Normotensive Subjects Research Articles

Complete intraureteral stent placement reduces stent-related pain in normotensive subjects and in diabetes: Subgroup analysis of a prospective randomized clinical trial

Purpose: Pain is a common symptom that is associated with ureteral stent placement, but its degree of perception might vary among individuals. Compared with conventional stent placement (C-SP), complete intraureteral stent placement (CIU-SP) has shown promise in reducing stent-associated pain. This study aimed to investigate the effect of patient characteristics and comorbidities on pain reduction after CIU-SP. Materials and methods: Patients who underwent ureteroscopic lithotripsy and stent placement were randomized into the CIU-SP and C-SP groups. Stent-associated symptoms were evaluated using the Ureteral Stent Symptom Questionnaire on day 7, immediately before stent removal. Stent-associated pain was determined by the answer to question P1 (yes or no). Subgroup analysis was conducted based on various patient characteristics and comorbidities. Results: Of the 103 randomized patients, 91 (45 in CIU-SP and 46 in C-SP) were included in the final analysis. Body pain was reported by 31 (68.9%) after CIU-SP and 41 (89.1%) after C-SP (P = 0.021). Compared with C-SP, CIU-SP significantly reduced pain in the normotensive population (66.7% versus 93.7%, P = 0.006) but not in hypertensive individuals (77.8% versus 76.9%, P = 1.000). Conversely, compared with C-SP, CIU-SP was associated with less pain in patients with diabetes (37.5% versus 88.9%, P = 0.05) but not in patients without diabetes (75.7% versus 89.2%, P = 0.221). Age, sex, stone laterality, body mass index, and smoking status did not influence the reduction of pain after CIU-SP. Conclusion: Compared with C-SP, CIU-SP was effective in reducing stent-associated pain, especially in normotensive and diabetic populations. These findings align with existing literature, which emphasized the potential impact of hypertension on decreased pain perception and highlighted the known association between diabetes and bladder hypersensitivity.

Diagnostic performance of single-lead electrocardiograms for arterial hypertension diagnosis: a machine learning approach.

Awareness and early identification of hypertension is crucial in reducing the burden of cardiovascular disease (CVD). Artificial intelligence-based analysis of 12-lead electrocardiograms (ECGs) can already detect arrhythmias and hypertension. We performed an observational two-center study in order to develop a machine learning algorithm to proactively detect arterial hypertension from single-lead ECGs. This could serve as proof of concept with an eye towards todays wearables that record single-lead ECGs. In a prospective observational study, we enrolled 1254 consecutive subjects (539 male, aged 60.22 ± 12.46 years), with and without essential hypertension, and no indications of CVD. A 12-lead ECG of 10 seconds duration in resting position was performed on each subject using a digital electrocardiograph and lead I was isolated for analysis using a calibrated Random Forest (RF). Our RF model classified hypertensive from normotensive subjects on a hold-out test set, with 75% accuracy, ROC/AUC 0.831 (95%CI: 0.781-0.871), sensitivity 72%, and specificity 82% (sensitivity and specificity calculated using a threshold of 0.675). Increasing age, larger values of body mass index, the area under the T wave divided by the QRS complex area, and the area under QRS segment adjusted for BMI, were the four most important features that drove the classification decisions of our model. This study demonstrates the potential to opportunistically detect an undiagnosed hypertension, using a single-lead ECG. While studies with data from wearables are required to translate our findings to actual smartwatch settings, our results could pave the way to innovative technologies for hypertension awareness.

Blood L-cystine levels positively related to increased risk of hypertension.

Hypertension is one component of metabolic syndrome (MetS). Here, the study evaluated hypertension-associated metabolites in relation to other MetS components. Fasting plasma samples were collected from 22 hypertensive and 63 normotensive subjects for non-targeted metabolomics. Compared with normotensive subjects, hypertensive patients were more diabetic (6.3%vs. 36.4%) and had dyslipidemia (27.0%vs. 63.6%) (both p<.05). By non-targeted metabolomics, 758 metabolites in 22 classes were identified and 56 were differentially regulated between hypertensive and normotensive groups. Amongst these 56 metabolites, receiver operating characteristic analysis showed that 14 had an area under the curve above 0.6. Multivariate-adjusted logistic regression analysis demonstrated that per one-fold increase of L-glutmatic acid, L-cystine, (9S,10E,12Z,15Z)-9-Hydroxy-10,12,15-octadecatrienoic acid, deoxyribose 5-phosphate, and falcarinolone, the odds ratios were 3.64, 4.61, 0.26, 0.26, and 0.37 for having the risk of hypertension, respectively. Of five metabolites, by Spearman's correlation analysis, only L-glutmatic acid and L-cystine levels were positively associated with systolic and diastolic blood pressure (all p<.05). Spearman's correlation analysis further revealed that L-glutmatic acid levels were positively correlated with to body mass index (BMI), fasting blood glucose, and serum triglyceride but negatively associated with HDL-c (all p<.05) whereas L-cystine levels were not related to any of these components (p ≥.13). Multivariate-adjusted linear regression analysis confirmed the positive correlation between L-cystine levels and systolic or diastolic blood pressure (β=2.66 for SBP; β=2.50 for DBP; both p<.05). In conclusion, L-cystine could be a potent metabolite for increased risk of hypertension.

Impairment of microvascular endothelial Kir2.1 channels contributes to endothelial dysfunction in human hypertension.

Hypertension is associated with decreased endothelial function through reduced contributions of nitric oxide (NO). We previously discovered that flow-induced NO production in resistance arteries of mice and humans critically depends on endothelial inwardly rectifying K+ (Kir2.1) channels. The goal of this study was to establish whether these channels contribute to the impairment of endothelial function, measured by flow-induced vasodilation (FIV) in peripheral resistance arteries of humans with hypertension. We measured FIV in vessels isolated from subcutaneous fat biopsies from 32 subjects: normotensive [n = 19; 30.6 ± 9.8 yr old; systolic blood pressure (SBP): 115.2 ± 7 mmHg; diastolic blood pressure (DBP): 75.3 ± 5.7 mmHg] and hypertensive (n = 13; 45.3 ± 15.3 yr old; SBP: 146.1 ± 15.2 mmHg; DBP: 94.4 ± 6.9 mmHg). Consistent with previous studies, we find that FIV is impaired in hypertensive adults as demonstrated by a significant reduction in FIV when compared with the normotensive adults. Furthermore, our data suggest that the impairment of FIV in hypertensive adults is partially attributed to a reduction in Kir2.1-dependent vasodilation. Specifically, we show that blocking Kir2.1 with ML133 or functionally downregulating Kir2.1 with endothelial-specific adenoviral vector containing dominant-negative Kir2.1 (dnKir2.1) result in a significant reduction in FIV in normotensive subjects but with a smaller effect in hypertensive adults. The Kir2.1-dependent vasodilation was negatively correlated to both SBP and DBP, indicating that the Kir2.1 contribution to FIV decreases as blood pressure increases. In addition, we show that exposing vessels from normotensive adults to acute high-pressure results in loss of Kir2.1 contribution, as high pressure impairs vasodilation. No effect is seen when these vessels were incubated with dnKir2.1. Overexpressing wtKir2.1 in the endothelium resulted in some improvement in vasodilation in arteries from all participants, with a greater recovery in hypertensive adults. Our data suggest that hypertension-induced suppression of Kir2.1 is an important mechanism underlying endothelial dysfunction in hypertension.NEW & NOTEWORTHY Impairment of endothelial function under high blood pressure is linked to the loss of inwardly rectifying K+ (Kir2.1) channels activity in human resistance arteries, leading to a reduction in flow-induced vasodilation and possibly leading to a vicious cycle between elevation of blood pressure, and further impairment of Kir2.1 function and flow-induced vasodilation.

Haemodynamic Forces: Emerging Markers of Ventricular Remodelling in Multiple Myeloma Cardiovascular Baseline Risk Assessment.

Multiple myeloma (MM) affects a population with a high prevalence of cardiovascular (CV) disease. These patients benefit from an accurate CV risk evaluation in order to choose the safest drug regimen. Haemodynamic forces (HDFs) analysis allows for the earlier detection of myocardial damage compared with standard markers; the role played by MM in HDFs alteration, with or without the influence of hypertension, is yet to be studied. Therefore, we aimed to identify differences in HDFs analysis in patients with MM, hypertension or both versus normotensive non-oncologic subjects. A total of 173 patients (MM hypertensive patients, MMHT; MM normotensive patients, MMNT; non-oncologic hypertensive patients, CoHT; and non-oncologic normotensive patients, CoNT) underwent transthoracic echocardiography for HDFs analysis and pulse wave velocity (PWV) assessment. Hypertensive patients (MMHT, CoHT) showed decreased ejection fraction (EF), global longitudinal strain (GLS) and HDFs values compared with CoNT, whereas ventricular mass (LVMi) and PWV increased. MMNT displayed a significant reduction in systolic HDFs (p < 0.006) and systolic ejection HDFs (p < 0.008) compared with CoNT, without significant change in EF, GLS, LVMi or PWV. In conclusion, MM leads to ventricular remodelling regardless of hypertension; HDFs application for MM patients could help detect early myocardial damage, especially in patients receiving cardiotoxic drugs.

O59 INFLUENCE OF CIRCADIAN BLOOD PRESSURE PATTERN ON RIGHT VENTRICULAR STRUCTURE AND FUNCTION IN PATIENTS WITH ARTERIAL HYPERTENSIION

Background and Objective: It is well proven, that arterial hypertension affects left side of the heart and causes its remodeling and functional changes. Since heart works as a unit and has ventricular interdependence, aim of the study was to assess influence of hypertension and circadian blood pressure (BP) profile on a right ventricular structure and function. Methods: 75 hypertensive patients (57.13±7.27 y/o) and 25 normotensive control subjects (57.56±7.55 y/o) were involved in a study. All of them were males without history of coronary artery disease, cerebrovascular or peripheral artery disease, obstructive lung disease, significant valvular heart disease or heart failure. All of them were either lifetime nonsmokers, or stopped smoking more than 5 years. All the patients underwent to 24-hour ambulatory BP monitoring and heart ultrasound with tissue doppler imaging. Results: Hypertensive patients with dipper circadian BP profile had higher TAPSE (19±1.586 vs 17.708±2.857; P&lt;0.05), higher right ventricular ejection fraction (55.103±4.597 vs 47.829±14.605; P&lt;0,005) and lower right ventricular outflow tract diameter (29.985±3.932 vs 32.639±3.510; P&lt;0/05). None of the echo parameters were different between normotensive subjects with different circadian BP pattern. Trans tricuspid valve early diastolic (E) and late diastolic (A) peak velocities were significantly lower in hypertensive patients (1.416±0.130 vs 0.897±1.49; P&lt;0.005). Hence, non-dipper hypertensives had significantly lower tricuspid E/A ratio in comparison with dippers (0.812±0.094 vs 1.048±0.101; P&lt;0.00001). Interventricular septum and posterior wall diameters were higher in non-dipper hypertensives (1.134±0.131 vs. 1.322±0.138; P&lt;0.00001 and 1.072±0.175 vs. 1.254±0.135; P&lt;0.001; respectively). Conclusion: Study data show increased interdependence between two ventricles. Patients with arterial hypertension have systole-diastolic dysfunction, which especially well is present in patients with non-dipper circadian BP profile.

P168 CHARACTERIZATION OF THE HEMODYNAMIC PATTERN OF CONTROLLED HYPERTENSIVE PATIENTS

Background: Hemodynamic alterations have been described in hypertensive disease. However, we still do not know if the identification of an altered hemodynamic pattern in patients with controlled hypertension could predict cardiovascular risk or evolution of hypertension. Objective: to identify the hemodynamic pattern of hypertensive patients with BP values in goals. Methods: Controlled hypertensive subjects were recruited (n = 107) and included a control group of normotensive subjects (n: 35.9). A non-invasive hemodynamic study (Z Logic, lying down / standing) was performed, and the cardiac index (CI) and vascular resistance index (VRI) data were recorded for the determination of the hemodynamic pattern. Hypodynamic pattern was considered: CI &lt;2.5 L / min / m2 and VRI&gt; 2500 dynas.seg.cm-5.m2; Hyperdynamic pattern IC&gt; 4,4 L / min / m2 and VRI &lt;2500 dynas.seg.cm-5.m2 Results: The SBP / DBP of the HTA group was 133.09 +/- 6.01 / 82.4 +/-7.2 mm Hg; and of the NT group was SBP/ DBP 123.6 +/- 9.7 / 75.5 +/- 8.9. The CI and VRI of the HTA group obtained was 2.81 l / m2 / min and 2842.31 dynas that, without corresponding to a hypodynamic pattern, showed a predominance of the VRI increase. In the control group of NT subjects, the values were 3.23 and 2289.23, respectively, corresponding to a normal pattern. The values obtained were different between both groups (p &lt;.05). Conclusions: Controlled hypertensive patients with hypertension goals have a hemodynamics pattern with an increase in the VRI different from that of normotensive subjects. These results coincide with those reported by Ferrario and col. The relevance of the imbalance found could only be analyzed in the context of long-term follow-up to identify whether it is a predictor of CV events and / or complications.

P133 ALTERED P-WAVE DISPERSION IN NEWLY DIAGNOSED YOUNG HYPERTENSIVES

Background and objective: P wave dispersion (Pd) is a useful electrocardiographic marker for predicting the onset of atrial fibrillation. It has been little studied in recent hypertension. The aim was to determine the behavior of maximum P wave duration (Pmax) and Pd in young hypertensive patients with recent onset and its relationship with other variables. Methods: A cross-sectional, prospective, comparative study was performed in 60 young men (30 hypertensive and 30 non-hypertensive). P wave measurements were obtained with 12-lead electrocardiogram. Statistical analysis included applications of simple linear correlation, sample means were compared by Student's t-test. Results: There were no significant differences in the baseline characteristics of both groups. Pmax (78.67 ± 5.71 ms) and Pd (42.33 ± 6.26ms) were found to be significantly prolonged (p&lt;0.001) in the hypertensive group compared to normotensive subjects (Pmax 61.00 ± 7.69 ms; Pd 25.00 ± 8.61 ms). Pd correlated significantly (r = 0.716; p&lt;0.001) with systolic and diastolic blood pressure (r = 0.696; p&lt;0.001). Conclusions: Pmax and Pd are found to be increased in young patients with recent-onset hypertension, and these values increase in direct proportion to blood pressure figures.

P166 EXPLORING AGE-ASSOCIATED CHANGES IN HEMODYNAMICS: INSIGHTS FROM 24-HOUR BLOOD PRESSURE MONITORING

Background and Objective: Aging is associated with progressive alterations in the structure and function of the heart and arteries, which can occur independently. This study aims to investigate the hemodynamic changes occurring in aging normotensive subjects concerning heart and arterial function. We employed a novel method based on blood pressure values obtained during 24-hour ambulatory blood pressure monitoring (24-h ABPM). Methods: A cross-sectional study was conducted involving 3,220 non-obese patients referred for 24-h ABPM, who did not have hypertension and were not taking any medications. 24-hour mean hemodynamics was obtained using a non-invasive method based on Ct. Ct was estimated as: Ct/BSA= 38/PPth+ 4/5 × Td/T - 3/7, where BSA: body surface area, Td: diastolic time, T: cardiac period, and PPth: theoretical pulse pressure. The stroke volume (SV) was estimation as: SV= Ct (PP+MSP ×Ts/τ), where PP: pulse pressure, MSP: mean systolic pressure, Ts: systolic time, τ: diastolic pressure decay time constant. Cardiac output (CO) and SVR were obtained using conventional formulas. Results: Among the participants, 64.6% were female, with an average age of 51.0±15.3 years, Ct of 0.96±0.21 mL/mmHg, CO of 5.2±0.68 L/min, and SRV of 1394±178 dyn.s/cm5. An age-related reduction in stroke index and cardiac index are noteworthy, stabilizing from the sixth decade of life onward (41.1±2.0 mL/m2 and 3.0±0.23 L/min/m2, respectively). Conversely, Ct exhibits an early increase from the third to fifth decades of life (1.04±0.18 mL/mmHg), followed by a continuous and gradual decline until the ninth decade (0.71±0.16 mL/mmHg). Meanwhile, SVR demonstrates an upward trend until reaching and maintaining high values from the sixth decade of life (1426±167 dyn.s/cm5) onward with a clear shift in arterial hemodynamics (Analysis of variance [ANOVA]; P value &lt;0.001) (Figure). Conclusions: The current method based on 24-hour ABPM effectively portrays the cardiac and arterial hemodynamics that mirror age-related circulatory alterations. This method offers a valuable pathophysiological basis for understanding the aging blood pressure profile.

Assessment of metabolic syndrome among hypertensive adult subjects in Enugu southeastern, Nigeria

Objective: Hypertension poses a significant burden on the general population, being responsible for increasing cardiovascular morbidity and mortality. The association of hypertension with dyslipidemia, enlarged waistline (obesity), and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. This study assessed the metabolic syndrome among adult hypertensive individuals in Enugu, Nigeria. Methods: One hundred and twenty participants(18-50 years) consisting of sixty hypertensive subjects, as test group and sixty normotensive subjects, as control group were recruited for this cross sectional study. Anthropometric parameters, waist circumference (WC), height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured and body mass index (BMI) calculated. Five milliliters of fasting blood samples were collected and used for the determination of fasting plasma glucose (FPG) and lipid profile (TC, TG, HDL-C, LDL-C, VLDL-C) using enzymatic colorimetric methods. Laboratory investigations were done in a hospital setting. Metabolic Syndrome (MetS) prevalence was estimated using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Data was analysed using the Statistical Package for the Social Sciences (SPSS) version 26. Results: The results showed a significant increase (P&lt; 0.05) in the mean ± SD of SBP (162.30 ± 18.94, 124.27 ± 8.85), DBP (106.77 ± 25.77, 83.40 ± 11.47), FPG (5.70 ± 1.90, 4.47 ± 0.64), TC (5.19 ± 0.913, 3.70 ± 0.94), LDL-C (3.05 ± 1.09, 1.68 ± 0.94) and a non-significant difference (P &gt; 0.05) in WC (91.48 ± 8.69, 91.96 ± 10.84), TG (1.35 ± 0.37, 1.26 ± 0.49), HDL-C (1.62 ± 0.45, 1.59 ± 0.50), VLDL-C (0.517 ± 0.16, 0.47 ± 0.64) of the hypertensive and normotensive subjects respectively. The prevalence of MetS in hypertensive subjects was 33.3%, while that of the control group (normotensives) was 3.3%. Conclusion: The study concludes that hypertension predisposes an individual to higher risk of developing MetS.

ACE I/D and A2350G Polymorphisms are Correlated with Body Mass Index, but Not with Body Weight and Essential Hypertension: Study in Javanese Postmenopausal Women

Background: Genetics was one of the risk factors for essential hypertension (EH). Research on ACE I/D and A2350G polymorphisms associated with risk factors for hypertension in Indonesia has never been done. Therefore, this study was conducted to analyze the relationship between the genotype and alleles of this gene with EH, body weight, and body mass index (BMI) in Javanese postmenopausal women.Materials and methods: This cross-sectional study involved 69 postmenopausal Javanese women according to several criteria related with hypertension risk factors. The data were obtained from the measurement and questionnaire results, along with Towards Health Card Records. The polymerase chain reaction (PCR) genotyping method used was the restriction fragment length polymorphism and allele-specific.Results: The prevalence of hypertension, prehypertension, and normotension in Javanese postmenopausal women were 0.246, 0.13, and 0.623, respectively. The frequency of BMI classification as underweight, normal, overweight, or obese were 0.029, 0.42, 0.261, and 0.29, respectively. The ACE I/D and A2350G polymorphism variant genotypes and frequencies found were II (0.464), ID (0.522), DD (0.014), and AA (1). Meanwhile, the alleles and their frequencies at ACE I/D gene polymorphism were I (0.725) and D (0.275). The II and ID genotype was mostly found in normotension subjects. The DD genotype was only available in hypertension subjects. There was no association between genotypes and alleles of ACE I/D, hypertension, body weight, and BMI classification (p&gt;0.05). There was an association between these genotypes, alleles, and BMI (p&lt;0.05).Conclusion: ACE I/D polymorphism is susceptible for BMI in Javanese postmenopausal women.Keywords: Javanese postmenopausal, essential hypertension, ACE I/D, ACE A2350G

The prognostic role of ECG and subsequent echocardiography in normotensive subjects with pulmonary embolism.

The prognostic role of ECG and subsequent echocardiography in normotensive subjects with pulmonary embolism.

Decreased postpartum exercise capacity after a diagnosis of pre-eclampsia: Implications for CVD risk prediction

BackgroundHypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies. MethodsPreeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum. ResultsRecruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e’ (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e’ (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001). ConclusionsPostpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.

Urinary hyaluronidase activity is closely related to vasopressinergic system following an oral water load in men: a potential role in blood pressure regulation and early stages of hypertension development.

Blood pressure (BP) regulation is a complex process involving several factors, among which water-sodium balance holds a prominent place. Arginin-vasopressin (AVP), a key player in water metabolism, has been evoked in hypertension development since the 1980s, but, to date, the matter is still controversial. Hyaluronic acid metabolism has been reported to be involved in renal water management, and AVP appears to increase hyaluronidase activity resulting in decreased high-molecular-weight hyaluronan content in the renal interstitium, facilitating water reabsorption in collecting ducts. Hence, our aim was to evaluate urinary hyaluronidase activity in response to an oral water load in hypertensive patients (HT, n=21) compared to normotensive subjects with (NT+, n=36) and without (NT-, n=29) a family history of hypertension, and to study its association with BP and AVP system activation, expressed by serum copeptin levels and urine Aquaporin 2 (AQP2)/creatinine ratio. Eighty-six Caucasian men were studied. Water load test consisted in oral administration of 15-20 ml of water/kg body weight over 40-45 min. BP, heart rate, serum copeptin, urine hyaluronidase activity and AQP2 were monitored for 4 hours. In response to water drinking, BP raised in all groups with a peak at 20-40 min. Baseline levels of serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio were similar among groups and all decreased after water load, reaching their nadir at 120min and then gradually recovering to baseline values. Significantly, a blunted reduction in serum copeptin, urinary hyaluronidase activity and AQP2/creatinine ratio was observed in NT+ compared to NT- subjects. A strong positive correlation was also found between urinary hyaluronidase activity and AQP2/creatinine ratio, and, although limited to the NT- group, both parameters were positively associated with systolic BP. Our results demonstrate for the first time the existence in men of a close association between urinary hyaluronidase activity and vasopressinergic system and suggest that NT+ subjects have a reduced ability to respond to water loading possibly contributing to the blood volume expansion involved in early-stage hypertension. Considering these data, AVP could play a central role in BP regulation by affecting water metabolism through both hyaluronidase activity and AQP2 channel expression.

Longitudinal trajectories of Alzheimer's disease CSF biomarkers and blood pressure in cognitively healthy subjects.

We examined whether hypertension (HTN) was associated with Alzheimer's disease-related biomarkers in cerebrospinal fluid (CSF) and how changes in blood pressure (BP) related to changes in CSF biomarkers over time. A longitudinal observation of cognitively healthy normotensive subjects (n=134, BP<140/90, withno antihypertensive medication), controlled HTN(n=36, BP<140/90, taking antihypertensive medication), and 35 subjects with uncontrolled HTN (BP ≥ 140/90). The follow-up range was 0.5to15.6 years. Total tau (T-tau) and phospho-tau181 (P-tau 181) increased in allbut controlled HTN subjects (group×timeinteraction: p<0.05 for both), but no significant Aβ42 changes were seen. SignificantBP reduction wasobserved in uncontrolled HTN, andit was related to increase in T-tau (p=0.001) and P-tau 181 (p<0.001). Longitudinal increases in T-tau and P-tau 181 were observed in most subjects; however, onlyuncontrolled HTN had both markers increase alongside BPreductions. We speculatecumulative vascular injury renders thebrain susceptible to relative hypoperfusion with BP reduction. Over the course of the study, participants with uncontrolled HTN at baseline showed greater accumulation of CSF total tau and phospho-tau181 (P-tau 181) than subjects with normal BP or with controlled HTN. In the group with uncontrolled HTN, increases in total tau and P-tau 181 coincided with reduction in BP. We believe this highlights the role of HTN in vascular injury and suggests decline in cerebral perfusion resulting in increased biomarker concentrations in CSF. Medication use was the main factor differentiating controlled from uncontrolled HTN, indicating that earlier treatment was beneficial for preventing accumulations of pathology.

#1550 Incident hypertension: immune biomarkers and vascular phenotypes

Abstract Background and Aims Blood pressure (BP) regulation is mediated by cardiac, vascular, endocrine, renal, and immune system interactions. Hence, hypertension may exist as different phenotypic variants, with different clinical features and susceptibility to target organ damage. We aimed to analyse the circulating protein biomarker ‘signature’ of: 1) untreated hypertension; 2) hypertensive phenotypes identified by arterial and blood pressure parameters. Method 61 patients with hypertension, and 61 controls were assessed using 24hr ambulatory BP monitoring; endothelial function, arterial stiffness, carotid intima-media thickness (CIMT), and cardiovascular variability [1]. Circulating protein biomarkers analysed using Olink® Inflammation plasma biomarker panel, reported as NPX (Normalized Protein eXpression), in Log2 scale. Results 34 biomarkers dominated by cytokines and chemokines differed between normotensive and hypertensive subjects (Fig. 1), though failed to meet Bonferroni-adjusted threshold. Inflammatory biomarkers correlated with BP and arterial stiffness, BP variability, and CIMT, but not endothelial function. Associations were concordant across systolic and diastolic BP; TPP1, CCL7, CCL11, and CCL21 positively correlating; IL18R1, and KYNU negatively. These relationships were more pronounced in hypertensive subgroup, 85 biomarkers correlating including CD molecules (CD200R1, CD22, CD58, CD6, CD70) and cytokines (IL-5, IL-11, IL-15, IL-18, IL-32, IL-1RL2, IL-22RA1, IL-5RA). HGF, AGE, and CCL21 showed greatest between group differences and correlated with multiple BP or vascular parameters. Systolic nocturnal dipping demonstrated negative correlation with biomarkers relating to immune cell interactions and cellular adhesion (CTRC, EPHA1, LGALS4, SIT1, SMOC, IL-18 and TNFSF11). Machine learning techniques identified three phenotypes of hypertension, ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ [1]. Sixteen of the 85 correlating biomarkers also differed between these phenotypic groups: Conclusion Hypertension is linked to alterations in circulating immune biomarkers. Multiple biomarkers correlated with both arterial stiffness and BP parameters. Some biomarkers are only correlated in the hypertensive group. Many also relate to nocturnal dipping, and differed across the hypertension endotypes. HGF is a promising biomarker for BP and arterial function; warranting further validation.

HYPERTENSION-SPECIFIC ASSOCIATION OF CARDIO-ANKLE VASCULAR INDEX WITH SUBCLINICAL LEFT VENTRICULAR FUNCTION IN A CHINESE POPULATION: DANYANG STUDY

Objective: The association of arterial stiffness, as measured by cardio-ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. Our study aims to examine their relationship in hypertensive patients compared with that in normotensive subjects. Design and method: Our study included 1887 subjects who were enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS-1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e’), and speckle tracking to estimate left ventricular (LV) global longitudinal strain (GLS). Results: Increased LV mass index (76.3, 80.0, and 84.0 g/m2), decreased GLS (21.1, 21.0, and 20.4%), lower E/A (1.2, 1.0, and 0.8) and e’ velocity (11.2, 9.4, and 8.2 cm/s), and higher E/e’ (7.6, 8.2, and 8.8) were significantly associated with higher CAVI on unadjusted analyses (P &lt; 0.001). After adjustment for covariates, GLS, E/A, and e’ were still significantly decreased from tertiles 1 to 3 of CAVI (P &lt; 0.04). Further sensitive analyses revealed similar association pattern for diastolic function. However, the relationship of higher CAVI to worse GLS was stronger in hypertensives (P = 0.008) but not normotensives (P = 0.167) (Figure 1). Compared with lowest tertile, subjects with top tertile of CAVI were at higher risk of subclinical LV systolic dysfunction in hypertensive patients (OR = 2.61; P = 0.005). Conclusions: Increased CAVI is associated with worse subclinical diastolic function. However, this relationship of CAVI to subclinical systolic function was more prominent in hypertensive patients.

Aerobic training reduces microglial activation and TNFα release in the hypothalamus of hypertensive rats

Spontaneously hypertensive rats (SHR) exhibit autonomic imbalance and blood-brain barrier (BBB) dysfunction, a pathophysiological condition that can be corrected by exercise training. Although microglia cells are not part of the structure of the BBB itself, they modulate it function through the synthesis and release of cytokines. In hypertension condition, for instance, microglia are activated releasing pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), which is able to break down different BBB constituents. Therefore, here we hypothesized that the benefit of exercise training to ameliorate BBB integrity of hypertensive rats could be due to the reduction in the release of TNFα by microglia at the hypothalamus level. Thus, our aim is to evaluate whether microglial activation, and consequent TNFα release, in the hypothalamus of SHR can be affected by aerobic exercise training. Wistar and SHR male rats (CEUA ICB/USP #3407080618) aged 90 days were divided into four groups: sedentary (W-S n=6) and trained Wistar (W-T n=6), sedentary (SHR-S n=6) and trained SHR (SHR-T n=6). Exercise trained animals were submitted to moderate intensity of aerobic training on a treadmill (50%-60% of maximum capacity, 1 h/day, 5 days/week, for 4 weeks). At the end of the 4th week of training, the hypothalamus, brainstem, and cortex of all groups were collected and processed for isolation of mononuclear cells, followed by flow cytometry analysis to evaluate the microglial labeling by CD45lowCD11b+, gated for TNFα+. All data as analyzed by two-way ANOVA followed by Bonferroni’s post-test. Trained animals showed performance gains compared to their control groups (Velocity: W-S: 1.07±0.23km/h vs. W-T: 1.7±0.36km/h, p&lt;0.0001 and SHR-S: 1.25±0.17km/h vs. SHT-T: 1.95±0.16km/h, p&lt;0.0001; Distance: W-S: 85±42m vs. W-T: 218±95m, p=0.0042 and SHR-S: 124±44m vs. SHT-T: 315±21m, p&lt;0.001). Hypertensive animals present an elevated neuroinflammation degree compared to normotensive subjects, by increased microglia activation (W-S: 0.65±0.39% vs. SHR-S: 7.0±1.4%, p&lt;0.0001) and TNFα release (W-S: 33.9±24.6% vs. SHR-S: 95.2±3.6%, p=0.0007). After training, hypertensive rats exhibited a reduction in hypothalamic microglial activation in a similar way to sedentary and trained Wistar (CD45lowCD11b+, SHR-T: 0.55±0.26%: vs. W-S:0.65±0.39% p=0.99; vs. W-T: 0.41±0.28% p=0.98; vs. SHR-S: 7.0±1.4% p&lt;0.0001). TNFα release also reduced in hypothalamus of SHR-T (CD11b+TNFα+, SHR-T: 59.4±17.0%: vs. W-S: 33.9±24.6% p=0.15; vs. W-T: 41.9±4.6% p=0.6; vs. SHR-S: 95.2±3.6% p&lt;0.01). SHR-S exhibit higher microglial activation and TNFα release in brainstem compared to W-S, but 4 weeks of training was not enough to reduce this condition. No difference was observed in cortex. In conclusion, exercise training of moderate intensity is effcient to reduce microglia activation and consequently TNFα release in the hypothalamus of hypertensive animals, which could be one of the causes affecting the integrity of the BBB in hypertensive animals. FAPESP #2018/14544-6; #2022/07465-8. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A POSITIVE FAMILY HISTORY, PARTICULARLY IN THE MOTHER, IS AN IMPORTANT DETERMINANT FOR THE DEVELOPMENT OF ARTERIAL HYPERTENSION

Objective: A positive family history is one of the non-modifiable risk factors directly linked to arterial hypertension (AH). This study aimed to show the influence of a positive family history of AH on the incidence of AH in the studied population. Design and method: A total of 1784 participants (a random sample of the general adult population in Croatia included in the ’Epidemiology of Hypertension in Croatia -2’ project) were examined. Data were systematically collected through a structured questionnaire. Results: Analysis showed a statistically significant difference in having a positive family history of AH in at least one parent between those having AH and the normotensive group (59.2% vs. 51.6%; p=0.002). Furthermore, 14.5% of subjects with AH and 9.4% of normotensive subjects reported at least one of the grandmothers with a history of AH (p=0.001). A significant correlation was observed for individuals reporting a positive history of AH in their paternal grandmother (p=0.004) and maternal grandfather (p=0.009), reported by 8.8% and 6.4% of subjects with AH, respectively, as opposed to 5.5% and 4.5% of the normotensive subjects. The most significant difference was found for a positive family history of AH in the mother, reported by 46.5% of subjects with AH and 38.5% of normotensive subjects (p&lt;0.001). Regression analysis indicated a statistically significant association between a positive family history of AH in the mother and an increased odds ratio for developing AH (OR 1.36 95% CI 1.11-1.66, p=0.003). Conversely, a positive family history on either the paternal or maternal side, at least one of the grandfathers, father, and paternal grandfather failed to exhibit a significant correlation with the occurrence of AH. Conclusions: Our study affirmed the importance of family history for arterial hypertension, which should be an elementary part of taking medical history. Subjects who had mothers with arterial hypertension were at higher risk of having AH themselves which is in line with the previous notion that the mother's hypertensive status is more important than the father's.

The Effect of Clothes on Blood Pressure Measurement in Normotensive and Hypertensive Subjects in a Real-Life Setting

Introduction: The effect of clothing on the recording of blood pressure in a normotensive and hypertensive population remains essential to diagnosing and managing. Methods: This is a cross-sectional study to measure blood pressure using a validated oscillometric sphygmomanometer in two populations. The records were made over the thicker sleeve arm and non-sleeved arm (either on bare arm or indicating the removal of the outermost garment). Clothing was categorized according to how patients attended the outpatient clinic based on the real world. Results: A total of 75 patients were included with a diagnosis of hypertension whose mean age was 67.1 years (SD ± 16.3). The group of normotension included 63 patients whose mean age was 21.1 years (SD ± 2.2). There was not variability related to technique or inherent to the condition of the subject on the first and second measurements of blood pressure. In the comparative analysis, the group with normotension did not report a significant difference in systolic or diastolic blood pressure due to the effect of clothing during the first or second measurement (p > 0.05). In the group with hypertension, a significant difference was observed in the first measurement, between the group over-the-sleeve and non-sleeved arm (systolic blood pressure, p: 0.021 and diastolic, p: 0.001). However, when the variable order of measurement was analyzed by randomizing the initial registry with or without clothing was not found a statistical difference. Conclusion: Clothing does not a significant difference in the measure of blood pressure in a normotensive or hypertensive population.