL rates for ischemic heart disease and ischemic stroke attributable to high SBP were high in northeast provinces, including Heilongjiang, Liaoning and Jilin.

Interpretation:

The deaths and YLLs for CVD attributable to high SBP increased substantially in recent years, especially for the elderly, although age-standardized CVD mortality rate has decreased in China between 2005 and 2018. Preventive interventions should be implemented to lower the prevalence of high SBP among Chinese overall in order to reduce the SBP-related CVD adverse health effect.
S-47-5: CURRENT STATUS OF HYPERTENSION IN KOREA: A NATIONWIDE POPULATION-BASED STUDY
Authors: Kim Hyeon Chang , Lee Hokyou , Lee Hyeok-Hee
Published: January 2023

The Korean Society of Hypertension (KSH)- Hypertension Epidemiology Research Working Group has analyzed national big data to provide an overview of the magnitude and management status of hypertension and their recent trends. The analyses included data for Korean adults aged 20 years or older of the 1998–2020 Korea National Health and Nutrition Examination Survey and the 2002–2020 National Health Insurance Big Data. As of year 2020, the population average of systolic/diastolic blood pressure was 118/76 mmHg in Korean adults aged 20 years or older showing little change in the recent decade. It is estimated that 29% of the adult population aged 20 or older (34% of adults aged 30 or older) have hypertension. The estimated number of people with hypertension was 7.2 million for men and 5.5 million for women. Among them, 2.0 million men and 3.0 million women are aged 65 or older. The number of people diagnosed with hypertension increased from 3.0 million in 2002 to 10.5 million in 2020. During the same period, the number of people using antihypertensive medication increased from 2.5 million to 9.9 million, and the number of people adherent to treatment increased from 0.6 million to 7.4 million. Among antihypertensive prescriptions, 40% of the patients received monotherapy, 44% received dual therapy, and 16% received triple or more therapy. The most commonly prescribed antihypertensive medication was angiotensin receptor blockers (ARB), followed by calcium channel blockers (CCB) and diuretics. Among the adult Korean population aged 20–64, there are 5.9 million controlled hypertension, 3.9 million treated-but-uncontrolled hypertension, 3.2 million diagnosed-but-untreated hypertension, and 1.5 million undiagnosed hypertension. Among the Korean elderly population aged 65 or older, there are 3.6 million have controlled hypertension, 1.5 million treated-but-uncontrolled hypertension, 0.8 million diagnosed-but-untreated hypertension, and 0.4 million undiagnosed hypertension.
S-50-2: ULTRAFAST LC-MS ANALYSIS FOR THE CHEMICAL ADHERENCE TESTING: SUB MINUTE RUN TIMES FOR A PANEL OF NINE CARDIOMETABOLIC MEDICATIONS
Authors: Lane Dan , Ng Leong , Jones Donald JL , Gupta Pankaj
Published: January 2023

Objective:

Non-adherence in hypertension can be as high as 30–45%. Chemical adherence testing (CAT) is the preferred method to assess non-adherence in European guidelines. New randomised controlled trials (RCTs), like the RADIANCE-HTN TRIO, have also started to implement CAT into their study framework to diagnoses non-adherence. Using high performance liquid chromatography (HPLC) in tandem mass spectrometry (MS/MS), existing quantitative urine CATs take > 40 minutes. These provide a yes/no answer. Recent guidance has suggested run-time be an area of development, along with the research of quantitative assays in plasma. Translated from the field of therapeutic drug monitoring, UltraFast (<1 minute) run times were explored using ultra performance short (UP)-LC columns with MS/MS for the detection and quantitation of nine cardiometabolic medications in plasma for use in CAT. UltraFast methods could increase clinical and research capacity while reducing cost.

Design:

An UltraFast quantitative CAT using UPLC-MS/MS was developed and optimised for the parallel detection of nine cardiometabolic medications in plasma. These medications were amlodipine, atenolol, atorvastatin, bisoprolol, edoxaban, enalapril, propranolol, ramipril, and saxagliptin.

Methods:

A mixed internal standard (IS; 10 ng/mL) was added to 100 μL of sample before the addition of 100 μL of water. The entire solution was added to pre-conditioned Oasis PRiME hydrophilic lipid balance (HLB) 96-well μElution solid phase extraction (SPE) plates. The loaded wells were washed (200 μL 5% methanol) and eluted (50 μL methanol/ acetonitrile) prior to UPLC-MS/MS analysis on a Waters Xevo TQ-XS triple quadrupole system. Sub 45 s run times were achieved using a Raptor Biphenyl Guard column cartridge (5 x 2.1 mm, 2.7 μm) as the UPLC column, used in reverse phase, and pumped at a 1.4 mL/min flow rate. Five replicate calibration curves were extracted over the range 0.01–500 ng/mL to assess model fits and detection limits.

Results:

All medications in plasma had lower limits of detection (LOD) between 0.01 ng/mL (atorvastatin) and 20 ng/mL (amlodipine). Optimum calibration curves were obtained. These were a mixture of quadratic and linear models. R2 ranged from 0.837 (enalapril) to 0.971 (atorvastatin). Clear chromatographic separation was achieved with the first eluted peak was atenolol, detected at 3 s. The last eluted peak was edoxaban at 22 s. Quantitation was possible over the range 0.01–500 ng/mL.

Conclusion:

A <45 second UPLC-MS/MS run time was achieved for a panel of nine cardiometabolic medications. LODs were well within the therapeutic range of interest, and quantitation was made possible over 0.01–500 ng/mL, the therapeutic range of interest. This method could be applied in clinical laboratories for same day adherence testing, or to large RCTs for their timely processing.
S-50-6: HOW TO ASSESS BENEFICIAL EFFECTS OF ANTIHYPERTENSIVE TREATMENTS
Authors: Piskorz Daniel Leonardo
Published: January 2023

Most hypertensive patients could have hypertension mediated organ damage (HMOD) at the moment of the diagnosis. Even in low 10-year cardiovascular risk patients HMOD is frequent. The presence of HMOD is related to increased cardiovascular risk and mortality, so, at the same time HMOD should be considered as a therapeutic target and a surrogate marker of blood pressure un/controlled.

The effects of impaired renal function and left-ventricular hypertrophy could identify patients at a mortality very high risk. Guidelines considered arterial stiffening evaluated as high carotid-femoral pulse wave velocity a factor influencing cardiovascular risk, and a documented carotid artery stenosis > 50 % as a marker of very high cardiovascular risk. The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) showed that 50% of the participants at risk category one had a mean of one atherosclerotic plaque, and 80.7 % of individuals at category two had a mean of 2.2 atherosclerotic plaques. The hazard ratio of having a vascular event could increase by 50% in the presence of one HMOD and by 3.8 times when three HMOD are present.

In this scenario, to prevent that at least some patients could be misclassified as low risk, screening of HMOD as modifiers of cardiovascular risk estimated by different scores could be recommended in hypertensive patients.

The non-significant net reclassification improvement of cardiovascular risk and the lack of evidence suggesting a relationship between vascular images biomarkers regression independently of blood pressure lowering and a reduction in cardiovascular events precludes the routine search of arterial stiffness or carotid atherosclerotic plaques out of research scenarios.

A reduction in left ventricular mass during treatment is a favorable prognostic marker that predicts lesser risk for subsequent cardiovascular morbidity and mortality. The association between left ventricular mass regression and cardiovascular outcomes is independent of baseline left ventricular mass, baseline clinic and ambulatory blood pressure, and degree of blood pressure reduction. Suboptimal blood pressure control is a significant covariate of persistent left ventricular hypertrophy, independent of the number and class of antihypertensive drugs.

RAS blockade is recommended as the initial treatment of hypertension in patients with reduced glomerular filtration rate or albuminuria since they are the most effective at reducing progression to end stage kidney disease, but a combination with calcium channel blockers or diuretics is recommended due to the difficulties to achieve the targets with monotherapy.
S-51-5: DIFFERENT CONTRIBUTION OF AFFERENT RENAL NERVES TO DEVELOPMENT OF HYPERTENSION AND HYPERTENSIVE HEART FAILURE IN SEVERAL RAT MODELS OF HYPERTENSION
Authors: Shinohara Keisuke , Ikeda Shota , Nakashima Ryosuke , Matsumoto Sho , Yoshida Daisuke , Ono Yoshiyasu , Tsutsui Hiroyuki
Published: January 2023

Objective:

Renal nerves contain efferent and afferent fibers. Acute stimulation of the afferent nerves increases central sympathetic outflow. This study aimed to investigate the contribution of afferent renal nerves to the development of hypertension and hypertensive heart failure in several rat models of hypertension.

Design and method:

Selective afferent renal nerve denervation (ARDN) or sham operation was performed in the following models: (1) SHRSP at 9 weeks of age; (2) 4% high-salt diet (HS)-fed SHRSP at 8 weeks (HS from 8 weeks); (3) 8% HS-fed Dahl salt-sensitive rats at 9 weeks (HS from 6 weeks); and (4) 8% HS-fed Dahl salt-sensitive rats at 9 weeks (HS from 7 weeks). Dahl rats fed 0.3% low-salt diet (LS) were used as controls for (3) and (4). Blood pressure (BP) was measured by telemetry in (1) and (2), and by tail-cuff method in (3) and (4). The experimental period ended at the following age: (1) 11 weeks; (2) 11 weeks; (3) 16 weeks (“HFrEF’’ phase); and (4) 19 weeks (“HFpEF’’ phase).

Results:

(1) Mean BP was significantly elevated from 9 weeks to 11 weeks in sham-SHRSP (155.2 ± 2.0 vs 144.0 ± 1.9 mmHg, n = 10, p < 0.05). Mean BP in ARDN-SHRSP (157.8 ± 2.7 mmHg, n = 10) was not different compared to sham-SHRSP at 11 weeks. (2) Mean BP was significantly increased from 8 weeks to 11 weeks in sham-HS-SHRSP (191.5 ± 8.1 vs 126.5 ± 4.0 mmHg, n = 6, p < 0.05). Mean BP in ARDN-HS-SHRSP (186.0 ± 7.1 mmHg, n = 6) did not differ from sham-HS-SHRSP at 11 weeks. (3) Systolic BP was significantly increased (243.6 ± 7.0 vs 140.0 ± 2.7 mmHg, n = 9 each, p < 0.05) and echocardiographic left ventricular fractional shortening (LVFS) was significantly decreased (25.9 ± 1.7 vs 48.8 ± 0.4 %, p < 0.05) in sham-HS-Dahl rats compared to LS-Dahl rats at 16 weeks. Compared to sham-HS-Dahl rats, systolic BP was not different (223.4 ± 5.5 mmHg, n = 7); however, the decreased LVFS was significantly attenuated (42.2 ± 1.2 %, p < 0.05) in ARDN-HS-Dahl rats. (4) Systolic BP was significantly increased in sham-HS-Dahl rats compared to LS-Dahl rats at 19 weeks (207.8 ± 4.5 vs 135.7 ± 3.2 mmHg, n = 8 and 6, p < 0.05), and this increase was not affected in ARDN-HS-Dahl rats (220.7 ± 2.9 mmHg, n = 7). By echocardiography, LVFS did not differ between the three groups, whereas E/e’ ratio was significantly increased in sham-HS-Dahl rats compared to LS-Dahl rats and was attenuated in ARDN-HS-Dahl rats.

Conclusion:

The signals from afferent renal nerves contribute to the development of HFrEF and HFpEF without affecting BP in Dahl salt-sensitive hypertensive rats, but not of hypertension in SHRSP and HS-fed SHRSP.
S-52-1: CARDIOVASCULAR OUTCOMES IN HYPERTENSIVE PATIENTS WHO DISCONTINUE STUDY MEDICATION IN A LARGE OUTCOME TRIAL. THE LIFE STUDY.
Authors: Wachtell Kristian , Julius Stevo , Okin Peter M , Greve Anders M , Devereux Richard B , Oparil Suzanne , Kjeldsen Sverre E , Boman Kurt
Published: January 2023

Objective:

Patient discontinuation of study medication during an outcome trial has significant implications for study power. However, patients who discontinue cardiovascular outcome trials are not well described. We aimed to assess readily available patient characteristics and outcomes in patients with hypertension and left ventricular hypertrophy (LVH) who discontinued the study drug but otherwise remained in the study until the end of follow-up.

Methods:

In patients who discontinued vs. those continuing, Cox proportional hazards models identified baseline variables that had a significant impact on the occurrence of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 9,193 hypertensive patients and LVH in the LIFE study.

Results:

During a mean follow-up of 4.8 years, 3,281 patients (35.7%) discontinued one or more days during the trial, not counting death as a reason for discontinuation. The distribution of days to discontinuation was highly skewed towards the first part of the study; the 25th percentile was at day 161, and the median was at day 669.

Reasons for discontinuation were a clinical adverse event (50%), a secondary study endpoint (19%), required study therapy (11%), withdrawal (2%), administrative (18%), and lost to follow-up (0.2%).

Those who discontinued were older, more often male, had slightly lower body mass index, higher systolic and lower diastolic pressure, higher Framingham Risk Score (FRS), and more ECG LVH determined by either Cornell voltage-duration product or Sokolow-Lyon criteria compared to those who continued in the study. Of particular note, the discontinuation rate between the two study drugs was not equal. Patients randomized to losartan discontinued less than those randomized to atenolol. Multivariate analyses showed that older age, male gender, FRS, Sokolow-Lyon criteria, atenolol treatment as well as a history of pre-study myocardial infarction, cerebral vascular disease, peripheral vascular disease, and atrial fibrillation as well as lower levels of hemoglobin, higher serum creatinine and lower cholesterol all independently predicted discontinuation from the study drug.

Conclusions:

Patients discontinued during the first part of the study mainly due to experience of a clinical adverse event. Patients who discontinued the study drug had, on average, more previous and concurrent cardiovascular disease than those who continued until the study ended. There is no risk reduction and futility if an outcome study recruits patients with too little risk. However, too high risk implies early drug discontinuation and thus reduction in the study power.
S-53-5: BUILDING A MONOLITH OF CARDIOVASCULAR CARE - THE MEDICAL DX AND PATIENT WELL-BEING
Authors: Bando Yasuko K
Published: January 2023

Sustainable development is the indispensable challenge to make the world a better place. More specifically, sustainable development is essential for transforming our world better and better by ensuring that all human beings can enjoy their lives by harmonizing economic, social, and technological progress with nature. Simultaneously, it has been emphasized that no one should not be left behind over this action. To bold and transformative achievement, the 17 Sustainable Development Goals (SDGs) and 169 targets have been globally announced and stimulate any activity by 2030. Healthy lives are one of the essential SDGs, but how are we doctors to dedicate ourselves to achieving the SDGs via our practices? How do we commit to making the world a better place? In this opportunity, focusing on hypertension practice, I would like to discuss the possible and ideal scenario for the medical SDGs by mentioning not only e-health/ICT but also new enlightenment of the medical approach by reflecting on every concern and issue in the current practice that lacks the inclusive, sustainable, and well-being support for patient and doctor relationship.
S-56-6: HOME BLOOD PRESSURE SURVEY IN SOUTHEAST AND EAST ASIA
Authors: Wang Tzung-Dau
Published: January 2023

Home blood pressure monitoring (HBPM) is a promising tool that can aid in the diagnosis and management of hypertension. Experts from 11 countries/regions in Asia conceptualized a large-scale survey to examine the current realities of HBPM. A cross-sectional survey was conducted among health care professionals from China, India, Indonesia, Japan, Malaysia, the Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam between November 2019 and June 2021. Physicians’ responses were summarized using descriptive statistics. A total of 7,951 physicians participated in the survey. Among all respondents, 50.3% and 33.5% viewed HBPM as highly recognized by physicians and patients in their country/region, respectively. Lack of understanding of HBPM and concern with the accuracy and reliability of HBPM devices were identified as key barriers to HBPM recognition. Nearly all physicians (95.9%) reported recommending HBPM to their patients; however, they reported less than 50% of their patients measured home blood pressure (HBP). Among physicians who recommended HBPM, only 22.4% and 54.1% cited HBP diagnostic threshold values and timing of taking antihypertensive drugs that were consistent with available guidelines, respectively. The survey reveals that the recognition of HBPM as a valuable tool to diagnose and manage hypertension is suboptimal in most parts of Asia. Despite high recommendation of HBPM to hypertensive patients by physicians, there are considerable discrepancies between guidelines recommendations and practice realities.
S-57-6: OBSTRUCTIVE SLEEP APNEA INDUCED GUT DYSBIOSIS STIMULATES A PROINFLAMMATORY RESPONSE THAT PROMOTES NEUROINFLAMMATION AND HYPERTENSION
Authors: Ayyaswamy Sriram , Zhang Bojun , Shi Huanan , Bryan Robert , Durgan David
Published: January 2023

Objective:

Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HT). We have demonstrated that OSA induces gut dysbiosis, and a dysbiotic microbiota is causal in the development of HT. The mechanisms linking gut dysbiosis to blood pressure (BP) regulation are unclear. Recent studies demonstrate gut dysbiosis induces a pro-inflammatory host response resulting in peripheral- and neuro-inflammation, key factors in the development of HT. We hypothesized that OSA induced gut dysbiosis elicits a pro-inflammatory response that promotes neuroinflammation and HT.

Methods:

OSA was induced in 8-week-old male rats by repeatedly inflating a surgically implanted tracheal balloon. Sham rats underwent balloon implantation without inflations. After two weeks of apneas, lymphocytes were isolated from aorta, brain, cecum, ileum, mesenteric lymph node, and spleen for assessment by flow cytometry. In studies examining IL-17, a monoclonal antibody to neutralize IL-17 was injected every 48 hours during the 2 weeks of OSA. To track lymphocytes originating from the gut, cells in the Peyers patches of the small intestine were labelled by injection of carboxyfluorescein succinimidyl ester (CFSE) dye.

Results:

Two weeks of OSA significantly decreased anti-inflammatory regulatory T (Treg) cells and increased TH17 (IL-17+) in the brain, cecum, and ileum (n = 7, p < 0.05). A significant increase in the Th17/Treg ratio was observed in brain, cecum and ileum of OSA, versus sham, rats (n = 7, p < 0.05). To examine the role of TH17 cells, we injected an IL-17 neutralizing antibody or control IgG antibody during the 2 weeks of OSA. Compared to OSA rats receiving IgG control, neutralization of IL-17 significantly reduced BP of OSA rats (n = 6, p < 0.05). Additionally, neutralization of IL-17 resulted in a significant increase of Tregs and decreased Th1 cells in brain, cecum and ileum of OSA rats (n = 6, p < 0.01). To examine the distribution of lymphocytes originating from the gut, cells in the Peyers patches of sham and OSA rats were labelled with CFSE. We observed significant increases in CFSE+ Th1, Th2, and Th17 cells in the brain, MLN and spleen of OSA as compared to sham rats (n = 6, p < 0.05).

Conclusion:

Overall, we found that OSA induced gut dysbiosis is associated with a pro-inflammatory response in the gut and brain that involves IL-17 signaling. Our findings suggest that gut dysbiosis may serve as the trigger for widespread inflammation, and treatment strategies to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and HT.
S-58-1: PATIENT PERSPECTIVES OF A CUFFLESS BLOOD PRESSURE DEVICE COMPARED TO CLASSIC OUT-OF-CLINIC METHODS
Authors: Gnanenthiran Sonali Rukshana , Liu Hueiming , Tan Isabella , Chan Justine , Schlaich Markus P , Schutte Aletta E
Published: January 2023

Objective:

Wearable cuffless blood pressure (BP) monitoring technology has emerged as a novel approach to continuously measure BP for weeks and months, rather than single snapshot clinic measures that are subject to substantial variability. Given poor patient engagement with home and 24-hour BP monitoring, we explored patient attitudes toward the use of a wrist-worn cuffless device, namely the Aktiia device (Switzerland) compared to classic methods.

Design and method:

Two researchers conducted in-depth, semi-structured audio-recorded interviews with consecutive participants (n = 15, age 59 ± 10 years, female 33%, hypertension 100%, coronary artery disease 6.7%) recruited in Perth, Australia. They compared experiences wearing the Aktiia device for at least 7 days versus a classic 24-hour ambulatory BP monitor (Microlife WatchBP O3, Switzerland) worn on 2 separate days within 14 days. Interview topics included device acceptability, factors affecting use and hypertension awareness. Transcribed interview data were analysed thematically and interpreted.

Results:

There was high participant preference, acceptability and engagement with the cuffless wearable device compared to 24-hour monitoring. Classic 24-hour monitoring was associated with low acceptability, sleep disturbance and functional limitation. Despite 14/15 participants owning a home BP device, they reported infrequent use and low acceptability of classic home BP monitoring. Key determinants of cuffless technology use identified by participants were affordability, availability, comfort and usability. Participant perception on the importance of the accuracy of cuffless BP devices was variable, with responses ranging from being uncertain about the importance of accuracy to stating that a 10% margin of error was acceptable given high usability and comfort. Knowledge of the harmful effects of hypertension was poor in the population. There was universal agreement that cuffless technology could improve long-term monitoring and management of BP. Participants also agreed that cuffless technology may better engage patients and promote improved identification of high BP in society, especially if marketed with additional functions such as timekeeping and steps.

Conclusions:

Cuffless BP wearable devices is a rapidly emerging alternative to conventional out-of-office cuff-based BP monitoring, with great promise due to the ability for numerous unobtrusive readings. Here we report high participant preference, acceptability and engagement. However, cuffless BP device accuracy is yet to be determined with appropriate methods as cuffless device validation protocols are still under development. Given the high proportion of people with undiagnosed hypertension in the community, there is need to balance high participant acceptability and need for increased BP awareness in the community with accuracy.
ISH-PL-1: GENETIC MECHANISMS OF BLOOD PRESSURE REGULATION AND HUMAN HYPERTENSION – WHAT HAVE WE LEARNT FROM KIDNEY MULTI-OMICS?
Authors: Tomaszewski Maciej
Published: January 2023

Genome-wide association studies (GWAS) have identified > 1000 genetic variants associated with blood pressure (BP) and hypertension. However, the identity of genes mediating these associations and the downstream molecular mechanisms remain largely unknown. Large panels of human kidney tissue characterised at multiple molecular levels together with the newest statistical advances have accelerated translation of GWAS signals into specific kidney mRNA isoforms, genes and pathways causally associated with BP. The lecture will illustrate how the human kidney transcriptomics, epigenomics and proteomics have enhanced our understanding of BP regulation and how they are paving the way to discovery of new diagnostic and therapeutic opportunities for hypertensive patients.
ISH-PL-3: MY ROAD TO ACADEMIC CARDIOLOGY
Authors: Oparil Suzanne
Published: January 2023

My road to academic cardiology started on our dairy farm in upstate New York, where I learned the pleasures and responsibilities of work at very young age. We were given a little lamb by a neighbor and I was given major responsibility as a young child for caring for him. The work ethic extended to schooling. I studied hard and completed undergraduate studies at Cornell and medical school at Columbia, then began medical residency at Columbia's teaching hospital. There my career was interrupted when the residency class ahead of me filled up with Vietnam veterans. That bad luck turned out to be the best of fortunes when I was introduced to Edgar Haber, then Chief of the Cardiac Unit at the Massachusetts General Hospital. Ed was an innovative scientist, a great mentor and a great leader in cardiovascular medicine. He spurred my interest for the first time in biomedical research and laboratory medicine. Under his guidance, I completed studies that showed for the first time that conversion of the inactive decapeptide angiotensin I to the pressor octapeptide angiotensin II occurred in the pulmonary circulation, not the systemic circulation or in plasma. Another simple study demonstrated the critical role of renin release in maintaining blood pressure when a person assumed the upright posture. The study showed that the renin angiotensin system functions abnormally in people with upright posture-induced vasovagal syncope.

I also developed a burning interest in heart disease in women, specifically, on whether postmenopausal women should use hormone replacement therapy to prevent cardiovascular disease. At that time, women were recommended not to use estrogen replacement therapy for cardiovascular disease prevention because previous studies, carried out in older post-menopausal women, showed no benefit from estrogen. I hypothesized that the integrity of estrogen receptors and the vasoprotective effects of estrogen disappear with aging and tested the hypothesis that favorable responses to estrogen treatment are lost in injured arteries of aging animals (rats). I found that aged ovariectomized rats lost the vasoprotective and anti-inflammatory responses to exogenous estrogen that were seen in younger animals. These results may explain the lack of estrogen responsive in vasoprotection in the vasculature of elderly post-menopausal women treated with hormones.

More recently, findings from my studies in isolated cells and animal models have led to the design and conduct of a variety of clinical studies of hypertension and its treatment in human subjects, including, most recently, pregnant women.
JS-WHO: ACHIEVING SDG 3.4: WHO GLOBAL UPDATES ON HYPERTENSION
Authors: Khan Taskeen
Published: January 2023

WHO and ISH have a recent MOU under which both organizations will work to reduce cardiovascular disease mortality and morbidity by focussing on treatment of hypertension through implementation of the HEARTS technical package.

This session serves to highlight the work WHO is doing at the global level on hypertension and highlight the recently launched WHO guideline on pharmacological treatment of hypertension in adults.

The second part of the sessions focuses on real examples of HEARTS (public health approach to managing hypertension at PHC) implementation highlighting progress of countries, as well as challenges and solutions.