Onset Of Hypertension Research Articles

Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey.

Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Many patients experience preventable end-organ injury due to delayed or missed diagnosis but data on the experience of patients are limited. We evaluated the lived experience of PA and determines factors associated with diagnostic delay through an international anonymous online cross-sectional survey, codesigned by researchers and PA consumers. We distributed the survey through academic medical centers, Amazon Mechanical Turk, Twitter, PA patient advocacy groups, and hypertension support groups on Facebook between March 21 and June 5, 2022. Of 684 eligible respondents, 66.5% were women. Diagnostic delay (defined as ≥5 years between the diagnosis of hypertension and PA) was reported in 35.6%. Delay was more likely in women than in men (odds ratio, 1.55 [95% CI, 1.10-2.20]) and respondents with ≥3 comorbidities versus none (odds ratio, 1.77 [95% CI, 1.05-3.02]), ≥10 symptoms versus none (odds ratio, 2.73 [95% CI, 1.74-4.44]), and on ≥4 antihypertensive medications versus none (odds ratio, 18.23 [95% CI, 6.24-77.72]). Three-quarters of patients (74.4%) experienced reduced symptom burden following targeted PA treatment. Quality of life improved in 62.3% of patients, and greater improvement was associated with being a woman (odds ratio, 1.42, [95% CI, 1.02-1.97]), receiving adrenalectomy (odds ratio, 2.36 [95% CI, 1.67-3.35]), and taking fewer antihypertensive medications following diagnosis (odds ratio, 5.28 [95% CI, 3.55-7.90]). One-third of patients with PA experienced prolonged diagnostic delays. Targeted treatment led to reduced symptom burden and improved quality of life. Gender differences in diagnostic delay and symptom burden are prominent. These findings suggest that routine screening for PA at the onset of hypertension may reduce diagnostic delay and facilitate timely diagnosis.

The Novel Ceramide- and Phosphatidylcholine-Based Risk Score for the Prediction of New-Onset of Hypertension.

Ceramides and other sphingolipids are implicated in vascular dysfunction and inflammation. They have been suggested as potential biomarkers for hypertension. However, their specific association with hypertension prevalence and onset requires further investigation. This study aimed to identify specific ceramide and phosphatidylcholine species associated with hypertension prevalence and onset. The 2002 FINRISK (Finnish non-communicable risk factor survey) study investigated the association between coronary event risk scores (CERT1 and CERT2) and hypertension using prevalent and new-onset hypertension groups, both consisting of 7722 participants, over a span of 10 years. Ceramide and phosphatidylcholine levels were measured using tandem liquid chromatography-mass spectrometry. Ceramide and phosphatidylcholine ratios, including ceramide (d18:1/18:0), ceramide (d18:1/24:1), phosphatidylcholine (16:0/16:0), and the ratio of ceramide (d18:1/18:0)/(d18:1/16:0), are consistently associated with both prevalence and new-onset hypertension. Ceramide (d18:1/24:0) was also linked to both hypertension measures. Adjusting for covariates, CERT1 and CERT2 showed no-longer-significant associations with hypertension prevalence, but only CERT2 predicted new-onset hypertension. Plasma ceramides and phosphatidylcholines are crucial biomarkers for hypertension, with imbalances potentially contributing to its development. Further research is needed to understand the underlying mechanisms by which ceramides will contribute to the development of hypertension.

Issue Involvement Moderates the Effect of Gain- and Loss-Framed Messages on Mothers’ Intentions to Give 5 Portions of Fruits and Vegetables to Their Children Every Day

Research suggests that issue involvement moderates the efficacy of gain and loss frames, yet the extent to which this is true across behaviors and contexts is an open question. In this study, I examined the moderating role of issue involvement in the context of fruit and vegetable intake in Lima, Peru. Only 11.3% of the Peruvian population 15 years old or older consume five servings of fruits and vegetables every day, even though this health behavior prevents the onset of chronic diseases, including diabetes and hypertension. Guided by the Reasoned Action Approach and research about the effects of gain and loss frames, I conducted an experiment (N=253, three conditions: gain-framed messages condition; loss-framed messages condition; and no-message, control condition) to assess the effect of gain- and loss-framed messages on mothers’ intentions to increase fruits and vegetables consumption among their 1- to 5-year-old children in Lima. Results indicated that mothers who saw gain-framed messages reported greater intentions than those who did not see any messages (control condition). However, issue involvement moderated the effect of gain frames, such that mothers low in issue involvement reported greater intentions after seeing the gain-framed messages. Theoretical and practical implications are discussed.

Postpartum follow-up of women with preeclampsia: facilitators and barriers — A qualitative study

BackgroundPregnancy causes physiological changes to the maternal organ systems that can be regarded as a cardiometabolic stress test for women. Preeclampsia, a pregnancy complication characterized by new onset of hypertension in combination with proteinuria or end-organ dysfunction, affects approximately 2–8% of pregnancies. Adverse pregnancy outcomes, including preeclampsia, have been described as a failed stress test and have been consistently linked with increased risk of cardiovascular disease later in life. The postpartum period is therefore often regarded as a window of opportunity for cardiovascular disease prevention. However, we lack knowledge about how women with preeclampsia experience current postpartum care in the Norwegian health system. The aim of this qualitative study is to uncover women’s perspectives and preferences regarding postpartum follow-up.MethodsSemi-structured telephone interviews were conducted with 17 women following a six-month lifestyle intervention study. Participants were 9–20 months postpartum, following a pregnancy complicated by preeclampsia. Data were analyzed using Malterud’s systematic text condensation.ResultsWe identified five themes, each with 2–3 subthemes, that demonstrate how women with recent preeclampsia experience postpartum follow-up: (1) fear and uncertainty (a body out of balance and facing an uncertain future), (2) a conversation on lifestyle – not really that difficult (preeclampsia as a gateway, a respectful approach, and a desire for more constructive feedback), (3) when your own health is not a priority (a new everyday life, out of focus, and lack of support), (4) motivation for lifestyle changes (an eye opener, lack of intrinsic motivation, and a helping hand), and (5) lack of structured and organized follow-up (there should be a proper system, a one-sided follow-up care, and individual variation in follow-up care).ConclusionsFindings from this study highlight the need for more systematic postpartum follow-up for women after a pregnancy complicated by preeclampsia. Further research is required to explore the potential use of standardized guidelines and routine invitations to postpartum care. Furthermore, exploring health care professionals’ experiences is crucial to ensure their engagement in postpartum care after complicated pregnancies.

Transcriptomics and proteomics revealed sex differences in human pulmonary microvascular endothelial cells.

Marked sexual dimorphism is displayed in the onset and progression of pulmonary hypertension (PH). Females more commonly develop pulmonary arterial hypertension, yet females with pulmonary arterial hypertension and other types of PH have better survival than males. Pulmonary microvascular endothelial cells play a crucial role in pulmonary vascular remodeling and increased pulmonary vascular resistance in PH. Given this background, we hypothesized that there are sex differences in the pulmonary microvascular endothelium basally and in response to hypoxia that are independent of the sex hormone environment. Human pulmonary microvascular endothelial cells (HPMECs) from healthy male and female donors, cultured under physiological shear stress, were analyzed using RNA sequencing and label-free quantitative proteomics. Gene set enrichment analysis identified a number of sex-different pathways in both normoxia and hypoxia, including pathways that regulate cell proliferation. In vitro, the rate of proliferation in female HPMECs was lower than in male HPMECs, a finding that supports the omics results. Interestingly, thrombospondin-1, an inhibitor of proliferation, was more highly expressed in female cells than in male cells. These results demonstrate, for the first time, important differences between female and male HPMECs that persist in the absence of sex hormone differences and identify novel pathways for further investigation that may contribute to sexual dimorphism in pulmonary hypertensive diseases.NEW & NOTEWORTHY There is marked sexual dimorphism in the development and progression of pulmonary hypertension. We show differences in RNA and protein expression between female and male human pulmonary microvascular endothelial cells grown under conditions of physiological shear stress, which identify sex-different cellular pathways both in normoxia and hypoxia. Importantly, these differences were detected in the absence of sex hormone differences. The pathways identified may provide novel targets for the development of sex-specific therapies.

Gestational Hypertension and Midlife Cognition: The CARDIA Study

AbstractBackgroundGestational hypertension (GH) increases the risk of cardiovascular diseases, which may contribute to worse cognitive outcomes, and yet little is known about the long‐term impact of GH on cognition. We investigated the association of GH with midlife cognitive performance and decline in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.MethodsWe studied 1,273 parous Black and White women (106 with GH and 1167 without GH) aged 18‐30 years at baseline (1985‐86) who were followed up to Year 30 (mean age 55.2±3.6 years) when five cognitive tests measuring global cognition, memory, processing speed, executive function, and verbal fluency were administered. Accelerated decline over five years was defined as a decline ≥1.5 standard deviations from the mean change on each of the three tests available at year 25, measuring processing speed, memory, and executive function. GH, defined as having new onset hypertension in pregnancy without proteinuria, was self‐reported for each pregnancy since the previous visit up to 30 years. We conducted linear and logistic regression to assess the association of GH with cognitive performance and decline.ResultsCompared with women who did not develop GH during pregnancy, those with GH were more likely to be Black (62% vs 50%) and have obesity (22% vs 11%), and lower diet quality (CARDIA A Priori Diet Quality Scores) at baseline. After adjusting for age, race, education, number of pregnancies, and baseline cardiovascular and behavior risk factors (diabetes, obesity, smoking, alcohol use, physical activity, and diet quality), having GH was significantly associated with lower cognitive performance (z‐standardized) at year 30 in global cognition (‐0.27, 95% CI ‐0.44 to ‐0.11), processing speed (‐0.25, 95% CI ‐0.44 to ‐0.07), and verbal fluency (‐0.20, 95% CI ‐0.38 to ‐0.02). Additional adjustment for hypertension, diabetes, and obesity up to Year 30 did not change the results. GH was also associated with higher odds of experiencing an accelerated decline in processing speed over 5 years (9.2% vs. 4.5%, odds ratio 2.48, 95% CI 1.07 to 5.74), after adjustment for all covariates.ConclusionGH is independently associated with worse cognitive performance and accelerated decline in midlife.

Obstructive sleep apneas and cardiovascular diseases

Obstructive sleep apneas (OSA) are a breathing disorder characterized by recurrent apneas and hypopneas associated with complete or partial obstruction of the upper airways during sleep, resulting in disturbed sleep architecture, repeated hypoxemia and awakenings, and daytime sleepiness. OSA syndrome affects up to 34% of men and 17% of women in Western countries. Abnormalities in upper airway anatomy (frequently due to obesity), muscle tone, or neural control of breathing are the main causes. OSA is associated with impaired cognitive function and favors the onset of hypertension, being a major determinant of resistant hypertension, and may favor cardiovascular diseases (e.g., coronary artery disease and heart failure), thereby increasing mortality. Polysomnography and (cardio)-respiratory portable systems are used to diagnose and determine the severity of OSA. Management of OSA includes lifestyle modifications, such as weight loss and avoidance of supine sleep position, and continuous positive airway pressure. Mandibular advancement devices and upper airway surgery may also be appropriate for some patients. Hypoglossal nerve stimulation and pharmacological interventions are currently investigated to improve symptoms and outcomes.

Mortality, cardiovascular disease and long covid at 3 months in individuals hospitalized with covid-19- a whf study

Abstract Background COVID-19 pandemic presents a number of unpredictable and long-lasting challenges. Understanding the short- and long-term effects of COVID-19 infection is crucial for better planning of preventive and management strategies for future pandemics. This study aims to determine short- and long-term clinical sequelae among COVID-19 hospitalized patients across low-middle-, upper-middle and high-income countries. Methods This global, multi-centre, prospective cohort study across 16 countries aimed to recruit 3300 patients hospitalized with COVID-19. We evaluated persistent long COVID symptoms, re-admissions, death, cardiovascular disease complications, new onset hypertension or diabetes, reinfection with COVID-19, vaccination, quality of life and costs at 1, 3, 6, 9-12-months post-hospital discharge using a standardized questionnaire over the phone. We are reporting interim descriptive analysis including demographic characteristics and short-term (3-month) clinical sequelae among COVID-19 hospitalized patients. Results We present baseline characteristics and follow-up data for 1,474 patients at the 3 months visit after hospital discharge. The patients were predominantly Asian (97%), male (55%) with a mean age (SD) of 56 (19.6) years and from low- and middle-income (82%), upper middle-income (4%) and high-income (14%) countries. 60% of the patients had received 2 doses of COVID-19 vaccination. 92% patients had fever and 90% had cough when admitted to hospital. More than one-third of patients (38%) reported at least one long COVID-19 symptom. Most commonly reported long COVID-19 symptoms were fatigue (22%), memory impairment, concentration, or decision-making (15%), and feeling more anxious (11%). Nearly half of the patients reported mild fatigue (46%) and 8% had severe fatigue. Less than 1% of patients reported loss of smell or taste. Most commonly reported post-discharge complications (new onset illnesses) were pulmonary embolism (8%), kidney involvement (2%) and new onset hypertension (1%). A quarter of patients reported problems in self-care, and 7%-12% patients reported pain or mobility issues or anxiety/depression. At 3-month follow-up, 3% of the patients had died and the most common causes of death were sudden cardiac arrest (33%), liver dysfunction/end stage renal disease (31%) and stroke or respiratory illness (13%). Conclusions Three months after hospitalized COVID-19, our interim analysis revealed a 3-month mortality rate of 3% mostly due to sudden cardiac arrest, liver dysfunction, stroke and respiratory diseases (relatively higher compared to studies from other regions). Patients commonly reported persistent symptoms, such as fatigue, memory/concentration impairment, and anxiety. Further, long-term follow-up data will guide health policies to prevent and manage long COVID sequelae worldwide.Table 1Figure 1

Cardiovascular impact on risk of preeclampsia, -an epidemiologic cohort study

Abstract Introduction Preeclampsia complicates 3-5% of pregnancies worldwide and accounts for approximately 45 000 maternal deaths yearly. Preeclampsia is defined as new onset hypertension with organ dysfunction after 20 weeks’ gestation. Preeclampsia and cardiovascular disease have common risk factors such as chronic hypertension, obesity, and diabetes. In addition, preeclampsia is an independent risk factor for later cardiovascular disease. Preeclampsia might result from maladaptation of the cardiovascular system to pregnancy, but it is not known if other cardiac diagnoses are also risk factors for developing preeclampsia. Purpose The aim of this study was to evaluate the impact of heart failure and other cardiovascular disease on the risk of developing preeclampsia. Methods This was a registry-based case-control study using data form Swedish national registers including the medical birth register, national patient register and the LISA register. For every case with preeclampsia (90 354 pregnancies) five controls were chosen (Figure 1). Controls were matched to cases on mother’s year of birth. A sub-analysis investigated the risk for preterm preeclampsia (delivery <37 gestational weeks) by risk-factor. Potential cardiac risk factors were congenital heart disease, pulmonary hypertension, aortic/peripheral artery disease, valvular heart disease, myocardial infarction, other coronary artery disease, arrythmia, hypertension, myocarditis/pericarditis. Also known cardiometabolic risk factors were analyzed. All diagnoses were defined by ICD-9 and ICD-10 codes. We used multiple logistic regression analysis adjusted for confounders (BMI, age, smoking, assisted reproductive technology, parity, multifetal pregnancy, and comorbidities before pregnancy). Results Women with preeclampsia were more often obese, less often nulliparous and had more often multifetal pregnancies compared with women with normotensive pregnancies. Heart failure, valvular heart disease, hypertension, and diabetes (type 1+2) were independent risk factors for preeclampsia (Figure 2). Women with heart failure (n=273) had an adjusted odds ratio (aOR) of 2.09 (95% confidence interval (CI) 1.58-2.75) for developing any preeclampsia and an aOR of 2.90 (95% CI 1.82-4.61) for developing preterm preeclampsia. For women with valvular heart disease (n=424), the aOR was 1.50 (95% CI 1.17-1.92) for any preeclampsia and 2.55 (1.62-4.01) for preterm preeclampsia. The remaining seven cardiac diseases were not independent risk factors for preeclampsia. Conclusion Women with heart failure and valvular heart disease are at increased risk of developing preeclampsia. This association was particularly strong in women with preterm preeclampsia. Our results support the theory of preeclampsia as a stress test for cardiovascular disease. Although a rare patient group, these women have to be monitored closely during pregnancy, both for cardiac complications and for development of preeclampsia.Figure 1.Flow chart.Figure 2.Results.

Brain-Splenic Immune System Interactions in Hypertension: Cellular and Molecular Mechanisms.

Hypertension represents a major worldwide cause of death and disability, and it is becoming increasingly clear that available therapies are not sufficient to reduce the risk of major cardiovascular events. Various mechanisms contribute to blood pressure increase: neurohormonal activation, autonomic nervous system imbalance, and immune activation. Of note, the brain is an important regulator of blood pressure levels; it recognizes the peripheral perturbation and organizes a reflex response by modulating immune system and hormonal release to attempt at restoring the homeostasis. The connection between the brain and peripheral organs is mediated by the autonomic nervous system, which also modulates immune and inflammatory responses. Interestingly, an increased autonomic nervous system activity has been correlated with an altered immune response in cardiovascular diseases. The spleen is the largest immune organ exerting a potent influence on the cardiovascular system during disease and is characterized by a dense noradrenergic innervation. Taken together, these aspects led to hypothesize a key role of neuroimmune mechanisms in the onset and progression of hypertension. This review discusses how the nervous and splenic immune systems interact and how the mechanisms underlying the neuroimmune cross talk influence the disease progression.

Role of beta-3 adrenergic receptor polymorphism TRY64ARG in heart failure

Abstract Introduction The TRY64ARG polymorphism of the beta-3 adrenergic receptor has been associated with the onset and maintenance of hypertension, diabetes and obesity, its role in heart failure has not been studied. Objectives To examine the role of the TRY64ARG beta-3 adrenergic receptor in the improvement of left ventricular ejection fraction (LVEF) in patients with Heart Failure due to ischemic heart disease. Methods This study is a retrospective analysis based on a 5-year follow-up of patients with heart failure with decreased LVEF due to ischemic heart disease. Results We studied a sample of 338 patients with decreased LVEF collected from our Genetic database during the period of time from January 2012 to December 2016. In the scrutiny 26 patients did not have complete data for analysis, resulting in a final sample of 312 patients with a minimum follow-up of 5 years. The mean age was 58.9 years (SD 14), 72% of the population were men (n = 244), the frequency of hypertension was 168 (53.85%), diabetes 119 (38.14%), obesity (18.27%). The definition of LVEF improvement was defined as an incremental in more than 15%. There was no statistical difference in the medical treatment and revascularization methods. Patients with the TRY64ARG β3 adrenergic polymorphism present less improvement in the LVEF (42% vs 58%, p< 0.001). Conclusions The expression of the TRY64ARG polymorphism of the beta-3 adrenergic receptor in patients with HF and low LVEF is related to a lack of incremental LVEF at 5 years.

Abstract 18128: How Long Should We Tilt?: Challenging the 10-Minute Cutoff in the Diagnosis of Postural Tachycardia Syndrome (POTS)

Background: Postural tachycardia syndrome (POTS) is defined by symptoms of orthostatic intolerance (OI) that correlate with an orthostatic tachycardia response. Current diagnostic criteria require a sustained increase in HR by ≥30 bpm [accentuated postural tachycardia (APT)], without a concurrent BP drop, within 10 minutes of standing or head-up tilt testing (HUTT). In many centers, the HUTT duration is predetermined to be 10 mins. However, many patients may exhibit APT after this cutoff. Research Question: How many patients with symptoms consistent with POTS demonstrate APT during HUTT after the 10-min cutoff, and what factors influence onset time? Methods: Using a cohort of 255 patients with OI, we characterized the temporal distribution of APT onset time during 45-minute HUTT at our referral center. We used multivariate linear regression to identify predictors influencing onset time, and plotted Kaplan-Meier failure function stratified by predictors. Results: The cohort's mean age was 33 years, 91% were female, 16% were obese, 13% had hypertension, 1.6% had diabetes, and 26% were smokers. Mean APT onset time was 17.5 mins (SD 10), and median onset time was 13 mins (IQR 11-22). About 15% had APT onset within 10 min, 60% in 15 mins, 75% in 20 mins, 90% in 30 mins, and 95% in 40 mins. Increasing age and BMI were associated with later APT onset time, whereas sex, diabetes, hypertension, and smoking were not influential Conclusion: The 10-min cutoff captured only 15% of patients with APT; extending the cutoff just 5 minutes longer captured an additional 60% patients. Our findings suggest that the current 10-min cutoff for POTS diagnosis is likely too restrictive, as a significant proportion of patients exhibit APT after this period but otherwise fit the clinical scenario of POTS. Increasing age particularly ≥40 yrs, and obesity were associated with a later APT response. Future definitions should consider extending the testing duration and cutoff time in the evaluation of POTS.

Abstract 17819: Latent Class Analysis of Heart Health in a Marginalized Black Community

BACKGROUND Mounting evidence associates Black American’s experiences of chronic stress with younger age hypertension (HTN) onset, higher prevalence rates, and poorer treatment outcomes. Epigenetic research findings attribute these trends to DNA methylation, commonly referred to as stress related premature biological aging. Guided by the current American Heart Association (AHA) Science Statement on heart health, this health equity study aims to examine positive Black identity as a measure of positive psychological health in Black adults. METHODS Our community-engagement survey measured self-reports of: (1) environmental wellbeing, positive self-regard, spirituality, chronic stress, Black identity, anxiety, depression, anger, and five AHA essential cardiovascular health (CVH) factors: (2) physical activity, fruit, vegetables, smoking tobacco, and sleep. Multivariable linear regressions examined psychological health and CVH as predictors of systolic blood pressure. Latent class analysis (LCA), using ordinal indicators, assessed for latent sample profiles as statistical probabilities of similar responses and sample heterogeneity. RESULTS In a community sample (N=201) of Black adults (age M=46.7, SD=15.9), primarily female (N=141, 69.5%), increases in systolic blood pressure (Mean=134, SD=20.9) were associated with more chronic stress and less environment wellbeing; decreases were associated with less expressed anger. The LCA results show a four-class statistical solution with greater heterogeneity in spirituality, anger, anxiety, and depression. Among the four profiles, two theoretical latent classes for high and low systolic blood pressure were distinct. Low systolic blood pressure is associated with higher levels of environmental wellbeing, physical activity, and self-regard, both more and less spirituality, more positive Black identity, moderate anger, anxiety, and depression, and checking your BP. CONCLUSION In addition to emotion regulation, physical activity, and self-care, our findings support CVH promotion strategies in marginalized communities of Black Americans designed to reduce chronic stress, improve environmental wellbeing, and support positive Black identity.

Prediction of adverse outcome by ophthalmic artery Doppler and angiogenic markers in pregnancies with new onset hypertension

ObjectivesTo compare the ophthalmic artery Doppler peak systolic velocity ratio (OA PSV-ratio) and soluble fms-like tyrosine kinase-1/placental growth factor ratio (sFlt-1/PlGF ratio) in predicting adverse maternal and perinatal outcomes in women presenting with new onset hypertension. Study designProspective cohort study in a specialist hypertension clinic, within a tertiary referral centre. Main outcome measuresComparison between the OA PSV-ratio and sFlt-1/PlGF ratio in predicting delivery within one week from presentation and adverse maternal and perinatal outcomes e.g. severe hypertension, neonatal unit admission, small for gestational age. ResultsWomen who delivered within one week, compared to those who did not, had a higher OA PSV-ratio (0.82 vs 0.71, p < 0.01) and sFlt-1/PlGF ratio (93.3 vs 40.5, p = 0.08). Independent predictors of the OA PSV-ratio included mean arterial pressure and maternal weight and predictors of the sFlt-1/PlGF ratio included diastolic blood pressure and use of antihypertensive medications. Prediction of adverse outcomes with both ratios were similar and only modest e.g. AUROC for predicting delivery within one week for OA PSV-ratio was 0.57 (95% CI 0.47–0.67) and for sFlt-1/PlGF ratio was 0.61 (95% CI 0.52–0.70) (p = 0.53). ConclusionsIn women presenting with new onset hypertension, the OA PSV-ratio and sFlt-1/PlGF ratio have similar and modest performance in predicting adverse outcomes.

Single Agent Tagraxofusp in Relapsed/Refractory CD123-Positive Acute Myeloid Leukemia: A Preliminary Analysis of Italian Gimema AML2020 Trial

Background and Aims: Tagraxofusp (SL-401; TAG) is a recombinant protein drug consisting of IL3 fused to a truncated diphtheria toxin payload that targets CD123, a subunit of the IL3 receptor, expressed on the surface of Acute Myeloid Leukemia (AML) blasts. TAG is currently approved for the treatment of blastic plasmacytoid dendritic cell neoplasm by the FDA and EMA. Here, we report the results of a preliminary analysis of the GIMEMA AML2020 trial which is the first study in Europe investigating the activity and safety of single agent TAG in patients with relapsed/refractory (R/R) CD123-positive AML. Patients and Methods: In this open-label, multi-center phase 2 study (NCT04342962) adult patients with R/R CD123-positive AML patients who received no more than 2 previous lines of therapy were eligible for enrollment. Tagraxofusp was administered at a dose of 12ug/kg from days 1 to 3 in the first cycle and then given for 5 days. Written informed consent for treatment, data collection and biobanking of biological samples was obtained for each patient enrolled. Results: As of July 2023, 23 patients have been enrolled. Median age was 65 years (41-75). Ten patients had refractory disease; 13 patients had relapsed disease. Nine patients were classified high risk at diagnosis according to ELN2017 classification. First-line treatment consisted of fludarabine-based induction, CPX-351, conventional anthracycline/Ara-C (3+7) induction for 22 patients and 1 patient received reduced intensity induction with hypomethylating agents + venetoclax. Second line treatments included azacytidine, azacytidine + venetoclax, gilteritinib; six patients received TAG as second line treatment. Two patients, who received allogeneic stem cell transplantation (allo-BMT) while in complete remission (CR), were enrolled at first relapse post-transplant. The median number of TAG cycles was 2 (range 1-10). Overall response rate (ORR) was 34.8% with 2 patients achieving MRD negative CR and 6 patients achieving partial remission (PR). As for treatment duration, 1 patient receiving 4 courses achieved PR and died due to CNS bleeding; 1 patient received 7 courses of TAG for early relapse after allo-BMT and achieved PR; 1 patient received 10 courses achieving PR. Early treatment discontinuation in the other cases was due to disease progression or adverse events (AEs). Emergent AEs are summarized in Figure 1. In addition, 3 patients developed leucocytosis immediately following TAG administration on the first course; in one case it was also associated with lung infiltrates. Capillary leak syndrome (CLS), a disorder characterized by leakage of intravascular fluids into the extravascular space, was reported in 5 patients: 2 patient experienced grade 2 (symptomatic) CLS which resolved with mild supportive treatment; 1 patient experienced grade 3 (severe), 1 grade 4 (life-threatening) and in one case the onset of CLS triggered by infectious event resulted fatal. One patient experienced the onset of acute renal failure and severe hypertension after C1 day 1 which resulted fatal, possibly being consistent with CLS. Conclusions: These results show that single agent TAG can exert anti-leukemic activity in R/R CD123-positive AML, even in cases with very unfavourable prognosis. However, further studies are necessary to disclose predictors of response and of the risk of adverse events. The safety profile observed here is similar to that previously observed for TAG requiring close monitoring of patients and timely supportive measures. However, overlapping of TAG-induced systemic inflammatory responses with refractory disease led to complex clinical management in some cases. Investigation of combinations strategies with TAG is warranted in order to optimize treatment efficacy, especially in the context of R/R AML.

Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease's progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.

A point-of-care urine test to predict adverse maternal and neonatal outcomes in Asian women with suspected preeclampsia.

To assess clinical utility of the urine Congo red dot test (CRDT) in predicting composite adverse maternal and neonatal outcomes in women with suspected preeclampsia (PE). CRDT result and pregnancy outcomes were prospectively documented in women with new onset or pre-existing hypertension, new or pre-existing proteinuria, PE symptoms and suspected PE-related fetal growth restriction or abnormal Doppler presenting from 20weeks' gestation between January 2020 and December 2022. Participants and clinicians were blinded to the CRDT result and managed according to internally agreed protocols. Composite maternal outcome was defined as PE, postpartum hemorrhage, intensive care unit admission, and maternal death. Composite neonatal outcome was defined as small for gestational age, preterm birth, 5-min Apgar score < 7, neonatal intensive care unit admission, and neonatal death. Two hundred and forty-four women out of two hundred and fifty-one (97.2%) had a negative CRDT. All seven women with positive CRDT had both adverse maternal and neonatal outcomes, giving positive predictive values (PPV) of 100%. Rates of composite adverse maternal and neonatal outcomes in CDRT negative women were 103/244 [42.2%, 95% confidence interval (CI) 36.2%-48.5%] and 170/244 (69.7%, 95% CI 63.6%-75.1%), respectively. CRDT negative predictive values (NPV) for adverse maternal and neonatal outcomes were, respectively, 141/244 (57.8%, 95% CI 48.6%-68.2%) and 74/244 (30.3%, 95% CI 23.8%-38.1%). CRDT had low NPV but high PPV for adverse maternal and neonatal outcomes in women with suspected PE. Its role in clinical management and triage of women with suspected PE is limited as it cannot identify those at low risk of developing adverse outcomes.

Global burden of new-onset hypertension associated with severe acute respiratory syndrome coronavirus 2 infection

Several reports documented a specific effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on blood pressure (BP), during and after the acute phase of infection. Clinical studies demonstrated that coronavirus disease 2019 (COVID-19) is associated with an increased risk of a persistent increase in BP requiring a new or intensified anti-hypertensive treatment during hospitalization. The picture is further complicated by the evidence from large databases showing an increased risk of new-onset hypertension in COVID-19 survivors on the long term. To further elucidate the epidemiological burden of this phenomenon, we performed a pooled analysis of 4 studies reporting crude incidence rates of new-onset hypertension among COVID-19 patients and contemporary controls. Overall, COVID-19 was associated with a 65% increased risk of new-onset hypertension when compared with controls (p<0.0001); furthermore, incidence of new-onset hypertension was 9% and 5% among COVID-19 patients and controls, respectively. In both the acute phase and recovery from infection, the interaction between spike proteins of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) receptors remain the most plausible mechanism explaining the raise in BP (ranking new onset hypertension as one of the most prevalent cardiovascular sequelae of COVID-19). In this area of research, it is worth to mention that new variants of SARS-CoV-2 exhibit specific mutations in the spike protein that promotes entry into viral cells via ACE2. Thus, the enhanced spike affinity for ACE2 of new variants has the potential to increase the risk of new-onset hypertension when compared with the original Wuhan strain.

Evolution of Cardiovascular Risk Factors in Post-COVID Patients.

(1) Background: SARS-CoV-2 infection has been a subject of extensive discussion in the medical field, particularly in relation to the risk factors and effective treatment strategies for reducing the negative health outcomes associated with the virus. However, researchers indicate that individuals in the recovery phase after COVID-19 experience a range of symptoms that significantly impact their overall well-being and quality of life. At present, there is insufficient evidence to substantiate the claim that patients in the post-acute phase of COVID-19 are at an elevated risk of developing new-onset hypertension or even metabolic syndrome. The current study aimed to assess the risk of cardiovascular diseases after COVID-19 and the optimal treatment of these conditions. (2) Methods: This research was conducted at the Cardiovascular Rehabilitation Clinic of the Iasi Clinical Rehabilitation Hospital (Romania) between the 1st of September and 31st of December 2022. From a total of 551 patients hospitalized in that period, 70 patients with multiple comorbidities were selected. This study included patients over 18 years old who were diagnosed with COVID-19 within the past 30 days. (3) Results: The included patients were mostly women (62.9%) from the urban area (61.4%). Comparing the post-COVID-19 period to the pre-COVID-19 one, it was observed that the risk of hypertension increased from 69.57% to 90% among the subjects (p = 0.005). Risk factors for the new onset of hypertension were identified as age, female gender, and an elevated body mass index. Moreover, the number of patients with dyslipidemia doubled, and a higher body mass index was noted. (4) Conclusions: Our findings suggest that patients affected by COVID-19 are at an increased risk of developing hypertension and related disorders.

FRI127 Delay Of A Decade In The Diagnosis Of Primary Aldosteronism In Patients With Onset Of Hypertension ≤ 40 Yo

Abstract Disclosure: S. Parisien-La Salle: None. A. Lacroix: None. I. Bourdeau: None. Introduction: Primary aldosteronism (PA) is a frequent and underdiagnosed cause of secondary hypertension. Mean age at diagnosis is 50-55 years old (yo), however, hypertension often precedes the diagnosis of PA by many years [1,2]. Objective: To evaluate the delay between the diagnosis of hypertension and the diagnosis of PA in patients with onset of hypertension ≤ 40 yo. Methods: We retrospectively collected the clinical information of patients with PA who were diagnosed with hypertension at ≤ 40 yo from our specialized genetics adrenal clinic. Results: We identified 47 patients with PA who presented with hypertension at ≤ 40 yo. Twenty-one patients (44.7%) were female. At diagnosis of PA, 76.6% (36/47) had hypokalemia, 29.8% (14/47) had sleep apnea, 17% (8/47) had type 2 diabetes, 8.5% (4/47) had coronary artery disease and 4.3% (2/47) had atrial fibrillation. More than half of patients (53.2%) were on 3 or more anti-hypertensive drugs. Mean age at diagnosis of hypertension was 30.8 and mean age at diagnosis of PA was 43.5 yo with an average delay of 12.7 years and a median delay of 10 years (IQR: 4,10,19,37).In the group diagnosed with PA within 10 years of the diagnosis of hypertension (n: 24), the average number of anti-hypertensive drugs per patient was 2.3 and 79.2% (19/24) had hypokalemia. In the group diagnosed with PA more than 10 years after the diagnosis of hypertension (n: 23), the average number of anti-hypertensive drugs per patient was higher at 3.4 with a similar prevalence of hypokalemia (73.9% (17/23)).In patients with hypertension diagnosed ≤ 30 yo (n: 23), the mean age at diagnosis of hypertension was 25.3 yo with a median of 28, and the mean age at diagnosis of PA was of 39.2 yo with a median of 34. Thus, the average delay was 13.9 years and the median was 10 years (IQR: 1.5, 10, 26.5, 37). However, in patients with hypertension diagnosed ≤ 20 yo (n: 5), the mean age at diagnosis of hypertension was 16.8 yo with a median of 18, and the mean age at diagnosis of PA was of 25.4 yo with a median of 21 yo. Thus, the average delay was 8.6 years and the median was 3 years (IQR: 2,3,10,28). Conclusion: We demonstrate that in our cohort the median delay is approximately of 10 years between the diagnosis of hypertension and PA for patients diagnosed with hypertension between 30 and 40 yo. Neither the number of antihypertensive drugs, nor the presence of hypokalemia seemed to determine a shorter delay of diagnosis. However, patients diagnosed with hypertension ≤ 20 yo had shorter delays of diagnosis of PA with a median of 3 years. Bibliography: 1. Alam, S.; Kandasamy, D.; et al. High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension. Clin Endocrinol (Oxf)2021, 94, 895-903, doi:10.1111/cen.14409.2. Turcu, A.F.; Yang, J.; Vaidya, A. Primary aldosteronism - a multidimensional syndrome. Nat Rev Endocrinol2022, 18, 665-682, doi:10.1038/s41574-022-00730-2. Presentation: Friday, June 16, 2023