bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-R01-9: THE PERILS OF GRAPEFRUIT: A POTENTIALLY LETHAL INTERACTION WITH VERAPAMIL
Authors: de Leon-Durango Ricardo , Hernandez-Lazaro Alba , Rios-Gomez Carlos , Santana-Ojeda Borja , Kuzior Agnieszka , Perez-Rivero Jennifer Maria , Arnas-Leon Claudia , Acosta-Calero Carmen , Gonzalez-Diaz Paula , Tocino-Hernandez Alba Lucía , Martin-Perez Marta , Martinez-Martin Francisco Javier
Published: January 2023

Objective:

Hereby we describe a case of severe toxicity induced by a standard dose of slow-release verapamil

Design and Methods:

Review of the patient's records and of the relevant literature.

Results (Case Description):

A 57-year old woman had been diagnosed with hypertension by her family physician, but her management had been complicated with intolerance to multiple antihypertensive drugs. On the occasion of a family conflict, she developed a hypertensive crisis, with a holocranial headache, tremor and palpitations, but no symptoms of ischemia on the EKG. After discharge from the Emergency Room she was referred to our Outpatient Hypertension Clinic in order to rule out secondary hypertension. For the workup, and in order to avoid interference with the renin-angiotensin-aldosterone system she was switched to slow-release verapamil 120 mg twice a day. One month afterwards the workup was completed: primary aldosteronism, pheochromocytoma/paraganglioma, renovascular hypertension and Cushing's syndrome had been ruled out. Her BP was adequately controlled with verapamil, with ABPM confirmation, and her tolerance was good. Considering her multiple drug intolerances, we decided to keep her on verapamil. Four months afterwards, the patient was brought back to the Emergency Room with severe hypotension and bradycardia, extreme asthenia, generalized rubor and diaphoresis, with normal lab tests except for mild creatinine elevation in the context of dehydration. Her SBP was 74 mmHg, with DBP not measurable, and HR 39 lpm; the EKG showed Wenckebach 2:1 AV block. After 48 hr in the Emergency Room with saline infusion and basic support measures the patient was discharged and referred again to our Clinic for reevaluation. A verapamil overdose was suspected, but the patient was adamant that she had always taken verapamil exactly as prescribed. A detailed anamnesis revealed that the patient had put on some weight the previous month and decided to lose it with a novelty diet based on the intake of about 2 liters of grapefruit fruit daily plus protein. She was switched to indapamide 2.5 mg daily with good tolerance and adequate BP control.

Conclusions:

Grapefruit juice contains 6’-7’dihydrohybergamottin, a powerful inhibitor of the key drug metabolizing enzyme CYP3A4, potentially causing accumulation of many common drugs such as verapamil, statins, ticagrelor, sildenafil, amiodarone or cisapride, and related toxicity. We need to remember that prescription drugs do not only interact among themselves but also with herbal remedies and common foodstuffs such as grapefruit.
PS-R02-1: THE HIDDEN HAND BEHIND AN AORTIC DISSECTION CASE
Authors: Li Xiangdong , Wang Zhiyuan , Yang Ping
Published: January 2023

According to the data of WHO, more than 1.1 billion people worldwide suffer from hypertension, which leads to complications such as aortic dissection, acute myocardial infarction, and heart failure seriously threaten human health. Previously, we believed that primary hypertension accounted for 80%-90% of all hypertension, but with the gradual increase in understanding and improvement of detection methods, the understanding of secondary hypertension factors is becoming clearer. Among the secondary hypertension, primary aldosteronism is receiving more and more attention. It is thought that the actual prevalence of primary aldosteronism may account for 30%-50% of hypertension. The dangers of primary aldosteronism are not only in the damage to target organs from blood pressure, but the damage to organs from elevated aldosterone appears much earlier. Early recognition of primary aldosteronism is important to reduce the emergence of complications. We report a case of a patient with aortic dissection with a previous history of thirty years of hypertension, regular medication and stable blood pressure control, who, after a sudden aortic dissection, had laboratory tests suggesting intractable hypokalemia and poor results with potassium supplementation. We further examined aldosterone and renin levels and found that renin levels were significantly lower, with an aldosterone/renin ratio of 72 (reference value: 0–38). Although the patient was not able to standardize medications at the time of examination due to his condition, the ARB, CCB and hydrochlorothiazide medications the patient was on were all elevated for renin. In this case, renin levels remained low and we have reason to believe that the patient could be diagnosed with primary aldosteronism. With this history, we recognize that screening for secondary hypertension is far from adequate, and some scholars believe that less than 1% of hypertensive patients worldwide are currently screened for secondary factors. We believe that screening for secondary hypertensive factors should be performed in all patients with aortic dissection, even whenever there is combined target organ damage in hypertensive patients, regardless of blood pressure values.
PS-R02-10: SYNCOPE ASSOCIATED WITH PAROXYSMAL ATRIAL FIBRILLATION AND ITS TREATMENT WITH CRYOABLATION
Authors: Ulusan Sebahat , Kuyumcu Mevlut Serdar
Published: January 2023

Aims:

The main objective to present this case is creating awareness about syncope attacks and cryoablation procedure.

Case report:

A 60-year-old female patient was admitted to the cardiology department of Suleyman Demirel University Research and Education Hospital from an external center with the complaint of syncope attacks. The patient stated that she fainted with loss of consciousness while working. Patient was diagnosed before with hypertension and is being under treatment with 5 mg of ramipril (1x1). Patient was examined with echocardiography and electrocardiogram, after evaluating results, pathology was not founded. Ejection fraction (EF) %60, mitral regurgitation and tricuspid regurgitation were minimum, pulmonary artery pressure was 28 mmHg. For further examination, rhythm Holter and tension Holter were preferred. As results of tension holter, tension was regular and there was no hypotension. As results of rhythm holter, multiple paroxysmal atrial fibrillation attacks with the longest 5.3 pause was observed. Average heart rate was 55 beats per minute, for this reason beta blockers werent chosen as a treatment. Patient was recommend to undergo cryoablation procedure. Cryoablation procedure was performed with Medtronic The Arctic Front Advance through femoral vein. Afterwards, a transeptal passage was made from the right atrium to the left atrium with a Brockenbrough needle. Four pulmonary veins in order of left lower, left upper, right lower, right upper were isolated from extra focuses electrophysiologically without complication. The patient was called for monthly checkups and prescribed with edoksaban tosilat. After checkups, syncope attacks and palpitations were not founded. In three month checkup, the patient was examined with rhythm Holter, pause and paroxysmal atrial fibrillation were not observed.

Results:

Syncope is a sudden consciousness with a loss of postural tone which caused by pathologies. Epidemiology and prognosis of syncope is various in general population. Syncope can be caused by neurological diseases or cardiovascular problems. Since syncope attacks occur as a symptom of many diseases, they ought to be investigated gradually. Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope. However, in our case, there were pauses due to atrial fibrillation with a slow ventricular response, and syncope probably developed due to this phenomenon. Therefore, ablation was a curative treatment in our patient. As a conclusion further studies are needed to figure out the relationship between syncope and cardivascular diseases.
PS-R02-11: CORONARY ARTERY ANEURYSM IN ADULT: KAWASAKI DISEASE?
Authors: Ulusan Sebahat , Kuyumcu Mevlut Serdar
Published: January 2023

Aims:

The main objective to present this case is creating awareness about Kawasaki Disease and the post- disease conditions such as aneurysm.

Case report:

A 62-year-old male patient was admitted to the cardiology department of Suleyman Demirel University Research and Education Hospital with the complaint of stable angina pectoris (Class 2, New York Heart Association Functional Classification). Patient was diagnosed before with diabetes mellitus, hyperlipidemia, atopic dermatitis, xerosis cutis and paroxysmal atrial fibrillation. Pateint was examined with effort test and after results of the effort test, patient was recommended to undergo coronary angiography to check up conditions of the coronary arteries. Coronary angiography of the selective left radial artery was performed with JL 3.5 and JR 4 catheters. Diffuse ectasia, coronary slow flow was observed in the coronary arteries. After looking and evaluating the coronary angiography results, patient was questioned about Kawasaki Disease. When we peruse the history of the patient, high fever disease was detected. This condition of the coronary arteries was explained and maximal medical treatment with beta blocker, ranolazine, statin and edoksaban tosilat was prescripted.

Results:

Kawasaki disease is an acute vasculitis disease that mostly affects infants and children. Coronary artery aneurysms occur in the majority of cases. Pediatricians and cardiologists should keep in their mind that this condition is significant and ought to be recognized. Further studies are needed to detect children with Kawasaki disease.
PS-BPB01-3: ANGIOTENSIN (1–7)-MEDIATED PREVENTIVE EFFECT OF ANGIOTENSIN II TYPE 1 RECEPTOR ANTAGONISTS ON ABDOMINAL AORTIC ANEURYSM PROGRESSION IN OPG-KO MICE
Authors: Karasaki Kohei , Kokubo Hiroki , Ishida Mari , Sakai Chiemi , Yoshizumi Masao
Published: January 2023

Objective:

Hypertension is one of the major risk factors for onset of abdominal aortic aneurysm (AAA), which is a local enlargement of the abdominal aorta. Therefore, anti-hypertensive drugs, including angiotensin (Ang) II type 1 receptor blocker (ARB), have been expected to limit AAA growth. However, the efficacy of ARB against AAA in clinical settings is controversial. In the present study, we attempted to elucidate a mechanism by which ARB inhibits AAA progression.

Design and method:

To examine the effect of ARB against AAA progression, olmesartan (20 mg/kg/day) was administered orally to male wild-type mice and osteoprotegerin (Opg)-knockout (KO) mice, from two weeks before the AAA induction by using a CaCl2 application on the abdominal aortae to the sacrifice date. Since Opg could bind to tumor necrosis factor-related apoptosis-inducing ligand (Trail) for inhibiting its activity, deficiency of the Opg gene has been reported to induce overactivation of the Trail induced-c-Jun N-terminal kinase (Jnk)/matrix metalloproteinase 9 (Mmp9) pathway in CaCl2-induced mouse AAA model, resulting in serious AAA progression. Here, we tested whether olmesartan could prevent AAA progression associated with Trail/Jnk/Mmp9 pathway.

Results:

We found that olmesartan prevented excessive aortic enlargement and serious degenerative change of the aortic tissue in Opg-KO mice at six weeks after AAA induction, but not affected AAA formation in wild-type mice. In Opg-KO mice, olmesartan reduced co-localized expression of phosphorylated Jnk and Mmp9 in the tunica media. Then, we tested whether Ang (1–7), the blood level of which is increased by ARB administration, is associated with the preventive effect of olmesartan, because Ang (1–7) had been reported to reduce the Jnk phosphorylation. Consistent with previous studies, olmesartan increased serum level of Ang (1–7) in our AAA model. In vascular smooth muscle cells, Ang (1–7) inhibited the phosphorylation of Jnk and the increase of downstream Mmp9 mRNA expression induced by Trail. Furthermore, administration of an Ang (1–7) antagonist, A779, to Opg-KO mice diminished the preventive effect of ARB against the AAA progression. Notably, olmesartan slightly lowered blood pressure in Opg-KO mice, while A779 did not affect the blood pressure-lowering effect of olmesartan.

Conclusions:

Our results indicate that ARB prevents the AAA progression in Opg-KO mice via the inhibition of Trail-induced Jnk-Mmp9 pathway. Furthermore, it is suggested that the increase of Ang (1–7) may play a key role in the preventive effect of ARB on the AAA progression.
PS-BPB01-7: ANGIOTENSIN II INDUCES AORTIC RUPTURE AND DISSECTION IN OSTEOPROTEGERIN-DEFICIENT MICE
Authors: Tsuruda Toshihiro , Yamashita Atsushi , Otsu Misa , Koide Masanori , Nakamichi Yuko , Hatakeyama Yoko Sekita , Hatakeyama Kinta , Funamoto Taro , Chosa Etsuo , Asada Yujiro , Udagawa Nobuyuki , Kato Johji , Kitamura Kazuo
Published: January 2023

Background:

The biological mechanism of action for osteoprotegerin (OPG), a soluble decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANKL) in the vascular structure, has not been elucidated. The study aim was to determine if OPG affects aortic structural integrity in angiotensin II-induced hypertension.

Methods and Results:

Mortality was higher (P < 0.0001 by Log-rank test) in 8-week-old male homozygotes of OPG gene knockout (OPG
-/-
mice given subcutaneous administration of angiotensin II (1,000 ng/kg/min) for 28 days, with an incidence of 21% fatal aortic rupture (Chi-square, 8.024, P = 0.005), and 23% aortic dissection (Chi-square, 4.285, P = 0.038), than in age-matched wild type mice. The absence of OPG was associated with decreased medial and adventitial thickness and increased numbers of elastin breaks as well as with 2.5-fold increased periostin expression and soluble RANKL concentrations. PEGylated human recombinant OPG administration decreased all-causes mortality (-22%, P < 0.001 by Log-rank test), the incidence of fatal aortic rupture (-13%, P = 0.08), and aortic dissection (-23%, P < 0.001) with decreasing numbers of elastin breaks (P = 0.0539) at the supra-renal aorta, periostin expressions (P = 0.0011), and soluble RANKL concentrations (P = 0.0012) in angiotensin II-infused OPG-/- mice.

Conclusions:

These data suggest that OPG protects against aortic rupture and dissection in Ang II-induced hypertension by inhibiting RANKL activity and periostin expression.
PS-BPB02-6: THE ROLE OF VEGFA G634C GENE POLYMORPHISM IN PREDICTING ADVERSE EVENTS DEVELOPMENT IN PATIENTS WITH ESSENTIAL HYPERTENSION AFTER STEMI
Authors: Kutia Inna , Rodionova Julia , Kopytsya Mikola , Shelest Boris
Published: January 2023

The aim was to study the role of the polymorphism of the vascular endothelial growth factor A (VEGF A) gene (rs 2010963) in prognosis of adverse events in hypertensive patients with ST elevation myocardial infarction (STEMI) within 12 months

Design and method:

135 patients with STEMI were enrolled into the study, 109 (80.7%) male and 26 (19.3%) female, with an average age of 59.21 ± 8.92 years. The blood flow was restored at the level of TIMI III in patients included in the study. The VEGF A concentration was measured by the ELISA. The allelic polymorphism of the G634C of the VEGF A gene (2010963) was performed by a real time polymerase chain reaction (PCR) method. Blood examination was done on 7 days and 12 months after the STEMI.

Results:

The baseline levels of VEGF A was significantly higher 314.01 [159.94:627.66] pg/ml in patients with the GG genotype compared with those who had the GC genotype 221.28 [77.58–440.82] pg/ml, p = 0.045. After 12 months the level of VEGF A significantly increased from 221.28 [77.58:440.82]pg/ml to 424.56 [230.60–556.93] pg/ml (p = 0.0018) in patients with the GC group of polymorphic variant of the G634C gene. The peptide increased also in the patients with the GG gene but it was not significant. After one year examination, there were significant reduction in the level of systolic blood pressure (SBP) (p = 0.015) and diastolic blood pressure (DBP), (p = 0.031) in the patients with the genotype GC, at the same time in those with the GG genotype this reduction was also signidficant; p = 0.039 and p = 0.033 respectively.

Conclusion:

The STEMI patients with GC genotype are predisposed for the better prognosis compared to the GG genotype in the one year follow up period.
PS-BPB06-5: URINARY CELL TRANSCRIPTOMICS: A NON-INVASIVE EXPRESSION READOUT OF KIDNEY GENES OF RELEVANCE TO HYPERTENSION
Authors: Eales James M , Bogdanski Pawel , Wystrychowski Wojciech , Szczechowska Ewa Zukowska , Zywiec Joanna , Woolf Adrian S , Samani Nilesh J , Keavney Bernard , Charchar Fadi J , Tomaszewski Maciej
Published: January 2023

Objective:

Hypertension affects 35% of the global adult population and is the leading preventable risk factor for premature death globally. The kidney is the key organ of blood pressure regulation in the body. Here, we compare the gene expression profile from renal cells shed naturally into the urine and kidney tissue to determine if urine can provide a non-invasive readout of kidney gene expression and whether hypertension-associated genes can be quantified in urine.

Design and Method:

Urinary cell and kidney tissue samples were collected from 33 human participants and were both profiled by poly-A RNA-sequencing, generating an average of 30 million paired reads per sample. These were quantified using the standard Genotype Tissue Expression (GTEx) project pipeline and were compared against 43 different human tissues and other bodily fluids using transcriptomic correlation. RNA-sequencing quality metrics were calculated by RNA-SeQC software. Gene set overrepresentation analysis for Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) employed Fishers exact test. Enriched and enhanced kidney genes were collected from the Human Protein Atlas (HPA).

Results:

Our RNA-sequencing metric analysis revealed that urinary cells can generate robust data of comparable or superior quality to that of saliva at similar read coverage. The top one hundred most highly expressed urinary cell genes show an enrichment for biological themes shared with the renal transcriptome, including immunity (P = 1.2x10–7), glucose metabolism (P = 1.3x10–5) and renal mineral reabsorption (P = 9.8x10–4). In an analysis all protein-coding genes across 43 human tissues/cell-types, urinary cells showed the highest level of transcriptomic correlation with kidney cortex (r2 = 0.65) and kidney medulla (r2 = 0.64). This correlation between urinary cells and kidney tissue was particularly strong (r2 = 0.72) in an analysis restricted to highly specific kidney genes (including uromodulin and the Na-K-Cl cotransporter NKCC2 [loop diuretic target]). 98% (176 out of 179) of kidney genes with a known causal association to blood pressure were expressed in urinary cells. Their urinary expression demonstrated strong correlation with their abundance in kidney cortex (r2 = 0.68) and medulla (r2 = 0.64).

Conclusions:

Standard poly-A RNA-sequencing of cells harvested from urinary sediments produces robust gene expression profiles. These profiles provide a non-invasive insight into transcriptome of the kidney and permit measuring expression of kidney genes of relevance to BP regulation and hypertension.
PS-BPB08-1: ANGIOTENSIN II AT1A RECEPTORS IN THE PROXIMAL TUBULES PLAY A CRITICAL ROLE IN THE DEVELOPMENT OF TWO-KIDNEY, ONE-CLIP GOLDBLATT HYPERTENSION
Authors: Li Xiao Chun , Hassan Rumana , de Oliveira Leite Ana Paula , Dugas Courtney , Sato Akemi , Sato Ryosuke , Zhuo Jia Long
Published: January 2023

Objective:

It is well recognized that the activation of the renin-angiotensin system (RAS) in the clipped kidney plays a critical role in the development of two-kidney, one-clip Goldblatt hypertension (2K1C) in animal models, but the roles of intratubular angiotensin II (Ang II) AT1 (AT1a) receptors and its downstream target, Na+/H+ exchanger 3 (NHE3) in the proximal tubules have not been determined previously. In the present study, we tested the hypothesis that genetic deletion of AT1a receptors selectively in the proximal tubules of the kidney attenuates the development of 2K1C Goldblatt hypertension via AT1a receptor-mediated, Na+/H+ exchanger 3 (NHE3)-dependent mechanisms.

Design and Methods:

To test the hypothesis, 2K1C Goldblatt hypertension was induced by placing a silver clip, 0.12 mm internal diameter, on the left renal artery for 4 weeks in adult male and female wild-type (WT), global AT1areceptor knockout (Agtr1a-/-
), proximal tubule (PT)-specific Agtr1a-/-
(PT-Agtr1a-/-
), or PT-Nhe3-/-
mice, respectively.

Results:

Systolic blood pressure increased in a time-dependent manner reaching a maximal response by Week 2–3 in wild-type mice (Basal: 112 ± 2 vs. 2K1C: 149 ± 4 mmHg, n = 12, P < 0.01). 2K1C Goldblatt hypertension in WT mice was associated with significant increases in renin mRNA expression in the clipped kidney (Control: 2066 ± 255 vs. Clipped: 3144 ± 569 copies/ng RNA, P < 0.01), and decreases in renin mRNA expression in the nonclipped right kidney (1738 ± 341 copies/ng RNA, P < 0.05). Plasma Ang II levels were significantly increased in WT mice with 2K1C Goldblatt hypertension (Control: 50.2 ± 7.2 vs. 2K1C: 109.7 ± 17.2 pg/ml, P < 0.05). Glomerular and tubulointerstitial fibrotic responses were also significantly increased in the clipped kidney (P < 0.01). In contrast to WT mice, the development of 2K1C hypertension was completely attenuated in global Agtr1a-/-
(Basal: 88 ± 4 vs. 2K1C: 92 ± 2 mmHg, n = 9, n.s.), PT-Agtr1a-/-
mice (Basal: 101 ± 2 vs. 2K1C: 104 ± 4 mmHg, n = 12, n.s.), or PT-Nhe3-/-
mice (Basal: 103 ± 3 vs. 109 ± 5 mmHg, n.s.). Renin mRNA expression was not different in clipped and nonclipped kidney of Agtr1a-/-
mice, but it was decreased in the nonclipped kidney of PT-Agtr1a-/-
mice (P < 0.05).

Conclusions:

Taken together, our results suggest that the activation of intratubular RAS in the proximal tubules and increase of NHE3-mediated proximal tubular Na+ reabsorption play a key role in the development of 2K1C Goldblatt hypertension in mice.
PS-BPB08-4: IMPAIRED TCA CYCLE METABOLISM IN DIABETIC NEPHROPATHY IS LINKED TO ALBUMINURIA AND KIDNEY INJURY
Authors: Azushima Kengo , Kovalik Jean Paul , Yamaji Takahiro , Gurley Susan Bailey , Coffman Thomas Myron
Published: January 2023

Objective:

Recent work has highlighted potential contributions of impaired renal energy metabolism, including mitochondrial dysfunction and altered fatty acid metabolism, in chronic kidney diseases including diabetic nephropathy (DN). However, causal connections between specific metabolic abnormalities and pathophysiology of DN have been difficult to establish. Here, we approach this question using a mouse model recapitulating characteristic features of human DN and a targeted metabolomics platform designed to assess key metabolic pathways involving amino acids, fatty acids, glycolysis and the TCA cycle.

Design and method:

We generated a mouse model of DN with underlying activation of the renin-angiotensin system (RAS) by a renin transgene (R) driven by the albumin promoter on the Akita background of type I diabetes (A). We have shown that on a susceptible 129/Sv background, Akita-ReninTg (AR) mice exhibit cardinal characteristics of human DN including high-grade albuminuria and glomerulosclerosis, whereas AR mice on a C57BL/6 background do not develop DN. To assess the impact of genetic background on energy metabolism in DN, kidneys from 24-week-old male AR mice on both backgrounds were evaluated by the targeted metabolome analysis. To further distinguish the impact of RAS activation on relevant pathways associated with kidney disease development, 12-week-old male 129/Sv AR mice were treated with the angiotensin receptor blocker (ARB) losartan 10 mg/kg/day for 12 weeks. 24-hour urine samples were collected in metabolic cages and urine albumin levels were measured by EIA. Kidneys from age-matched parental 129/Sv and C57BL/6 wild-type mice were analyzed as controls.

Results:

A distinct metabolic profile was observed in kidneys of DN-susceptible 129/Sv AR mice including reduced levels of C2 acetyl-carnitine that reflect a deficiency in acetyl-CoA, perturbations of TCA cycle intermediates and increased lactate levels. In addition, levels of phosphorylated-AMPK were reduced. These metabolic changes were absent in DN-resistant C57BL/6 AR mice. Treatment of 129/Sv AR mice with the ARB dramatically reduced albuminuria (906 ± 169 vs 193 ± 42 μg/day, p < 0.01) and attenuated kidney pathology while restoring levels of C2 acetyl-carnitine, TCA intermediates, lactate and phosphorylated-AMPK toward normal. ARB treatment also increased kidney ATP content. In 129/Sv mice, there were statistically significant correlations between albuminuria and kidney levels of lactate, acetyl-carnitine, citrate and succinate.

Conclusions:

Thus, there is a distinct profile of impaired energy metabolism associated with DN susceptibility that is attenuated by RAS blockade. Impaired TCA cycle function and coincident increases in lactate are linked to albuminuria in mice with DN, and may contribute to kidney injury.
PS-BPB09-3: CIGARETTE SMOKE EXTRACT INDUCES DNA DAMAGE AND TRIGGERS AN INNATE IMMUNE RESPONSE
Authors: Ishida Mari , Ueda Keitaro , Sakai Chiemi , Kobayashi Yusuke , Yoshizumi Masao , Nakano Yukiko , Ishida Takafumi
Published: January 2023

Objective:

Elevated blood pressure and tobacco smoking are causes of preventable mortality. The effects of tobacco smoking on blood pressure are complex and chronic effects are inconsistent. We have previously reported increased DNA damage in peripheral mononuclear cells of smokers compared to nonsmokers. In this study, we investigated the effects of cigarette smoke extract (CSE) on DNA damage and the physiological influence of DNA damage in endothelial cells.

Design and method:

The effect of CSE extracted from tobacco smoke was examined in human umbilical vein endothelial cells (HUVECs). CSE was added to HUVECs and the formation of DNA damage was quantified by fluorescent immunostaining. The mRNA expression of inflammatory cytokines was quantified by real-time RT PCR.

Results:

CSE increased double-strand breaks in HUVEC by 72 hours. CSE also increased oxidative DNA damage both in the nucleus and mitochondria, and decreased mitochondria membrane potential. Mitochondrial dysfunction partially induced mitochondrial outer membrane permeabilization, resulting in the partial activation of caspase-3 and nuclear translocation of caspase-activated deoxyribonuclease, which fragments DNA in the nucleus. It was suggested that this is one of the mechanisms of nuclear DNA double-strand breaks. CSE induced the accumulation of nuclear and mitochondrial DNA in the cytosol. We further examined whether accumulated cytosolic DNA activated cytosolic DNA-sensing pathways. The production of cGAMP, a second messenger in cGAS (a DNA-sensing receptor) signaling, was increased by CSE, followed by nuclear translocation of NF-kB and increased mRNA expression of IL-6. The increase in IL-6 expression was suppressed by si-cGAS.

Conclusions:

Our study revealed that continuous exposure to CSE induces DNA damages not only in the nucleus but also in the mitochondria, which leads to cytosolic DNA accumulation, and evokes chronic inflammation via the cGAS pathway.
PS-BPC01-4: NONINVASIVE CONTINUOUS BLOOD PRESSURE MONITORING BASED ON WEARABLE RADAR SENSOR WITH PRELIMINARY CLINICAL VALIDATION
Authors: Liu Jiaqi , Wen Li , Dong Shuqin , Zhang Zhi , GU Changzhan , Mao Junfa
Published: January 2023

This paper proposes a novel sensing system for noninvasive and continuous estimation of blood pressure (BP), which is based on a custom designed wearable 120 GHz Doppler radar sensor. With radar signals detected from brachial artery at the elbow, the moving trajectory of the pulses can be accurately demodulated with micrometer accuracy, and thus the reflective pulse transit time(RPTT) can be obtained for the prediction model to estimate blood pressure. Clinical trials have been launched with invasive blood pressure as reference. Patients keep their arms straight with palms facing upward, and a transducer set for medical invasive blood pressure measurement called DTXPlus is set up. DTXPlus has one end connected to a monitor, and the other end connected to the arterial catheter that reaches the brachial artery. The blood pressure signals for reference standard are collected by a data acquisition card (DAQ) from the transmission wire between DTXPlus and monitor. Meanwhile, the 120 GHz radar sensor with concentrated energy and high frequency is used to obtain the pulse wave signals from the brachial artery at the elbow, which is almost the same place detected by both invasive and noninvasive methods. The radar sensor continuously transmits electromagnetic signals to the human body, and the throb of the artery modulates the electromagnetic waves in the phase and the backscattered signals return to the radar receiver. For comparison later, the radar outputs are acquired by the DAQ in synchronization with the blood pressure signals. Experiments were carried out in the operating room with permission, patients with cardiovascular diseases were tested for several minutes after operations. The experimental results show a great performance of the designed wearable radar sensor in the detection of weak pulse signatures. Compared to the ground truth of the invasive blood pressure, the estimated blood pressures by radar have mean errors below 3mmHg for most subjects. The results reveal the possibility for the proposed radar-based BP estimation technique to be employed inside and outside the clinic, such as applications in the vast internet-of-things (IoT) and in-home health monitoring.
PS-BPC03-1: DEVELOPMENT OF CUFFLESS AND CALIBRATION-LESS BLOOD PRESSURE MEASUREMENTS
Authors: Shimizu Kosuke
Published: January 2023

Objective:

The characteristics of dynamic short-term blood pressure variability caused by numerous triggers vary greatly among individuals. Wearable devices that continuously and noninvasively capture beat-by-beat blood pressure values are a necessity to further study blood pressure.

The development of cuffless blood pressure measurements, which, unlike sphygmomanometers, do not require pressurization and depressurization time, has attracted much attention in recent years for its potential to capture beat-by-beat blood pressure values. However, cuffless blood pressure measurements approved in Europe and the United States require calibration before use. This indicates that the function is limited to estimation of blood pressure variation from the time of calibration.

In this study, we conducted a measurement test aiming at the practical application of the cuffless and calibration-less blood pressure measurements.

Design and Method:

In this study, we recruited adults aged 20 years and older to evaluate whether a wearable device without pre-calibration could meet the standards of BHS, ESH, ISO81060–2:2018 and IEEE1708a-2019 and ensure the same accuracy as existing sphygmomanometers.

For each measurement test, the cuff was wrapped around the subject's upper left arm and a wearable device was attached to the ipsilateral wrist, and the subject was asked to maintain a sitting posture. Measurements were taken with the reference sphygmomanometer every 3 minutes for 7 times. To minimize the effect of the venous congestion on the measurements, the measurement period with the wearable device was from 30 seconds after the completion of the cuff depressurization until the start of the next pressurization. The blood pressure value measured by the wearable device was evaluated against the average of the values measured by the reference sphygmomanometer before and after.

Results:

219 participants were included in the analysis. Participants with systolic blood pressure values ranging from 80 to 204 and diastolic blood pressure values ranging from 46 to 140 were included. The mean and SD of the differences between the estimates and the reference were -1.27 ± 4.97 mmHg for SBP and 0.74 ± 2.55 mmHg for DBP.

Conclusion:

The overall accuracy of the cuffless and calibration-less blood pressure measurements device satisfied the criteria shown in ISO81060–2 against various adults in the sitting posture. This study showed the strong potential of the cuffless and calibration-less blood pressure measurements.
PS-BPC04-1: CHARACTERISTICS OF MONTH-BY-MONTH BLOOD PRESSURE VARIABILITY IN HEMODIALYSIS PATIENTS
Authors: Amari Yoshifumi , Morimoto Satoshi , Okuda Hidenobu , Bokuda Kanako , Oyama Yasuo , Yurugi Takatomi , Nakajima Fumitaka , Ichihara Atsuhiro
Published: January 2023

Objectives:

It is well known that blood pressure (BP) exhibits BP variation in patients with hemodialysis (HD). We have previously reported that high visit-to-visit blood pressure variability is independently correlated with cardiovascular mortality in maintenance HD patients. However, the characteristics of long-term BP variability remains to be elucidated in these patients. The present study, therefore aimed to investigate the characteristics of month-by-month blood pressure variability, as an indicator of long-term blood pressure variability, and the relationship between month-by-month blood pressure variability and cardiovascular mortality in these patients.

Design and method:

A total of 324 maintenance HD patients, who could be followed for 60 months, were recruited. We used variation independent of the mean (VIM), which was estimated using systolic BP (SBP) in pre-dialysis and post-dialysis at the beginning of the month in 12 consecutive months (pre-VIM-SBP and post-VIM-SBP), as an index of month-by-month BP variability. We also estimated the average of 12 values of differences between the highest and lowest SBP values during a dialysis session (average Δ SBP) and the difference between SBP in January and February and SBP in July and August (seasonal variability of SBP).

We investigated (1) the reproducibility of these values, (2) the relationship between these values and background factors, and (3) the association between these values and mortality.

Results:

(1) Pre-VIM-SBP and post-VIM-SBP showed significant reproducibility (intraclass correlation, 0.456 (P < 0.001) and 0.522 (P < 0.001), respectively]. Seasonal variability of pre-SBP and Δ SBP was observed both at beginning / after 12 months [5.0 (-5.0–19.0) / 5.3 ± 18.3, 7.2 ± 16.7 / 5.0 ± 12.8, respectively]. (2) Higher pre-VIM-SBP was associated with higher interdialytic weight gain and poor nutritional status. Higher post-VIM-SBP was associated with glucose intolerance, higher interdialytic weight gain and poor nutritional status. Higher Δ SBP was associated with glucose intolerance and higher interdialytic weight gain. (3) Higher post-VIM-SBP was associated with a higher rate of cardiovascular deaths independent of other factors (hazard ratio: 1.104, 95% confidence interval: 1.011–1.207, P = 0.028).

Conclusions:

Month-by-month blood pressure variability in HD patients is reproducible and associated with various background factors. Month-by-month blood pressure variability in post-dialysis SBP is independently correlated with cardiovascular mortality. Further studies are necessary to confirm the mechanism of increased month-by-month blood pressure variability and to clarify whether reducing month-by-month blood pressure variability will improve the prognosis for HD patients.
PS-BPC04-3: LOWER NOCTURNAL SYSTOLIC BLOOD PRESSURE IS ASSOCIATED WITH CARDIOVASCULAR MORTALITY IN HEART FAILURE WITH REDUCED EJECTION FRACTION PATENTS
Authors: Kim Andrew T , Ito Asahiro , Ito Ayaka , Hayashi Hiroya , Ogawa Mana , Kitada Ryoko , Ishikawa Sera , Iwata Shinichi , Izumiya Yasuhiro , Fukuda Daiju
Published: January 2023

Objective:

Blood pressure (BP) and its variability, especially nocturnal were associated with all-cause death and cardiovascular mortality in general population. However, little is known about the association between nocturnal BP variables (average value and variability) and cardiovascular mortality in patients with heart failure with reduced ejection fraction (HFrEF).

Design and method:

This study population consisted of 230 patients (mean age, 65 ± 13 years) who were admitted to our hospital due to HFrEF. Nocturnal BP was measured hourly using a home BP monitoring device, and its variability were expressed as the coefficient of variation of all readings.

Results:

During median follow-up period of 37 months, 19 (8%) patients had cardiovascular mortality. Compared with survivors, nocturnal systolic BP was significantly lower in cardiovascular mortality patients (125 ± 24 mmHg vs 110 ± 17 mmHg, p = 0.007). Univariate analysis showed that age, chronic kidney disease, nocturnal systolic and diastolic BP were associated with cardiovascular mortality. Cox proportional hazards models showed that nocturnal systolic BP was associated with cardiovascular mortality after adjustment for age and CKD (odds ratio: 0.97; 95% confidence interval: 0.94–0.99; P = 0.01), whereas nighttime diastolic BP and their variables (average value and variability) were not. Similarly, nocturnal systolic BP < 108 mmHg was predictive of cardiovascular mortality (odds ratio: 3.84; 95% confidence interval: 1.53–9.67; P = 0.004),

Conclusion:

Lower nocturnal systolic BP was associated with cardiovascular mortality in patients with HFrEF. Intervention for nocturnal systolic BP could avoid cardiovascular events and consequently reduce the risk of cardiovascular mortality.
PS-BPC05-2: ADMISSION AND DISCHARGE BLOOD PRESSURE INFLUENCE MEDICAL PRESCRIPTION AND CLINICAL OUTCOMES OF PATIENTS WITH DECOMPENSATED HEART FAILURE
Authors: Jo Sang Ho
Published: January 2023

Background:

There has been no study evaluating whether admission blood pressure (BP) influences medical treatment and clinical outcomes in acute decompensated heart failure patients.

Methods:

We analyzed the data form Korean Acute Heart Failure (KorHF) Registry. A total of 3,200 acute decompensated heart failure patients were included in the registry. We investigated the association of initial blood pressure at admission and clinical outcomes and prescription of ACEI, ARB and beta-bolcker(BB). The primary outcome was composite of mortality and readmission during 1-year after hospital discharge.

Results:

Admission systolic (SBP) and diastolic BP (DBP) increase was associated with decrease in primary outcomes (by 1mmHg increase of SBP, crude hazard ratio [HR] 0.9963, 95% CI: 0.9943–0.9982, p < 0.0001 and by 1mmHg increase of DBP, crude HR 0.99, 95% CI: 0.9867–0.9932, p < 0.0001). By multiple regression analysis DBP was an independent risk factors of mortality and re-hospitalization (HR 0.9927, 95% CI 0.9867–0.9988, p < 0.0196), but SBP was not. Age, history of heart failure, hypertension, cholesterol level and ACE/ARB use were also associated with primary outcomes. The cut-off value of SBP and DBP for increasing clinical outcomes were 118.5 mmHg (sensitivity 0.3965, specificity 0.6727) and 78.5mmHg (sensitivity 0.5682, specificity 0.5228), respectively by ROC curve. The SBP < 118.5 mmHg and DBP < 78.5mmHg were independent predictor for primary outcomes (adjusted HR 1.33, 95% CI 1.15–1.54, p < 0.0001 and adjusted HR 1.23, 95% CI 1.12–1.48, p = 0.0004, respectively).

The cut off SBP/ DBP value of not using in-hospital ACE/ARB/BB were 129.5/80.5mmHg. DBP of 80.5mmHg was an independent determinants of not prescribing the drugs (adjusted OR 0.755, 95% CI: 0.582–0.977, p = 0.0329). Both lower SBP (< 129.5) and DBP (< 80.5mmHg) combined with no use of the drugs were independent predictor of poor clinical outcomes at 1-year. (adjusted HR 1.677, 95% CI: 1.380–2.037, p < 0.0001 and adjusted HR 1.653, 95% CI: 1.355–2.017, P < 0.0001, respectively)

Conclusions:

Lower blood pressure at admission increase mortality, re-hospitalization at 1-year and decrease in-hospital prescription of ACE/ARB and BB in patients with acute decompensated heart failure. The cut-off value of SBP/DBP for primary outcome was 118.5/78.5 mmHg and that for use of ACE/ARB/BB was 129.5/80.5mmHg.
PS-BPC06-2: CLINICAL CHARACTERISTICS OF COMORBID HYPERTENSION AND CORONARY ARTERY DISEASE IN 10 YEARS: RESULTS FROM CHINA
Authors: Wang Chi , Liu Tongbo , Xue Hao
Published: January 2023

Background:

Little is known regarding the clinical profiles of patients with comorbid hypertension and coronary artery disease (HT-CAD) in China.

Methods:

The current study was conducted in a large-scale tertiary hospital that gathered nationwide patients of China. A total of 32,355 CAD patients with and without hypertension admitted from 5 August 2008 to 22 July 2018 were identified in this cross-sectional study. The demographic characteristics, diagnosis records, relevant examinations, treatment patterns, and in-hospital outcomes of patients were abstracted via electronic medical record database. We analyzed the overall comorbidity rate, blood pressure control, clinical characteristics and their temporal change of patients with HT-CAD in the current study.

Results:

The overall comorbidity rate of hypertension in patients with CAD was 64.12% (N = 20,747) and did not significantly change during 2008 to 2018. Female CAD patients and CAD patients in east coastal regions had significantly higher comorbidity rate of hypertension. Among patients with HT-CAD, the BP was controlled at < 140/90 mmHg in 52.39% and < 130/80 mmHg in 27.03%. The control rate of < 130/80 mmHg increased during 2008 to 2018, whereas the control rate of < 140/90 mmHg did not change significantly. Compared with the counterparts with nonHT-CAD, patients with HT-CAD had higher incidence of cardiovascular-related comorbidities, and most of these comorbidities showed an increasing trend over the study period.

Conclusions:

Hypertension is the most prevalent comorbidity in Chinese patients with CAD. Patients with HT-CAD have an increasing health burden and should be paid with special attention to improve their cardiovascular outcomes.
PS-BPC06-4: RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS VERSUS CALCIUM CHANNEL BLOCKERS IN ASSOCIATION WITH MORTALITY RATE IN COVID-19 HYPERTENSIVE PATIENTS: THE EFFECT OF AGE
Authors: Hassan Dina Ahmed , Elamin Maha Ismail , Bashir Intisar Abdelrahim , Mahmoud Tarig Elhadi
Published: January 2023

Objective:

To study the association of calcium channel blockers (CCBs), the renin-angiotensin-aldosterone system (RAAS) inhibitors or their combination as antihypertensive medications and the clinical outcome of COVID-19 infection.

Design and method:

This is a retrospective cohort study using de-identified data retrieved from clinical records of COVID-19 patients in two isolation centers. Medical history, demographic data, symptoms, complications and laboratory investigations were extracted from clinical records of 406 confirmed COVID-19 hospitalized patients between Feb 2020 and July 2021. Hypertension and antihypertensive treatments were confirmed by medical history and clinical records. Continuous variables were presented as means ± standard deviation (SD) while categorical variables were presented as percent proportions. Logistic regression was used to assess the impact of antihypertensive drugs (RAAS inhibitors, CCBs, combination of RAAS inhibitors and CCBs and those not receiving medication) on the prognosis of COVID-19 patients and to explore the risk factors associated with mortality.

Result:

Out of 406 hospitalized COVID-19 patients, 242 (59.6%) had a history of hypertension. Hypertensive patients under the age of 65 years and receiving RAAS inhibitors or the combination of both RAAS inhibitors and CCBs were at higher risk of mortality than those on CCBs only (odds ratio [OR]: 4.45, 95% confidence interval [CI]: 1.56–12.56, P = 0.005 and OR:3.57, CI: 1.03–12.36, P = 0.045 respectively). Antihypertensive medications did not seem to influence mortality rates among hypertensive patients above 65 years. Routine laboratory investigations were not significantly different between the subgroups receiving different antihypertensive medications regardless of age.

Cough was the only symptom associated with mortality among patients under 65 years (OR:2.34, CI:1.24–4.41, P = 0.009). Type II respiratory failure was significantly associated with death among hypertensives under 65 years (OR:5.43, CI:1.08–28.07, P = 0.044) whereas acute kidney injury and septic shocks are the common complications related to death among hypertensives above 65 years (OR:3.59, CI:1.54–8.36, P = 0.003 and OR:7.87, CI: 1.68–36.78, P = 0.009 respectively).

Conclusion:

Administration of CCBs may improve the outcome of COVID-19 hypertensive patients under 65 years of age. Antihypertensive treatment does not seem to influence the prognosis of COVID-19 patients above 65 years. Such results may affect management strategy of COVID-19 hypertensive patients. Type-II respiratory failure among patients under 65 years of age, acute kidney injury and septic shock among those above 65 years are the most serious complications that can lead to death regardless of blood pressure.
PS-BPC06-7: ASSOCIATION BETWEEN ISOLATED DIASTOLIC HYPERTENSION AND MICROALBUMINURIA AMONG KOREAN ADULTS
Authors: Moon Jenny , Lee Hokyou , Kim Hyeon Chang
Published: January 2023

Objective:

Microalbuminuria acts as a sensitive marker of early nephropathy development and increased cardiovascular risk. Studies have reported that isolated diastolic hypertension (IDH) has an age-dependent association with cardiovascular disease (CVD) risks. However, little is known regarding renal dysfunctions associated with IDH. Therefore, this cross-sectional study aimed to evaluate the age-stratified association between IDH and microalbuminuria.

Design and method:

A total of 13,818 adults, including 5,916 men and 7,897 women, from Korea National Health and Nutritional Examination Survey (KNHANES) between 2011–2014 were included. Participants were categorized as having IDH or no IDH according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline. Microalbuminuria was defined as a urinary albumin-to-creatinine ratio of 30 to 300 mg/g from single-spot morning urine sample in accordance with the International Diabetes Federation definition. The youngest age group was defined as 19–39 years. The association between IDH and microalbuminuria was evaluated using logistic regression analysis with adjustment for covariates.

Results:

The mean age of participants with IDH was 47 years, younger than those with no IDH. There was a two-fold higher proportion of women than men with no IDH, and a higher proportion of men with IDH. Prevalence of microalbuminuria was higher in IDH group compared to no IDH group. With no IDH as a reference, the odds ratio (OR) of IDH for microalbuminuria in total was 1.21 (95% CI: 1.14–1.68). IDH also had significant ORs for prevalence of microalbuminuria in both of the older age groups (OR: 1.57, 95% CI: 1.17 -2.13 at 40–59 years, OR: 1.17, 95% CI: 1.06–2.10 at age ≧ 60). However, opposite result was found in the youngest age group (OR: 1.35, 95% CI: 0.98–2.38).

Conclusion:

IDH was positively associated with prevalence of microalbuminuria among middle-aged Koreans, but not with young adults. This study suggests potential significance of IDH in the development of cardiovascular diseases.