bluuebunny/crossref_metadata_2025 huggingface dataset:
SP-1: AGGRESSIVE BP MANAGEMENT IN OLDER ASIAN PEOPLE
Authors: Zhang Weili
Published: January 2023

With a rapidly aging population, adequate blood pressure (BP) control is critical for hypertension management and prevention of cardiovascular events. Impressive cardiovascular benefits have been observed with intensive BP control (SBP target, <120 mmHg) in the SPRINT (Systolic Blood Pressure Intervention Trial) study, even in patients 75 years of age or older. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC (The Blood Pressure Lowering Treatment Trialists’ Collaboration) showed that BP lowering is effective in older people for reducing major cardiovascular events. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study-a multicenter, randomized, controlled trial conducted in China, provided important evidence that intensive BP treatment (SBP target, 110 mmHg to < 130 mmHg) benefits older hypertensive patients (aged 60–80 years) and reduced the incidence of cardiovascular events than standard treatment (target 130 mmHg to < 150 mmHg). Because Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people. Home BP monitoring is helpful to facilitate hypertension management for older patients. It should also be noted that clinical decision-making should be on a patient basis, such as fragility, diabetes, stroke, and other comorbidities, with tailored BP targets.
S-07-1: TARGETING SENESCENT CELLS AS A NOVEL THERAPEUTIC STRATEGY FOR AGE-ASSOCIATED DISEASE
Authors: Minamino Tohru
Published: January 2023

Epidemiological studies have shown that age is the dominant risk factor for lifestyle-related diseases. The incidence and the prevalence of diabetes, heart failure, coronary heart disease and hypertension increase with advancing age. However, the molecular mechanisms underlying the increased risk of such diseases that is conferred by aging remain unclear. Cellular senescence is originally described as the finite replicative lifespan of human somatic cells in culture. Cellular senescence is accompanied by a specific set of phenotypic changes in morphology and gene expression including negative regulators of the cell cycle such as p53. Primary cultured cells from patients with premature aging syndromes are known to have a shorter lifespan than cells from age-matched healthy persons. It is also reported that the number of senescent cells increases in various tissues with advancing age. Interestingly, such accumulation of senescent cells in aged animals is attenuated by caloric restriction that regulates the lifespan regulatory system and delays age-associate phenotypes. I therefore hypothesize that cellular senescence in vivo contributes to the pathogenesis of age-associated disease and have shown a critical role of cellular senescence in age-related pathologies. However, a direct inhibition of cellular aging signaling would lead to the increased incidence of cancer, so we need to develop anti-senescent therapy without cancer development. Here I will show our recent data on a novel strategy of anti-senescent therapy for age-associated disease by targeting cellular senescence (Seno-antigens, Seno-metabolites, SASP), which would not promote tumorigenesis.
S-10-5: OPTIMAL BLOOD PRESSURE AND CARDIOVASCULAR RISK MANAGEMENT IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Lip Gregory
Published: January 2023

Hypertension is one of the most common cardiovascular disorders. On a population basis, and high blood pressure (BP) is a major independent risk factor for incident atrial fibrillation (AF) and AF-related complications. Given the high prevalence and both disorders being commonly asymptomatic, opportunistic arrhythmia screening in hypertensive patients is needed. In terms of management, AF could be regarded as a manifestation of hypertensive target organ damage, and optimal BP control is recommended, ideally aiming for a target systolic BP of 120–129mmHg, and diastolic BP of < 80mmHg. There is a close link between hypertension and the risk of stroke in AF, as well as the risk of serious bleeds in anticoagulated AF patients. Also, hypertension burden can be related to other AF-related complications, such as dementia and end renal disease. BP control should also be complementary to lifestyle factors, such as weight reduction, smoking cessation, alcohol reduction and regular exercise, given the close association with incident AF and AF-related complications such as stroke, major adverse cardiac events (MACE) and heart failure.

Contemporary management of AF has moved towards a more holistic or integrated care approach to AF management, summed up as the ABC (Atrial fibrillation Better Care) pathway: A/Avoid stroke with Anticoagulation; B/ Better symptom control with patient-centred symptom-directed decisions on rate or rhythm control; and C/Cardiovascular risk and comorbidity management, including lifestyle changes. Adherence to the ABC pathway is associated with a profound reduction in death, hospitalisation, stroke and bleeding in AF patents [Fgure].

In summary, increased awareness, diagnosis and proactive management of detected hypertension is crucial in patients with AF. Optimised blood pressure control is an essential component of such a holistic approach to AF care.
S-12-7: THE RENIN ANGIOTENSIN SYSTEM IN BASIC AND CLINICAL RESEARCH
Authors: Unger Thomas
Published: January 2023

The renin-angiotensin-system (RAS) is one of the oldest known hormonal systems preserved in multiple species over millions of years. A key enzyme of the system, renin, was discovered in 1898, and ever since a huge body of research has continuously revealed physiological and pathophysiological features of the RAS. Classically, these include, via the so-called angiotensin AT1 receptor, powerful vasoconstriction, regulation of the body fluid balance by inducing thirst, stimulation of aldosterone release from the adrenal cortex, renal salt retention, stimulation of the sympathetic nervous system and, more recently discovered, pro-fibrotic and pro-inflammatory effects. Pathophysiological actions of the RAS, with its extension to those of aldosterone (RAAS), include the induction of arterial hypertension, cardiac and vascular hypertrophy, lung and renal fibrosis, vascular atherosclerosis, perivascular fibrosis or chronic inflammation and others.

Attempts to inhibit the RAS in hypertension and other cardiovascular diseases first led to the clinical introduction of ACE-inhibitors some forty years ago, followed by selective antagonists of the AT1 receptor, the sartans. After a multitude of evidence-generating trials and global success in clinical practice, both approaches are now firmly established in the therapy of hypertension as well as cardio-metabolic and renal diseases. More recently, research has focused on the so-called protective arm of the RAS, mediated by stimulation of the angiotensin AT2 receptor by or by the Mas receptor stimulated by the angiotensin 1–7 peptide. Activation of these systems has exhibited beneficial effects in numerous preclinical studies via opposing AT1-mediated actions and beyond. Other degradation peptides of the angiotensin precursor, angiotensinogen, may also exhibit protective effects via these receptors. Agonists for the AT2 receptor as well as for the ACE2-Mas system have been developed and are currently under clinical evaluation.

It remains to be seen whether the pharmacological stimulation of the protective arm of the RAS will become an effective clinical tool in various cardiovascular and metabolic indications. Theoretically, it would make sense not only to block the harmful RAS but, at the same time, also stimulate the beneficial actions of the system.
S-13-4: INHIBITORY IMPACTS OF CHLOROGENIC ACID ON ADRENAL CATECHOLAMINE SECRETION
Authors: Lim Dong Yoon , Koh Young Youp
Published: January 2023

(Objective) Chlorogenic acid (CGA) is one of the most available phenolic acid compounds in foods, such as coffee and tea. Thus, the present study was aimed to determine the characteristics of CGA on secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to validify its mechanism of action. (Design and Methods) The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. (Results) CGA (30∼300 μM), administered into an adrenal vein for 90 min, reduced ACh-induced CA secretion in a dose- and time-dependent manner. CGA also time-dependently depressed the CA secretion induced by McN-A-343 (a selective muscarinic M1 receptor agonist), DMPP (a selective neuronal nicotinic receptor agonist), and angiotensin II. CGA itself failed to influence spontaneous CA secretion. Also, During the perfusion of CGA for 90 min, the CA secretory responses induced by high K+ (56 mM, a direct membrane depolarizer), veratridine (a voltage-dependent Na+ channel activator, cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator were suppressed. However, in the simultaneous presence of CGA and L-NAME (an inhibitor of NO synthase), the CA secretory responses induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the control level compared to those of the inhibitory effects of CGA-treatment alone. Virtually, the adrenal NO release was significantly enhanced by CGA-treatment. Also, in the coexistence of CGA and olmesartan, ACh-induced CA secretion was markedly reduced compared to that of olmesartan-treatment alone. (Conclusion) Taken together, we present the first evidence that CGA suppresses the CA secretion induced by activation of cholinergic receptors as well as AT1-receptors. This CGA-induced inhibitory effect seems to be exerted by reducing both the influx of Na+ and Ca2+ through their ionic channels into the adrenomedullary chromaffin cells as well as by suppressing the Ca2+ release from the cytoplasmic calcium store, at least through the elevated NO release by the activation of NO synthase, which is associated to the blockade of neuronal cholinergic receptors and AT1-receptors. Based on these results, the ingestion of CGA may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of adrenal CA secretion and consequent decreased CA level in the circulation. Co-administration of CGA and Olmesartan (ARB) may be clinically beneficial for treatment of cardiovascular diseases, including hypertension and angina pectoris.
S-16-1: RESISTANT HYPERTENISION: CLINICAL CHARACTERISTICS AND BLOOD PRESSURE CONTROL
Authors: Carcel Cheryl , Neal Bruce , Rogers Kris , Oparil Suzanne , Narkiewicz Krzysztof , Wang Jiguang , Schiffrin Ernesto L. , Azizi Michel , Poulter Neil , Chalmers John
Published: January 2023

Objectives:

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

Methods:

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

Results:

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

Conclusion:

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

Objective:

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

Design and methods:

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

Results:

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

Conclusions:

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

Uric acid (UA) is the final product of purine metabolism and its increase in the circulating blood defines the presence of hyperuricaemia commonly considered as a concentration of uric acid in serum above the threshold level of 7 mg/dL (416 mol/L) in men and > 6 mg/dL in women. The typical consequence of elevated UA levels is the development of gout, a condition affecting 2–3% of the general population but beside the effects on gout, the elevated levels of UA have been associated with a significant increase in the risk of hypertension, metabolic syndrome, and cardiovascular disease (CVD) regardless of the presence of serum urate deposition. All this evidence clearly supports a primary cardiovascular role for elevated serum UA probably based on multiple and interactive mechanisms of action not necessarily involving the articular and tissue deposition.

The interaction between elevated UA and cardiovascular diseases has been extensively investigated in the last 10 years providing interesting results in terms of patients identification, threshold of risk, pathophysiology, results of clinical trials and effects of drugs not primary involved in the management of uric acid levels. In particular, the evidence supports an increase of CV mortality and morbidity in patients with levels of SUA between 4.5 and 5.5 that are common in a large proportion of subjects and patients with overt cardiovascular diseases. This observation along with the differences in the mechanism leading to elevated UA (hyperproduction vs. underexcretion) will allow a more functional identification of patients suitable for pharmacological treatment with urate lowering drugs (ULT). Furthermore, the dynamic analysis of time-dependent trajectories of UA levels is a new approach to the interpretation and clinical management of cardiovascular disease. The overall representativity of a pattern of modification seems to better define the prognostic role of elevated UA and could be probably improved by an integrated interpretation of the different patterns beyond the role of risk cards and algorithms. Very recently, the management of elevated UA has also included the effects of non-ULT drugs as Losartan, SGLT-2 inhibitors, vericiguat whose administration in randomized clinical trials has improved uric acid levels with a linear proportion with the amount of UA reduction.

The interaction between hyperuricemia and CVD is a very dynamic issue that has been recently enriched with several additional information that have allowed a more effective identification of those subsets of patients that can successfully treated in daily clinical practice
S-17-2: CLUSTER ANALYSIS OF DIABETES AND HYPERTENSION
Authors: Shimabukuro Michio
Published: January 2023

Diabetes mellitus is classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) according to etiology. T1DM occurs due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency, whereas T2DM occurs due to a heterogenous combination of a relative insulin deficiency and insulin resistance. A data-driven cluster analysis reported five exclusive subgroups for diabetes: cluster 1 (severe autoimmune diabetes [SAID]), cluster 2 (severe insulin-deficient diabetes [SIDD]), cluster 3 (severe insulin-resistant diabetes [SIRD]), cluster 4 (mild obesity-related diabetes [MOD]), and cluster 5 (mild age-related diabetes [MARD]) (Ahlqvist et al, 2018). The subgroups have an advantage over the other classification because it uses simple but pathophysiologically feasible factors and is proven to apply to ethnic and racial differences to estimate diabetic complications (Diabetes Res Clin Pract 2021:180;109067). The SIRD cluster shows obesity and moderate to severe insulin resistance with hyperinsulinemia. Under severe metabolic deterioration based on insulin resistance through ectopic fat accumulation, individuals with SIRD are at high risk of developing atherosclerotic cardiovascular disease (ASCVD). SIRD confers the highest risk of developing diabetic kidney disease (DKD), commonly in Caucasians [Ahlqvist et al., 2018)] and non-Caucasians [Tanabe, 2020]. I will discuss the possible connection between cluster-derived diabetes subgroups and hypertension-associated complications.
S-17-4: EFFECTIVENESS OF STATIN INTENSIVE THERAPY IN TYPE 2 DIABETES WITH HIGH VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY
Authors: Ikeda Shota , Shinohara Keisuke , Enzan Nobuyuki , Matsushima Shouji , Tohyama Takeshi , Funakoshi Kouta , Kishimoto Junji , Itoh Hiroshi , Komuro Issei , Tsutsui Hiroyuki
Published: January 2023

Objective:

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

Design and method:

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

Results:

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

Conclusion:

Statin intensive therapy targeting LDL-C < 70 mg/dL had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit to visit SBP variability. Stratification based on visit-to-visit SBP variability might be a novel and useful strategy to determine the target LDL-C levels in statin lipid-lowering therapy among T2DM patients with microvascular complications.
S-19-2: EXTRACELLULAR VESICLES: BIOMARKERS AND BEYOND
Authors: Burger Dylan
Published: January 2023

Extracellular vesicles (EVs) are small membrane-enclosed particles that are released by cells into the extracellular environment. They are increasingly recognized as key participants in intercellular signaling where they may either promote or prevent vascular injury depending on the context. Moreover, as their molecular composition is reflective of their cell/tissue of origin, they are increasingly employed as biomarkers of vascular injury. This presentation will discuss key work from our laboratory and others focused on EVs in hypertension and related cardiovascular diseases such as diabetes.
S-20-3: PLASMA ATRIAL AND BRAIN NATRIURETIC PEPTIDES LEVELS AND THE RISK OF INCIDENT ATRIAL FIBRILLATION: THE SUITA STUDY
Authors: Kokubo Yoshihiro , Kashima Rena , Teramoto Masayuki , Arafa Ahmed , Shimamoto Keiko , Gao Qi , Higashiyama Aya , Kohmo Kyoko Honda , Watanabe Makoto , Dohi Tomoharu , Matsumoto Chisa , Kusano Kengo
Published: January 2023

Background:

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

Objectives:

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

Methods:

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

Results:

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

Conclusions:

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

Objective:

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

Design and method:

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

Results:

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

Conclusions:

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

Background:

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

Aim:

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

Methods:

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

Results:

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

Conclusions:

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

Introduction:

Cardiovascular disease (CVD) in the Philippines showed hypertension as the highest (38.6%), followed by stroke (30%), coronary artery disease (17.5 %), heart failure (10.4%). Risk factor were: diabetes at 3.9%, dyslipidemia at 72%, smoking at 31%, obesity at 4.9% (BMI). Latest hypertension prevalence is 37%. Aware hypertensives were 19%, unaware was 18%. Treatment rate was 68%, compliance was 86%, blood pressure (BP) control rate was 37%. Mortality from CVD were stroke, mostly infarct (22.6%), MI (6.5%), Heart Failure (6.5%). Drugs used were angiotensin receptor blockers (64%), calcium channel blockers (42%), beta-blockers (6%), ACE inhibitors (4%) and diuretics (1%).

Current status of home BP monitoring (HBPM): HBPM is performed by 23% of hypertensive population in the Philippine. Barriers to its use include cost, availability and lack of trust regarding the accuracy of digital BP devices. Currently, physicians encourage patients to monitor BP at home to better assess their treatment to rule out white coat, masked hypertension and other parameters.

Philippine sub-analysis of AsiaBP@Home study: Data on HBPM offer solution to problems encountered particularly in Asia. Based on AsiaBP@Home study as a multi-national Asian specialty center performance regarding home and clinic BP control, majority of uncontrolled hypertension simulated by the new lower ACC/AHA guideline threshold gave additional 18% increase in sustained uncontrolled hypertension (SUCH) and to additional 5% increase in white-coat uncontrolled hypertension (WUCH). In a sub-group analysis of the Philippines in this study (Fig.1), using conventional threshold values, well-controlled clinic SBP was only 69% and well controlled morning home SBP was 79%. Using the new threshold levels, the well-controlled clinic SBP decreased to 43% and well controlled morning home SBP was lower at 67%. Comparing the conventional to the new thresholds, controlled hypertension decreased from 62% to 37%, masked morning hypertension decreased from 8% to 6%, Sustained hypertension increased from 13% to 27%, and white-coat hypertension increased from 18% to 31%.

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

Aim:

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

Study methods:

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

Results:

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

Conclusion:

Community screening MMM programmes help identify the prevalence of hypertension especially also help to identify those at high cardiometabolic risk. More emphasis should be given to monitoring those in high cardiometabolic risk categories and older age groups./.
S-39-2: EFFECTS OF RAS INHIBITORS ON TISSUE ACE2 EXPRESSION IN ANIMAL MODELS
Authors: Kai Hisashi , Kai Mamiko
Published: January 2023

Angiotensin-converting enzyme 2 (ACE2) protects against organ damages by overactivated renin-angiotensin system (RAS). Also, ACE2 exerts a role as the receptors for SARS-CoV-2 to enter host target cells. Based on limited number of articles reporting that RAS inhibitors induced upregulation of cardiac or renal ACE2 in animal models, concern have arisen that RAS inhibitors may aggravate SARS-CoV-2 infection and COVID-19 severity. Therefore, we performed a comprehensive review by applying the standard searching strategy for systematic reviews to investigate the effects of RAS inhibitors on cardiac, vascular, renal and pulmonary mRNA/protein ACE2 expression in healthy animals and disease animal models. We identified 88 eligible articles including 167 experiments. In RAS inhibitors-treated healthy animals, only 3 (heart 2, kidneys 1) of 37 experiments showed ACE2 expression greater than twice of the control (overexpression) whereas others showed no/marginal change in the heart, arteries, kidneys, lungs, and other organs. Among 102 disease models (130 experiments), baseline ACE2 was overexpressed in 16 models (18 experiments), less than half the control level (repression) in 28 models (40 experiments) and remained no/marginal change in 51 models (74 experiments). RAS inhibitors induced ACE2 overexpression from no/marginal change levels in only 7 experiments, 4 (myocardial infarction 2, heart failure 1, diabetic nephropathy 1) of which were not supported by other experiments under similar conditions. In 36 experiments, RAS inhibitors reversed or prevented disease-induced repression, yielding no/marginal change. Thus, ACE2 overexpression is a rare consequence of RAS inhibitors treatment in healthy animals and disease models. Future studies should clarify the pathophysiological significance of reversal or prevention of ACE2 repression induced by RAS inhibitors in disease models.
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.