Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy.

BACKGROUND: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification. However, the exact role of septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. METHODS: We investigated the function and mechanism of septin4 in hypertensive nephropathy to discover a theoretical basis for targeted treatment. Mouse models including Rosa 26 (Gt(ROSA)26Sor)-SIRT2 (silent mating type information regulation 2 homolog-2)-Flag-TG (transgenic) (SIRT2-TG) mice SIRT2-knockout, and septin4-K174Q mutant mice, combined with proteomic and acetyl proteomics analysis, followed by multiple molecular biological methodologies, were used to demonstrate mechanisms of SIRT2-mediated deacetylation of septin4-K174 in hypertensive nephropathy. RESULTS: Using transgenic septin4-K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of septin4 exacerbates Ang II (angiotensin II)- induced hypertensive renal injury resulting from oxidative stress. Proteomics and Western blotting assays indicated that septin4-K174Q activates the cleaved-PARP1 (poly [ADP-ribose] polymerase family, member 1)-cleaved-caspase3 pathway. In septin4-knockdown human renal podocytes, septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by Ang II. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the septin4 GTPase domain and deacetylates septin4-K174. In Sirt2-deficient mice and SIRT2-knockdown renal podocytes, septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes reexpressing wild-type SIRT2, septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. CONCLUSIONS: Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating Ang II-induced hypertensive renal injury. These findings indicate that septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.

Causal effects of hypertensive disorders of pregnancy on structural changes in specific brain regions: a Mendelian randomization study.

This study utilized Mendelian randomization to explore the impact of hypertensive disorders of pregnancy and their subtypes on brain structures, using genome-wide association study data from the FinnGen consortium for hypertensive disorders of pregnancy exposure and brain structure data from the ENIGMA consortium as outcomes. The inverse-variance weighted method, along with Cochran's Q test, Mendelian randomization-Egger regression, Mendelian randomization-PRESSO global test, and the leave-one-out approach, were applied to infer causality and assess heterogeneity and pleiotropy. Findings indicate hypertensive disorders of pregnancy are associated with structural brain alterations, including reduced cortical thickness in areas like the insula, isthmus cingulate gyrus, superior temporal gyrus, temporal pole, and transverse temporal gyrus, and an increased surface area in the superior frontal gyrus. Specific associations were found for hypertensive disorders of pregnancy subtypes: chronic hypertension with superimposed preeclampsia increased cortical thickness in the supramarginal gyrus; preeclampsia/eclampsia led to thinner cortex in the lingual gyrus and larger hippocampal volume and superior parietal lobule surface area. Chronic hypertension was associated with reduced cortical thickness in the caudal and rostral anterior cingulate and increased surface area of the cuneus and thickness of the pars orbitalis cortex. Gestational hypertension showed no significant brain region changes. These insights clarify hypertensive disorders of pregnancies' neurological and cognitive effects by identifying affected brain regions.

OTUD6A in tubular epithelial cells mediates angiotensin II-induced kidney injury by targeting STAT3.

Kidney fibrosis is a prominent pathological feature of hypertensive kidney diseases (HKD). Recent studies have highlighted the role of ubiquitinating/deubiquitinating protein modification in kidney pathophysiology. Ovarian tumor domain-containing protein 6 A (OTUD6A) is a deubiquitinating enzyme involved in tumor progression. However, its role in kidney pathophysiology remains elusive. We aimed to investigate the role and underlying mechanism of OTUD6A during kidney fibrosis in HKD. The results revealed higher OTUD6A expression in kidney tissues of nephropathy patients and mice with chronic angiotensin II (Ang II) administration than that from the control ones. OTUD6A was mainly located in tubular epithelial cells. Moreover, OTUD6A deficiency significantly protected mice against Ang II-induced kidney dysfunction and fibrosis. Also, knocking OTUD6A down suppressed Ang II-induced fibrosis in cultured tubular epithelial cells, whereas overexpression of OTUD6A enhanced fibrogenic responses. Mechanistically, OTUD6A bounded to signal transducer and activator of transcription 3 (STAT3) and removed K63-linked-ubiquitin chains to promote STAT3 phosphorylation at tyrosine 705 position and nuclear translocation, which then induced profibrotic gene transcription in epithelial cells. These studies identified STAT3 as a direct substrate of OTUD6A and highlighted the pivotal role of OTUD6A in Ang II-induced kidney injury, indicating OTUD6A as a potential therapeutic target for HKD.NEW & NOTEWORTHY Ovarian tumor domain-containing protein 6 A (OTUD6A) knockout mice are protected against angiotensin II-induced kidney dysfunction and fibrosis. OTUD6A promotes pathological kidney remodeling and dysfunction by deubiquitinating signal transducer and activator of transcription 3 (STAT3). OTUD6A binds to and removes K63-linked-ubiquitin chains of STAT3 to promote its phosphorylation and activation, and subsequently enhances kidney fibrosis.

Dynamic dysregulation of transcriptomic networks in brainstem autonomic nuclei during hypertension development in the female spontaneously hypertensive rat.

Neurogenic hypertension stems from an imbalance in autonomic function that shifts the central cardiovascular control circuits toward a state of dysfunction. Using the female spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat model, we compared the transcriptomic changes in three autonomic nuclei in the brainstem, nucleus of the solitary tract (NTS), caudal ventrolateral medulla, and rostral ventrolateral medulla (RVLM) in a time series at 8, 10, 12, 16, and 24 wk of age, spanning the prehypertensive stage through extended chronic hypertension. RNA-sequencing data were analyzed using an unbiased, dynamic pattern-based approach that uncovered dominant and several subtle differential gene regulatory signatures. Our results showed a persistent dysregulation across all three autonomic nuclei regardless of the stage of hypertension development as well as a cascade of transient dysregulation beginning in the RVLM at the prehypertensive stage that shifts toward the NTS at the hypertension onset. Genes that were persistently dysregulated were heavily enriched for immunological processes such as antigen processing and presentation, the adaptive immune response, and the complement system. Genes with transient dysregulation were also largely region-specific and were annotated for processes that influence neuronal excitability such as synaptic vesicle release, neurotransmitter transport, and an array of neuropeptides and ion channels. Our results demonstrate that neurogenic hypertension is characterized by brainstem region-specific transcriptomic changes that are highly dynamic with significant gene regulatory changes occurring at the hypertension onset as a key time window for dysregulation of homeostatic processes across the autonomic control circuits.NEW & NOTEWORTHY Hypertension is a major disease and is the primary risk factor for cardiovascular complications and stroke. The gene expression changes in the central nervous system circuits driving hypertension are understudied. Here, we show that coordinated and region-specific gene expression changes occur in the brainstem autonomic circuits over time during the development of a high blood pressure phenotype in a rat model of human essential hypertension.

Relationship between Androgens and Vascular and Placental Function during Pre-eclampsia.

Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men's pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998-2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

Racial and Economic Segregation Over the Life Course and Incident Hypertensive Disorders of Pregnancy Among Black Women in California.

Black women in the United States have the highest incidence of hypertensive disorders of pregnancy (HDP) and are disproportionately burdened by its adverse sequalae, compared with women of all racial and ethnic groups. Segregation, a key driver of structural racism for Black families, can provide information critical to understanding these disparities. We examined the association between racial and economic segregation at 2 points and incident HDP using intergenerationally linked birth records of 45,204 Black California-born primiparous mothers (born 1982-1997) and their infants (born 1997-2011), with HDP ascertained from hospital discharge records. Women's early childhood and adulthood neighborhoods were categorized as deprived, mixed, or privileged based on the Index of Concentration at the Extremes (a measure of concentrated racial and economic segregation), yielding 9 life-course trajectories. Women living in deprived neighborhoods at both time points experienced the highest odds of HDP (from mixed effect logistic regression, unadjusted odds ratio = 1.26, 95% confidence interval: 1.13, 1.40) compared with women living in privileged neighborhoods at both time points. All trajectories involving residence in a deprived neighborhood in early childhood or adulthood were associated with increased odds of HDP, whereas mixed-privileged and privileged-mixed trajectories were not. Future studies should assess the causal nature of these associations.

Study Design and Protocol of the Multisite Pregnancy 24/7 Cohort Study.

Hypertensive disorders of pregnancy and other adverse pregnancy outcomes (APOs) are associated with an increased risk of future maternal cardiovascular disease. Physical activity during pregnancy reduces the risk of these APOs, yet few meet physical activity guidelines during pregnancy. Little is known about the role of sedentary behavior or sleep in APOs, a critical gap in knowledge given these behaviors comprise the majority of a 24-hour day. To address this knowledge gap, the Pregnancy 24/7 cohort study (2020-2025) uses 2 devices for 24-hour activity assessment in each trimester of pregnancy to examine associations of sedentary behavior, sleep, and the 24-hour activity cycle (composition of sedentary behavior, physical activity, and sleep) with hypertensive disorders and other APOs. Participants (n = 500) are recruited from the University of Iowa, University of Pittsburgh, and West Virginia University in early pregnancy and followed through delivery. The activPAL3 micro and Actiwatch Spectrum Plus are worn in each trimester for 7 days of 24-hour wear to assess the 24-hour activity cycle. APOs are abstracted from medical charts. This study will provide critical data to fuel future research examining how modifying the 24-hour activity cycle in pregnancy can improve maternal health.

Natural history of blood pressure in sickle cell disease pregnancy.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non-SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSß0 group than in the non-SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSß0 group and non-SCD controls, whereas the mean SBP and DBP in the HbSC/HbSß+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSß0 .

Blood pressure thresholds for the diagnosis of hypertensive disorders of pregnancy in sickle cell disease.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared the characteristics of subjects with new or worsening proteinuria (NWP) during pregnancy to those without. We then constructed receiver operating characteristic (ROC) curves to determine the blood pressure (BP) that best identifies those with NWP. The SBP or DBP thresholds which maximized sensitivity and specificity were 120 mmHg SBP (sensitivity: 55.2%, specificity: 73.5%) and 70 mmHg DBP (sensitivity: 27.6%, specificity: 67.7%). The existing BP threshold of 140/90 mmHg lacked sensitivity in both genotype groups (HbSS/HbSß0 : SBP = 21% sensitive, DBP = 5.3% sensitive; HbSS/HbSß+ : SBP = 10% sensitive, DBP = 0% sensitive). Finally, percent change in SBP, DBP and MAP were all poor tests for identifying NWP. Existing BP thresholds used to diagnose hypertensive disorders of pregnancy (HDP) are not sensitive for pregnant people with SCD. For this population, lowering the BP threshold that defines HDP may improve identification of those who need increased observation, consideration of early delivery and eclampsia prophylaxis.

Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum.

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models.

Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Fucoidan modulates SIRT1 and NLRP3 to alleviate hypertensive retinopathy: in vivo and in vitro insights.

BACKGROUND: Hypertension influences the inflammatory pathological changes in the retina. The function of the inflammasomes is significant. To see if Sirtuin 1 (SIRT1) regulates angiotensin II (Ang II)-induced hypertensive retinopathy and inflammation by modulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation and the potential protective effects of fucoidan (FO) in mouse retinal vascular endothelial cells (mRECs) and mice retina. METHODS: The diagnosis of hypertensive retinopathy was made after three weeks of Ang II infusion (3000 ng/kg/min). One day prior to the commencement of Ang II infusion, the mice were treatment with NLRP3 inhibitor MCC950 (10 mg/kg/day, intraperitoneal injections) or FO (300 mg/kg/day, oral gavage). A blood pressure was recorded. Hematoxylin and eosin (H&E) staining was used to conduct pathological alterations, dihydroethidium bromide (DHE) was utilized to assess oxidative stress damage in the retina, and fluorescence angiography was used to identify vascular disorders in the eye. Using immunohistochemical labeling, NLRP3 expression was found. Reactive protein and mRNA expression levels in mouse retina and cells were assessed using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: NLRP3 inflammasome activation and SIRT1 decrease were brought about by Ang II infusion. Retinopathy and dysfunction were lessened by MCC950 target-induced NLRP3 inflammasome activation, while overexpression of SIRT1 had the opposite impact on NLRP3 inflammasome activation, indicating that SIRT1 functions as an upstream regulator of NLRP3 activity. FO may improve SIRT1 expression and decrease NLRP3 activation in retinopathy and dysfunction brought on by Ang II, and the effects were consistent across both in vivo and in vitro models. CONCLUSIONS: SIRT1 adversely regulates the NLRP3 inflammasome pathway, which in turn increases Ang II-induced inflammation and hypertensive retinopathy. FO may mitigate Ang II-induced retinopathy and dysfunction via modulating the expression of SIRT1/NLRP3. This implies practical approaches to the management of hypertensive retinopathy.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Pregnancy outcomes in patients with familial Mediterranean fever: systematic review and meta-analysis.

OBJECTIVE: The relationship between FMF and pregnancy outcomes remains unclear. This systematic review and meta-analysis aimed to clarify this association. METHODS: Electronic databases-PubMed, Web of Science, Cochrane, and EMBASE-were searched on 20 December 2022, using specific search terms. Case-control, cohort, and randomized clinical trial studies comparing patients with FMF and healthy controls were considered eligible. We excluded systematic reviews, meta-analyses, case series with fewer than five cases, republished articles without new findings on pregnancy outcomes, studies targeting paternal FMF, and those not published in English. The results were summarized in the form of odds ratios (ORs) and 95% CIs, using a random-effects model. This study was registered in the University hospital Medical Information Network Clinical Trials Registry (Japan) as UMIN000049827. RESULTS: The initial electronic search identified 611 records, of which 9 were included in this meta-analysis (177 735 pregnancies, 1242 with FMF, and 176 493 healthy controls). FMF was significantly associated with increased odds of preterm deliveries (OR, 1.67; 95% CI, 1.05-2.67; I2 = 22%) and insignificantly associated with increased odds of fetal growth restriction (OR, 1.45; 95% CI, 0.90-2.34; I2 = 0%) and hypertensive disorders during pregnancy (OR, 1.28; 95% CI, 0.87-1.87; I2 = 0%). CONCLUSION: FMF was significantly associated with preterm delivery and insignificantly associated with fetal growth restriction and hypertensive disorders. All of the included studies were observational studies. Treatment characteristics were not fully collected from the articles, and further analysis of treatments for FMF in pregnancy is still warranted.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase.

BACKGROUND: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. METHODS: 800 patients aged 17-90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension. RESULTS: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (ß [95% CI] 8.0 [4.9-11.1]) and diastolic (2.4 [0.4-4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2-9.4]) and diastolic BP (4.5 [1.9-7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1-7.5]) and fully adjusted (5.5 [1.1-10.0]) models. There was no difference in maximum diastolic BP between groups. CONCLUSION: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.

Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment.

Hypertensive heart disease (HHD) presents a substantial global health burden, spanning a spectrum from subtle cardiac functional alterations to overt heart failure. In this comprehensive review, we delved into the intricate pathophysiological mechanisms governing the onset and progression of HHD. We emphasized the significant role of neurohormonal activation, inflammation, and metabolic remodeling in HHD pathogenesis, offering insights into promising therapeutic avenues. Additionally, this review provided an overview of contemporary imaging diagnostic tools for precise HHD severity assessment. We discussed in detail the current potential treatments for HHD, including pharmacologic, lifestyle, and intervention devices. This review aimed to underscore the global importance of HHD and foster a deeper understanding of its pathophysiology, ultimately contributing to improved public health outcomes.

The Role of Osteogenic Effect and Vascular Function in Bone Health in Hypertensive Rats: A Study of Anti-hypertensive and Hemorheologic Drugs.

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.

Deep Learning for Discrimination of Hypertrophic Cardiomyopathy and Hypertensive Heart Disease on MRI Native T1 Maps.

BACKGROUND: Native T1 and radiomics were used for hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) differentiation previously. The current problem is that global native T1 remains modest discrimination performance and radiomics requires feature extraction beforehand. Deep learning (DL) is a promising technique in differential diagnosis. However, its feasibility for discriminating HCM and HHD has not been investigated. PURPOSE: To examine the feasibility of DL in differentiating HCM and HHD based on T1 images and compare its diagnostic performance with other methods. STUDY TYPE: Retrospective. POPULATION: 128 HCM patients (men, 75; age, 50 years ± 16) and 59 HHD patients (men, 40; age, 45 years ± 17). FIELD STRENGTH/SEQUENCE: 3.0T; Balanced steady-state free precession, phase-sensitive inversion recovery (PSIR) and multislice native T1 mapping. ASSESSMENT: Compare HCM and HHD patients baseline data. Myocardial T1 values were extracted from native T1 images. Radiomics was implemented through feature extraction and Extra Trees Classifier. The DL network is ResNet32. Different input including myocardial ring (DL-myo), myocardial ring bounding box (DL-box) and the surrounding tissue without myocardial ring (DL-nomyo) were tested. We evaluate diagnostic performance through AUC of ROC curve. STATISTICAL TESTS: Accuracy, sensitivity, specificity, ROC, and AUC were calculated. Independent t test, Mann-Whitney U-test and Chi-square test were adopted for HCM and HHD comparison. P < 0.05 was considered statistically significant. RESULTS: DL-myo, DL-box, and DL-nomyo models showed an AUC (95% confidential interval) of 0.830 (0.702-0.959), 0.766 (0.617-0.915), 0.795 (0.654-0.936) in the testing set. AUC of native T1 and radiomics were 0.545 (0.352-0.738) and 0.800 (0.655-0.944) in the testing set. DATA CONCLUSION: The DL method based on T1 mapping seems capable of discriminating HCM and HHD. Considering diagnostic performance, the DL network outperformed the native T1 method. Compared with radiomics, DL won an advantage for its high specificity and automated working mode. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Hypertensive disorders of pregnancy and the risk of maternal dementia: a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders of pregnancy, including preeclampsia, are associated with an increased risk for maternal cardiovascular disease, stroke, and chronic kidney disease. However, their association with subsequent maternal dementia or cognitive impairment is less well understood. This study aimed to review and synthesize the published literature on hypertensive disorders of pregnancy and the subsequent risk for maternal dementia or cognitive impairment. DATA SOURCES: PubMed, Web of Science, Pyschinfo, and CINAHL were searched from database inception until July 31, 2022, for observational studies of hypertensive disorders of pregnancy and maternal dementia or cognitive impairment. STUDY ELIGIBILITY CRITERIA: Selected studies included the following: a population of pregnant women, exposure to a hypertensive disorder of pregnancy of interest, and at least 1 primary outcome (dementia) or secondary outcome (cognitive impairment). Two reviewers were involved in study selection. METHODS: We followed the Meta-analyses of Observational Studies in Epidemiology guidelines throughout. Random-effects meta-analyses were used to calculate the overall pooled estimates. Bias was assessed using an adapted version of the validated Newcastle-Ottawa Quality Assessment tool. RESULTS: A total of 25 eligible studies were identified and included 2,501,673 women. Preeclampsia was associated with a significantly increased risk for vascular dementia (adjusted hazard ratio, 1.89; 95% confidence interval, 1.47-2.43), whereas no clear association was noted between preeclampsia and Alzheimer's disease (adjusted hazard ratio, 1.27; 95% confidence interval, 0.95-1.70), nor between preeclampsia and any (undifferentiated) dementia (adjusted hazard ratio, 1.18; 95% confidence interval, 0.95-1.47). However, in an analysis restricted to women aged 65 years and older, preeclampsia was associated with an increased risk for Alzheimer's disease (adjusted hazard ratio, 1.92; 95% confidence interval, 1.35-2.73) and any dementia (adjusted hazard ratio, 1.87; 95% confidence interval, 1.21-2.91). CONCLUSION: Women whose pregnancies were complicated by preeclampsia seem to be at a substantially increased future risk for vascular dementia. The longer-term risks among these women with regards to Alzheimer's disease and other forms of dementia are less clear.