bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-42-3: HIV INFECTION AND ANTIRETROVIRAL THERAPY ARE ASSOCIATED WITH INCREASED ARTERIAL STIFFNESS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Defo Alvin Kuate , Chalati Mhd Diaa , Labos Christopher , Fellows Lesley K , Mayo Nancy E , Daskalopoulou Stella S 
Published: January 2023

Objective:
Incidence of cardiovascular disease (CVD) in people living with human immunodeficiency virus (HIV) infection has increased as overall survival has improved due to combination antiretroviral therapy (cART). Arterial stiffness is a composite indicator of CVD risk independent of traditional risk factors. We therefore aimed to synthesize the evidence on the effect of HIV and of cART on arterial stiffness.

Design and Methods:
We conducted a systematic review of Medline/PubMed, Embase, CINAHL, and the Cochrane Library, searched independently by two reviewers using a predefined search strategy, for studies relating HIV/cART to arterial stiffness until June 2019. Studies were limited to humans and publication in English or French. A standardized extraction form was used to collect data from published reports. Random-effects meta-analyses were performed to produce standardized mean differences (SMDs) and 95% confidence intervals (CIs) from studies reporting carotid-femoral pulse wave velocity.

Results:
We retrieved 995 citations. Seventy-four studies (N = 18,711 participants/13,119 with HIV) were included: 59 cross-sectional, 9 cohort studies and 6 randomized controlled trials. In meta-analyses of 17 studies, arterial stiffness was found to be increased overall in individuals with HIV relative to healthy controls (SMD 0.44 m/s; 95% CI, 0.25–0.63) and in cART-treated versus untreated individuals with HIV (SMD 0.35 m/s; 95% CI, 0.13–0.57). Several studies suggested that cumulative exposure to cART is associated with a continual increase in arterial stiffness. However, early initiation of treatment might improve arterial stiffness later in life by negating the effect of the HIV.

Conclusions:
Evidence suggests that HIV infection is associated with increased arterial stiffness, while cART is linked to a further increase, highlighting the need for monitoring of CVD risk in this population, and the need for development of novel treatments. The cross-sectional nature of most studies (59/74) mainly allowed for the exploration of associations. Large longitudinal studies are needed to confirm the observed relationships and establish causality between HIV/cART and arterial stiffness.
S-42-5: NEW ONSET HYPERTENSION AND EARLY CHANGES IN LEFT VENTRICULAR FUNCTION IN POST COVID -19 CONDITION
Authors: Tselov Nikolay , Rasheva Ani , Hristova Krasimira , Genova Kamelia 
Published: January 2023

Background:
Post COVID19 condition occurs in individuals with a history of probable or confirmed SARS Cov2 infection, usually 3 months from the onset of COVID19 with symptoms that last for up to at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction, but also arterial hypertension (AH) and generally have an impact on everyday function.

Aim:
COVID 19 pneumonia initiates new onset AH and aggravates the structural and functional myocardium remodeling in the long term after hospitalization.

Methods:
The study population /initially questioned 1500 patients for symptoms after acute COVID 19 pneumonia / included 220 patients without history of any disease, mean age of 45 ± 12 years, male 145 (43 ± 10 years) female 75 (52 ± 14 years). The global longitudinal strain (GLS) was extracted for left ventricle (LV)and right ventricle(RV) and AMBP analysis, mean arterial pressure (MAP)and heart rate HR were performed at baseline /30–40 days after acute infection/ 3rd and 12th months follow up. CMR was performed at 3rd (3mFU) and 12th months (12mFU) also to confirm our resulst.

Results:
From initial population /1500 pts/ self-reported symptoms at 12mFU are 1265 (84.6 %) and 235 /15.4 %) are symptom free at 12mFU. At 3mFU HR and MAP increased significantly / from 75 ± 6 beats /min to 88 ± 12 beats/ min, 109 ± 15 mmHg to 118 ± 19mmHg. Sys BP increased slightly at 3mFU /128 ± 14, p = 0.6/ and continue at 12mFU / 129 ± 12, p = 0.7/. Diastolic BP increased significantly at 12mFU /86 ± 12.3 to 91 ± 10.0, p > 0.01/ and AH presence at 3mFU in 143 (65%)up to 161(73%) at 12mFU. Symptoms of heart failure with preserved EF were found at 3mFU in 91 pts (41%) and in 99 pts (45%) at 12mFU. Echocardiography showed predominantly decrease of the load on the right heart at 3mFU and 12mFU (RV FAC % p < 0.019, TAPSE p < 0.05, RVOT VTI p < 0.01). LV function showd increased EDD, ESD, EDV, ESV, and decreased EF and GLS at 3mFU and slightly improvement at 12mFU. Despite normal EF, GLS / 18.5 %,p < 0.01) and segmental LS in all apical and mid anteroseptal, inferoseptal and basal anteroseptal and inferoseptal levels (16% to 18%, p < 0.01) and RV (22.3% to 24%) at 12mFU shown diminished and still preserved values.

Conclusion:
New onset AH is one of major symptoms after COVID 19 and remains at 12mFU. Despite of satisfactory improvement of conventional parameters for LV and RV function, GLS indicate worsening of the LV systolic function.
S-45-3: PARP INHIBITION AMELIORATES VEGF INHIBITOR-ASSOCIATED VASCULAR DYSFUNCTION VIA TRPM2
Authors: Neves Karla B , Lopes Rheure Alves , Lang Ninian , Montezano Augusto C , Touyz Rhian M 
Published: January 2023

Hypertension is a common unwanted effect of VEGF inhibitors (VEGFi) commonly used as anti-angiogenic drugs in cancer patients. The combination of VEGFi with olaparib, a PARP inhibitor (PARPi), has been shown to reduce VEGFi-induced hypertension. However underlying molecular mechanisms are unknown. PARP plays major role in the activation of TRPM2, a redox-sensitive calcium channel, which is associated with hypertension-induced vascular dysfunction.

Objective:
to elucidate whether PARP/TRPM2 axis is involved in the protective mechanisms of the combination VEGFi/PARPi in vascular cells. Design and Methods: Human vascular smooth muscle cells (VSMC), aortic endothelial cells (HAEC), and mice mesenteric arteries were used. Cells/arteries were exposed to axitinib (VEGFi) alone and in combination with olaparib (PARPi). Wire myography assessed vascular function. Reactive oxygen species (ROS) production, Ca2+ influx, protein/gene analysis, PARP activity, and TRPM2 siRNA were assessed in VSMC, and nitric oxide (NO) levels in HAEC.

Results:
Axitinib increased ROS production in hVSMC (RUL: 0.8 ± 0.2 [Ct] vs. 1.1 ± 0.09 [Axi]), which was followed by an increase in PARP activity (a.u.: 0.09 ± 0.03 [Ct] vs. 0.14 ± 0.004 [Axi]). Axitinib reduced ACh-induced vasodilation (% relaxation: 70.5 [Ct] vs. 34.8 [Axi]), an effect blocked by olaparib. U46619- and ET-1-induced vasoconstriction (% KCl-U4: 101.2 [Ct] vs. 141.4 [Axi]; ET-1: 122.6 [Ct] vs. 152.5 [Axi]) were increased by axitinib, which not observed with the combination axitinib plus olaparib. TRPM2 channel blocker (8-Br-cADPR) attenuated the hypercontractile effects and endothelial dysfunction induced by axitinib in mesenteric arteries. PARP and TRPM2 blockage also overturned the increase in VSMC Ca2+ influx induced by axitinib (AUC: 17541 ± 4708 [Ct] vs. 22249 ± 1438 [Axi]). This was also confirmed by TRPM2 siRNA. Phosphorylation of MLC20 in VSMC (a.u.: 0.028 ± 0.02 [Ct] vs. 0.04 ± 0.01 [Axi]), and eNOS (Thr495) in HAEC (a.u.: 0.99 ± 0.35 [Ct] vs. 1.35 ± 0.10 [Axi]) were enhanced by axitinib and prevented by olaparib and TRPM2 siRNA. HAEC exposed to the combination olaparib and axitinib showed
NO levels similar to VEGF-stimulated cells. Pro-inflammatory markers (IL-6, MCP-1 and IL-1B) were also upregulated in axitinib-stimulated VSMC (p < 0.01), which was reduced by ROS and PARP-TRPM2 inhibition.

Conclusions:
We identify that PARP inhibition, by reducing TRPM2 activation, attenuates the vascular deleterious effects of axitinib. Our study defines novel mechanisms whereby the combination VEGFi/PARPi may reduce vascular dysfunction in VEGFi-treated cancer patients.
S-46-5: THE INTRA-WEEK VARIABILITY ON HOME BLOOD PRESSURE WITH OR WITHOUT ANTIHYPERTENSIVE MEDICATION: NOSE STUDY
Authors: Kubo Mio , Godai Kayo , Kabayama Mai , Wada Arisa , Kido Michiko , Hashimoto Sumiyo , Higashi Makiko , Hatanaka Hiromi , Kikuchi Takeshi , Dodo Takayuki , Tabara Yasuharu , Asayama Kei , Ohkubo Takayoshi , Rakugi Hiromi , Kamide Kei 
Published: January 2023

Objective:
Few studies have investigated weekly variations in long-term home blood pressure (BP) measurement. The aim of this study was to examine the intra-week variability and the difference in the day of the week on long-term home BP with or without antihypertensive medication.

Design and method:
This study was based on an ongoing community-based intervention study in Nose, Osaka, which was designed to assess the effect of home BP measurement on prolonging healthy life expectancy. The study included 510 participants aged 40–91 years. Participants measured their BP with an electronic oscillometric device (HEM-7281; Omron Healthcare CO., Ltd) and wrote the value on the recording book twice in morning and evening for about six months to a year. The intra-week variability in home BP were calculated as maximum minus minimum BP (MMD: maximum-minimum difference). Home BP recording for 62916 days were obtained by extracting weeks in which BP were measured on 7 consecutive days. The participants were divided into 2 groups according to with or without antihypertensive medication. The mean BP values according to the day of the week of home BP measurement were compared by one-way analysis of variance. MMD means were compared with the t-test. To identify the factors influencing on the intra-week variability in home BP, Multiple linear regression models were applied to examine.

Results:
Among participants without antihypertensive medication, morning systolic BP(SBP) was lowest on Saturday (p < 0.001) as compared with all other days of the week and evening SBP tends to be highest on Sunday. Among participants with antihypertensive medication, morning SBP tends to be lowest on Saturday and evening SBP was highest on Sunday (p < 0.001). The characteristics of the day of the week were similar for the two groups. Antihypertensive medication was not significantly associated with MMD in morning SBP in the multiple linear regression model. MMD in morning SBP had significant positive relationships with female(β = 0.05) and age(β = 0.07), measurement in winter(β = 0.04), morning SBP means(β = 0.25), respectively by p < 0.001.

Conclusions:
Evening SBP was highest on Sunday regardless of antihypertensive medication. This may be related with clinical evidence that cardiovascular events occur more frequently in the morning on Monday. Considering a variety of factors associated with the intra-week variability in home BP with or without antihypertensive medication, this observation suggested that treatment decisions against hypertension may be based on long-term home BP measurements.
S-48-3: PHYSICAL ACTIVITY AND HEALTHY AGING
Authors: Shimada Hiroyuki 
Published: January 2023

Hypertension is a risk factor for dementia, and physical activity has been reported to be effective in reducing the risk of hypertension and dementia. Several technical devices are available to monitor and promote changes in behavior toward higher activity. In particular, smartphones are becoming the primary platform for recognizing human activity. However, the effects of behavior change techniques that promote physical, cognitive, and social activities on incident dementia in older adults remain unknown. We are conducting a randomized controlled trial aims to examine the effects of behavior change techniques on the prevention of dementia among community-dwelling older adults using a smartphone as a behavior change tool. The study cohort comprises 3,498 individuals, aged 60 years and over, randomized into two groups: the smartphone group (n = 1,749) and the control group (n = 1,749). Intervention. The smartphone group will be asked to use smartphone applications for at least 30 minutes daily to self-manage and improve their physical, cognitive, and social activities. The smartphone group will perform 60-minute group walking sessions using application-linked Nordic walking poles with cognitive stimulation twice a week during the intervention period. The walking poles are a dual-task exercise tool that works with a smartphone to perform cognitive tasks while walking, and the poles are equipped with switches to answer questions for simple calculation and memory tasks. The smartphone and control groups will receive lectures about general health that will be provided during the baseline and follow-up assessments. Incident dementia as primary outcome will be detected using cognitive tests (at baseline, after 15 months, and after 30 months) and by preparing diagnostic monthly reports based on data from the Japanese Health Insurance System. Participants without dementia at baseline who will be diagnosed with dementia over the 30-month follow-up period will be considered to have incident dementia. This study has the potential to provide the first evidence of the effectiveness of information communication technology and Internet of Things in incident dementia. If our trial results show a delayed dementia onset for self-determination interventions, the study protocol will provide a cost-effective and safe method for maintaining healthy cognitive aging.
S-49-4: URINARY BIOMARKER ANALYSES ON JAPANESE, MEDITERRANEAN AND EURO-WESTERN POPULATIONS: WHICH IS BETTER FOR POST-PANDEMIC LONGEVITY?
Authors: Yamori Yukio , Sagara Miki , Mori Hideki , Mori Mari 
Published: January 2023

Objective:
Since nutrition could extend lifespan even in stroke-prone rats developing stroke genetically, our WHO-Collaborating Center for Primary Prevention of Cardio-vascular Diseases (CVD) started world-wide hearth examination to investigate nutrition good for healthy longevity by collecting 24-hour urine (24U) samples.

Design:
Urinary biomarkers of nutritions, sodium for salt, potassium (K) for vegetables and fruits, isoflavones(Is) for soy, taurine(Ta) for fish and magnesium (Mg) for beans and nuts were analyzed in 24U among 4211 participants (49.7% females(F)), aged 48–56 years in 50 populations from 22 countries according to WHO-CARDIAC(Cardiovascular Diseases and Alimentary Compression) Study Protocol, and studied comparatively in 6 Japanese(J), 6 Mediterranean(M) populations from Greece, Italy(2), Spain(2), Portugal and 6 Euro-Western(EW) populations from Sweden, Ireland, Scotland, Canada, Australia, New Zealand.

Results with Discussion:
The quintile analyses of Ta and Mg/creatine ratio in the world were inversely associated with CVD risks. The Odds ratios of obesity, hypercholesterolemia and hypertension in the lowest quintile of both Ta and Mg were 6.3, 4.6 and 1.8, respectively. J and M populations had significantly higher Ta and Mg therefore, lower CVD risks than EW, but J and M took more salt increasing the risk of stroke (Table 1). Despite the high salt intake, M had the merit of significantly high K intake to attenuate the adverse salt effect. J had a merit to take Is from soy containing Mg. Since Is intake was inversely associated with lower BMI in the world populations, high Japanese Mg intake was related to high Is intake which was inversely associated with obesity in Japan. In fact, the Japanese populations who took significantly higher T and Mg had lower BMI as well as higher HDL and folic acid in the blood, expected to prevent atherosclerosis and dementia. In contrast to M and EW, particularly severe obesity over BMI 30 was obviously less in J, ranking 182nd among 190 populations (WHO). The mortality rates of COVID-19 were significantly positively related to the ratio of severe obesity among 20 major countries in the world and this mortality was obviously lower in J, suggestive of the potential of J diet for post-pandemic longevity.

Conclusion:
24U biomarker analyses indicated low-salted J and M diets are recommendable for CVD prevention. J diet is so far better than M diet because of lower CVD risks such as obesity and lipidemia, which were proven by urinary biomarkers to be related with traditional fish and soy intakes.
S-49-5: PRACTICAL AND PERSONAL EDUCATION OF DIETARY THERAPY IN HYPERTENSIVE PATIENTS
Authors: Tsuchihashi Takuya 
Published: January 2023

Hypertension is the most important risk factor of cardiovascular death in Japan. The annual number of deaths due to hypertension is estimated to be 100,000 persons. The number of hypertensives in Japan is estimated to be 43 million. Of these individuals, 33% are estimated to be unaware of hypertension, 11 % are aware but untreated, and 29% are poorly controlled despite ongoing treatment. Thus, measures to reduce the number of untreated and poorly controlled hypertensive patients are needed.
Lifestyle modifications including dietary therapy are quite important regardless of the use of antihypertensive drugs. Especially, salt reduction is most important because Japanese individuals still consume a significant amount of salt. The Dietary Reference Intakes for Japanese 2020, issued by the Ministry of Health, Labour and Welfare, propose a salt intake goal of < 7.5 g/day for men and < 6.5 g/day for women. Regarding the goal of salt reduction in hypertensive patients, the hypertension guideline by the Japanese Society of Hypertension 2019 (JSH2019) proposes a goal of < 6 g/day. Although salt intake in Japan gradually decreased in the early 2000 s, the declining trend has not been seen in recent years, and thus it seems difficult to achieve these target salt intake levels. To overcome this challenge, the JSH announced the JSH Tokyo Declaration and pledged to create a specific action plan to achieve the target salt intake level of < 6 g/day.
Since the awareness of salt reduction may not necessarily lead to actual salt reduction, the assessment of salt intake of the individuals is essential when the medical stuffs provide the guidance of salt reduction. In the practical clinical settings, the combination of the assessment of dietary contents using simple questionnaires and the estimation of salt intake using spot urine specimen is recommended. Repeated assessment of salt intake and the practical guidance by the medical stuffs is useful for the long-term adherence of salt reduction. Nevertheless, it is difficult to achieve the target salt intake levels. To support individuals’ efforts to reduce salt intake, the JSH Salt Reduction Committee certifies 124 delicious low-salt foods as of April, 2022. Annual sales of these products are about 45 billion yen and the reduction in salt consumption is estimated to be about 1,000 tons. Through the utilization of these products and the efforts to improve the food environment, a society with low-salt and healthy diet will be expected to come.
S-51-4: RENAL DENERVATION IMPROVES FLUID RETENTION BY MODULATING RENAL SGLT2 FUNCTION IN RATS WITH HEART FAILURE
Authors: Katsurada Kenichi , Nandi Shyam S , Patel Kaushik P , Kario Kazuomi 
Published: January 2023

Objective:
Renal denervation (RDN) has been developed as a neuromodulation therapy for patients with treatment-resistant hypertension. RDN is expected to prevent not only hypertension but also heart failure (HF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to ameliorate HF and widely used for HF patients. The present study was conducted to assess the effect of RDN on HF and the interaction between renal sympathetic nerves and SGLT2 function in HF.

Design and method:
HF was induced by coronary artery ligation in rats. Four weeks after coronary artery ligation surgery, surgical bilateral RDN was performed. Western blot analysis was performed to assess the expression levels of SGLT2. One week after RDN surgery, as a functional test for SGLT2 activation, natriuretic response to intravenous injection of SGLT2 inhibitor dapagliflozin (0.5 mg/kg, i.v.) was investigated. Furthermore, the changes in expression and localization of SGLT2 were assessed in human embryonic kidney cells treated with norepinephrine directly, in vitro.

Results:
Western blot analysis indicated that renal SGLT2 expression is increased in rats with HF. RDN significantly reduced enhanced renal SGLT2 expression in HF. Natriuretic response to dapagliflozin were greater in HF than Sham (Cumulative sodium excretion at 120 min, 227 ± 35 vs. 133 ± 13 μEq/gkw, P < 0.05, n = 6). RDN significantly attenuated natriuretic response to dapagliflozin in HF (Cumulative sodium excretion at 120 min, 138 ± 19 vs. 227 ± 35 μEq/gkw, P < 0.05, n = 6). Direct application of norepinephrine on human embryonic kidney cells, in vitro, resulted in an increased expression of SGLT2 and specifically promoted the translocation of SGLT2 from the cytosol to the cell surface (Cytosolic SGLT2/GAPDH 0.51 ± 0.05 vs. 0.86 ± 0.08, Membranous SGLT2/Na-K-ATPase 1.06 ± 0.10 vs. 0.54 ± 0.03, P < 0.01, n = 6). Moreover, RDN increased the cytosolic SGLT2 while decreasing membranous SGLT2 in the kidneys of rats with HF (Cytosolic SGLT2/GAPDH 1.30 ± 0.11 vs. 0.58 ± 0.09, Membranous SGLT2/Na-K-ATPase 0.51 ± 0.10 vs. 2.08 ± 0.08, P < 0.01, n = 6).

Conclusions:
These findings suggest that the excessive activation of renal sympathetic nerves in HF increases the expression of SGLT2 protein trafficked by norepinephrine to cell membrane in proximal tubules resulting in greater sodium retention associated with HF condition. RDN mitigates the enhanced expression and activity of SGLT2 and ameliorates the subsequent sodium and water retention associated with HF, suggesting the potential therapeutic use of RDN for HF.