bluuebunny/crossref_metadata_2025 huggingface dataset:
SP-5: PRESENTATION ZEN: THE ART OF PRESENTING WITH IMPACT
Authors: Reynolds Garr
Published: January 2023

Dynamic presentation skills are more important now than ever before for medical professionals. Effective and modern presentation skills are absolutely necessary, and having such skills can make a big difference in your professional effectiveness. Many medical professionals have teaching as a major aspect of their job. Increasingly, clinicians are required to construct presentations that facilitate real learning and not just a way to deliver loads of data and information. Delivering presentations with passion and enthusiasm will facilitate more effective learning and by extension may even impact patient care and outcomes.

Bullet-point filled slides with lots of text and small, poorly designed visuals become a barrier to good communication. We have become accustomed to visually busy and hard to see slides which cause a disconnect between the audience and the presenter. Many medical professionals are fed up with dense, hard to comprehend text-filled slides and presenters who just read a script and deliver a dull presentation. A presentation is a great opportunity for teaching and helping people to understand your findings and ideas so that they may make a change for the better. Presenters often unintentionally deliver their ideas in a way that is confusing for the audience. However, the presenter should ask themselves: How can I take this complicated topic and make it easy for the audience to understand and remember? Achieving this goal take creativity and an empathy for the audience.

I have been interested in multimedia and presentation since I was a child, and this interest is largely why I went to work for Apple in Silicon Valley. At Apple I was inspired by Steve Jobs presentation skills and became convinced that all professionals could become much better presenters by studying the arts of storytelling and visual communication.

The Presentation Zen approach challenges the conventional wisdom of making slide presentations today and encourages medical professionals to think differently and more creatively about the preparation, design, and delivery of presentations. Based on research from the cognitive sciences, combined with principles from the world of the Zen arts, graphic design and visual communications, Presentation Zen will dispel popular myths about what is an effective presentation and offer up effective alternatives and approaches for designing and delivering better presentations. All throughout the presentation, the common themes are (1) restraint and clarity in preparation, (2) simplicity in design, and (3) naturalness in delivery.
S-02-3: A REVIEW AND NEW INSIGHTS FROM THE SPRINT MIND TRIAL DATA
Authors: Williamson Jeff Douglas
Published: January 2023

Background:

Proven treatments for reducing the risk of mild cognitive impairment (MCI) and dementia have been lacking. The impact of intensive treatment of hypertension on the incidence of Mild Cognitive Impairment (MCI) and dementia was tested in the Systolic Blood Pressure Intervention Trial (SPRINT-MIND) by prospectively assessing the effect of intensive blood pressure control to a target systolic blood pressure of <120 mmHg versus a standard target (<140 mmHg). This presentation reviews the SPRINT results demonstrating a reduction in risk of developing dementia and MCI and presents additional data on the reliability of the MCI and dementia diagnosis. We will also provide preliminary evidence for differential cognitive benefit from specific antihypertensive medicines and evidence for lack of benefit after onset of cognitive impairment

Results:

At one year, mean systolic blood pressure was 121.4 mmHg in the intensive-treatment group and 136.2 mmHg in the standard-treatment group. Treatment was stopped on 8/20/2015 due to CVD benefit after a median follow up of 3.26 years, but cognitive assessment continued. Participant mean age was 67.9 years (35.6% women) and 8,626 (92.1%) completed at least one follow-up cognitive assessment. There was a significantly lower rate of adjudicated incident MCI (HR 0.81, CI 0.67–0.97) and a non-significant reduction in probable dementia (HR 0.83, CI 0.69–1.04). The combined outcome of MCI plus probable all cause dementia was significantly lower (HR 0.85, CI 0.74–0.97) in the intensive versus standard treatment group. Most cases occurred in persons over age 70. At 2 years, MCI classification was 10X more likely to transition to dementia than normal cognition and 30% of classified as MCI reverted to normal, consistent with other large epidemiologic studies of MCI trajectory

Conclusions:

Among ambulatory adults at increased risk for CVD but without diabetes, treating to a SBP target < 120 mmHg compared to a target of < 140 mmHg reduces the risk of incident MCI and combined MCI/probable dementia. Reduction of dementia risk by cardiovascular interventions is feasible in the elderly population.
S-04-2: AUTOMATED OFFICE BLOOD PRESSURE IN RESEARCH VERSUS CLINICAL PRACTICE
Authors: Myers Martin G.
Published: January 2023

A white coat response which increases BP when recorded in clinical practice has been recognized as a cause of apparent hypertension. Automated office (AO) BP measurement was developed to improve the accuracy of office BP. By recording multiple readings using an automated sphygmomanometer with the patient resting quietly alone, the white coat response which averaged 15 mmHg was eliminated, with AOBP being similar to the awake ambulatory (A) BP. In a Spanish study of 27,211 patients in the community, the difference between awake ambulatory BP and routine office BP was even greater (25 mmHg). Based on these studies, Canadian and American guidelines now recommend AOBP as the preferred method for recording BP in the office.

However, European guidelines continue to focus on improving the accuracy of office BP by stricter adherence to proper BP measurement technique. AOBP is considered to be impractical, with concerns that readings take too long, require a dedicated room and lack support from longitudinal outcome studies. In reality, none of these criticisms are valid. Guidelines on the proper measurement of BP in the office have been published as far back as 1939, yet, there has never been a meta-analysis showing that routine office BP is as good a predictor of cardiovascular outcome as the BP recorded under research conditions.

Awake ABP is a gold standard for determining the risk of future cardiovascular morbidity and mortality. In 19 research studies, mean systolic AOBP was only 0.3 mmHg different from the mean awake ABP. When data comparing attended versus unattended AOBP in research studies were analysed, the mean systolic attended AOBP was still 6 mmHg higher. The presence of office staff appears to be sufficient to increase office BP.

AOBP has been criticized for being too variable. In a recent study comparing AOBP to home BP readings, both types of measurements exhibited similar degrees of variability, yet only home BP is recommended as an alternative to 24-hour ABPM. This conclusion ignores data showing mean AOBP, home BP and awake ABP being similar.

Guidelines for clinical practice should be evidence-based. It may not be possible to record AOBP on every patient. However, AOBP readings should be recommended as the optimum method for recording BP in routine clinical practice, whenever it is feasible to do so.
S-04-3: VALIDATION OF BLOOD PRESSURE DEVICES AS PER 2020 WHO TECHNICAL SPECIFICATIONS: A SCOPING REVIEW OF GLOBAL LITERATURE
Authors: Murthy Shruti , Rajwar Eti , Johnson Rosemol , Shrivastava Krati , Kamath Prashanthi , Rahman Rinsy , Devaria Abhinav , Ismavel Vijay Anand , Vetter Beatrice , John Oommen
Published: January 2023

Objective:

To (1) identify and summarize the global research literature on validation of automated non-invasive blood pressure measurement devices (BPMD) with upper arm cuff, (2) develop a repository of validated BPMD in compliance 2020 WHO technical specifications (3) identify challenges and gaps in evidence base on validated BPMD and develop novel strategies to address them.

Design and method:

A scoping review was conducted according to the Joanna Briggs Institute methodology using ‘Population, Concept, Context’ concept. Empirical studies validating BPMD complying with the 2020 WHO technical specifications (i.e. semi-automated/automated non-invasive with upper arm cuff), published in English between 2000 and 2022 were eligible for inclusion in the review. We searched MEDLINE, Web of Science, Scopus, EMBASE, CINAHL, CENTRAL, ProQuest and daBL website. We snowballed references from website reports. Title-abstract, full-text screening, and data extraction was conducted in duplicate by four reviewers (PICOPortal, MS Excel). Descriptive data analysis was performed on MS Excel and Tableau.

Results:

Of 11,825 identified records, we included 269 studies that fulfilled the inclusion criteria. A total of 251 BPMD from 89 manufacturers were assessed for validation methods. Omron (29%), Microlife (10%) and A&D Company (8%) were the top three BPMD manufacturers that underwent validations. China (20%), UK (13%) and USA (12%) were the top three countries where these validations were undertaken. The three most frequently used validation protocols were (Figure1): European Society of Hypertension-International protocol (ESH-IP) 2002 (27%), ESH-IP 2010 (25%) and Modified British Hypertension Society 1993 (16%). Nearly 50%, 40% and 48% of the validated BPMD were intended for use in clinical- and home/self-measurement, and for general adults, respectively. Of the 55% studies that were funded, 72% received support (finances/ BPMD) from device manufacturers. The publications did not reveal details about the following: device manufacturer (13%), country of validation (26%), settings for intended BPMD use (29%), and the target population for BPMD use (22%).

Conclusions:

While most (89%) of the BPMD included in the review fulfilled the validation criteria, there are considerable gaps in terms of the settings and countries of validation. In designing validation studies, research methods should focus on validating BPMD for specific target population and conditions (e.g. pregnancy or children), and take range of arm circumferences into considerations. Finally, we call for improvement in quality of reporting the validation studies to improve transparency and comparability. This could be best achieved by initiating a dialogue with all stakeholders in blood pressure research and practice.
S-04-6: CARDIOVASCULAR END POINTS AND MORTALITY ARE NOT CLOSER ASSOCIATED WITH CENTRAL THAN PERIPHERAL PULSATILE BLOOD PRESSURE COMPONENTS
Authors: Huang Qi-Fang
Published: January 2023

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular endpoints are tighter for central than peripheral systolic or pulse pressure (cSBP, pSBP, cPP, pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular endpoint occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP (HR), were 1.50 (95% confidence interval, 1.33–1.70) for cSBP, 1.36 (1.19–1.54) for cPP, 1.49 (1.33–1.67) for pSBP, and 1.34 (1.19–1.51) for pPP (P < 0.001). Further adjustment of cSBP and cPP, respectively for pSBP and pPP, and vice versa, removed the significance of all HRs. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P < 0.001) with generalized R2 increments ranging from 0.37 to 0.74%, but adding a second BP to a model including already one did not. Analyses of the secondary endpoints, including total mortality (204 deaths), coronary endpoints (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary endpoints with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.
S-05-3: INFLUENCE OF THE AMBIENT TEMPERATURE ON BLOOD PRESSURE IN ASIA
Authors: Park Sungha
Published: January 2023

It is well known that cold weather is associated with increased risk of myocardial infarction and stroke. It is also well known that colder weather increases blood pressure while warmer weather lowers blood pressure. This may have clinical significance as global warming is resulting in increase in average temperature in the Asia/Pacific region. Long term, climate change may have a significant impact on the epidemiology of of hypertension and cardiovascular disease. In this talk, we will discuss how ambient temperature influences seasonal variation of BP and how they may impact the management strategy for patients with hypertension.
S-06-3: EMERGENT BLOOD PRESSURE LOWERING WITH INTRAVENOUS NICARDIPINE FOR JAPANESE PATIENTS WITH ACUTE INTRACEREBRAL HEMORRHAGE: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS
Authors: Toyoda Kazunori , Yoshimura Sohei , Doi Mayumi Fukuda , Qureshi Adnan I. , Koga Masatoshi
Published: January 2023

Objective:

Intensive lowering of elevated blood pressure is one of the few promising therapies for acute intracerebral hemorrhage. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined.

Design and method:

A systematic review and individual participant data analysis of articles before October 1, 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase 6 mL or more from baseline to 24-h computed tomography. In this study, data on Japanese patients were extracted. The study is registered with PROSPERO (CRD42020213857).

Results:

Three studies, ATACH-1, ATACH-2, and SAMURAI-ICH, met the eligibility criteria. Of 1,271 patients enrolled, 500 were registered from Japan, and all of these were Japanese. A patient with available data on the hourly blood pressures only for < 4 timepoints was excluded, and the other 449 patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5v± 18.3 / 109.1 ± 17.2 mmHg) were studied. Death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.26, 95% confidence interval 1.04–1.53 per 10 mmHg) and hematoma expansion (1.47, 1.17–1.85). These odds ratios were relatively high as compared to the reported ones for global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00–1.26) and 1.16 (1.02–1.32), respectively] (Toyoda K, et al: Int J Stroke 2021).

Conclusions:

Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h was associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.
S-07-5: ASPROSIN INDUCES VASCULAR ENDOTHELIAL- TO-MESENCHYMAL TRANSITION IN DIABETIC LOWER EXTREMITY PERIPHERAL ARTERY DISEASE
Authors: You Mei , Liu Yushuang , Wang Bowen , Yan Zhencheng
Published: January 2023

Objective:

Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated. In this study, we investigated the effect of asprosin accounting for the lower extremity vascular injury in diabetic patients based on the metabolic profiles of PAD.

Design and method:

33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM+PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and its control db/m mice. Moreover, human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT).

Results:

The circulating levels of asprosin in DM+PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD (P = 0.049). Logistic regression analysis revealed that asprosin is an independent risk factor for PAD (OR:3.944, 95%CI:1.656 − 9.393, P = 0.002) and receiver-operator characteristic (ROC) curve determined a cut-off value at 188.70 ng/ml with a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD (Area under curve:0.788, 95%CI:0.694 − 0.863, P < 0.001). Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in which TGF-beta signaling pathway might plays a critical role in patients with PAD. In addition, activation of TGF-beta signaling pathway also appeared in the aortic tissue of db/db mice, suggesting a causal relationship between TGF-beta signaling pathway and artery injury. Asprosin directly induces EndMT in HUVECs in a TGF-beta-dependent manner as TGF-beta signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT.

Conclusions:

Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-beta signaling pathway.
S-07-6: NEUTROPHIL EXTRACELLULAR TRAPS AS MEDIATORS OF ENDOTHELIAL DAMAGE IN HYPERTENSION AND DIABETES
Authors: Landry Chloe , Xiao Fengxia , Thibodeau Jean Francois , Holterman Chet E , Xhu Lihua , Gutsol Alex , Kennedy Christopher RJ , Burger Dylan
Published: January 2023

Objective:

Endothelial dysfunction (ED) plays a key role in the pathogenesis of hypertension and diabetes, yet its molecular determinants are poorly understood. Concomitant hypertension and diabetes can synergistically increase damage to the vasculature, with increasing evidence suggesting that resulting immune dysregulation may contribute to endothelial injury. Neutrophil extracellular traps (NETs), networks of chromatin and protein-containing extracellular fibers released to fight infection, are generated from neutrophils following activation of the citrullinating enzyme peptidylarginine deiminase 4 (PAD4). PAD4 has been shown to be upregulated in atherosclerosis, vasculitis, and various inflammatory autoimmune diseases, leading to NET-induced endothelial injury. Whether NETs could contribute to hypertension- and diabetes-induced ED has not been established. The objective of the present study is to investigate the impact of hypertension and diabetes on PAD4 activity and the contribution of NETs to resulting vascular injury.

Design and Methods:

Promyelocytic HL-60 cells were differentiated to neutrophil-like cells and treated with angiotensin II (10−7 M) and/or high glucose (25 mM) for 24 hours, with or without subsequent NET-inducing PMA stimulation (500 nM). NETs were isolated from the culture medium by differential centrifugation and assessed by Western blot analysis of citrullinated histone H3 (citH3, a primary NET component). Isolated NETs were used to treat Human Umbilical Vein Endothelial Cells (HUVECs) at 0.5–500 ng/ml for 24 hours, after which cell viability (XTT cell assay) and proliferation (BrdU assay) were measured. We also assessed NETosis in mice expressing human renin in the liver (TTRhRen) intercrossed with OVE26 diabetic mice [i.e. hypertensive-diabetic, HD mice], compared with wild-type (WT) FVBN/J mice. We examined kidney levels of citH3, neutrophil elastase (NE), and PAD4 expression by immunohistochemistry.

Results:

Treatment with high glucose, but not angiotensin II, increased citH3 levels in neutrophil-like cells. NETs isolated from PMA-stimulated cells decreased HUVEC viability by ∼2-fold at 5 ng/ml (P = < 0.0001), and dose dependently decreased proliferation from 0.5–500 ng/ml, with a ∼80% decrease at 500 ng/ml. In HD mice, we observed a significant increase in kidney levels of citH3 (P < 0.0001), NE (P < 0.0001), and PAD4 (P < 0.0001), which was associated with the presence of albuminuria and increased blood pressure levels.

Conclusion:

These results suggest that NETs are upregulated in hypertension and diabetes and may contribute to endothelial damage and microvascular injury.
S-09-1: HIGH BLOOD PRESSURE AND ALBUMINURIA, BOTH THERAPEUTIC TARGETS FOR CARDIOVASCULAR DISEASE PROTECTION?
Authors: Zeeuw Dick de
Published: January 2023

High blood pressure is associated with high cardiovascular (CV) risk, and lowering it is associated with risk reduction. Recently, albuminuria has been associated with increased CV risk. This association was explained by albuminuria being the consequence of CV disease rather than the cause. Thus, efforts to explain CV protective effects of new drugs by their ability to lower albuminuria were largely discarded. However, throughout the recent decades many new therapeutic approaches showed that the individual degree of reduction of albuminuria predicts the individual degree of CV protection irrespective of the intervention used (low protein diet, ACE-inhibitors, AII-antagonists, endothelin antagonist or even SGLT2-inhibitors) and irrespective of the underlying disease (healthy population, CV risk population, diabetes, chronic kidney disease of varying origin).

Should one conclude that albuminuria should be aggressively reduced under the motto ‘the lower the better’ (just like blood pressure). Further studies showed the issue to be much more complex. Both blood pressure lowering as well as albuminuria lowering by itself showed to be beneficial in one individual and had no or even bad effects in other individuals. This led to discovery and creation of a therapy response score as a better CV protection predictor. It showed a picture that was similar to the discovery of CV risk scores: a combination of the different risk markers gives a much better CV risk prediction than any risk factor by itself. Logically, drugs targeted to lower a single risk factor may not effectively predict CV protection, since it depends on the composite effect of the drug on all risk factors (be it a fall in one but a rise in another).

Today we are dealing with a new world in which CV risk is determined not only by high blood pressure or albuminuria, but by a host of different risk factors. CV protection thus needs a multiparameter approach improving all of them. This is best shown by the very recent studies with SGLT-2 inhibitors, which have glucose lowering as their registered target, but may also lower blood pressure, albuminuria, and even body weight! Interestingly, CV protection of this class appears overwhelming in all kinds of different diseases. Thus, drugs or combinations of drugs should not have single targets but should be tailored to the risk profile and response profile of each individual person. The time for true Personalized Medicine in cardiovascular disease treatment has clearly arrived.
S-09-3: ROLE OF SACUBITRIL/VALSARTAN IN THE CONTROL OF BLOOD PRESSURE
Authors: Ruilope Luis Miguel
Published: January 2023

Sacubitril/valsartan an angiotensin receptor-neprilysin inhibitor has been shown to reduce the risk of cardiovascular risk death or heart failure hospitalization and improve symptoms among patients with chronic heart failure with reduced ejection fraction. The drug was born initially as an antihypertensive agent and showed an excellent capacity to decrease blood pressure superior to that of angiotensin receptor antagonists. Theoretically the combination seemed to be particularly suitable for difficult to control or resistant hypertension. Unfortunately the administration of sacubitril could translate into increased amyloid beta deposition albeit it was not fully confirmed. In fact John McMurray presented in the meeting of the European Society of Cardiology (25/aug/2022) the double blind trial PERSPECTIVE devoted to fully assess the long neurocognitive effects of sacubitril /valsartan versus valsartan that demonstrated that there was no difference in the cognitive capacity between the two groups of patients. These data permit to consider that the use of sacubitril/valsartan is not accompanied by relevant potential concerns. It opens then the use of this combination in hypertension that requires unlike heart failure longer periods of treatment. The clinical data available and the fact the the drug is being used in Japan in daily clinical prsctice facilitates the consideration of opening many other countries to the combination leading to a better control of blood pressure accompanied by simultaneous cardiorenal protection.
S-09-5: EPIDEMIOLOGY AND CARDIOMETABOLIC DISORDERS - UPDATE OF SGKT2-IS RCT META-ANALYSIS
Authors: Yang Xuanyi , Cao Yu , Yan Cen , Zhang Yuejie , Dong Yuan , Feng Yingmei
Published: January 2023

Diabetes and hypertension are chronic diseases. They often coincide in the same patients and enhance the risk of cardiovascular and renal complications in a multiplicative manner. As one of the main regulators in glucose homeostasis, sodium glucose cotransporter 2 (SGLT2) is expressed in the proximal tubule of the nephron and facilitates glucose reabsorption from glomerulus along the nephron. Based on this function, several SGLT2 inhibitors (SGLT2i) were developed as a novel class of antidiabetic drugs, including empagliflozin, dapagliflozin, catagliflozin, ertugliflozin, and sotagliflozin. By far, totaled 10 RCTs involving 68,916 patients have been performed that tested the long-term outcomes associated with SGLT2i use. In five RCTs where all the patients enrolled had heart failure history (n = 21947), 87.9% were hypertensive and 76.3% were diabetic. Following a median of 0.8 to 2.3 years of treatment, HRs were 0.72 (0.67, 0.78) for first hospitalization for heart failure, 0.87 (0.79, 0.95) for cardiovascular death, and 0.92 (0.86, 0.99) for all-cause death. In another meta-analysis on five RCTs (n = 43467) that mainly recruited type 2 diabetic patients with uncontrolled hyperglycemia, more than 87% were hypertensive. After a median of 1.5 to 4.2 years of follow up, HRs were 0.87 (0.82, 0.93) for major adverse cardiovascular endpoints (MACE), 0.68 (0.62, 0.75) for heart failure, 0.82 (0.72, 0.93) for cardiovascular death, 0.87 (0.79, 0.96) for myocardial infarction, and 0.61 (0.56, 0.67) for worsening chronic kidney disease. The risk of heart failure and chronic kidney disease, but not MACE, decreased with more blood pressure lowering. Nevertheless, stricter glycemic control was associated with higher heart failure risk, but unrelated to MACE or chronic kidney disease. When dissecting the dosage effects of catagliflozin on lipid profiles, the results of a meta-analysis using 12 RCTs indicated that canagliflozin 100 mg or 300 mg significantly reduced systolic and diastolic blood pressure, but increased LDL and HDL cholesterol in a dose-dependent effect. Taken together, SGLT2i could reduce cardiovascular risk in diabetic and non-diabetic patients. The impact of SGLT2i on metabolic traits needs further investigation.
S-10-2: OPTIMAL BLOOD PRESSURE TARGET TO PREVENT SEVERE HYPERTENSION IN PREGNANCY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Abe Makiko , Arima Hisatomi , Yoshida Yuichi , Fukami Ako , Sakima Atsushi , Metoki Hirohito , Tada Kazuhiro , Mito Asako , Morimoto Satoshi , Shibata Hirotaka , Mukoyama Masashi
Published: January 2023

Objective:

Severe hypertension in pregnancy is a hypertensive crisis that requires urgent and intensive care due to its high maternal and fetal mortality. However, there still remain some discrepancies between guidelines in a target blood pressure to prevent severe hypertension in pregnancy. This study aimed to find the optimal blood pressure (BP) levels to prevent severe hypertension in pregnant women with nonsevere hypertension.

Design and method:

We searched Ovid MEDLINE and the Cochrane Library to identify all randomized controlled trials, which compared effects of antihypertensive drugs and placebo/no treatment or more intensive and less intensive BP-lowering treatments on adverse maternal and fetal pregnancy outcomes among pregnant women with nonsevere hypertension. A random effects model meta-analysis was performed to estimate the pooled risk ratio (RR) and 95% confidence interval (CI) for the outcomes.

Results:

Forty RCTs with 6355 patients were included in this study. BP lowering treatment significantly prevented severe hypertension (RR, 0.46; 95% CI, 0.37 to 0.56), preeclampsia (RR, 0.82; 95% CI, 0.69 to 0.98), severe preeclampsia (RR, 0.38; 95% CI, 0.17 to 0.84), placental abruption (RR, 0.52; 95% CI, 0.32 to 0.86), and preterm birth (before 37 weeks; RR, 0.81; 95% CI, 0.71 to 0.93), while the risk of small for gestational age infants was increased (RR, 1.25; 95% CI, 1.02 to 1.54). An achieved systolic blood pressure (SBP) of lower than 130 mmHg reduced the risk of severe hypertension to nearly one-third compared with an achieved SBP of 140 mmHg or higher, with a significant interaction of the BP levels achieved with BP lowering therapy. There was no significant interaction between BP lowering treatment and the subtypes of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and chronic hypertension.

Conclusions:

BP lowering treatment aimed at a SBP of lower than 130 mmHg and accompanied by careful monitoring of fetal growth might be recommended to prevent severe hypertension among pregnant women with nonsevere hypertension.
S-12-5: IMPAIRMENT OF RENAL BLOOD FLOW AUTOREGULATION AND PRESSURE-NATRIURESIS: ROLE IN THE DEVELOPMENT OF HEART FAILURE IN REN-2 TRANSGENIC HYPERTENSIVE RATS
Authors: Honetschlagerova Zuzana , Sadowski Janusz , Jezierska Elzbieta Kompanowska , Cervenka Ludek
Published: January 2023

Objective:

The prognosis of patients with heart failure (HF), particularly those who were hypertensive before the onset of HF, remains poor and new therapeutic strategies are needed, based on understanding the pathophysiology of the progression of HF. We hypothesized that the kidney is here not simply a victim but also a culprit of the progression. Specifically, we hypothesized that the impairment of renal blood flow (RBF) autoregulation and pressure-natriuresis relationship is present in the very early HF phase, and precedes HF decompensation.

Design and method:

In Ren-2 transgenic rats (TGR), a model of hypertension with increased endogenous activity of the renin-angiotensin system (RAS), HF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). One week after ACF creation or sham-operation animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and pressure-natriuresis relationship after stepwise changes in renal arterial pressure (RAP) that were induced by aortic clamps. Sham-operated TGR were evaluated at physiological level of RAP, then at RAP reduced to 125, 100, 90 and 80 mmHg. In ACF TGR RAP was reduced to 100, 90 and 80 mmHg, followed by period of RAP increased to 125 mmHg.

Results:

In sham-operated TGR as compared with ACF TGR the basal mean arterial pressure (156 ± 3 vs. 98 ± 3 mmHg), RBF (11.45 ± 0.6 vs. 8.13 ± 0.3 ml.min-1.g-1), urine flow (UF) (38.3 ± 3.1 vs. 8.7 ± 1.0 μl.min-1.g-1) and absolute sodium excretion (UNaV) (4.77 ± 0.54 vs. 0.46 ± 0.11 μmol.min-1.g-1) were all significantly lower. In sham-operated TGR reductions in RAP resulted in significant decreases in RBF whereas in ACF TGR it did not change in response to RAP alterations. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former.

Conclusions:

Our data show that at the physiological RAP level ACF TGR displayed marked reduction in RBF, UF and UNaV as compared with sham-operated TGR. However, in contrast to sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and better slope of pressure-natriuresis relationship. Thus, even in the very early HF stage the renal dysfunction is demonstrable but such dysfunction and the subsequent onset of HF decompensation cannot be simply ascribed to impaired RBF autoregulation and pressure-natriuresis relationship, at least not in the high-output HF model of originally RAS-dependent hypertensive rat.
S-13-2: PATHOLOGY UPDATE OF CUSHING'S SYNDROME AND PRIMARY ALDOSTERONISM ACCORDING TO WHO 2022
Authors: Sasano Hironobu , Yamazaki Yuto , Satoh Fumitoshi
Published: January 2023

New pathology classification of endocrine and neuroendocrine tumours is currently being updated as one of WHO classification of tumours version 5. Not only pathologists but also clinicians involved in the clinical management of those patients should be familiar with novel classification including their new concepts. Therefore in this presentation, we will introduce newly updated concepts of adrenocortical diseases associated with Cushing's syndrome and primary aldosteronism.

In Cushing's syndrome, primary bilateral nodular adrenal cortical disease has turned out to harbor multiple independent clonal proliferations and the term hyperplasia should not be used in these adrenocortical disorders. Hyperplasia should be only reserved for those associated with ACTH overproduction from pituitary or others. Various somatic and/or genomic mutations of the genes involved in intracellular signaling pathways have been reported in almost all bilateral micronodular adrenal cortical disease and the great majority of bilateral macronodular adrenal cortical disease associated with Cushing's syndrome.

For instance, bilateral micronodular adrenocortical disease harbors pathogenic germline mutations resulting in the activation of the protein kinase A or PKA pathway including PRKAR1A, PRKAR1A, PRKACA, PDE11A, PDE8B and 2p16 CNC2 locus alterations. On the other hand, bilateral macronodular adrenal cortical disease has been linked to several germline alterations including ARMC5, MEN1, FH, APC and others.Clinical significance of those genetic abnormalities above including potential therapeutic manipulation is being studied at this juncture.

In primary aldosteronism, the introduction of CYP11B2 has enormously contributed to the establishment of new concept of adrenocortical pathology. Primary aldosteronism can be generally classified into two categories. The one in which aldosterone production diffusely occurs in the hyperplastic zona glomerulosa and the other harboring localized aldosterone production. The former is generally bilateral and the latter unilateral or bilateral. The latter category also includes both nodule and adenoma, which could be differentiated according to the status of intra-lesional distribution of CYP11B2. CYP11B2 positive localized proliferation of the zona glomerulosa cells is frequently detected in non hypertensive subject and should be termed aldosterone producing nodules (APN) rather than aldosterone producing cell clusters (APCC). The potential cascade from these aldosterone producing nodules in normal subject to those associated with clinically overt primary aldosteronism is being investigated including the possible concept of pre- or subclinical primary aldosteronism.
S-13-3: AN APPROACH TO IDENTIFY THE UNDETERMINED ADIPOCYTE-DERIVED FACTOR(S) THAT STIMULATE ALDOSTERONE SYNTHASE GENE (CYP11B2) EXPRESSION
Authors: SHIMADA HIROKI , Sato Ikuko , Yokoyama Atsushi , Nakmura Yasuhiro , Sugawara Akira
Published: January 2023

Objectives:

Hypertension is a frequently observed complication among obese patients. Recently, undetermined adipocyte-derived factor(s) have been recognized as one of the causes of the obesity-related hypertension independent of angiotensin (A) II. In this study, we aim to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression aldosterone secretion that may induce hypertension.

Methods:

We first differentiated mouse fibroblast 3T3-L1 cells into adipocytes and collected their supernatants. The supernatants were incubated with human adrenocortical carcinoma H295R cells, and their CYP11B2 mRNA expression was measured by quantitative PCR with reverse transcription (qRT-PCR). Thereafter, the supernatants were fractionated by ammonium sulfate precipitation to purify adipocyte-derived factor(s) that stimulate CYP11B2 expression. The precipitates were collected in 30%, 60% and 90% saturated concentration of ammonium sulfate. Each of precipitates was concentrated using 100 kDa ultrafiltration membrane and incubated with H295R cells. CYP11B2 mRNA expression in H295R cells was measured by qRT-PCR. Then, we purified the precipitation of the supernatants that obtained in 60% ammonium sulfate by anion-exchange chromatography. Each of the fractions was incubated with human adrenocortical carcinoma H295R cells, and their CYP11B2 mRNA expression was measured by qRT-PCR.

Results:

The supernatants obtained from 3T3-L1 adipocytes were demonstrated to stimulate CYP11B2 expression. Fractionation of the supernatants by ammonium sulfate precipitation demonstrated that the ability to stimulate CYP11B2 expression was detected in fractions precipitated in 60% saturated concentration. Fractionation of the supernatants by anion-exchange chromatography demonstrated that the ability to stimulate CYP11B2 expression was detected in two specific fractions. Specific fractions were analyzed by mass spectrometry, resulting in the identification of 39 specific proteins. We are now investigating that the relationship between CYP11B2 gene expression and 39 proteins.
S-14-3: WHICH IS THE OPTIMAL BP TARGET TO ACHIEVE? SHOULD GUIDELINES BE UPDATED?
Authors: Verdecchia Paolo , Angeli Fabio , Reboldi Giampaolo
Published: January 2023

Hypertension Guidelines disagree on the definition of the more appropriate blood pressure (BP) target to achieve. A shared feature of Guidelines was the definition of precise (albeit differing across Guidelines) BP targets in different patient categories (Table).

Does the evidence support the definition of precise BP targets overall and in different patient categories?

Evidence from observational studies. A direct relation between BP and risk of cardiovascular disease emerged from observational studies including a large meta-analysis (Lancet 2002). Most studies showed that after correction for several confounders (cancer; heart failure etc) the lowest cardiovascular risk occurred at low values of achieved BP (<120/80 or even < 100/60 mmHg).

Evidence from intervention studies. Meta-analyses of randomized studies between different drugs or BP targets showed two main findings:

(a) The larger the BP difference between randomized groups in the achieved BP the greater the benefit (particularly on stroke and heart failure) in the group with the lower achieved BP.

(b) When comparing a more intensive with a less intensive BP target (i.e. 120 vs 140 mmHg) the risk of major cardiovascular disease was lower with the more intensive strategy. In a meta-analysis a more intensive strategy reduced stroke by 20%; myocardial infarction by 15%; heart failure by 25%; cardiovascular death by 18% and all-cause death by 11% (Hypertension 2016) when compared to a less intensive strategy. BP targets considerably differed across the studies.

Evidence regarding tolerability of treatment. Some Guidelines suggest that a more intensive BP target could be achieved at condition that the treatment is well tolerated. However the concept of good treatment tolerability holds at any level of achieved BP (not only below 140/90 mmHg) irrespective of the BP target. There is no evidence supporting safety thresholds not to be exceeded when the treatment is well tolerated.

Conclusion:

The lowest well tolerated BP is a reasonable and evidence-based BP target irrespective of the cardiovascular risk status of the patient.

Table: BP targets according to major hypertension Guidelines.
S-18-3: SGLT2 INHIBITOR CANAGLIFLOZIN ANTAGONIZES SALT-SENSITIVE HYPERTENSION THROUGH MODIFYING TRPC3 MEDIATED VASCULAR CALCIUM HANDLING
Authors: Zhao Yu , Li Li , Lu Zongshi , Hu Yingru , Zhang Hexuan , Sun Fang , Li Qiang , He Chengkang , Shu Wentao , Wang Lijuan , Cao Tingbing , Yan Zhencheng , Liu Daoyan , Gao Peng , Zhu Zhiming
Published: January 2023

Objectiv:

Salt-sensitive hypertension is highly prevalent and associated with cardiorenal damage. Large clinical trials have demonstrated that Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert hypotensive effect and cardiorenal protective benefits in hypertensive patients with and without diabetes. However, the underlying mechanism remains elusive.

Methods:

Dahl salt-sensitive (SS) rats and salt-insensitive controls were fed with 8% high salt diet to establish salt-sensitive hypertensive model, some of them were treated with canagliflozin. The blood pressure, urinary sodium excretion, vascular function and remodeling were detected. Rat aortic proteomics and TRPC3 knockout mice were used to explain the mechanism of the effect of canagliflozin on salt-sensitive hypertension.

Results:

Canagliflozin treatment significantly reduced high salt induced hypertension and this effect was not totally dependent on urinary sodium excretion in SS hypertensive rats. Assay of vascular function and proteomics showed that canagliflozin significantly inhibited vascular cytoplasmic calcium increase and vasoconstriction in response to high salt diet. High salt intake increased vascular expression of TRPC3 in salt-sensitive rats, which could be alleviated by canagliflozin treatment. Overexpression of TRPC3 mimicked salt-induced vascular cytosolic calcium increase in vitro and knockout of TRPC3 erased the anti-hypertensive effect of canagliflozin. Mechanistically, high-salt-induced activation of sodium/calcium exchanger 1 (NCX1) reverse mode increased cytoplasmic calcium level and vasoconstriction, which required TRPC3, and this process could be blocked by canagliflozin.

Conclusions:

We define a previously unrecognized role of TRPC3/NCX1 mediated vascular calcium dysfunction in the development of high salt induced hypertension, which can be improved by canagliflozin treatment. This pathway is potentially a novel therapeutic target to antagonize salt sensitive hypertension.
S-21-3: EFFECTIVENESS AND ACCEPTABILITY OF MOBILE PHONE TEXT MESSAGING INTERVENTION TO IMPROVE BLOOD PRESSURE CONTROL (TEXT4BP) AMONG HYPERTENSIVE PATIENTS IN NEPAL
Authors: Bhattarai Buna Bhandari , Narasimhan Padmanesan , Jayasuriya Rohan , Vaidya Abhinav , Schutte Aletta E
Published: January 2023

Objectives:

In LMICs, the rapid uptake and availability of mobile phones provide excellent opportunities for host of an intervention. However, research on the effectiveness and acceptability of mHealth in these settings remains limited. The main objective of this feasibility study was to assess the effectiveness and acceptability of a mobile phone text messaging intervention (TEXT4BP) to improve blood pressure control and treatment adherence among hypertensive patients in Nepal.

Design and Methods:

The TEXT4BP study was a two-arm, parallel-group, unblinded, randomized controlled pilot trial that recruited 200 clinically diagnosed hypertensive patients aged 18–69 years visiting at a tertiary referral hospital in Kathmandu, Nepal. We co-designed the contextual text messages informed by the formative qualitative studies that used COM-B (capability, opportunity, motivation, and behavior) model and Technology Acceptance Model (TAM) model. Patients in the intervention arm (n = 100) received text messages containing information on hypertension, diet, medication, and physical activity three times per week for three months. The control arm (n = 100) received standard care. Primary outcomes were changes in blood pressure and medication adherence at three months. Secondary outcomes included blood pressure control, medication adherence self-efficacy, and hypertension knowledge. Feasibility measures, such as attrition rate, was calculated. A nested qualitative study assessed the acceptability of the intervention.

Results:

Over the 12 weeks of follow-up, the retention rate was 77%. The intervention group had a greater reduction in systolic and diastolic BP vs usual care [-7.09/-5.86 (p = 0.003) vs -0.77/-1.35 (p = 0.28) mmHg] [adjusted difference: systolic B = -6.50 (95% CI, -12.6; -0.33) and diastolic BP B = -4.60 (95% CI, -8.16; -1.04)] (fig 1), coupled with a greater proportion achieving target BP (70% vs 48%, p = 0.006) at three months. The intervention arm showed an improvement in compliance to antihypertensive therapy (p < 0.001), medication adherence (p < 0.001), medication adherence self-efficacy (p = 0.023), and knowledge on hypertension and its treatment (p = 0.013). In addition, intervention participants expressed a high rate of acceptability and desire to continue the TEXT4BP intervention in the future too.

Conclusion:

The TEXT4BP study has generated promising evidence that text messaging intervention is feasible, acceptable, and effective in improving blood pressure control in low-resource settings like Nepal. The findings will inform further large-scale mHealth research and contribute to clinical practice with evidence-based hypertension guidelines in Nepal.

Trial reg: ACTRN12619001213134