Hypertension-mediated Organ Damage Research Articles

Systematic Review Article: New Drug Strategies for Treating Resistant Hypertension-the Importance of a Mechanistic, Personalized Approach.

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomizedclinicaltrialsperformed with these drugs as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage

Introduction Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. Design and methods Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. Results Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05–2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34–0.95), p = 0.03). Conclusions None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

Ambulatory blood pressure monitoring profiles in Asia.

High blood pressure (BP) remains a major health problem globally, with a proportion of hypertension-mediated organ damage (HMOD) increasing worldwide including in Asia region. Cardiovascular (CV), cerebral and kidney diseases related to hypertension were reported to be closely associated with morning surge and nocturnal hypertension-a subset of BP variability-which can be detected by out-of-office BP measurement. Ambulatory BP monitoring (ABPM) and Home BP monitoring (HBPM) have been recommended by major guidelines to be used in the evaluation of BP variability and outcomes' prediction of hypertension patients. However, an interesting profile of ABPM in Asia has been reported and hypothesized to correlate with different outcomes. This review will focus on the current recommendation of ABPM use by the guidelines, the major different profiles of ABPM in Asia as compared to Western countries according to clinical indications, and the challenges in implementing optimal use of ABPM in Asian countries based on available evidence.

Unattended automatic blood pressure measurements versus conventional office readings in predicting hypertension-mediated organ damage.

Hypertension is a leading cardiovascular risk factor. Accurate blood pressure measurement is pivotal in hypertension diagnosis and management. Conventional office measurements (OBP) are error-prone, exacerbated by the white coat effect. Unattended automated office blood pressure measurement (UAOBP) is emerging as an alternative, mitigating the white coat effect. However, its ability to predict hypertension-mediated organ damage (HMOD) remains disputable. This study compares UAOBP with OBP in terms of their association with various HMODs, including left ventricular hypertrophy, left atrial enlargement, left ventricular systolic and diastolic dysfunction, intima-media complex thickening, microalbuminuria and abnormal pulse wave velocity. A total of 219 hypertensive patients were recruited, interviewed, and examined. Subsequently, blood pressure measurements were conducted in a randomized manner: 1) UAOBP: after 5 minutes of solitary rest in the examination room, the patient's blood pressure was automatically measured three times at 1-minute intervals. 2) OBP: after 5 minutes of rest, a physician performed three consecutive blood pressure measurements at 1-minute intervals. Subsequent evaluations aimed to detect HMODs, including echocardiography, carotid artery ultrasound, pulse wave velocity assessment, and laboratory tests. The blood pressure values in UAOBP were significantly lower than those in OBP (mean (SD) 124.7 (14.4) vs. 128.2 (14.2) mmHg, P <0.001 for systolic, and 73.3 (10.2) vs. 75.2 (10.6) mmHg, P <0.001 for diastolic). Correlation and ROC curve analyses revealed no method's superiority in predicting HMOD. The UAOBP did not prove superior in predicting HMOD compared to OBP, Further research is warranted to determine the role of UAOBP in clinical practice.

Cardio-Ankle Vascular Index As A Marker Of Left Ventricular Hypertrophy In Treated Hypertensives: Findings From The Pamela Study.

Findings regarding the association between Cardio-Ankle Vascular Index (CAVI) and cardiac hypertension-mediated organ damage (HMOD), such as left ventricular hypertrophy (LVH) assessed by echocardiography, in elderly hypertensive patients are scanty. We sought to investigate this issue in the hypertensive fraction of the general population treated with anti-hypertensive drugs enrolled in the Pressioni Monitorate E Loro Associazioni (PAMELA) study. The study included 239 out of 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory blood pressure (BP),blood examinations, echocardiography and CAVI measurements. In the whole study sample (age 69+9 years, 54% males), CAVI was positively correlated with age, office, home, ambulatory systolic BP, LV mass (LVM) index and negatively associated with body mass index (BMI). In multivariate analysis, CAVI was associated with LVM index (p< 0.05) independently of major confounders. The participants with LVH exhibited significantly higher CAVI (10.6+2.8 vs 9.2+1.8 m/sec. P<0.001), larger left atrial diameter and lower LV ejection fraction values than their counterparts without it. The CAVI value of 9.4 m/sec was the best cut-off for prediction of LVH in the whole sample. Our study provides new evidence of an independent association between CAVI and LVH in treated elderly hypertensive patients and suggests that the use of this metric of arterial stiffness could not only be used to evaluate vascular damage but also to stratify the risk of LVH.

Association between Expression of Insulin-like Growth Factor-1 (IGF-1), IGF-1 Receptor (IGF-1R), and Hypertension-Mediated Organ Damage (HMOD) Parameters in Leukocytes and Plasma of Children/Adolescents with Primary Hypertension.

A decrease in IGF-1 is often linked to inflammation. Low systemic and local IGF-1 production and downregulation of IGF-1R expression may precede and predict PH development in children/adolescents. Leukocyte mRNA expression of IGF-1 and its receptor (IGF-1R) and plasma IGF-1 were measured in a group of 39 PH children/adolescents (29 boys and 10 girls) and 35 age-matched normotensive children (19 boys and 16 girls) using the RT-PCR and ELISA tests. The expression of the IGF-1R protein was assessed by flow cytometry. Plasma IGF-1 concentration was evaluated with ELISA. The expression of IGF-1 and IGF-1R and plasma concentrations of IGF-1 did not differ between groups. However, the PH children had a decreased percentage in IGF-1R-bearing lymphocytes (p = 0.02) and monocytes (p = 0.0003), as well as a low density of IGF-R in monocytes (p = 0.02). The IGF-1 expression was negatively correlated with pulse-wave velocity (PWV) (r = -0.49), systolic blood pressure (SBP) (-0.44), and carotid intima-media thickness (cIMT) (-0.43). The IGF-1R expression was negatively correlated with PWV (r = -0.42) and SBP (r = -0.41). Our results suggest that early subclinical hypertensive arterial injury is associated with lower activity of IGF-1-IGF-1R expression and loss of protective actions.

Mitophagy in hypertension-mediated organ damage.

Hypertension constitutes a pervasive chronic ailment on a global scale, frequently inflicting damage upon vital organs, such as the heart, blood vessels, kidneys, brain, and others. And this is a complex clinical dilemma that requires immediate attention. The mitochondria assume a crucial function in the generation of energy, and it is of utmost importance to eliminate any malfunctioning or surplus mitochondria to uphold intracellular homeostasis. Mitophagy is considered a classic example of selective autophagy, an important component of mitochondrial quality control, and is closely associated with many physiological and pathological processes. The ubiquitin-dependent pathway, facilitated by PINK1/Parkin, along with the ubiquitin-independent pathway, orchestrated by receptor proteins such as BNIP3, NIX, and FUNDC1, represent the extensively investigated mechanisms underlying mitophagy. In recent years, research has increasingly shown that mitophagy plays an important role in organ damage associated with hypertension. Exploring the molecular mechanisms of mitophagy in hypertension-mediated organ damage could represent a critical avenue for future research in the development of innovative therapeutic modalities. Therefore, this article provides a comprehensive review of the impact of mitophagy on organ damage due to hypertension.

Myocardial injury and myocardial infarction in hypertensive emergency patients; systematic review

This systematic review aimed to determine the prevalence of myocardial injury, myocardial infarction (MI), and its subtypes in individuals presenting with hypertensive emergency. To find all pertinent published articles from 2017 to 2023 that reported studies on the prevalence of hypertensive emergencies and hypertension-mediated organ damage from inception to the date of database search were included. A systematic search of the Web of Science, PubMed, and MEDLINE databases was conducted. Finally eight articles were selected for the review. The authors collaborated using Google Sheets and Google Documents. Of the selected studies, three were retrospective, two were cross sectional, and three were prospective. In men admitted for hypertensive crises, psychomotor agitation and the burden of cardiovascular risk were much higher. Around one-third of patients experiencing hypertensive crises had elevated cardiac troponin, which can be used to identify individuals who are at a greater risk of death early and to provide important prognostic information. A lower BMI was associated with lower initial and serial troponin levels; this obesity paradox was especially prominent in older and female individuals. Three main factors that contributed to hypertensive emergencies (HE) and urgencies (HU) were stress, excessive salt consumption, and non-compliance. Renin-angiotensin system blockers seemed to be the cornerstone of therapy. The case fatality rate for patients undergoing hypertensive episodes was quite significant.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency

Abstract: Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) – if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the ‘impending HTN-E’ group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. ‘Impending HMOD’ means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Early vascular damage in retinal microcirculation in arterial hypertension: the Czech post-MONICA study.

A total of 398 randomly selected individuals from an urban population aged 25-65 years, residing in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry, with data evaluable in 343 patients. Complete data were available for 342 individuals divided into four groups based on blood pressure and control status of hypertension: normotensive individuals ( n  = 213), treated controlled hypertensive individuals ( n  = 30), treated uncontrolled hypertensive individuals ( n  = 26), and newly detected/untreated hypertensive individuals ( n  = 73). There was a tendency to higher wall thickness in treated but uncontrolled hypertensive patients (compared to normotensive and treated controlled hypertensive individuals). WLR was significantly increased in treated but uncontrolled hypertensive patients as well as in individuals with newly detected thus untreated hypertension or in patients with known but untreated hypertension. There was no difference in WLR in treated, controlled hypertensive patients compared with normotensive individuals. Our results show that an increased WLR, reflecting early vascular damage, was found in newly detected individuals with hypertension and in untreated hypertensive patients, reflecting early hypertension-mediated vascular damage. Early initiation of hypertension treatment may be warranted.

Ten year follow-up study regarding treatment compliance and cardiovascular events in young first diagnosed and never treated hypertensives of a European Society of Hypertension Excellence Center

Abstract Background Early onset arterial hypertension (AH) is associated with a considerably increased risk for cardiovascular (CV) disease if left untreated. Treatment is based on the estimation of CV risk in each hypertensive patient. The compliance of each individual hypertensive in proposed life style changes and medical treatment is paramount. We aimed to investigate the compliance in medical treatment and we set as primary endpoint of the study the incidence of any CV events [CV death, acute myocardial infarction (AMI), stroke] and all-cause death of a cohort of young first diagnosed and never treated hypertensives of a European Society of Hypertension (ESH) Excellence Center. Population and Methods: We studied 220 young, non-diabetic (&amp;lt;50 years old) first diagnosed and never treated hypertensive patients (42+7 years, 70% males, 41% smokers, BMI=29+5, 24-h ambulatory blood pressure monitoring (ABPM) =142+10/91+9 mmHg, LDL=133+36 mg/dl, 49% had &amp;gt;1 HMOD) visiting our ESH Excellence Center (2004-2021). All patients were apparently healthy with no co-morbidities. In each patient, the presence of hypertension mediated organ damage (HMOD) was evaluated at baseline (aortic stiffness, left ventricular hypertrophy, coronary flow reserve, diastolic dysfunction. The cohort was re-evaluated at 10+4 years post-medical treatment initiation regarding compliance as well as the primary endpoint of the study. Results 191/220 (87%) young hypertensives (at baseline, 42+7 years, 70% males, 40% smokers, BMI=29.5, 24-h ABPM=142+10/91+9 mmHg, LDL=133+36 mg/dl, 49% had&amp;gt;1 HMOD) participated in the follow-up study while 29 (13%) patients were lost. We found that 17/191 (9%) quit medical treatment. Home or office BP was confirmed as controlled (&amp;lt;140/90 mmHg) in 151/191 (79%) patients. Regarding CV events, 7/191 (4%) hypertensive patients (at baseline, 44+4 years, 86% males, 71% smokers, BMI= 30+4, 24-h ABPM=142+12/89+10 mmHg, LDL=175+33 mg/dl, 87% had&amp;gt;1 HMOD) had an acute myocardial infarction (AMI) at 6+4 years post-treatment initiation while 1/191 (0.5%) patient died due to lung cancer. Hypertensive patients with CV events differed regarding increased LDL levels at baseline (168+35 vs.131+36, p=0.007), more smokers (p=0.04) and HMOD &amp;gt;1 (p=0.02) compared to the rest of the young hypertensive population. Conclusions Compliance regarding medical treatment was sustained in 9/10 young hypertensive patients during the 10-year follow-up. Just 4% of the population, smokers with increased LDL and HMOD&amp;gt;1, suffered an AMI despite compliance in medical antihypertensive treatment. Subsequently, treating AH in young people needs both life style changes (quit smoking) and medical treatment (hypertension plus hyperlipidemia) in order to prevent future CV events.CV events in young hypertensives

Male patients with first diagnosed and never treated essential hypertension accompanied by organ damage are at high risk for non-alcoholic fatty liver disease indicated by Hepatic steatosis index

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome as well as to arterial hypertension and overall cardiovascular (CV) disease. We aimed to investigate if those first diagnosed and never treated patients with essential hypertension at high risk for NAFLD, measured by the Hepatic Steatosis Index (HSI), already have an impaired CV risk profile estimated by increased blood pressure burden and accompanied by the presence of hypertension-mediated organ damage (HMOD). Methods We studied 300 non-diabetic, first diagnosed and never-treated young hypertensive patients [mean age=51+11 years, 60% males, 32% smokers]. Ambulatory blood pressure monitoring (24h ABPM), CV risk factors [smoking, obesity (BMI), hyperlipidemia and HMOD [aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac hypertrophy (LVMI), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) and endothelial dysfunction (PBR5-25)] were estimated in each patient before treatment initiation. HIS was calculated as 8 times (ALT/AST ratio) +BMI (+2, if female; +2, if diabetes mellitus). Increased HIS levels predispose for augmented risk for NAFLD. Results The whole hypertensive population was divided regarding HSI median value=39.5 in two groups, Group A (higher risk for NAFLD group, n=150, age=50+10, 59% males, 33% smokers) and Group B (lower risk for NAFLD group, n=150, age=51+11, 60% males, 31% smokers). Group A patients had increased BMI (32+5 vs. 27+3, p&amp;lt;0.001), systolic night-time ABPM (127+15 vs. 124+11, p=0.05), office systolic (152+19 vs. 145+17 mmHg, p=0.004) and diastolic BP (94+11 vs. 90+11 mmHg, p=0.002), central systolic BP (146+20 vs. 137+15, p=0.006), Chol (216+39 vs. 206+35, p=0.02), LDL (138+35 vs.130=33 mg/dl, p=0.04) and Trigl (139+75 vs. 112+63, p=0.001), E/Ea (7+2 vs. 6+2, p=0.01) and LVMI (83+18 vs. 79+17, p=0.03) compared to Group B. All other studied demographic, laboratory, ABPM and HMOD parameters (PWV, MAU, CFR and cIMT) were similar between groups. HSI was related to BMI (p&amp;lt;0.001) and office BP, both systolic (p=0.001) and diastolic (p=0.008) in total population as well as to LVMI (r=0.17, p=0.02) in males. Finally, in multiple regression analysis, we found that HSI was independently associated with LVMI (beta=0.14, p=0.05) only in male hypertensives. Conclusions Patients first diagnosed arterial hypertension and augmented CV risk (smoking, obesity, hyperlipidemia, BP burden and HMOD) are also at high risk for NAFLD. As successful antihypertensive treatment may lead to HMOD regression, probably there is still time for those patients to be treated for hypertension disease and hyperlipidemia and quit smoking, in order to reduce future CV risk.LVMI and HSI in male hypertensives

Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension: three years follow-up

Abstract Background Several recently published sham-controlled trials of high methodological quality confirm the safety and antihypertensive effectiveness of radiofrequency renal denervation. However, special clinical interest represents a suggestion that this type of treatment may improve hypertension-mediated organ damage. Purpose Comparative evaluation of renal denervation versus pharmacological treatment on diastolic function in patients with resistant hypertension. Methods The study enrolled 125 hypertensive patients who, following 4 weeks of standardized treatment with three antihypertensive remedies, one of which were a thiazide-like diuretic in maximum tolerated daily doses (Losartan, Amlodipine and Indapamid) and confirmation of their resistance, were randomly assigned into three groups depending on the treatment supplemented to the previously administered one: group I – Moxonidine, group II – Bisoprolol and group III – renal denervation (RDN). All patients were evaluated by transthoracic echocardiography at baseline, one, two and three years follow-up. A renal denervation was performed in the main renal arteries and their branches. Results At 1-year follow-up Bisoprolol and RDN treatment groups showed an authentic improvement in all diastolic function parameters, while Moxonidine group noted amelioration of only E/A ratio, LAVI and TR velocity. Two years of evaluation were marked by statistically significant changes of all diastolic parameters in all three observational groups. The improvement of diastolic function parameters continued until the end of the study, when the difference in dynamics between groups is evident thanks to the inferior effect of Moxonidine compared to Bisoprolol, RDN demonstrating superiority over both pharmacological treatment groups (Table 1). Conclusions Renal denervation demonstrated efficacy in improving of all parameters of diastolic function starting with 12 months of evaluation, the beneficial effect being maintained until the end of the surveillance period. At the same time, minimally invasive treatment has been shown to be superior to pharmacological treatment with SNS- blockers in improving diastolic function.

Prognostic significance of the wall to lumen ratio of retinal arterioles evaluated by adaptive optics

ObjectiveMicrovascular structural alterations may be considered an important form of hypertension-mediated organ damage. An increased media-to-lumen ratio of subcutaneous small arteries evaluated with locally invasive techniques (micromyography) predicts the development of cardiovascular (CV) events. However, it is not known whether retinal arteriole structural alterations evaluated with a noninvasive approach (Adaptive Optics) may have a prognostic significance. Design and methodsTwo-hundred and thirty-seven subjects (mean age 58.7 ± 16.1 years, age range 13–89 years; 116 males) were included in the study: 65 normotensive subjects (27.4 %) and 172 patients with essential hypertension or primary aldosteronism (72.6 %). All subjects underwent a non-invasive evaluation of retinal arteriolar wall-to-lumen ratio (WLR) by Adaptive Optics. Subjects were re-evaluated after an average follow-up time of 4.55 years in order to assess the occurrence of clinical events (non CV and/or CV death or events). ResultsFifty-four events occurred in the study population:26 were cardio-cerebrovascular events (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, cardiac valvular disease) while the remaining were deaths for any cause, or neoplastic diseases. Subjects with events were older and had a WLR of retinal arterioles significantly greater than those without events. The event-free survival was significantly worse in those with a baseline WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (Cox's proportional hazard model). The evidence was confirmed after restricting the analysis to CV events. ConclusionsStructural alterations of retinal arterioles evaluated by Adaptive Optics may predict total and CV events.

Expression of functional mineralocorticoid receptor (MR) and G-protein coupled estrogen receptor (GPER) in human T lymphocytes

Aldosterone plays a key role in controlling blood pressure (BP) values by maintaining body salt, water, and fluid homeostasis. Excess aldosterone production is associated with arterial hypertension, cardiovascular and metabolic diseases, partly via generation of an inflammatory state followed by fibrotic changes in the organs that are target of hypertension. Aldosterone exerts genomic effects that are known to involve activation of the mineralocorticoid receptor (MR). Other aldosterone effects, including those usually defined as ‘rapid’ or ‘non genomic’, involve additional receptors as the G-protein coupled estrogen receptor (GPER). To date, the receptor(s) implicated in the inflammatory action of aldosterone in cells of the innate and adaptive immunity are unknown. Considering the potential role of T-lymphocytes in adaptive immunity in arterial hypertension and related hypertension-mediated organ damage (HMOD), we herein investigated and quantified the expression of the MR and GPER in human CD4+ and CD8+ T-cells. Results provided compelling evidence for the presence at the mRNA and protein level and suggest a functional role of these receptors in the two T-lymphocyte subtypes, thus indicating that they can represent a potential target for modulation of steroid hormone-induced inflammation and ensuing HMOD.

FRI126 Autoreactive T Cells To Angiotensin II Type 1 Receptor In Salt-dependent Hypertension Due To Primary Aldosteronism

Abstract Disclosure: R. Scarpa: None. M. Piazza: None. B. Caroccia: None. S. Carraro: None. F. Vianello: None. F. Cinetto: None. C. Agostini: None. T.M. Seccia: None. G. Rossi: None. Compelling evidence suggested a role of acquired immunity in hypertension and hypertension-mediated organ damage (HMOD), but the pathogenic role of this acquired immunity is still unknown. Primary Aldosteronism, the paradigm of salt-dependent hypertension, is characterised by a more prominent HMOD than primary (‘essential’) hypertension and by high titer of autoantibodies against the type 1 angiotensin receptor (AT1R). As T cells are broadly recognised as HMOD-mediators, we aim to investigate: 1) the presence of AT1R-autoreactive T cells in PA; 2) aldosterone rapid and chronic effect on AT1R-autoreactive T lymphocytes; 3) the presence and functional role of know aldosterone receptors on T lymphocytes. The presence of AT1R-autoreactive T cells in 11 PA patients was investigated by flow cytometry after stimulation with pool of peptides spanning the full length of AT1R. The expression of mineralocorticoid receptor (MR) and G Protein-Coupled Estrogen Receptor (GPER) on T cells was tested by measuring mRNA copy number by droplet digital PCR and immunoblotting from healthy donors (HD) subjects and PA patients. Peripheral blood mononuclear cells (PBMCs) from PA patients were exposed to aldosterone 10-10 M with or without MR antagonist (canrenone) and GPER agonist (G1) and antagonist (G36). We evaluated the effect of aldosterone on CD8+ T cells by measuring IFNɣ release with flow cytometry. PA patients were found to have CD8+ AT1R-autoreactive T cells after activation of PBMC with AT1R peptides. MR and GPER were detected both at mRNA and protein level in CD4+ and CD8+ T cells with the following rank of expression GR&amp;gt;MR&amp;gt;&amp;gt;GPER. Aldosterone significantly increased IFNɣ release in CD8+ T-cell both under chronic and acute stimulation. Chronic exposure to aldosterone increased IFN-γ production by CD8+ T cells by acting via the MR, as it was prevented (p &amp;lt; 0.004) by canrenone, while the rapid aldosterone action was MR and GPER mediated, as it was reduced by canrenone (p &amp;lt; 0.003), but also by G36 (p &amp;lt; 0.02), and mimicked by G1. These results showed the presence of AT1R-autoreactive T cells in patients with PA. Moreover, upon of MR and GPER receptor stimulation with aldosterone, AT1-R specific CD8+ T cells undergo profound changes that mediated a strong cytotoxic response towards AT1-R-expressing organs. Presentation: Friday, June 16, 2023

The Importance of Out-of-Office Blood Pressure Measurement, as Highlighted by the Correlation with Left Ventricular Hypertrophy in an Untreated Hypertensive Population.

Background and Objectives: Hypertensive heart disease, especially left ventricular hypertrophy (LVH), is considered to be one of the main types hypertension-mediated organ damage. Hence, the purpose of this study was to examine which method of measuring BP (office BP measurement (OBPM), 24 h ambulatory BP monitoring (ABPM), or home BP monitoring (HBPM)), can be better correlated with echocardiographic LVH in the untreated hypertensive population. Materials and Methods: This study's population consisted of 202 patients 58 ± 15 years old (40.8% males). All patients reported elevated home BP measurements for at least 3 months, but they had never been treated before for hypertension. Office and out-of-office BP measurements, including ABPM on a usual working day and seven-day HBPM, as well as 2D echocardiography, were performed. Results: In the univariate analysis, LVH was associated (p < 0.05) with a mean 24 h systolic BP (OR: 1.93, CI: 1.29-2.91), a mean 24 h diastolic BP (OR: 1.30, CI: 1.16-1.80), ambulatory daytime systolic (OR: 1.11, CI:1.01-1.82) and diastolic BP (OR: 1.13, CI:1.09-1.17), ambulatory nighttime systolic BP (OR: 2.11, CI: 1.04-4.31), and mean home systolic BP (OR: 1.05, CI:1.01-1.12). Pearson's correlation analysis showed a significant correlation between the LV mass index and the mean 24 h systolic BP (r = 0.58, p < 0.05), daytime systolic BP (r = 0.59, p < 0.05), and nighttime systolic BP (r = 0.57, p < 0.05). Most of the population with confirmed LVH presented confirmed hypertension (based on ABPM, 48.1% or HBPM, 40%). The second most dominant phenotype was masked hypertension (ABPM, 32.7% and HBPM, 23.7%). The majority (59.3%) had non-dipping status, 20.4% had a reverse dipping pattern, 13% had a dipping pattern, and only 7.3% had extreme dipping BP. Conclusions: Out-of-office BP measurement devices seemed to be superior compared to in-office. This advantage is highlighted by better correlations in the identification of LVH as well as the diagnosis of masked hypertension, a condition also highly correlated with LVH.

Hypertension-mediated organ damage involving multiple sites is an independent risk factor for cardiovascular events.

Chronic pressure overload determines functional and structural alterations, leading to hypertension-mediated organ damage (HMOD), affecting multiple districts. We aim at evaluating the prognostic impact of the absence vs. presence of HMOD in one or more sites and of blood pressure (BP) and metabolic control in hypertensive patients. The study included 7237 hypertensive patients from the Campania Salute Network Registry, followed up for 5.3 ± 4.5 years. As HMOD, we analysed the presence of left ventricular hypertrophy, carotid plaques, and chronic kidney disease (CKD-EPI ≥3 stage) and evaluated the impact of zero vs. one vs. two vs. three sites of HMOD on the occurrence of major adverse cardiovascular events (MACEs). Blood pressure control and Metabolic Score for Insulin Resistance (METS-IR) were also considered. Optimal BP control was achieved in 57.3% patients. Major adverse cardiovascular events occurred in 351 (4.8%) patients. The MACE rate in patients without HMOD was 2.7%, whereas it was 4.7, 7.9, and 9.8% in patients with one, two, and three sites with HMOD, respectively. By using Cox multivariate models, adjusted for age, BP control, mean heart rate, mean METS-IR, number of HMOD sites, and drugs, MACE was found to be significantly associated with ageing, mean METS-IR, anti-platelet therapy, and multiple sites with HMOD, whereas a negative association was found with renin-angiotensin system inhibitor drugs. In hypertensive patients, the risk of MACE increases with the incremental number of districts involved by HMOD, independent of BP control and despite the significant impact of metabolic dysregulation. Hypertension-mediated organ damage involving multiple sites is the deleterious consequence of hypertension and dysmetabolism but, when established, it represents an independent cardiovascular risk factor for MACE occurrence.

Central blood pressure obtained by cuff-based oscillometry as a determinant of left ventricular hypertrophy in hypertensive patients.

Limited and conflicting data have been reported on the prognostic relevance of central blood pressure (CBP) compared with brachial blood pressure (BP) in the anticipation of hypertension-mediated organ damage and the majority of data derived using applanation tonometry with its known complexities. The objective of the present study was to investigate the diagnostic factors of left ventricular hypertrophy (LVH) with a special highlight on the utility of non-invasive oscillometric CBP measurement and derived hemodynamic indices compared to brachial BP as indicators of LVH. This cross-sectional study included 300 hypertensive patients (mean age 55.3 years, 61.3% female, 51.7% obese) with a mean duration of hypertension was 5.8 years. They underwent measurement of brachial BP, using a mercury sphygmomanometer, and CBP, using a Mobil-O-Graph, alongside the determination of left ventricular (LV) mass by two-dimensional transthoracic echocardiography. LVH and LV geometric patterns were defined by LV mass index/height 2.7 and relative wall thickness. Bivariate then multivariate analysis showed that age, BMI, central systolic BP (SBP), and pulse wave velocity (PWV) were significant determinants of LVH and optimally controlled brachial BP was a significant negative determinant for LVH. Central SBP had an acceptable diagnostic performance to determine LVH in patients with hypertension (AUC = 0.722, 95% confidence interval: 0.618-0.824, SE = 0.21, P -value <0.001). Using one-way ANOVA, a comparison of means among age groups showed that the steady increase in central SBP and PWV with aging was greater among LVH patients than non-LVH patients. Estimated central SBP using Mobil-O-Graph showed a significantly higher correlation to LVH than brachial SBP values. The consistent increase in central SBP and PWV with aging was greater among LVH patients than non-LVH patients.

Prevalence and predictors of resistant hypertension among out-patients in Ilorin, Nigeria

Introduction: Systemic hypertension (SH) contributes the highest number of deaths from cardiovascular diseases worldwide. Patients  with resistant hypertension (RH) are more prone to hypertension-mediated organ damage. RH has not been well-studied in Africa,  despite the fact that the prevalence of SH is highest in Africa. The aim of the study was to establish the prevalence and predictors of RH  among out-patients managed in the cardiology unit of the University of Ilorin Teaching Hospital, Ilorin, Nigeria.&#x0D; Method: A cross-sectional study of 201 patients selected via systematic random sampling between April and September 2019.&#x0D; Results:  Mean age of the participants was 59.6 (SD 13.8) years, females 58.7%, 32.3% were non-obese, 17 (8.5%) consumed alcohol and three (1.5%) smoked tobacco. 30 participants (14.9%) had co-morbid diabetes mellitus. Systolic blood pressure (SBP) and diastolic blood  pressure (DBP) were significantly higher among patients with RH 152.5 (SD 18) mmHg vs 131.9 (SD 18.4) mmHg (p&lt;0.001) and 89.43 (SD  13.8) mmHg vs 79.46 (SD 10.5) mmHg (p=0.008). Eighteen patients (8.96%, 95% CI: 5.5-14%) had RH. The predictors of RH were obesity  (OR= 3.754; p=0.009), SBP at patients’ first clinic visit, (OR=1.029, p=0.032), DBP at patients’ first clinic visit, (OR=1.048, p=0.014), and serum  phosphorus, (OR=1.047, p=0.047).&#x0D; Conclusion: The prevalence of RH among our patients is low and is similar to that in studies  with similar blood pressure cut-off values and case definition.