Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. OBJECTIVE: This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval, -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively). CONCLUSION: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

Effect of different anti-cardiovascular disease treatments on the severity of obstructive sleep apnea.

Obstructive sleep apnea (OSA) and cardiovascular co-morbidities have a mutually reinforcing effect, but existing studies have focussed only on the improvement of the associated co-morbidities by treatment for OSA. To provide fresh guidelines for the treatment of OSA from a co-morbidity standpoint, we conducted a systematic search of Web of Science, PubMed, EMBASE, and the Cochrane Library for articles published from inception up to 2 May 2023. Fourteen original studies of patients with OSA with cardiovascular co-morbidities and who received related treatment were included in the analysis. We found that diuretic treatment can reduce the apnea-hypopnea index in patients with OSA and hypertension (-19.41/h, p = 1.0 × 10-5 ), aldosterone-angiotensin inhibitors also have a 9.19/h reduction (p = 0.003), while the effect of renal sympathetic denervation is insignificant (-2.32/h, p = 0.19). The short-term treatment (<4 weeks) did not show an improvement (-2.72/h, p = 0.16), while long-term treatment (>4 weeks) produced surprising outcomes (-12.78/h, p = 0.002). Patients with milder disease (baseline AHI < 35/h) had insignificant improvements (-1.05/h, p = 0.46), whereas those with more severe disease (baseline AHI > 35/h) could achieve satisfactory outcomes (-14.74/h, p < 0.00001). In addition, it also showed some improvement in the oxygen desaturation index and blood oxygen. Our results support the additional benefit of antihypertensive treatment for OSA symptoms, and the efficacy can be affected by different therapy, treatment duration, and severity levels. It could be useful in developing clinical therapy, educating patients, and exploring interaction mechanisms. The proposal was registered with PROSPERO (CRD42022351206).

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Molecular Imaging of Renin Activity using Fluorogenic Nanoprobes for Precision Antihypertensive Therapy.

Life-threatening hypertension remains inadequately controlled in clinics due to its heterogeneous renin levels. Rapid stratification of hypertension through renin analysis is crucial for effective personalized treatment, yet an ultrasensitive detection approach is currently lacking. Here, we report activatable renin nanoprobes (ARNs) for non-invasive and ultrasensitive profiling of renin activity and guiding antihypertensive treatment decision through near-infrared fluorescence (NIRF) in vivo imaging and in vitro urinalysis. ARNs are intrinsically non-fluorescent due to NIRF reporter connected to a gold nanocluster through a renin-responsive peptide. In hyperreninemia mouse models, ARNs specifically react with renin to liberate the renal clearable NIRF reporter for accurate renin detection that outperforms the gold standard radioimmunoassay. Such specific and sensitive detection also enables imaging-based high-throughput screening of antihypertensive drugs. In hypertensive rat models, ARNs enable ultrasensitive detection of both plasma and urinary renin, facilitating renin-guided precision treatment and significantly improving hypertension control rate (90 % versus 58 %). Our nanoprobe platform holds great potential for assisting clinicians in rapidly and accurately classifying hypertensive patients and improving outcomes through tailored treatment selection.

[Antihypertensive therapy in patients with arterial hypertension and concomitant diseases in real clinical practice (according to the National Registry of Arterial Hypertension, 2019-2022)].

BACKGROUND: Arterial hypertension (AH) remains the leading risk factor associated with cardiovascular diseases (CVDs), cerebrovascular disease and chronic kidney disease. About 70% of patients with AH who are on monotherapy cannot achieve blood pressure (BP) targets, and therefore all quidelines for the management of AH have recently recommended prescribing combination therapy (PCT). In real clinical practice (RCP), there remains significant uncertainty in the effectiveness and rationality of therapy, despite the wide availability of antihypertensive drugs (AHD) and the presence of recommendations for a stepwise approach to prescribing combinations of specific groups of AHD in different clinical situations. AIM: Analyze the real ongoing antihypertensive therapy, including the PCT; international nonproprietary names of drugs and their dosages in RCP; compliance of therapy with clinical recommendations; changing trends in the PCT. MATERIALS AND METHODS: An analysis was carried out of the data from the register of AH, the compliance of treatment in different clinical groups of patients and the achievement of BP and low-density lipoprotein cholesterol targets in the sample of 2019-2022 (n=5012). The prescription of AHD and achievement of targets values were assessed in accordance with current clinical guidelines for the management of AH and hypercholesterolemia. Data from 2010 (n=7782) and 2020 (n=3061) were analyzed to assess the dynamics of prescription of monotherapy and PCT. RESULTS: The greatest increase in the number of AHD was observed in patients with hypertension in combination with coronary heart disease, heart failure, and atrial fibrillation. In a small group of patients with hypertension without other CVDs, the recommended combinations of AHD were not prescribed; preference was given to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-adrenoblocker (ß-AB). PCT mainly differed from the recommended combinations by the wider use of drugs from the ß-AB group. The PCT of recommended drugs was highest in patients with hypertension and coronary artery disease - more than 90%, hypertension and heart failure in 56.2%, hypertension and atrial fibrillation - 33.3%, hypertension and chronic kidney desease - 19.6%. Achievement of BP and low-density lipoprotein cholesterol targets was insufficient in all analyzed groups. Among the international nonproprietary names of drugs, the most frequently prescribed are the following: bisoprolol, metoprolol, lisinopril, perindopril, losartan, spironolactone, amlodipine, torasemide, indapamide, hypochlorothiazide, moxonidine. The prescribed daily dosages were closer to the initial recommended ones. By 2020, the prescription of PCT with ß-AB and a more uniform prescription of various combinations will come to the fore, while PCT in 2010 is characterized by the presence of one or two leaders combinations. CONCLUSION: The described features of prescribing AHD partially reproduce clinical recommendations for the management of AH. Differences in therapy provided in RCP may be associated with an attempt to intensify the treatment of hypertension in patients with other concomitant CVDs. At the same time, analysis of combinations and dosages of prescribed drugs suggests the presence of wide opportunities for further escalation of therapy. The presented data can provide insight into current patterns of antihypertensive therapy prescription in patients in RCP and lay the foundation for optimizing therapy in different categories hypertensive patients.

Angiotensin Receptor Neprilysin Inhibitor Use and Blood Pressure Lowering in Patients With Heart Failure With Reduced Ejection Fraction Across the Spectrum of Kidney Function: An Analysis of the Veterans Administrative Health System.

BACKGROUND: A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function. METHODS: Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates. RESULTS: There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P < 0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P < 0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73m2 or continuously across a wide range of eGFR (Pinteraction > 0.10 for both). CONCLUSION: The use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease.

Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. RESULTS: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). CONCLUSIONS: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.

Linkage between electronic prescribing data and pharmacy claims records to determine primary adherence: the case of antihypertensive therapy in the Lisbon and Tagus Valley Region, Portugal.

BACKGROUND: Hypertension (HT) is highly prevalent and a major risk factor for cardiovascular disease. Over 42% of Portuguese adults have HT. Even though the benefits of antihypertensive (AHT) drugs have been demonstrated, HT control remains inadequate. One major reason is that patients often fail to take their medications as prescribed. This paper aims to determine primary adherence to AHT therapy in newly diagnosed and treated hypertensive patients in Primary Health Care (PHC) units of Lisbon and Tagus Valley Health Region. METHODS: This study reports data from a population-based, retrospective, cohort study from patients diagnosed with HT in PHC units of Lisbon and Tagus Valley Region from 1 January to 31 March 2011, with no prior use of AHT drugs. Primary adherence rate was expressed as number of claims records/total number of prescriptions records. Data were collected from SIARS for each patient during a 2-year period. RESULTS: Overall primary adherence rate was 58.5%, increasing with age. Rates were higher for men, living in the Lisbon Metropolitan Area and diagnosed with uncomplicated HT. Drugs acting on the renin-angiotensin system had the highest rates, increasing for fixed-dose combinations and diminishing with the increase of cost for the patient. CONCLUSIONS: Overall, almost 1 out of 2 prescribed AHT drugs were not dispensed. Until this study, little was known in Portugal about primary adherence. Our findings imply that the potential benefits of AHT therapy cannot be fully realized in this population.

Hypertension in children and adolescents.

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Features and Comparative Characteristics of Fucosylated Glycans Expression in Endothelial Glycocalyx of Placental Terminal Villi in Patients with Preeclampsia Treated with Different Antihypertensive Regimens.

Antihypertensive therapy is an essential part of management of patients with preeclampsia (PE). Methyldopa (Dopegyt®) and nifedipine (Cordaflex®) are basic medications of therapy since they stabilize blood pressure without affecting the fetus. Their effect on the endothelium of placental vessels has not yet been studied. In this study, we analyzed the effect of antihypertensive therapy on the expression of fucosylated glycans in fetal capillaries of placental terminal villi in patients with early-onset PE (EOPE) and late-onset PE (LOPE), and determined correlation between their expression and mother's hemodynamic parameters, fetoplacental system, factors reflecting inflammatory response, and destructive processes in the endothelial glycocalyx (eGC). A total of 76 women were enrolled in the study: the comparison group consisted of 15 women with healthy pregnancy, and the main group comprised 61 women with early-onset and late-onset PE, who received one-component or two-component antihypertensive therapy. Hemodynamic status was assessed by daily blood pressure monitoring, dopplerometry of maternal placental and fetoplacental blood flows, and the levels of IL-18, IL-6, TNFα, galectin-3, endocan-1, syndecan-1, and hyaluronan in the blood of the mother. Expression of fucosylated glycans was assessed by staining placental sections with AAL, UEA-I, LTL lectins, and anti-LeY MAbs. It was found that (i) expression patterns of fucosylated glycans in eGC capillaries of placental terminal villi in EOPE and LOPE are characterized by predominant expression of structures with a type 2 core and have a similar pattern of quantitative changes, which seems to be due to the impact of one-component and two-component antihypertensive therapy on their expression; (ii) correlation patterns indicate interrelated changes in the molecular composition of eGC fucoglycans and indicators reflecting changes in maternal hemodynamics, fetoplacental hemodynamics, and humoral factors associated with eGC damage. The presented study is the first to demonstrate the features of placental eGC in women with PE treated with antihypertensive therapy. This study also considers placental fucoglycans as a functional part of the eGC, which affects hemodynamics in the mother-placenta-fetus system.

[Obstructive sleep apnea syndrome and cardiovascular risk factors in the antihypertensive therapy "escape" phenomenon].

AIM: To assess the role of obstructive sleep apnea and other cardiovascular (CV) risk factors in the development of the antihypertensive therapy (AHT) efficacy "escape" phenomenon in patients with arterial hypertension (AH). MATERIALS AND METHODS: The data of 75 patients with AH stage I-II, grades 1-3 were proceeded. All patients included in the study underwent night respiratory monitoring. After AHT prescription, blood pressure (BP) was monitored by three measurement methods (office, daily monitoring and self-control of blood pressure) - initially, in 1, 3 and 6 months after the inclusion - in order to confirm the initial therapy efficacy and to identify or exclude the "escape" phenomenon. RESULTS: In 36.0% of patients, the "escape" phenomenon was diagnosed in 1 or 3 months of observation. When comparing the group with the "escape" phenomenon, an initially higher level of systolic BP was revealed according to office measurements, 24-hour monitoring and self-control BP monitoring (134.0±4.7 mmHg vs 126.0±8.5 mmHg; 129.0±2.3 mmHg vs 121.0±7.7 mmHg; 131.0±8.2 mmHg vs 121.5±6.2 mmHg resp.; р<0,05). There were no differences in sleep apnea and CV risk factors between the groups. However in patients with a minimal SpO2≤85% during sleep, there were a higher levels of office systolic BP both before the AHT prescription, and during its use (157.6±10.4 mmHg vs 152.4±8.1 mmHg resp., р<0,05; 132.0±6.8 vs 127.1±8.9 mmHg resp.; р<0,05), and mean 24-hour systolic BP (125.7±5.9 vs 121.6±8.2 mmHg resp.; р<0,05) - compared with patients with a minimum SpO2>85%. CONCLUSION: The higher BP level in patients with lover nocturnal hypoxemia does not allow us to exclude the delayed negative impact of obstructive sleep apnea, especially severe, on the BP profile in case of initially successful AH control.

[Relationship between the pain severity, use of non-steroidal anti-inflammatory drugs and blood pressure in elective large joint arthroplasty of the lower extremities].

AIM: To evaluate the changes in blood pressure (BP), the severity of pain syndrome and non-steroidal anti-inflammatory drugs (NSAIDs) use patterns in patients hospitalized for elective arthroplasty of large joints of the lower extremities during the postoperative period. MATERIALS AND METHODS: This study included 374 patients. In all patients, medical history, antihypertensive therapy and history of NSAIDs usage were collected, BP was measured, and the severity of pain was assessed via a 10-point scale before surgery, as well as 1 and 3 months after arthroplasty. RESULTS: The study included 132 (35.3%) males and 242 (64.7%) females. Among these, 289 (77.3%) patients had hypertension [grade 1 - 35 patients, grade 2 - 136 patients, grade 3 - 118 (25.0%) patients]; 280 (74.9%) patients were taking NSAIDs (121 - daily, 135 - 2-3 times per week). The median pain severity before surgery was 8 points [7; 9], 1 month after surgery - 2 points [1; 4], 3 months after surgery - 1 point [0; 3]. At 1 month after arthroplasty, 23 (7.9%) patients reported a decrease in BP. In 17 (5.9%) patients, correction of previously prescribed antihypertensive therapy with a decrease in drug doses was required. At 1 month after arthroplasty, 256 patients discontinued NSAIDs. The analysis of the relationship between the severity of pain, NSAIDs use and the level of BP revealed a significant effect of pain syndrome (p<0.0001) and the use of NSAIDs (p=0.014). CONCLUSION: In the population of patients with elective arthroplasty of large joints of the lower extremities, a significant incidence of hypertension and a high prevalence of NSAIDs use are noted. During the postoperative period, a significant trend towards a decrease in the severity of pain was found, as well as the relationship of pain and NSAIDs with a decrease in BP.

Society for Maternal-Fetal Medicine Statement: Antihypertensive therapy for mild chronic hypertension in pregnancy-The Chronic Hypertension and Pregnancy trial.

The recently published Chronic Hypertension and Pregnancy study provides important data to inform the management of mild chronic hypertension in pregnancy. The purpose of this statement is to review the results of this trial and provide guidance for the implementation of the study findings. Based on the available evidence, SMFM recommends treatment with antihypertensive therapy for mild chronic hypertension in pregnancy to a goal blood pressure of <140/90 mm Hg. Patients with treated chronic hypertension should continue established antihypertensive therapy during pregnancy or change to a regimen compatible with pregnancy to achieve this treatment goal.

Toward personalized management of chronic hypertension in pregnancy.

Chronic hypertension complicates 1% to 2% of pregnancies, and it is increasingly common. Women with chronic hypertension are an easily recognized group who are in touch with a wide variety of healthcare providers before, during, and after pregnancy, mandating that chronic hypertension in pregnancy be within the scope of many practitioners. We reviewed recent data on management to inform current care and future research. This study is a narrative review of published literature. Compared with normotensive women, women with chronic hypertension are at an increased risk of maternal and perinatal complications. Women with chronic hypertension who wish to be involved in their care can do by measuring blood pressure at home. Accurate devices for home blood pressure monitoring are now readily available. The diagnostic criteria for superimposed preeclampsia remain problematic because most guidelines continue to include deteriorating blood pressure control in the definition. It has not been established how angiogenic markers may aid in confirmation of the diagnosis of superimposed preeclampsia when suspected, over and above information provided by routinely available clinical data and laboratory results. Although chronic hypertension is a strong risk factor for preeclampsia, and aspirin decreases preeclampsia risk, the effectiveness specifically among women with chronic hypertension has been questioned. It is unclear whether calcium has an independent effect in preeclampsia prevention in such women. Treating hypertension with antihypertensive therapy halves the risk of progression to severe hypertension, thrombocytopenia, and elevated liver enzymes, but a reduction in preeclampsia or serious maternal complications has not been observed; however, the lack of evidence for the latter is possibly owing to few events. In addition, treating chronic hypertension neither reduces nor increases fetal or newborn death or morbidity, regardless of the gestational age at which the antihypertensive treatment is started. Antihypertensive agents are not teratogenic, but there may be an increase in malformations associated with chronic hypertension itself. At present, blood pressure treatment targets used in clinics are the same as those used at home, although blood pressure values tend to be inconsistently lower at home among women with hypertension. Although starting all women on the same antihypertensive medication is usually effective in reducing blood pressure, it remains unclear whether there is an optimal agent for such an approach or how best to use combinations of antihypertensive medications. An alternative approach is to individualize care, using maternal characteristics and blood pressure features beyond blood pressure level (eg, variability) that are of prognostic value. Outcomes may be improved by timed birth between 38 0/7 and 39 6/7 weeks' gestation based on observational literature; of note, confirmatory trial evidence is pending. Postnatal care is facilitated by the acceptability of most antihypertensives (including angiotensin-converting enzymes inhibitors) for use in breastfeeding. The evidence base to guide the care of pregnant women with chronic hypertension is growing and aligning with international guidelines. Addressing outstanding research questions would inform personalized care of chronic hypertension in pregnancy.

Systemic Hypertension in Infants with Bronchopulmonary Dysplasia.

PURPOSE OF REVIEW: Neonatal hypertension is increasingly recognized as improvements in neonatal intensive care have led to increased survival of premature infants. Among infants with bronchopulmonary dysplasia (BPD), the rates of hypertension are much higher than the general neonatal population. However, the etiology and pathophysiology of this increased risk of hypertension in neonates with lung disease remain unclear. RECENT FINDINGS: Among infants with bronchopulmonary dysplasia, the rates of hypertension are much higher than the general neonatal population. New studies suggest outcomes in neonates with BPD with hypertension are usually good, with resolution of hypertension in most infants with lung disease. Several potential mechanisms of hypertension in this patient population have been recently proposed. This review focuses on the recent epidemiologic data on prevalence of hypertension in neonates with bronchopulmonary dysplasia, reviews the typical clinical course, and discusses available strategies for management of infants with bronchopulmonary dysplasia that develop hypertension.

Poor guideline adherence in a real-world evaluation of hypertensive emergency management.

BACKGROUND: The American College of Cardiology and American Heart Association define hypertensive emergency (HTN-E) as a systolic blood pressure greater than 180 mmHg or a diastolic blood pressure greater than 120 mmHg with evidence of end-organ damage (EOD). Based on expert opinion, current guidelines recommend antihypertensive therapy to reduce blood pressure (BP) at specific hourly rates to reduce progression of EOD, outlined by four criteria. Our goal was to describe compliance with guideline recommendations for early management of HTN-E and to analyze safety outcomes related to pharmacologic intervention. METHODS: This was a retrospective chart review including patients presenting to the emergency department with HTN-E between September 2016 and August 2020. We excluded patients with a compelling indication for altered therapeutic goals (e.g. acute aortic dissection, hemorrhagic or ischemic stroke, and pheochromocytoma). The primary outcome was complete adherence with guideline recommendations in the first 24 h. RESULTS: Of 758 screened records, 402 were included. Mean age was 54 years and majority Black race (72%). Overall, total adherence was poor (<1%): 30% received intravenous therapy within 1 h, 64% achieved 1-h BP goals, 44% achieved 6-h goals, and 9% had appropriate 24-h maintenance BP. Hypotensive events (N = 67) were common and antihypertensive-associated EOD (N = 21) did occur. Predictors of hypotension include treatment within 1 h and management with continuous infusion medication. CONCLUSIONS: Current practice is poorly compliant with guideline criteria and there are risks associated with recommended treatments. Our results favor relaxing the expert opinion-based recommendations.

Questioning the renoprotective role of L-type calcium channel blockers in chronic kidney disease using physiological modeling.

Chronic kidney disease (CKD) is characterized by the progressive functional loss of nephrons and hypertension (HTN). Some antihypertensive regimens attenuate the progression of CKD (blockers of the renin-angiotensin system). Although studies have suggested that calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, there are few long-term clinical studies that have determined the impact of CCBs in patients with hypertensive CKD. Dihydropyridine (DHP) or L-type CCBs preferentially vasodilate the afferent arteriole and have been associated with glomerular HTN and increases in proteinuria in animal models with low renal function. Small clinical studies in vulnerable populations with renal disease such as African Americans, children, and diabetics have also suggested that DHP CCBs exacerbate glomerular injury, which questions the renoprotective effect of this class of antihypertensive drug. We used an established integrative mathematical model of human physiology, HumMod, to test the hypothesis that DHP CCB therapy exacerbates pressure-induced glomerular injury in hypertensive CKD. Over a simulation of 3 yr, CCB therapy reduced mean blood pressure by 14-16 mmHg in HTN both with and without CKD. Both impaired tubuloglomerular feedback and low baseline renal function exacerbated glomerular pressure, glomerulosclerosis, and the decline in renal function during L-type CCB treatment. However, simulating CCB therapy that inhibited both L- and T-type calcium channels increased efferent arteriolar vasodilation and alleviated glomerular damage. These simulations support the evidence that DHP (L-type) CCBs potentiate glomerular HTN during CKD and suggest that T/L-type CCBs are valuable in proteinuric renal disease treatment.NEW & NOTEWORTHY Our physiological model replicates clinical trial results and provides unique insights into possible mechanisms that play a role in glomerular injury and hypertensive kidney disease progression during chronic CCB therapy. Specifically, these simulations predict the temporal changes in renal function with CCB treatment and demonstrate important roles for tubuloglomerular feedback and efferent arteriolar conductance in the control of chronic kidney disease progression.

Real-life appraisal on blood pressure targets achievement in adult outpatients at high cardiovascular risk.

BACKGROUND AND AIM: Although hypertension guidelines highlight the benefits of achieving the recommended blood pressure (BP) targets, hypertension control rate is still insufficient, mostly in high or very high cardiovascular (CV) risk patients. Thus, we aimed to estimate BP control in a cohort of patients at high CV risk in both primary and secondary prevention. METHODS AND RESULTS: A single-center, cross-sectional study was conducted by extracting data from a medical database of adult outpatients aged 40-75 years, who were referred to our Hypertension Unit, Rome (IT), for hypertension assessment. Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: a)<130/80 mmHg in individuals aged 40-65 years; b)<140/80 mmHg in subjects aged >65 years. Primary prevention patients with SCORE <5% were considered to be at low-intermediate risk, whilst individuals with SCORE ≥5% or patients with comorbidities were defined to be at very high risk. Among 6354 patients (47.2% female, age 58.4 ± 9.6 years), 4164 (65.5%) were in primary prevention with low-intermediate CV risk, 1831 (28.8%) in primary prevention with high-very high CV risk and 359 (5.6%) in secondary prevention. In treated hypertensive outpatients, uncontrolled hypertension rate was significantly higher in high risk primary prevention than in low risk primary prevention and secondary prevention patients (18.4% vs 24.4% vs. 12.5%, respectively; P < 0.001). In high risk primary prevention diabetic patients only 10% achieved the recommended BP targets. CONCLUSIONS: Our data confirmed unsatisfactory BP control among high-risk patients, both in primary and secondary prevention, and suggest the need for a more stringent BP control policies in these patients.

Serum uric acid change in relation to antihypertensive therapy with the dihydropyridine calcium channel blockers.

PURPOSE: We investigated serum uric acid changes in relation to the achieved clinic and ambulatory blood pressure after 8 weeks of antihypertensive therapy with two dihydropyridine calcium channel blockers. MATERIALS AND METHODS: The study participants were patients with clinic and ambulatory hypertension, enrolled in a randomised controlled trial that compared amlodipine (5-10 mg, n = 215) and nifedipine gastrointestinal therapeutic system (GITS, 30-60 mg, n = 203). Hyperuricaemia was defined as a serum uric acid concentration of ≥420 µmol/L in men and ≥360 µmol/L in women. Analysis of covariance and multiple regression analyses were performed to study the associations between serum uric acid changes and the achieved clinic and ambulatory blood pressure during follow-up. RESULTS: At baseline, 67 (16.0%) of the 418 patients had hyperuricaemia. Antihypertensive treatment reduced clinic and 24-h daytime and night-time systolic/diastolic blood pressure by a mean (±standard error [SE]) change of -17.4 ± 0.6/-8.6 ± 0.4 mm Hg and -13.7 ± 0.5/-8.3 ± 0.3 mm Hg, -13.8 ± 0.6/-8.4 ± 0.4 mm Hg, and -12.7 ± 0.7/-8.0 ± 0.4 mm Hg, respectively. Antihypertensive treatment reduced serum uric acid by a mean (±SE) change of -9.3 ± 2.8 µmol/L. The serum uric acid changes differed according to the achieved clinic and ambulatory blood pressure, and were statistically significant (mean ± SE -20.6 ± 6.6 to -10.7 ± 2.9 µmol/L, p ≤ 0.04) at the systolic/diastolic ranges of 130-139/≥90 mm Hg in clinic pressure, and <130/75-84 mm Hg, <145/80-84 mm Hg and <120/65-69 mm Hg in 24-h, daytime and night-time ambulatory pressure. CONCLUSION: Our study showed that antihypertensive therapy with a dihydropyridine calcium channel blocker was associated with reduced serum uric acid, especially when 24-h ambulatory systolic blood pressure was controlled.

Anti-Inflammatory Activities of Captopril and Diuretics on Macrophage Activity in Mouse Humoral Immune Response.

Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy.