Target Organ Damage Research Articles

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Systemic Immune Inflammatory Index as Predictor of Blood Pressure Variability in Newly Diagnosed Hypertensive Adults Aged 18–75

Background: Accumulating evidence from clinical trials, large registries, and meta-analyses of population studies shows that increased Blood Pressure Variability (BPV) is predictive of Cardiovascular (CV) outcomes, independently of the average Blood Pressure (BP) values. One of the mechanisms explaining the relationship between BPV and target organ damage is the inflammatory response. The Systemic Immune Inflammation Index (SII), which relies on peripheral blood cell counts, including platelets, neutrophils, and lymphocytes, has emerged as a predictor of prognosis and outcomes in various diseases. The aim of this study was to investigate the association of the SII with Ambulatory Blood Pressure Variability (ABPV) in newly diagnosed hypertensive patients. Methods: This study was designed as a cross-sectional observational study. A total of 1606 consecutive newly diagnosed Hypertension (HT) patients were included in the study. The population was evaluated across 3 different categories according to HT grades (5 groups), eligibility for antihypertensive therapy (2 groups) and ABPV levels (2 groups). Results: Significant differences were observed between ABPV groups in terms of Neutrophil to Lymphocyte ratio, Platelet to Lymphocyte ratio, glucose, SII, high-sensitive CRP, HT grade, Inter-Ventricular Septum, Posterior Wall thickness, and Left Ventricular Mass (p < 0.005). There was a significant relationship between SII and ABPV (r: 0.619, p < 0.05). At the cutoff value of 580.49, SII had 77% sensitivity and 71% specificity for ABPV > 14 (AUC: 0.788). Conclusions: SII may assist in developing an early treatment approach to minimize complications in patients with high ABPV who are at a higher risk of CV events.

Dendritic cell mineralocorticoid receptor controls blood pressure by regulating T helper 17 differentiation: role of the Plcβ1/4-Stat5-NF-κB pathway.

Dendritic cells (DCs) are closely related to blood pressure (BP) regulation. Mineralocorticoid receptor (MR) is an important drug target for antihypertensive treatment. However, the role of DC MR in the pathogenesis of hypertension has not been fully elucidated. This study aimed to determine the role of DC MR in BP regulation and to explore the mechanism. Renal biopsy and peripheral blood samples were collected from hypertensive patients (HTN) for immunostaining and flow cytometry. Dendritic cell MR knockout (DCMRKO) mice, DC MR overexpressing (DCMROV) mice, DCMROV/IL-17A knockout (DCMROV/IL-17AKO) mice and finerenone-treated C57BL/6 mice were infused with angiotensin II (Ang II) to establish hypertensive models. Western blotting, chromatin immunoprecipitation, co-immunoprecipitation, and in vivo DC depletion or adoptive transfer were used to delineate the functional importance of DC MR in hypertension development. Mineralocorticoid receptor antagonists (spironolactone and finerenone) suppressed DC aggregation and activation, as well as hypertension in HTN and mice. Compared with littermate control (LC) mice, dendritic cell MR knockout mice had strikingly decreased BPs and attenuated target organ damage after Ang II infusion. Flow cytometry showed that DC MR deficiency mitigated Ang II-induced DC activation and T helper 17 (Th17) cell differentiation. RNA sequencing revealed that MR-deficient DCs had elevated expression of Plcβ1 and Plcβ4, knockdown of which reversed the inhibitory effect of MR deficiency on DC activation and Th17 differentiation. Adoptive transfer of MR-deficient DCs protected Ang II-induced hypertension, whereas knockdown of Plcβ1/4 eliminated the protective effects. At the molecular level, MR negatively regulated Plcβ1/4, which recruited SHP-1 to inactivate of Stat5 activity, resulting in enhanced NF-κB activation and Th17 polarization. Furthermore, DCMROV mice manifested more elevated BPs and target organ damage than control mice after Ang II infusion, and these differences were abolished in DCMROV/IL-17AKO mice. Finally, MR antagonists decreased the aggregation of Th17 in HTN and mice. Dendritic cell MR plays important roles in the pathogenesis of hypertension by regulating Th17 through Plcβ1/4-Stat5-NF-κB signalling, and blockade of DC MR is beneficial for treating hypertension.

What are the risk factors for ascending aorta dilatation in the non-diabetic normotensive population? A cross-sectional study in China

ObjectivesAscending aorta dilatation (AAD) has been suggested as a surrogate marker for vascular organ damage in the hypertensive population. However, limited data are available on AAD in normotensive individuals. This...

Thoracic Aortic Three-Dimensional Geometry.

Aortic structure impacts cardiovascular health through multiple mechanisms. Aortic structural degeneration occurs with aging, increasing left ventricular afterload and promoting increased arterial pulsatility and target organ damage. Despite the impact of aortic structure on cardiovascular health, three-dimensional (3D) aortic geometry has not been comprehensively characterized in large populations. We segmented the complete thoracic aorta using a deep learning architecture and used morphological image operations to extract multiple aortic geometric phenotypes (AGPs, including diameter, length, curvature, and tortuosity) across various subsegments of the thoracic aorta. We deployed our segmentation approach on imaging scans from 54,241 participants in the UK Biobank and 8,456 participants in the Penn Medicine Biobank. Our method provides a fully automated approach towards quantifying the three-dimensional structural parameters of the aorta. This approach expands the available phenotypes in two large representative biobanks and will allow large-scale studies to elucidate the biology and clinical consequences of aortic degeneration related to aging and disease states.

Hypertension guideline implementation and blood pressure control in Matlosana, South Africa.

High systolic blood pressure remains a leading modifiable risk factor for cardiovascular diseases worldwide and in South Africa (SA). Information about the extent of guideline implementation and blood pressure (BP) control is lacking in Matlosana Sub-district, North West province, SA. The study aimed to assess the implementation of the South African Hypertension Practice Guideline (SAHPG) and BP control in adults attending primary care facilities in Matlosana. Cross-sectional study was conducted, using 523 randomly sampled medical records. Data collected included demographic information, recorded BP readings, anthropometry, screening for target organ damage (TOD), hypertension complications, comorbidities, lifestyle advice and drug therapy. According to the reviewed records the mean age of the participants was 56.77 years with a standard deviation of 12.4 years and 376 (71.9%) records belonged to females. Blood pressure control was documented in 229 (43.8%) of the medical records, with better control recorded in a group with comorbid human immunodeficiency virus (HIV) than in groups with other comorbidities. The study found poor documentation of the SAHPG recommendations among patients with hypertension. According to the patient records BP control was suboptimal, the most common documented comorbid illness was HIV, and screening for TOD was generally poorly documented.Contribution:Programmes that audit and improve the quality of hypertension guideline implementation and BP control in primary care require ongoing support and research.

Antihypertensive treatment of masked hypertension guided by ambulatory blood pressure monitoring: a double-blind, placebo-controlled trial

Abstract Background Masked hypertension, office normotension combined with out-of-office hypertension, is associated with target organ damage (TOD), but whether antihypertensive treatment guided by out-of-office blood pressure (BP) would reduce TOD is unproven. Purpose To assess TOD change on antihypertensive treatment guided by ambulatory BP monitoring. Methods We conducted a double-blind, placebo-controlled randomized trial at 15 Chinese hospitals. Enrolment started on February 14, 2017 and follow-up ended on October 31, 2021. Patients of either sex, aged 30-70 years, not on antihypertensive drugs were eligible, if at two screening visits 1-week apart office BP was <140/<90 mm Hg and the 24 hour, daytime or nighttime ambulatory BP was ≥130/≥80, ≥135/≥85, or ≥120/≥70 mm Hg, respectively. Patients had ≥1 sign of TOD: ECG left ventricular hypertrophy (LVH), brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s, or urinary albumin-to-creatinine ratio (ACR) ≥3.5 mg/mmol in women and ≥2.5 mg/mmol in men. Active antihypertensive treatment consisted of allisartan starting at 80 mg/day to be increased to 160 mg/day at month 2 and to be combined with amlodipine 2.5 mg/day at month 4, if the ambulatory BP remained uncontrolled. Matching placebos were used likewise in the control group. The primary endpoint included normalization of baPWV, ACR or LVH or ≥20% reduction in baPWV or ACR. Results Of 320 patients (43.1% women; mean age 54 years), 153 were randomized to active antihypertensive treatment and 167 to placebo. At baseline, office BP averaged 130/81 mm Hg and the 24 hour BP 136/84 mm Hg. The prevalence of elevated baPWV, ACR and LVH was 97.5%, 12.5%, and 7.8%. The 24-hour systolic/diastolic decreased by 9.0/5.6 mm Hg (95% CI: 7.5-10.5/4.8-6.5 mm Hg) on active treatment and by 1.4/1.0 mm Hg (-0.1-2.8/0.2-1.8 mm Hg) on placebo. Regression of TOD, the primary outcome, occurred more frequently in patients randomized to active treatment than in those assigned to placebo with 1 year rate of 45.8% (95% CI: 37.9-53.7%) and 25.8% (19.1-32.4%), respectively (P<.001 for between-group differences in BP and TOD). Per-protocol and subgroup analyses were confirmatory. Conclusions Masked hypertensive patients require antihypertensive treatment guided by out-of-office BP monitoring before subclinical TOD progresses to major cardiovascular complications.

Exaggerated blood pressure response to submaximal exercise must be considered relative to fitness: strong associations with hypertensive target organ damage

Abstract Exaggerated systolic blood pressure (SBP) during submaximal exercise is associated with increased cardiovascular (CV) risk. However, findings are mixed and new evidence indicates that cardiorespiratory fitness should be considered for proper clinical interpretation of exercise SBP responses. This study aimed to determine the relationship between SBP response to submaximal effort corrected for fitness and abnormalities of cardiac structure and function. Methods Each of 231 participants (age 54±12 years; 53% females) with controlled clinic BP, no evidence for ischemic heart disease, valvular heart disease or heart failure underwent cardiopulmonary exercise testing (Bruce protocol), resting and exercise echocardiography and 24h ABPM. Submaximal exercise SBP (measured at the 2nd stage of Bruce protocol) was corrected for two fitness variables: 1) peak VO2 and 2) maximal workload in METs (SBP/peakVO2 and SBP/METs). Results There were no, or weak, associations with exercise SBP and target organ damage. However, there was a progressive deterioration of cardiac function and structure parameters across the exercise SBP tertiles corrected for fitness (Table 1). Both SBP/peakVO2 and SBP/METs significantly correlated with left ventricular (LV) mass, LV diastolic and systolic, and left atrial parameters (Table 2). ROC analysis revealed good performance of corrected SBP response to submaximal exercise in detection of LV hypertrophy and diastolic dysfunction (AUC 0.792 and 0.808, and 0.771 and 0.802 for SBP/peakVO2 and SBP/METs, respectively; Figure). Conclusions Fitness-corrected SBP responses to submaximal exercise can identify more profound target organ damage with respect to cardiac function and structure even among patients with controlled clinic BP. Exaggerated BP response to exercise must be considered relative to fitness for proper clinical interpretation of BP responses to exercise testing.Figure

The relationship between lung MIBG uptake and clinical response to renal denervation

Abstract Background Renal denervation (RDN) reduces the sympathetic overdrive and can optimize blood pressure control in patients with difficult-to-treat hypertension (DTH). However, a substantial proportion of patients undergoing RDN do not show a clinical response to the procedure, making it critical to identify novel and more accurate predictors. The metaiodobenzylguanidine (MIBG) scintigraphy allows non-invasive assessment of sympathetic nerve activity. Yet, studies evaluating the heart and kidney MIBG uptake as predictors of clinical response to RDN provided conflicting results, and a comprehensive evaluation of the MIBG uptake in different organs of DTH patients undergoing RDN is lacking. Purpose To explore if a more comprehensive evaluation of MBG uptake in the kidneys, heart and lungs can predict the clinical response to RDN. Methods Eighteen patients with DTH underwent evaluation of their clinical and pharmacological history, office and ambulatory BP values and levels of cardiovascular risk factors. A rest echocardiography, carotid vascular ultrasound and MIBG scintigraphy were also performed before RDN. The patient’s pharmacological history and office and ambulatory BP values were re-evaluated after 3 months from RDN. We considered responders (R) those subjects with a significant reduction of the office BP values on stable BP-lowering treatment or a reduced burden of BP-lowering medications while maintaining optimal control of the office BP. Results Ten patients could be classified as R (1 woman, mean age 49±10 years), while 7 were non-responders (NR, 2 women, mean age 53±8 years). The reduction in office systolic and diastolic BP (baseline vs 3 months) was significantly larger in R vs NR (p=0.01 for both). The burden of BP-lowering medications after the procedure was reduced by 39% in R, compared to 2% in NR (p<0.01). Responders had a higher baseline HR and prevalence of carotid atherosclerosis than NR (p<0.05 for both). In early MIBG acquisitions, the lung/mediastinum ratio on both sides showed higher MIBG uptake in R vs NR (p<0.05). There was a higher MIBG uptake in the right vs. left lung in the whole population and in R vs NR. In late acquisitions, only the left side showed a significant difference between R and NR (p<0.05). The associations between the lung/mediastinum ratio MIBG uptake and response to RDN remained significant after adjusting for the baseline clinical predictors of the RDN response. All other MIBG scintigraphy parameters were similar between groups. Conclusions Our results suggest that RDN might be less effective in patients with an advanced burden of hypertension-mediated target organ damage and confirm a higher HR as a reliable predictor of the clinical response to the procedure. We also document a novel association between the lung/mediastinum ratio MIBG uptake and response to RDN that, if confirmed in future studies, might provide a novel marker to improve the selection of patients undergoing RDN.

Integrity of central nervous autonomous tracts is associated with cardiac function, cardiovascular risk factors, organ damage and major adverse cardiovascular events

Abstract Background Alterations in the central autonomic nervous system have been linked to the pathogenesis of cardiovascular (CV) risk and disease. Moreover, these conditions are treatable by pharmacological or interventional modification of the activity of the autonomic nervous system. Purpose The UK Biobank enables the investigation of the relationship between changes in the CAN and CV function or disease within a large population. Microstructural integrity of the CAN was assessed for associations with cardiac function, CV risk and damage representations, and major adverse cardiovascular events (MACE). Method Microstructural diffusion metrics for 7 CAN tracts were estimated using a Bayesian approach, which determines the three components of a standard white matter-based tissue model: 1. the free water fraction (CSF); 2. the fraction within neuronal processes, i.e. axons and dendrites (INTRA); and 3. the fraction outside of axons or dendrites (EXTRA), representing the cellular compartment and the extracellular matrix. Volume fractions of the three microstructural components were analysed for associations with cardiac index, blood pressure, CV target organ damage (arterial stiffness, left ventricular mass, and wall thickness), and MACE, using covariate-adjusted regression models that corrected for multiple comparisons. Results Analysis of cardiac function in 26,302 participants revealed significant associations between cardiac index and CAN regions in the cortical and subcortical networks. Arterial stiffness was significantly associated with markers of microstructural integrity in the cortical networks only (n=22,491), while systolic (n=34,114) and diastolic blood pressure (n=34,130), left ventricular mass (n=22,491) and wall thickness (n=22,491) showed extensive associations with the cortical and subcortical CAN. MACE (n=33,444) was associated with cortical markers of microstructural integrity of the CAN in limbic pathways (significant CANs all p<0.002) and the CAN pathways connecting cortical areas (significant CANs left all <0.001, right=0.001). The observed pattern of microstructural metrics suggests that the integrity of neural connections (intra-fraction) positively correlates with adverse outcomes, while an increase in free fluid (CSF) volume was typically associated with a negative impact. Conclusion In this analysis, markers of CAN integrity and degradation showed extensive associations with indicators of CV function, risk factors, damage parameters, and outcomes. This evidence supports the crucial role of autonomic regulation in cardiovascular disease. Future research is needed to determine whether these associations indicate harmful processes, such as neuroinflammation, contributing to cardiovascular (CV) risk and disease development, or if they are consequences of pre-existing elevated risk factors or events.CANs associated with MACEAssociations of CAN with CV organ damage

The role of IL15 in angiotensin II-mediated cardiac remodelling

Abstract Hypertension (HTN) mediated target organ damage, such as cardiac remodelling, is a major cause of death and disability. Cytokines are important regulators of cardiac function, inflammation, and remodelling in cardiovascular disease. Increased levels of interleukin 15 (IL15) have been noted in HTN, but its role in HTN heart disease remains unknown. This study investigates the role of the IL15 axis in the pathogenesis of cardiac remodelling in HTN. Male 12-week-old IL15 receptor α knock-out (IL15RAKO), IL15 knock-out (IL15KO) and matching wild type (WT) mice were administered vehicle or angiotensin II (AngII) (490 ng/min/kg) for 2 weeks by osmotic minipump. Blood pressure was measured by tail cuff (n=5-8). Cardiac function was analysed by echocardiography (n=3-4). Cardiac infiltrating immune cells were analysed by flow cytometry (n=2-3 for IL15RAKO, n=6-10 for IL15KO). Cardiac remodelling was assessed by picrosirius red, WGA staining (n=5-8) and expression of markers of remodelling using RT-qPCR and western blots (n=5-8). Data are presented as mean±SEM and analysed using two-way ANOVA. AngII infusion caused a significant increase in systolic blood pressure in WT and IL15KO animals. In contrast, in IL15RAKO, the response to AngII was blunted. This was in line with a decrease in ejection fraction, however only WT mice had an increase in global longitudinal strain (-20.3±2.0 vs -10.9±1.2, p=0.0039 in WT and 19.9±0.8 vs -16.0±2.1, p=0.1878 in IL15RAKO). HTN was associated with increased cardiac IL15 protein levels in mice. The heart-to-body ratio, along with cardiomyocyte cross-sectional, were significantly increased in WT, but not in IL15RAKO HTN mice. Furthermore, histological analysis showed significantly higher cardiac collagen accumulation in WT but not IL15RAKO upon AngII infusion (5.8±1.0% in WTvvs. 2.1±0.5% in IL15RAKO, p=0.0021). This was in line with a higher expression of col1a1 in WT but not IL15RAKO HTN hearts (20.0±6.0 vs 4.5±1.7, p=0.0173). Similarly, the FN1 protein level was significantly increased in WT but not IL15RAKO AngII-treated mice. These changes were associated with a higher number of Cd11b+ macrophages accumulated in WT hypertensive hearts only. In contrast to IL15RAKO, mice lacking IL15 showed similar increases in global longitudinal strain, heart hypertrophy, and cardiomyocyte cross-sectional area as WT mice upon AngII infusion. Similarly, IL15KO hypertensive hearts showed a significant increase of col1a1 and FN1 in comparison to vehicle-treated mice. A similar level of Cd11b+ macrophages was found in hypertensive IL15KO and WT mice's hearts. In conclusion, IL15RA, but not IL15, plays a critical role in cardiac remodelling mediated by AngII infusion. This suggests that the IL15-IL15RA axis may play an important yet complex role in hypertensive heart disease.

One-year risk of all-cause death and major cardiovascular events in patients presenting with hypertensive crisis. A report from a global federated research health network

Abstract Background Few data are available about the clinical course of patients presenting with hypertensive crisis who are discharged alive from hospital. Purpose To assess the long-term risk of adverse events in patients with hypertensive crises. Methods Retrospective study utilizing a research health network. Based on the ICD-10-CM codes recorded between 2000 and 2022, from 85 health care associations mainly located in the United States, patients with hypertensive crisis were subdivided into hypertensive urgencies (I16.0) and hypertensive emergencies (I16.1). In those with hypertensive emergencies, the type of target organ damage was reported, ie. central nervous system (ischemic stroke, hypertensive encephalopathy, intracerebral hemorrhages), cardiovascular (CVS: myocardial infarction (MI), heart failure (HF), aorta dissection (AD)), or renal (acute kidney failure). Primary outcomes were the one-year risks of all-cause death, and major cardiovascular events (MACE: MI, stroke, cardiac arrest, AD, and HF). Secondary outcomes were the risks for each type of MACE. Cox regression analysis after propensity score matching (PSM) 1:1 was used to produce hazard ratios (HRs) and 95% Confidence Intervals (95%CIs). Results Overall, we identified 25 294 patients with hypertensive emergency (age 62.4±15.7, 46.1% females) and 21,737 patients with hypertensive urgency (age 63.5±17.2, 55.5% females). Patients with hypertensive emergency were more likely males, Black or African American origin and showed a higher prevalence of chronic hypertensive-related complications, vs. those with hypertensive urgency. After PSM, patients with hypertensive emergency showed a higher risk of all-cause death (HR, 1.34, 95%CI 1.25-1.44) and MACE (HR 4.09, 95%CI 3.87-4.33), vs. those with hypertensive urgency. Of the secondary outcomes, patients with hypertensive emergency had increased risks of MI (HR 3.33, 95%CI 3.03-3.67), stroke (HR 4.73, 95%CI 4.33-5.17), cardiac arrest (HR 1.30, 95%CI 1.07-1.58), AD (HR 5.49, 95%CI 3.90-7.73), and HF (HR 3.01, 95%CI 2.74-3.14). All the different types of organ involvement during the hypertensive emergency were each associated with similar long-term risks of adverse events (Figure 1). Conclusion Patients with hypertensive emergency have a high long-term risk of MACE and all-cause death. Preventing the onset of target organ damage in patients with hypertensive crisis is crucial to mitigate their long-term risk of adverse events.

Improvement of the Immunity System Through Sports: Novel Regulatory Mechanisms for Hypertension.

Hypertension and its resulting target organ damage is a complex process associated with a range of physiological and molecular factors, including immune regulation. The profound effects of exercise on normal immune system function and the development and progression of hypertension are well known. This review aims to create new avenues for preventing and treating hypertension and its associated target organ damage. This narrative review emphasizes the role of exercise training in the prevention/treatment of hypertension development through immune response modulation and presents current perspectives on the available scientific evidence. Several studies have shown that exercise regulates hypertension by altering immune cells, which is partly attributable to the anti-inflammatory effects of exercise training. Regular exercise modifies immune modulation and could represent a new mechanism for regulating hypertension. Although the utilization of exercise training and the immune system in conjunction for treating and preventing hypertension is still in its early stages, current scientific literature indicates numerous potential physiological links between exercise training, the immune system, and hypertension.

Differences in target organ damage between captopril challenge test-defined definitive-positive and borderline-range groups among patients with primary aldosteronism.

The new Japanese guidelines for primary aldosteronism introduce a category in the judgment of functional confirmatory tests that is called the "borderline range," which is rare in the other international guidelines. The clinical characteristics of this borderline group are not yet understood. To investigate whether this borderline group has any significant differences in terms of target organ damage, we used data from a Japanese nationwide registry (JPAS-II) of individuals with primary aldosteronism or essential hypertension to compare the borderline group with the definitive-positive group and the negative group. We analyzed the cases of 1785 patients based on their captopril-challenge test results. Since the JPAS-II database contains plasma aldosterone concentration values obtained based on both radioimmunoassay (n = 1555) and chemiluminescent enzyme immunoassay (n = 230) principles, we converted these values to their equivalents as if measured by chemiluminescent enzyme immunoassay and conducted all analyses under the simulated condition. Multicovariate-adjusted models revealed significant prevalance odds ratios for chronic kidney disease (2.01, 95% confidence interval: 1.13 to 3.61), electrocardiographic abnormalities (1.66, 95% confidence interval: 1.16 to 2.37). No significant difference was observed between the borderline and negative groups in these assessments (odds ratio [95% confidence interval] for chronic kidney disease: 0.73 [0.26 to 2.02] and electrocardiographic abnormalities: 1.01 [0.60 to 1.70]). We confirmed that the prevalence of target organ damage increases linearly as the aldosterone-to-renin ratio rises following the captopril challenge test. These results provide material to consider regarding the significance of the provisionally established borderline group.

Parathyroid carcinoma: molecular pathology and correlation with clinicopathologic features, a single center experience

Abstract Introduction/Objective Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single center regarding the clinic-pathologic and genetic analysis of parathyroid carcinoma cases. Methods/Case Report The study is a retrospective review of all patients with parathyroid carcinoma that were evaluated at a tertiary oncologic center from 2001 until 2023. Results (if a Case Study enter NA) A total of nine cases (6 male and 3 female) were identified, with a mean age at diagnosis of 52 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 7), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and a mean PTH of 1123 pg/ml (<a href=“tel:276- 2500”>276-2500</a>). En bloc surgical resection was performed in 6 patients and 3 patients underwent adjuvant radiotherapy. Recurrence was observed in 4 cases (44.4%) after a median of 24 months following surgery. Negative immunohistochemical staining of parafibromin was noted in 3/4 cases of recurrence. Parathyroid carcinoma was diagnosed on the basis of finding lesions with vascular or perineural invasion, capsular penetration, and/or documented metastases. Immunohistochemical staining for parafibromin, Ki-67, and E-cadherin was performed on formalin-fixed, paraffin-embedded tissue samples. Next generation sequencing (NGS) was performed in 6/9 cases and CDC73 mutations were present in 38.5% of analyzed patients. Loss of TP53 and RB1 alleles and CCND1 amplification were other reported genetic alterations in the study cohort. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Inactivating CDC73 alterations which include truncating or frameshift mutations, as well as missense mutations lead to the loss of parafibromin immunoreactivity. Other molecular alterations like PTEN and PIK3CA mutations may represent potential targets for molecular therapy. An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish parathyroid carcinoma from other parathyroid neoplasms.

Diagnostic and Therapeutic Approach to the Major Secondary Causes of Arterial Hypertension in Young Adults: A Narrative Review

Arterial hypertension in young adults, which includes patients between 19 and 40 years of age, has been increasing in recent years and is associated with a significantly higher risk of target organ damage and short-term mortality. It has been reported that up to 10% of these cases are due to a potentially reversible secondary cause, mainly of endocrine (primary aldosteronism, Cushing’s syndrome, and pheochromocytoma/paraganglioma), renal (renovascular hypertension due to fibromuscular dysplasia and renal parenchymal disease), or cardiac (coarctation of the aorta) origin. It is recommended to rule out a secondary cause of high blood pressure (BP) in those patients with early onset of grade 2 or 3 hypertension, acute worsening of previously controlled hypertension, resistant hypertension, hypertensive emergency, severe target organ damage disproportionate to the grade of hypertension, or in the face of clinical or biochemical characteristics suggestive of a secondary cause of hypertension. The 2023 Guideline of the European Society of Hypertension recommends starting pharmacological therapy from grade 1 hypertension (BP ≥140/90 mm Hg), with the aim of achieving BP control of less than 130/80 mm Hg. It is important to highlight that the prevalence of secondary hypertension in these patients could be underestimated, given that there is little evidence available on the management of high BP in young adults, which is why we developed this narrative review on the diagnostic and therapeutic approach to the major secondary causes of arterial hypertension in young adults.

HYPERTENSIVE CRISES: HYPERTENSIVE EMERGENCY AND CRISIS MANAGEMENT DURING ANESTHESIA

Introduction: hypertensive crisis is characterized by an acute and massive increase in blood pressure. Hypertensive crises encompass several clinical situations with different severity and prognosis, including hypertensive urgency and hypertensive emergency. The difference between the latter depends on whether the situation is life-threatening for the affected individual. Objective: to detail current information related to hypertensive crises, especially hypertensive emergency, definition, differentiation, etiology, epidemiology, pathophysiology, histology, clinical history, physical examination, management, differential diagnosis, prognosis and complications. Methodology: a total of 28 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 15 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: hypertensive crises, hypertensive emergencies, hypertensive emergencies, arterial hypertension. Results: approximately 1-2% of adults with hypertension suffer hypertensive crises. Multiple case series show that short-term treatment of hypertensive emergencies has good results; however, long-term results are unknown. The main drawback is that follow-up of individuals is lost and the medication regimen is frequently modified. Untreated hypertensive emergencies have very high morbidity and mortality and if the patient does not receive adequate education about the severity of hypertension, this trend is likely to continue. Conclusions: given the high prevalence of hypertension, it is crucial that health care professionals are able to differentiate between hypertensive emergencies and hypertensive emergencies to provide appropriate and timely treatment. Rapid blood pressure reduction is critical in the treatment of hypertensive emergencies. The choice of medications should consider both efficacy and safety to avoid further complications. A detailed clinical evaluation can help identify the underlying cause and guide treatment, highlighting the importance of an individualized approach. Lack of timely treatment can lead to severe consequences, emphasizing the need for proper management in critical situations. Constant training in the management of hypertensive emergencies is essential to reduce the morbidity and mortality associated with this condition.The management of hypertension during anesthesia is critical, as its prompt detection and control are fundamental to prevent serious complications. Despite the lack of specific criteria to suspend surgery in hypertensive patients, it is essential to evaluate each case individually, prioritizing target organ damage over blood pressure levels. KEY WORDS: crisis, emergency, urgency, hypertension.

Sirtuins and mechanisms of diabetic lung damage: a scientific discussion. A review

Induced tissue damage in target organs (kidneys, heart, eyes, liver, skin, nervous system) significantly contributes to the morbidity and mortality of patients from diabetes mellitus (DM). In recent decades, the question has been actively discussed: should the lungs be regarded as a target organ for diabetes? The c collected data demonstrate histological and functional lung disorders in DM patients. This suggests that the lungs are a target organ for diabetes. It is known that sirtuins regulate a number of physiological processes and affect obesity, insulin resistance, type 2 DM, heart disease and aging. In this review, we have tried to summarize the knowledge about the contribution of sirtuins to cellular regulation and the formation of pulmonary disease in patients with type 2 DM.

Role of aldosterone in various target organ damage in patients with hypertensive emergency: a cross-sectional study

BackgroundHypertensive emergency is a critical disease that causes multiple organ injuries. Although the renin-angiotensin-aldosterone system (RAS) is enormously activated in this disorder, whether the RAS contributes to the development of the organ damage has not been fully elucidated. This cross-sectional study was conducted to characterize the association between RAS and the organ damage in patients with hypertensive emergencies.MethodsWe enrolled 63 patients who visited our medical center with acute severe hypertension and multiple organ damage between 2012 and 2020. Hypertensive target organ damage was evaluated on admission, including severe kidney impairment (eGFR less than 30 mL/min/1.73 m2, SKI), severe retinopathy, concentric left ventricular hypertrophy (c-LVH), thrombotic microangiopathy (TMA), heart failure with reduced ejection fraction (HFrEF) and cerebrovascular disease. Then, whether each organ injury was associated with blood pressure or a plasma aldosterone concentration was analyzed.ResultsAmong 63 patients, 31, 37, 43 and 8 cases manifested SKI, severe retinopathy, c-LVH and ischemic stroke, respectively. All populations with the organ injuries except cerebral infarction had higher plasma aldosterone concentrations than the remaining subset but exhibited a variable difference in systolic or diastolic blood pressure. Twenty-two patients had a triad of SKI, severe retinopathy and c-LVH, among whom 5 patients manifested TMA. Furthermore, the number of the damaged organs was correlated with plasma aldosterone levels (Spearman’s coefficient = 0.50), with a strong association observed between plasma aldosterone (≥ 250 pg/mL) and 3 or more complications (odds ratio = 9.16 [95%CI: 2.76–30.35]).ConclusionIn patients with hypertensive emergencies, a higher aldosterone level not only contributed to the development of the organ damage but also was associated with the number of damaged organs in each patient.

The association of obesity and hyperuricemia with ambulatory blood pressure in children.

Primary hypertension (HTN) in children is on the rise and linked to the childhood obesity epidemic. Recent studies support the role of hyperuricemia in the pathogenesis of HTN. With this study we intend to evaluate the effect of body mass index (BMI) and uric acid levels on daily blood pressure (BP) parameters/phenotypes and target organ damage (TOD). A mean ambulatory systolic and/or diastolic BP ≥ 95th percentile or above the adolescent cut points was defined as 'HTN'. Patients were grouped as group 1 normal weight, and group 2 overweight/obese. Of the 140 children (89 male/51 female) with a mean age of 13.9 ± 2.6years, 21 were overweight and 86 were obese. Mean 24-h systolic BP (SBP) and daytime SBP were higher in group 2 (p = 0.015, p = 0.011). BMI was positively correlated with 24-h SBP (r = 0.272, p = 0.001) and daytime SBP (r = 0.280, p = 0.001). Uric acid level showed a moderate correlation with daytime SBP (r = 0.311, p < 0.01). Logistical regression analysis showed that daytime SBP is independently associated with obesity (OR 7.44, 95%CI 2.7-20.6, p < 0.001) and male sex (OR 4.60, 95%CI 2.0-10.2, p < 0.001), but not uric acid. Left ventricular hypertrophy was more common in non-dippers (p = 0.044). Male sex and BMI are independently associated risk factors for systolic BP. The association between non-dipping pattern and TOD suggests the widespread use of ambulatory blood pressure monitoring (ABPM) in childhood HT. In this paper, we could not demonstrate an independent association between uric acid and SBP. The effect of uric acid on SBP seems to be regulated by other metabolic factors in addition to uric acid.