bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-BPC07-2: EFFECTS OF MINERALOCORTICOID RECEPTOR ANTAGONISTS ON SEX HORMONES AND BODY COMPOSITION IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Ishikawa Toru , Morimoto Satoshi , Ichihara Atsuhiro
Published: January 2023

Objective:

Mineralocorticoid receptor antagonists are frequently used for the treatment of primary aldosteronism. Steroidal mineralocorticoid receptor antagonists may have antagonistic actions on androgen receptors, agonistic actions on progesterone receptors, and antagonistic actions on mineralocorticoid receptors. Because anti-androgen effects may cause body fat accumulation and skeletal muscle atrophy, there are concerns that this drug may have adverse effects on body composition.

Design and method:

Therefore, in this randomized prospective study, we compared the adverse effects of spironolactone, a steroidal mineralocorticoid receptor antagonist, and esaxerenone, a nonsteroidal mineralocorticoid receptor antagonist, on sex hormone levels and body composition in patients with primary aldosteronism without severe renal dysfunction.

Results:

The serum concentration of free testosterone was significantly higher in the spironolactone group than in the esaxerenone group in both males and females. However, the levels of estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone did not significantly increase. Changes in body fat percentage and muscle mass rate were not significantly different between the two groups. No patient showed a serum potassium level > 6.0 mEq/L; however, serum potassium levels were significantly higher in the spironolactone group than in the esaxerenone group.

Conclusions:

These data indicate that spironolactone may have antagonistic effects on androgen receptors. Esaxerenone did not show any apparent adverse effects, suggesting that it can be safely used in patients with primary aldosteronism.
PS-BPC07-7: REDUCED EFFICACY OF BLOOD PRESSURE LOWERING DRUGS IN THE PRESENCE OF DIABETES MELLITUS: RESULTS FROM THE TRIUMPH RANDOMISED CONTROLLED TRIAL.
Authors: Gnanenthiran Sonali Rukshana , Webster Ruth , Silva Asita de , Salam Abdul , Schutte Aletta E , Patel Anushka , Rodgers Anthony
Published: January 2023

Objective:

People with diabetes mellitus (DM) have a higher prevalence of suboptimal blood pressure (BP) control compared to those without DM. Whether the presence of DM affects the ability of antihypertensive therapies to lower blood pressure (BP) is uncertain. We investigated whether DM affects the efficacy of a low dose triple combination pill or usual care among people with mild-moderate hypertension.

Design and method:

TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomized controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients were randomised to a once-daily low-dose triple combination polypill (telmisartan 20 mg/amlodipine 2.5 mg/chlorthalidone 12.5 mg) or usual care. This analysis compared BP reduction and percentage of time below target BP in people with and without DM, both in the intervention and control groups over 24-week follow-up. Predicted efficacy of prescribed therapy was calculated using the estimation methods of Law et al.

Results:

The trial randomized 700 patients (56 ± 11yrs, 31% DM). There was no difference in the number of drugs prescribed or predicted efficacy of therapy between people with DM and without DM. However, the observed BP reduction from baseline to week 24 was lower in those with DM compared to non-diabetics in both the triple pill (25/11 vs 31/15 mmHg, p ≦ 0.01) and usual care (17/7 vs 22/11, p ≦ 0.01) groups. People with DM achieved lower time at target BP than non-diabetics on both the triple pill (44% vs 73%, p < 0.001) and usual care (27% vs 51%, p < 0.001). DM was a negative predictor of change in BP (beta-coefficient -0.08, p = 0.02) and spending majority of time at target BP (OR 0.54, p = 0.006).

Conclusions:

Patients with DM experienced reduced efficacy of BP lowering therapies as compared to patients without DM, irrespective of the type of BP lowering therapy received. The triple pill still produced greater BP reduction compared to usual care in patients with mild-moderate hypertension even in the presence of DM.
PS-BPC08-7: ORAL SALT LOADING TEST REFLECTS NOCTURNAL HYPERTENSION AND HIGH URINARY ALBUMIN EXCRETION IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Yoshimura Saki , Yoshida Yuichi , Kinoshita Mizuki , Miamoto Shotaro , Ozeki Yoshinori , Okamoto Mitsuhiro , Gotoh Koro , Masaki Takayuki , Shibata Hirotaka
Published: January 2023

Objective:

In the present study, which confirmatory test was most useful for reflecting the severity of primary aldosteronism (PA) was determined by evaluating 24-h blood pressure (BP), urine albumin, left ventricular mass (LVM), and intima media thickness (IMT).

Design and method:

This study included 113 patients (80 PA and 33 non-PA hypertensive patients) who were admitted to Oita University Hospital and evaluated using ambulatory blood pressure monitoring (ABPM). First, casual blood pressure (BP) and ABPM parameters were compared between PA and non-PA patients. Second, patients were divided into PA-positive and PA-negative groups based on confirmatory tests including the saline infusion test (SIT), captopril challenge test (CCT), and oral salt loading test (OSLT), and casual BP and ABPM parameters were compared between the two groups. In addition, urine albumin excretion, LVM, and maximum IMT as markers of organ damage were compared between the two groups.

Results:

The ABPM parameters but not casual BP, were higher in PA patients than in non-PA patients (nocturnal SBP: 118.3 ± 1.6 mmHg, 107.6 ± 2.7 mmHg, p < 0.001; 24-h SBP: 123.4 ± 1.6 mmHg, 113.2 ± 2.6 mmHg, p < 0.001, respectively). Nocturnal and 24-h systolic BP (SBP) in OSLT-positive patients were significantly higher than in OSLT-negative patients (nocturnal SBP: 124.3 ± 3.2 mmHg, 114.4 ± 3.2 mmHg, p = 0.036; 24-h SBP: 129.2 ± 3.3 mmHg, 119.9 ± 3.0 mmHg, p = 0.044, respectively). ABPM parameters in other confirmatory tests were not different between the PA-positive and PA-negative groups. Urine albumin excretion in OSLT-positive patients was significantly higher than in the OSLT-negative patients (51.6 ± 22.5 mg/day and 3.0 ± 0.3 mg/day, p = 0.043). However, in other confirmatory tests, organ damage markers (such as LVM and IMT) were not different between the two groups.

Conclusions:

The OSLT is potentially useful not only for the diagnosis of PA but also for assessment of 24-h SBP and organ damage, as indicated by urine albumin excretion.
PS-BPC08-10: IMPORTANCE OF DIETARY SALT RESTRICTION IN PRIMARY ALDOSTERONISM DURING TREATMENT WITH MINERALOCORTICOID RECEPTOR ANTAGONISTS: ROLE OF POSTTREATMENT PLASMA RENIN LEVELS
Authors: Yoshida Yuichi , Fujiki Rika , Kinoshita Mizuki , Sada Kentaro , Miyamoto Shotaro , Ozeki Yoshinori , Mori Yumi , Noguchi Takaaki , Matsuda Naoki , Okamoto Mitsuhiro , Gotoh Koro , Masaki Takayuki , Shibata Hirotaka
Published: January 2023

Objective:

The purpose of this study is to measure the estimated dietary salt intake (eU-NaCl) when primary aldosteronism (PA) is treated with mineralocorticoid receptor antagonists (MRAs) and to evaluate whether it is important to reduce salt intake even while on MRA medications.

Design and method:

The eU-NaCl values were investigated in 26 PA patients who were treated with MRAs at pre-treatment and 6-month treatment. The eU-NaCl was calculated as follows: eU-NaCl (g/day) = 21.98 * {urinary sodium (mmol / L) /  * (Body Weight (kg) × 14.89 + Height (cm) × 16.14 - age × 2.043 - 2244.45)}.

Results:

Data are shown as median {first quartile - third quartile}. Various clinical parameters of 26 PA patients were compared between pre-treatment and 6 months MRA treatment; Systolic blood pressure (138 mmHg {124.5–157.7} vs 125 mmHg {117.8–130.8}, p < 0.01) and diastolic blood pressure (86 mmHg {80.5–95.0} vs 78 mmHg {74.5–86.3}, p = 0.02) were decreased, serum potassium (3.9 mmol/L {3.8–4.3} vs 4.3 mmol/L {4.0–4.6}, p < 0.01) and active renin concentration (ARC) (2.6 pg/mL {1.2–3.8} vs 6.1 pg/mL {3.5–10.3}, p < 0.01) were increased significantly. The eU-NaCl (8.9 g/day {8.0–10.2} vs. 10.0 g/day {7.8–12.0}, p = 0.27) did not change. The correlation between the difference in eU-NaCl (ΔeU-NaCl) and the difference in ARC (ΔARC) before and after MRA treatment showed a significant inverse correlation (r = -0.418, p = 0.03). Furthermore, when the 26 patients were divided into 2 groups of ARC >5 pg/mL and ARC < 5 pg/mL after MRA treatment, ΔeU-NaCl and ΔARC showed no significant correlation in 16 patients with ARC ≧ 5 pg/mL (r = -0.481, p = 0.11), whereas a strong inverse correlation in 10 patients with ARC < 5 pg/mL (r = -0.7599, p = 0.01).

Conclusions:

The present data indicate that post-MRA treatment ARC of less than 5pg/mL reflects insufficient improvement of salt sensitivity, suggesting the importance of dietary salt restriction even in the presence of MRA treatment.
PS-BPC10-8: POST-VACCINATION SARS-COV-2 IGG ANTIBODY TITER IN DIALYSIS PATIENTS
Authors: Yoshida Sumiko , Tsuji Seijirou , Miya Keiko , Shima Hisato , Tashiro Manabu , Inoue Tomoko , Minakuchi Jun , Okada Kazuyoshi , Endo Itsuro , Abe Masahiro
Published: January 2023

Background:

Dialysis patients have a higher COVID-19 fatality rate than the general population and are priority candidates for SARS-CoV-2 vaccination. However, dialysis patients are immunocompromised, suggesting that they may develop a less immune response to COVID-19 vaccination than healthy individuals.

Objective and Methods:

A total of 358 hemodialysis patients who were twice-vaccinated with BNT162b2 were included. SARS-CoV-2 IgG antibody titer was measured within 7 days to 1 month, 1∼2 months, and 3∼4 months after the second vaccination, and factors influencing antibody titer were statistically investigated. SARS-CoV-2 IgG measurement was performed using SARS-CoV-2 IgG II Quant Reagent (Abbott), which is a reagent to quantitatively measure IgG antibodies against the receptor-binding domain of SARS-CoV-2 spike protein.

Results:

The patients were 240 males (67%) and 118 females, ranging from 37 to 95 years old, with a median age of 70 years. Causes of kidney failure were diabetes mellitus in 35.2%, hypertensive kidney disease in 7.3%, glomerular disease in 30.5%, and polycystic kidney disease in 4.5% of the patients. Comorbidities were hypertension in 64.3% and diabetes in 48.9%. Steroids or immunosuppressive drugs were used in 9% of the patients. SARS-CoV-2 IgG antibody titers at 7 days to 1 month, 1 to 2 months, and 3 to 4 months (median 10, 42, and 98 days) after the second vaccination have the median of 4092 AU/mL(with interquartile range: 1354, 7592), 2199 (927, 4692), and 789 (323, 1559), respectively. Post-vaccination SARS-CoV-2 IgG titers were significantly correlated with Kt/V, the presence of autoimmune diseases, the use of steroids or immunosuppressive drugs, malignancy treatment, and serum albumin and hemoglobin levels. Multivariate analysis showed that the factors that decreased post-vaccination SARS-CoV-2 IgG titer were the use of steroids and immunosuppressive drugs, the presence of malignant tumors under treatment, and hypoalbuminemia.

Conclusion:

Compared to healthy subjects in previous reports, dialysis patients had lower SARS-CoV-2 IgG titers after COVID-19 vaccination, suggesting that the vaccine may not be sufficiently effective. In addition, SARS-CoV-2 IgG titers are likely to be even lower in patients at high risk for decreased immune response due to medications or comorbidities. Additional vaccination may be essential for hemodialysis patients who are expected to have low SARS-CoV-2 IgG titers.
PS-BPC11-7: SEX DIFFERENCES IN BLOOD PRESSURE CONTROL FOLLOWING REMOTE PATIENT MONITORING IMPLEMENTATION WITH AND WITHOUT CARE COORDINATION: A PROSPECTIVE COHORT STUDY
Authors: Persell Stephen D , Petito Lucia C , Anthony Lauren , Peprah Yaw , Lee Ji Young , Li Jim , Sato Hironori
Published: January 2023

Objective:

Evaluate sex and race/ethnicity subgroup differences in the effects of care coordinator-assisted implementation of remote patient monitoring (RPM) and RPM implementation alone for hypertension in primary care compared to usual care.

Design and Methods:

Subgroup analysis of 3-arm pragmatic pilot cohort study. At two clinics, nurse care coordinators with physician approval, offered RPM to eligible patients and assisted with initiation. At two clinics, RPM was solely at physician discretion. Twenty clinics continued with usual care. Eligible patients were aged 65–85y with Medicare insurance and had uncontrolled hypertension (last two office BP > = 140/90 mm Hg). The primary outcome assessed at 6 months was controlling high blood pressure (< 140/90 mm Hg) at the most recent measurement. We tested for interactions between group and sex and between group and race ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic and others) in generalized linear models adjusted for age and baseline systolic BP.

Results:

In this cohort (234 RPM plus care coordination, 600 RPM only, 1617 usual care), we detected effect heterogeneity by sex (p = 0.02) but not race/ethnicity (p = 0.17). In sex-stratified analyses, the odds of controlling high blood pressure at 6 months in the RPM plus care coordination compared to control were 1.62 times higher (95% CI 1.09–2.41, P = 0.02) for women and 1.17 times higher (0.65–2.13, P = 0.6) for men. Corresponding odds comparing the RPM alone to control were 1.63 (1.24–2.13, P < 0.001) for women and 0.86 (0.55–1.34, P = 0.51) for men. RPM uptake in the care coordination group was 18% (27/153) for women and 14% (11/81) for men, compared with 0.7% (3/422) for women and 0% (0/178) for men in the RPM alone group. Among RPM-prescribed patients with baseline BP > = 140/90 mm Hg in the care coordination plus RPM group, usage following a RPM prescription was high (90% for women and 100% in men), antihypertensive medication intensification over the course of 6 months occurred for the plurality of patients (37% and 47%). SBP decline at 6 months was substantial (mean [SD] 23.6 [27.2] and 21.1 [21.2] mmHg).

Conclusions:

Introducing remote patient monitoring with and without care coordination appeared to have greater effects on BP control in women. Greater rates of RPM prescribing to women compared to men may account for these findings. Larger studies are needed to explore these differences.
PS-BPC11-8: ASSOCIATION OF CARDIOMETABOLIC INDEX AND SUBCLINICAL RENAL DAMAGE: A CROSS SECTIONAL STUDY
Authors: Sun Yue , Mu Jianjun
Published: January 2023

Objective:

Subclinical renal damage (SRD) has become a major health issue due to its dormant onset and poor prognosis. Recent studies have found that cardiometabolic index (CMI) is closely related to diabetes, hypertension, stroke and cardiovascular disease. However, the correlation between CMI and SRD among adults without diabetes still remain unclear. The present study is aimed to investigate the association between CMI and SRD among non-diabetic individuals in a Chinese cohort.

Design and method:

A total of 2222 participants (male n = 1208) from our previously established cohort of Adolescent Hypertension Study were included in the cross-sectional survey. CMI was calculated by triglyceride to high density lipoprotein cholesterol ratio multiply waist-to-height ratio. Renal function was assessed with estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR). The participants were divided into three groups according to CMI scores. The logistic regression model was established to analyze the relationship between CMI and the risk of SRD.

Results:

CMI was positively correlated with SRD. Compared to participants in the lowest tertile of CMI, those in the highest tertile of CMI had higher risk of SRD(OR:1.918, 95%CI:1.391–2.643,P < 0.001). The association remained significantly after adjusting related factors such as sex, age, history of hypertension, smoking, alcohol use, heart ratio and fasting blood glucose(OR:1.458, 95%CI:1.023–2.079, P < 0.05).

Conclusions:

Our study showed that cardiometabolic index was significantly associated with the risk of SRD in Chinese adults without diabetes. CMI may be used as a simple marker for detection of subclinical renal damage in non-diabetic subjects.
PS-BPP01-1: OUTCOME-BASED THRESHOLD FOR CAROTID-FEMORAL PULSE WAVE VELOCITY: THE IDCARS STUDY
Authors: An Dewei , Cheng Yibang , Huang Qifang , Li Yan , Staessen Jan A
Published: January 2023

Objective:

Current guidelines recommend a carotid-femoral pulse wave velocity (cf-PWV) > 10m/s of as a sign of large arterial stiffening, which was mainly based on cross-sectional analyses on the distribution of cf-PWV in healthy populations. Using data from the International Database of Central Arterial Properties for Risk Stratification (IDCARS), we aimed to determine an outcome-driven threshold for cf-PWV.

Methods:

Adults (> = 18 years) recruited from eight IDCARS centres and followed up for 6 months or longer were qualified for inclusion in the current meta-analysis. Cf PWV was measured using the Sphygmocor device. The primary endpoint consisted of fatal and nonfatal cardiovascular events. Secondary endpoints were total and cardiovascular mortality, and fatal and nonfatal coronary events. We calculated multivariable-adjusted hazard ratios (HRs) versus the average risk of the whole population for cf-PWV ranging from the 10th to the 90th percentile with an increment of 0.1 m/s. We plotted the HRs and their 95% confidence limits versus the increasing cutoff points of cf-PWV with the goal to determine at which level the lower confidence limit crossed unity.

Results:

Of 3494 participants (mean age: 52.2 years; women: 55.3%; mean cf-PWV: 7.8 m/s) followed up for a median of 5.0 years, 156 (4.5%) experienced the primary endpoint and 104 (3.0%) died. Multivariable adjusted outcome-driven thresholds of cf-PWV (m/s) were 8.6 for the primary cardiovascular endpoint, and 9.1, 8.7 and 8.6 for all-cause and cardiovascular mortality and coronary event, respectively. Subjects with a cf-PWV > = 9 m/s (n = 752, 21.5%), compared with the rest of the population, had an increased risk of the primary cardiovascular endpoint (HR: 1.75; 95% CI: 1.20–2.54, P = 0.004).

Conclusions:

The outcome-based threshold of > = 9 m/s for cf-PWV is close to the cut-off proposed by the current guidelines, according to which 20% of the IDCARS participants had arterial stiffness and were associated with increased cardiovascular risk.
PS-BPP04-9: THE RXPATH RANDOMIZED TRIAL OF THE HYPERTENSION CANADA PROFESSIONAL CERTIFICATION PROGRAM: A NOVEL IMPLEMENTATION STRATEGY FOR HYPERTENSION GUIDELINES
Authors: Tsuyuki Ross Tadao , Watson Kaitlyn Elizabeth , Pan Bo , Hamarneh Yazid Nabil Al
Published: January 2023

The uptake of clinical practice guidelines into practice is poor for many chronic conditions, including hypertension. We designed a guidelines-based educational program for primary care clinicians, the Hypertension Canada Professional Certification Program (HC-PCP, www.hypertension.ca/professional-certification-program). It consists of four online modules, an online prospective patient registry, and expert evaluations of the blood pressure measurement technique and case management by the learner. We then evaluated its impact on patient level outcomes.

Objective:

The objective of RxPATH was to determine the effect of the HC-PCP for pharmacists on systolic blood pressure reduction in patients with poorly controlled hypertension.

Design and Methods:

Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy).

Setting:

Community pharmacies in Alberta, Canada

Population:

Pharmacists with prescriptive authority volunteered to participate. We enrolled patients with poorly controlled hypertension (BP > 140/90mmHg or > 130/80mmHg in those with diabetes), identified by their pharmacist.

Intervention:

Pharmacists were enrolled in the HC-PCP. They then provided this care to their patients with poorly controlled hypertension.

Control:

Pharmacists were given a copy of the Hypertension Canada Guidelines and provided usual care to their patients prior to undertaking the HC-PCP.

Outcomes:

The primary outcome was difference in change in systolic blood pressure between intervention and control groups at 3 months. We also evaluated patient satisfaction using the Consultant Satisfaction Questionnaire (CSQ).

Results:

We enrolled 890 patients from 61 pharmacies (104 pharmacists). Mean age was 61.6 (SD 14.1) years, 46% were female, 35.5% had diabetes, and mean baseline BP was 152.4 (SD 13.8)/87.0 (SD 10.6)mmHg. Change in systolic BP was 9.9 (SD 16.5) for the intervention group, compared to 9.9 (SD 16.2) mmHg in the control group, p = 0.29. Patient satisfaction using the CSQ was high at 76 (of 90 maximum).

Conclusions:

Most educational programs do not get evaluated at the patient level. RxPATH demonstrated that the HC-PCP intervention did not result in a greater reduction in systolic BP compared to control. While both groups did have clinically meaningful reductions in BP, possible reasons for lack of a difference with the intervention include: COVID-19 staffing/workload issues in pharmacies, selection bias for pharmacists interested in hypertension/contamination of usual care group, and short follow-up duration. Feedback on the HC-PCP from pharmacists was positive, patient satisfaction was high, and we plan to make this program widely available to primary care providers.
PS-BPP05-9: IMPACT OF EVACUATION ON THE LONG-TERM TREND OF HYPERTENSION AFTER THE GREAT EAST JAPAN EARTHQUAKE
Authors: Eguchi Eri , Satou Haruka , Funakubo Narumi , Nakano Hironori , Imano Hironori , Iso Hiroyasu , Ohira Tetsuya
Published: January 2023

Objective:

Increases in lifestyle-related diseases have been reported after the Great East Japan Earthquake, but the long-term effects are not clear. The aim of this study was to examine the trend of hypertension in the 10 years before and after the earthquake.

Design and method:

A cumulative total of 3,860,698 Fukushima residents aged 40 to 74 years who participated in specific health check-ups between 2008 and 2017, for whom blood pressure data were available were the subject of this study. Fukushima was divided into mountainous, central, coastal, and evacuation areas, and the age adjusted prevalence of hypertension in each area and years were calculated stratified by gender and age groups (> = 60 and < 60) and compared between before (2008–2010) and after (2011–2017) the disaster using Poisson regression models. Furthermore, inflection point analysis was used to calculate the annual percentage change (APC) in each year. Hypertension was defined as a systolic/diastolic blood pressure of 140/90 mmHg and/or taking antihypertensive medication.

Results:

The proportion of hypertension increased in 2011, the year of the earthquake, in coastal, central and evacuation areas, and the change in the prevalence in evacuation areas was particularly pronounced in men, with a 2.3-point increase in men and a 1.7-point increase in women. The prevalence of hypertension in the evacuation areas returned to its original level in 2013 for women, but not for men in which a significant upward trend was observed throughout the decade in all four areas, with an average APC (95% confidence interval) of 0.8 (0.2–1.4) in the evacuation areas. There were no significant differences according to age group stratification.

Conclusions:

Prevalence of hypertension in Fukushima Prefecture after the disaster was higher than before the disaster, especially in evacuated areas, and this trend continued for a long period of time, especially in men. Determinants of hypertension trends, such as lifestyles and overweight will be examined in detail.
PS-BPP06-2: ASSOCIATIONS BETWEEN URIC ACID LEVELS AND HYPERTENSION INCIDENCE IN AN APPARENTLY HEALTHY JAPANESE POPULATION
Authors: Salim Anwar Ahmed , Kawasoe Shin , Kubozono Takuro , Ojima Satoko , Kawabata Takeko , Ikeda Yoshiyuki , Miyahara Hironori , Tokushige Koichi , Ohishi Mitsuru
Published: January 2023

Objective:

Uric acid (UA) has been linked to the development of hypertension. However, it is not known if this association is significant in men and women who are apparently healthy at baseline.

Design and Methods:

This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseirin Hospital from October 2008 to April 2019. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. To assess the association between baseline UA levels and 5 year hypertension incidence, we performed univariable and multivariable logistic regression analysis by sex according to their UA quartiles as follows: In men: 1st quartile ≧ 4.8 mg/dL, 2nd quartile 4.9 to 5.6 mg/dL, 3rd quartile 5.7 to 6.4 mg/dL, and 4th quartile ≧ 6.5 mg/dL; In women: 1st quartile ≧ 3.4 mg/dL, 2nd quartile 3.5 to 4.0 mg/dL, 3rd quartile 4.1 to 4.7 mg/dL, and 4th quartile ≧ 4.8 mg/dL. The ORs were adjusted for age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), current smoking, alcohol consumption, exercise habit, serum triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, fasting plasma glucose and eGFR. Hypertension incidence was defined as SBP ≧ 140 mmHg and/or DBP ≧ 90 mmHg at follow up, or newly prescribed antihypertensive medication during 5 years of follow up.

Results:

In total, 21,514 participants (age, 52.9 ± 10.9 years; men, 39.8%), were enrolled. During the 5 year of follow-up, 1415 (16.5%) men and 1408 (10.9%) women developed hypertension. In univariable analysis, the UA levels were significantly associated with hypertension in both men (OR for fourth to first quartile, 1.45; 95% confidence interval [CI], 1.24 to 1.70, P < 0.0001) and women (OR for fourth to first quartile, 1.62; 95%CI, 1.38 to 1.90, P < 0.0001). After adjusting for covariates, the UA levels were significantly associated with hypertension in men (OR for fourth to first quartile, 1.35; 95%CI, 1.13 to 1.62, P = 0.0011), but was not in women (OR for fourth to first quartile, 1.14; 95%CI, 0.95 to 1.36, P = 0.1541)

Conclusion:

Elevated UA levels are associated with hypertension incidence in Japanese men without hypertension, diabetes, dyslipidemia, obesity, and decreased kidney function.
PS-BPP06-6: THE ASSOCIATION BETWEEN CARBON AND NITROGEN STABLE ISOTOPE RATIOS OF HUMAN HAIR AND HYPERTENSION
Authors: Ahn Song Vogue , Lee Sihoon
Published: January 2023

Background:

The relationship between stable isotope ratios and dietary protein sources has been reported. However, few studies have examined the effect of stable isotope ratios on metabolic risk in humans. We investigated whether the stable isotope ratios of carbon and nitrogen in human hair are associated with blood pressure and hypertension.

Methods:

We conducted a cross-sectional study of 392 subjects (228 men and 164 women). Hair samples of the subjects were used for the measurement of stable isotope ratios of carbon (Δ13C) and nitrogen (Δ15N).

Results:

The Δ13C and Δ15N values showed positive correlations with diastolic blood pressure in the subjects without antihypertensive medication. In the subjects without antihypertensive medication, the multivariable-adjusted odds ratio (95% confidence interval) for hypertension was 1.55 (1.04 - 2.30) per 1‰ increase in Δ15N and 1.22 (0.86 - 1.73) per 1‰ increase in Δ13C, respectively. However, in the subjects with antihypertensive medication, neither Δ13C nor Δ15N values showed a significant association with hypertension.

Conclusions:

The stable isotopic ratio of nitrogen in scalp hair is independently associated with hypertension in subjects without antihypertensive medication. The hair Δ15N value might be used as a surrogate marker to screen a high-risk population for hypertension.
PS-BPP06-7: ASSOCIATION BETWEEN SALT INTAKE AND BLOOD PRESSURE IN COMMUNITY-DWELLING OLDER PEOPLE: THE SONIC STUDY
Authors: Yoshida Hiroko , Kabayama Mai , Godai Kayo , Akasaka ken , Yamamoto Kouichi , Ikebe Kazunori , Yasumoto Saori , Gondo Yasuyuki , Rakugi Hiromi , Kamide Kei
Published: January 2023

Objective:

It is well known that excessive salt intake is associated with hypertension (HT) and salt intake reduction lowers blood pressure. However, the knowledge of salt intake and blood pressure in the older people is not sufficient. This study aimed to clarify the relationship between salt intake and blood pressure among community-dwelling Japanese older people.

Design and method:

This study was cross-sectional design based on a prospective cohort study called the SONIC (Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians) study. We used data collected from 2010 to 2012. The dependent variable was the blood pressure at the venue and the independent variable was salt intake.

Salt intake was calculated using the brief-type self-administered diet history questionnaire (BDHQ). After adjustment for energy using the residual method, Salt intake was classified into quartiles. Blood pressure values for each quartile were compared by Jonckheere-Terpstra test.

Results:

The number of participants was 2,163 (female: 53.3%). Persons who may have over- or under-reporting nutrition and had no blood pressure data was excluded. Participants of 70 ± 1 years old were 947 (HT: 50.2%), 80 ± 1 years old were 951 (HT: 63.9%), 90 ± 1 years old were 265 (HT: 50.6%).

There was no clear difference of systolic blood pressure among the four quartiles of salt intake. Participants taking angiotensin II receptor blocker (ARB) were 448, and mean systolic blood pressure in the four quartiles of salt intake were Q1:142.1 ± 17.7mmHg, Q2: 145.2 ± 17.3, Q3: 146.1 ± 17.2, and Q4: 147.8 ± 18.8. There was a stepwise increase in systolic blood pressure with increasing salt intake quartile (p = 0.018 for trend).

Conclusions:

For the elderly taking ARBs, salt reduction was shown to improve blood pressure control, but for the other elderly, no effect of salt intake was observed. Further studies are needed to examine including other factors what affects blood pressure for older population.
PS-BPR01-1: SUCCESSFUL TREATMENT WITH ESAXERENONE IN A PREGNANT WOMAN WITH PRIMARY ALDOSTERONISM AND SUPERIMPOSED PREECLAMPSIA
Authors: Yamashita Kaoru , Morimoto Satoshi , Inoue Yuko , Hirata Kiyotaka , Kimura Shihori , Seki Yasufumi , Bokuda Kanako , Watanabe Daisuke , Ichihara Atsuhiro
Published: January 2023

Background:

During pregnancy, there is no established treatment for idiopathic hyperaldosteronism (IHA), the most common form of primary aldosteronism (PA) due to bilateral adrenal hyperplasia. Here, we report the case of a pregnant patient with IHA who was successfully treated with esaxerenone, a non-steroidal mineralocorticoid receptor (MR) antagonist.

Case:

A 39-year-old woman was referred to our outpatient clinic for hypertension with high plasma aldosterone concentration (PAC). Her PAC was 204 pg/mL (radioimmunoassay) and plasma renin activity was 1.2 ng/mL/h at the time of referral. She was diagnosed with PA since the saline-loading test for PA was positive. She had no hypokalemia and computed tomography scans showed no adrenal tumors. Adrenal vein sampling indicated overproduction of aldosterone in both adrenal glands leading to the diagnosis of IHA. She was commenced on nifedipine controlled release (CR) 20 mg daily because she desired to be pregnant. After one year, she became pregnant. Her blood pressure was well controlled until 34 weeks of gestation when her home blood pressure became elevated up to 140/90 mmHg. Although the dose of nifedipine CR was increased to 80 mg daily, her blood pressure increased to 151/97 mmHg and urinary test showed proteinuria of 2 + in 35 weeks of gestation. She was diagnosed with superimposed preeclampsia (SPE) and additionally treated with esaxerenone. Her blood pressure decreased to 120–140/98–100 mmHg and the proteinuria improved to +/-. A successful cesarean section at 37 weeks resulted in the delivery of a healthy baby boy. Esaxerenone was discontinued 2 weeks after delivery, because she was eager to breast-feed the baby and no safety data of esaxerenone in breast-feeding woman was available. Her blood pressure has been well controlled by nifedipine CR 80 mg daily even after 100 days of postpartum.

Conclusions:

This is the first case of a pregnant woman who was successfully treated with esaxerenone despite being an elderly pregnant woman who had been diagnosed with IHA and developed SPE. Further studies are needed to investigate the efficacy and safety of non-steroidal selective MR antagonist in similar pregnant patients with IHA, to establish better treatment strategy for these patients.
PS-BPR01-6: A CASE SERIES OF UNILATERAL PRIMARY ALDOSTERONISM TREATED BY RADIOFREQUENCY ABLATION
Authors: Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Morimoto Ryo , Oguro Sota , Takase Kei , Tanaka Tetsuhiro , Satoh Fumitoshi
Published: January 2023

Background:

In primary aldosteronism (PA), early and appropriate management based on its subtype is crucial to abolish an enhanced cardiovascular risk. Mineralocorticoid receptor antagonists (MRAs) are the mainstay of PA treatment, while a unilateral adrenalectomy (ADX) has been considered as the gold standard intervention for unilateral PA, mainly caused by an aldosterone-producing adenoma. The laparoscopic ADX is a less-invasive procedure than open surgery, whereas the procedure harbors a perioperative risk associated with general anesthesia. Herein, we report 3 PA cases where we employed radiofrequency ablation (RFA) as an alternate therapy for their aldosterone-producing tumors. In those cases, RFA successfully and safely led to remission of PA with more reduced physical burden, compared with the laparoscopic ADX.

Case presentation:

We performed RFA in 3 unilateral PA cases with aldosterone-producing tumors; Case 1, a 46-year-old man with a right adrenal tumor (14 mm); Case 2, a 65-year-old man with a right adrenal tumor (15 mm); Case 3, a 47-year-old man with a left adrenal tumor (19 mm). At baseline, their blood pressure levels were 124/87, 118/79 and 142/88 mmHg under 1, 2 and 2 antihypertensive agents, respectively. Plasma aldosterone concentrations and renin activity levels were as follows; 29.70, 25.7 and 48.6 ng/dL and 0.5, < 0.2 and < 0.2 ng/mL/hr, respectively. In all cases, we confirmed the presence and localization of PA with confirmatory tests and segmental adrenal venous sampling. Before the RFA procedure, we initiated and titrated MRAs to sufficiently block effects of hyperaldosteronism. Percutaneous RFA was guided by computed tomography under intravenous anesthesia without intubation. Complete tumor ablation was achieved within 1 hour, confirmed by enhanced adrenal imaging. No major complication was observed, and physical activity was almost recovered on the same day. Three months after RFA, all 3 patients showed normotension without any antihypertensives. For biochemical parameters, plasma aldosterone levels decreased to 2.47, < 0.40 and 1.41 ng/dL in Case 1, 2 and 3, respectively, followed by mild restoration of plasma renin activity (1.4, 0.5 and < 0.2 ng/mL/hr, respectively).

Conclusion:

This case series demonstrates that RFA is an alternate treatment for unilateral PA. Based on accurate localization of hyperaldosteronism, RFA could cause necrosis of only an adrenal-producing tumor and spare an ipsilateral adjacent adrenal gland, resulting in remission of PA with minimal physical burden.
PS-B03-2: SGC STIMULATOR, BAY41 8543, FOR THE TREATMENT OF HEART FAILURE WITH REDUCED EJECTION FRACTION AND CARDIORENAL SYNDROME
Authors: Gawrys Olga , Skaroupkova Petra , Huskova Zuzana , Honetschlagerova Zuzana , Vanourkova Zdenka , Kikerlova Sona , Melenovsky Vojtech , Cervenka Ludek
Published: January 2023

Objective:

Heart failure with reduced ejection fraction (HFrEF) imposes a significant health and socioeconomic burden. The life expectancy and prognosis are particularly dreadful for patients that develop simultaneous renal dysfunction, so called cardiorenal syndrome, hence new treatment strategies are still in a great demand. Recent therapies for HFrEF include targeting the nitric oxide (NO)/ soluble guanylyl cyclase (sGC)/ cyclic guanosine monophosphate (cGMP) pathway by sGC stimulators. These compounds bind to the heme moiety of the sGC and stimulate the sGC in the absence of NO (NO independent action), but also they sensitize sGC to low levels of endogenous NO by stabilizing NO/sGC binding.

Design and method:

We explored the efficiency of sGC stimulator (BAY41 8543, an analogue of vericiguat) in the animal model of HFrEF with kidney dysfunction. We used ren2 transgenic hypertensive rats (TGR) with aortocaval fistula (ACF), in which HFrEF is due to volume overload. Firstly, we investigated the long term activity of BAY41 given alone (3 mg/kg/day in the food) or combined with an ACE inhibitor (ACEi, Trandolapril, 0.25 mg/kg/day in drinking water) on the survival rate of ACF induced HFrEF in TGR (30 weeks). In separate series of experiments the impact of BAY41 on blood pressure was measured by telemetry. Blood, urine and in the end tissue samples were collected to evaluate the levels of cGMP, albuminuria and the production of nitric oxide during the two week treatment.

Results:

sGC stimulator significantly improved the survival rate of ACF TGR in comparison to untreated animals with ACF. However, BAY41 administered together with ACEi decreased its beneficial activity. The overall survival in BAY41+ACEi treated group was 50%, while in the group which received only ACEi it was still 90% in the end of the observation. Noteworthy, a temporary blood pressure decrease (10 mmHg) was recorded during first few days after sGC stimulator administration, but early on SBP started to rise and by the end it was on the same level as in untreated ACF TGR (127 ± 3 vs 131 ± 6 mmHg, respectively; NS).

Conclusions:

It seems that the NO independent stimulation of sGC is a promising strategy to treat HFrEF with cardiorenal syndrome, however, more caution and additional studies are necessary to enlighten the puzzling decrease in survival rate in the group that received combined treatment with sGC stimulator and ACEi. Perhaps selected dose regimen was not optimal for the combined treatment (e.g. due to hypotension).
PS-B03-12: DIETARY CAPSANTHIN INHIBITS ATHEROSCLEROTIC INFLAMMATION IN APOLIPOPROTEIN E-DEFICIENT MICE
Authors: Joo Hee Kyoung , Kim Sungmin , Lee Yu Ran , Lee Eun-Ok , Jin Hao , Choi Yeon-Hee , Choi Eun Ju , Jeon Byeong Hwa
Published: January 2023

Objective:

Among carotenoids, capsanthin is a lipophilic red pigment responsible for the red pigmentation of paprika fruits (Capsicum annuum L.) However, its role in atherosclerosis is yet to be fully elucidated. In this study, we investigated the role of dietary capsanthin on vascular inflammation in atherosclerotic mice.

Design and method:

We evaluated the anti-atherosclerotic effects of daily oral administration of capsanthin (0.5 mg/kg of body weight/day) in apolipoprotein E-deficient mice fed a Western-type diet (WD).

Results:

Dietary capsanthin significantly inhibited the WD-induced elevation in the plasma levels of total cholesterol, low-density lipoprotein, and triglyceride in mice. The WD group showed a remarkable increase in oil red O-positive lesions indicating aortic plaque formation in whole and cross-sectional aorta. Interestingly, capsanthin reduced aortic plaque formation and VCAM-1 expression, which is vascular inflammation, in atherosclerotic mice. Furthermore, capsanthin significantly reduced the levels of proinflammatory cytokines and the neutrophil-lymphocyte ratio, a systemic inflammatory marker, in atherosclerotic mice.

Conclusions:

Taken together, our data demonstrate that dietary capsanthin plays a protective role against atherosclerosis in hyperlipidemic mice.
PS-B04-9: ELUCIDATING EFFECT OF INHIBITING ALDOSTERONE SYNTHESIS ON HUMAN ADRENOCORTICAL CELLS
Authors: Long Kha Chin , Sukor Norlela , Tan Geok Chin , Murad Nor Azian Abdul , Brown Morris Jonathan , Azizan Elena Aisha
Published: January 2023

Introduction:

Modern human diet is high in salt. High salt stimulates decrease of aldosterone by down-regulation of aldosterone synthase (encoded by the gene CYP11B2) in the zona glomerulosa (ZG). Aldosterone regulates blood pressure and volume by regulating salt secretion. Interestingly, adult human adrenal ZG is sparse and confined to discrete islets of cells unlike rodent adrenal where the zone encompasses the whole periphery of the adrenal. We therefore hypothesize that ZG cell function change from synthesis to apoptosis/migration mode when aldosterone is not required due to the high salt diet.

Objective:

Herein, we intend to characterise human adrenocortical cells silenced for CYP11B2.

Methods:

We transfected HAC15, a subclone of the H295R human adrenocortical cancer cell line with scrambled siRNA (siScrambled) or siRNA targeting CYP11B2 (siCYP11B2) using the Neon Transfection System. 48-h post-transfection, cell apoptosis rate was assessed using the Pacific Blue Annexin V/SYTOX AADvanced apoptosis kit. The supernatants and cells were harvested for aldosterone and cortisol measurements, and RNA isolation. A representative sample of siCYP11B2 and siScrambled from each independent experiment was selected for RNA-Sequencing (RNAseq). The EZMTT Proliferation Assay was performed on equally seeded HAC15 cells, 72-h post-transfection with either siScrambled or siCYP11B2 using the Lipofectamin 3000 Transfection reagent. Experiments were repeated 3 times independently in triplicates.

Results:

siCYP11B2 transfection limited the production of aldosterone by 69.8% (p = 0.001) and down-regulated the expression of CYP11B2 by 83.0% (p = 0.001). We confirmed that the silencing was specific to CYP11B2 despite the gene being highly homologous to CYP11B1 as there were no significant change on cortisol production and CYP11B1 mRNA expression. RNAseq analysis found 3 genes, CYP11B2, HNRNPA1, and UHMK1, consistently down-regulated in siCYP11B2 by 32%, 65% and 67% respectively. The most enriched pathways among the differentially expressed genes (DEG) were mitophagy and autophagy. No difference in cell apoptosis was seen in siCYP11B2 cells. Instead, an increase in cell proliferation was detected with the EZMTT assay.

Conclusion:

Our findings suggest that silencing of CYP11B2 does not affect apoptosis but does affect cell proliferation. Interestingly, the mitophagy and autophagy pathways were enriched in the DEGs of siCYP11B2 cells.
PS-B09-10: CANAGLIFLOZIN, A SODUIM-GLUCOSE TRANSPORTER 2 INHIBITOR IMPROVES GLUCOCORTICOID-INDUCED CARDIAC AND RENAL LIPID MISHANDLING BY SUPPRESSING LACTATE PRODUCTION IN FEMALE RATS
Authors: Olatunji Lawrence Aderemi
Published: January 2023

Evidence exist that lactate production has pathophysiological implications in the development of hyperinsulinemia-linked cardiac and renal dysfunctions. The cardio-renal protective effects of sodium-glucose co-transporter-2 inhibitor (SGLT2i) has not been associated with lactate production. The study therefore sought to test the hypothesis that SGLT2i would ameliorate insulin resistance and cardiorenal lipid mishandling by suppressing lactate production. Wistar female rats weighing between 140 and 160 g were randomly allotted into control, DEX and DEX+CANA groups (6 rats per group). The groups received (p.o.) vehicle (distilled water), dexamethasone (0.2 mg/kg) and and a combination of Dex with a SGLT2i (Canagliflozin; 10.0 mg/kg), respectively for a period of 6 days.

Data showed that DEX exposure led to hyperinsulinemia, insulin resistance, elevated atherogenic plasma lipid index, accumulation of cardiac and renal triglyceride, free fatty acid, and increased lipid peroxidation in the hearts and kidneys as well as enhanced lactate production. However, the induced alterations by DEX were ameliorated by SGLT2i, CANA.

Collectively, the present results demonstrate that glucocorticoid-linked hyperinsulinemia-mediated lipid mishandling in the heart and kidney is ameliorated by CANA, a SGLT2i. The implication of the findings of the study is that SGLT2i could reduce lipid accumulation in the hearts and kidneys, at least, by suppression of the lactate production
PS-C17-6: MATERNAL ENDOTHELIAL MITOCHONDRIAL DYSFUNCTION IN GESTATIONAL DIABETES MELLITUS
Authors: Reyes Agafe , Kereliuk Stephanie , Xiao Fengxia , Dolinsky Vernon , Burger Dylan
Published: January 2023

Objective:

Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes, and short and long-term maternal and neonatal cardiovascular risks. Our laboratory has shown that elevated levels of endothelial extracellular vesicles (EVs) in pregnant women is predictive of adverse pregnancy outcomes in type 1 diabetes. However, this matter has not been explored in GDM. We therefore investigated the impact of GDM on maternal vascular health, focusing on the mitochondria.

Design and method:

We determined the mitochondrial protein expression altered by GDM in rat kidneys by Western blot analysis. We examined the levels of circulating endothelial EVs and EV mitochondrial DNA (mtDNA) from rat plasma samples via flow cytometry and quantitative real-time PCR, respectively. We assessed the effects of high glucose exposure for 48 hours on endothelial mitochondrial function in human umbilical vein endothelial cells (HUVECs).

Results:

In a rat model of diet-induced GDM (Pereira, 2015 J Physiol), we observed significant decreases in expression of oxidative phosphorylation Complexes I (p < 0.05) and II (p < 0.01) in kidneys. We also observed a three-fold increase in late gestational levels of circulating endothelial EVs in GDM rats (p < 0.01) as well as increases in levels of EV-associated mtDNA, COX2 (p < 0.05) and ND2 (p < 0.01), suggesting mitochondrial dysfunction. In cultured HUVECs exposed to high glucose for 48 hours, we observed a significant decrease in Complex II expression (p < 0.01) and five-fold increases in EV mtDNA levels. This effect persisted even after removing high glucose exposure for 24 hours.

Conclusion:

These data show maternal endothelial dysfunction in GDM, accompanied by mitochondrial dysfunction and increased endothelial EV release. These findings suggest that endothelial mitochondrial health may represent a novel approach to reduce risks associated with GDM.