Monitorización ambulatoria de la presión arterial en adultos y población pediátrica. Una revisión narrativa / Ambulatory blood pressure monitoring, adult and pediatric population. A narrative review

La hipertensión arterial (HTA) se ha convertido en un factor de riesgo central para el desarrollo de enfermedades cardiovasculares (CV), lo que subraya la importancia de su diagnóstico preciso. Numerosos estudios han establecido una estrecha relación entre los valores elevados de la presión arterial sistólica (PAS) y diastólica (PAD) y un incremento en el riesgo de padecer algún evento cardiovascular (ECV). Tradicionalmente, las mediciones de la presión arterial (PA) realizadas en entornos clínicos han sido el principal método para diagnosticar y evaluar la HTA. No obstante, en los últimos años, se ha reconocido que las mediciones de la PA obtenidas fuera del ambiente clínico, mediante la automedida de la presión arterial (AMPA) y la monitorización ambulatoria de la presión arterial (MAPA), ofrecen una perspectiva más realista de la vida cotidiana de los pacientes y, por lo tanto, brindan resultados más fiables. Dada la evolución de los dispositivos médicos, los criterios diagnósticos y la creciente relevancia de componentes de la MAPA en la predicción de ECV, se requiere una actualización integral que sea práctica para la clínica. Esta revisión tiene como objetivo proporcionar una actualización de la MAPA, enfocándose en su importancia en la evaluación de la HTA. Además, se analizarán los umbrales diagnósticos, los distintos fenotipos según el ciclo circadiano y las recomendaciones en diferentes poblaciones, asimismo, se ofrecerán sugerencias concretas para la implementación efectiva de la MAPA en la práctica clínica, lo que permitirá a los profesionales de la salud tomar decisiones fundamentadas y mejorar la atención de sus pacientes.(AU)

Hypertension has become a central risk factor for the development of cardiovascular disease, underscoring the importance of its accurate diagnosis. Numerous studies have established a close relationship between elevated systolic (SBP) and diastolic (DBP) blood pressure and an increased risk of cardiovascular event (CVE). Traditionally, blood pressure (BP) measurements performed in clinical settings have been the main method for diagnosing and assessing hypertension. However, in recent years, it has been recognized that BP measurements obtained outside the clinical setting, using self-monitoring blood pressure (SMBP) and ambulatory blood pressure monitoring (ABPM), offer a more realistic perspective of patients’ daily lives and therefore provide more reliable results. Given the evolution of medical devices, diagnostic criteria, and the increasing relevance of certain components of ABPM in the prediction of adverse cardiovascular outcomes, a comprehensive update that is practical for daily clinical practice is required. The main objective of this article is to provide an updated review of ABPM, focusing on its importance in the evaluation of hypertension and its impact on public health in Colombia. In addition, it will discuss the implications of changes in diagnostic thresholds and provide concrete recommendations for the effective implementation of ABPM in clinical practice, allowing health professionals to make informed decisions and improve the care of their patients.(AU)

Duct Stenting in Duct-Dependent Systemic Blood Flow, Past, Present, and Future.

Arterial duct stenting, pioneered in the early 1990s for newborns with a duct-dependent pulmonary and systemic circulation, has evolved significantly over the past decades. This progressive technique has led to the development of novel therapeutic strategies, including the Hybrid approach introduced three decades ago, and more recently, a complete transcatheter approach for treating newborns with hypoplastic left heart syndrome (HLHS). Subsequently, the transcatheter method has been extended to bi-ventricular lesions and patients with pulmonary hypertension, establishing a reverse Potts-shunt pathophysiology. Considering current experiences, this review aims to assess the strengths, weaknesses, and complications associated with ductal stenting, which represents a critical component of these complex treatment strategies. Despite advancements, the mortality rate of Norwood and Hybrid stage-1 procedures has plateaued, underscoring the importance of enhancing the quality of life of affected patients as the primary therapeutic goal. The prerequisite is a gentle, almost atraumatic medicine, particularly during the newborn period. It is essential to recognize that both the Hybrid and total transcatheter approaches demand comparable experience to Norwood surgery. Successful outcomes hinge on much more than merely inserting a stent into the duct; they require meticulous attention to detail and comprehensive management strategies.

Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension.

BACKGROUND: Previous studies have indicated that neutrophil extracellular traps (NETs) play a pivotal role in pathogenesis of pulmonary arterial hypertension (PAH). However, the specific mechanism underlying the impact of NETs on pulmonary artery smooth muscle cells (PASMCs) has not been determined. The objective of this study was to elucidate underlying mechanisms through which NETs contribute to progression of PAH. METHODS: Bioinformatics analysis was employed in this study to screen for potential molecules and mechanisms associated with occurrence and development of PAH. These findings were subsequently validated in human samples, coiled-coil domain containing 25 (CCDC25) knockdown PASMCs, as well as monocrotaline-induced PAH rat model. RESULTS: NETs promoted proliferation of PASMCs, thereby facilitating pathogenesis of PAH. This phenomenon was mediated by the activation of transmembrane receptor CCDC25 on PASMCs, which subsequently activated ILK/ß-parvin/RAC1 pathway. Consequently, cytoskeletal remodeling and phenotypic transformation occur in PASMCs. Furthermore, the level of NETs could serve as an indicator of PAH severity and as potential therapeutic target for alleviating PAH. CONCLUSION: This study elucidated the involvement of NETs in pathogenesis of PAH through their influence on the function of PASMCs, thereby highlighting their potential as promising targets for the evaluation and treatment of PAH.

Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in pulmonary arterial hypertension.

BACKGROUND: Extrachromosomal circular DNAs (eccDNAs) have been reported to play a key role in the occurrence and development of various diseases. However, the characterization and role of eccDNAs in pulmonary arterial hypertension (PAH) remain unclear. METHODS: In the discovery cohort, we first explored eccDNA expression profiles by Circle-sequencing analysis. The candidate eccDNAs were validated by routine polymerase chain reaction (PCR), TOPO-TA cloning and Sanger sequencing. In the validation cohort, 30 patients with PAH and 10 healthy controls were recruited for qPCR amplification to detect the candidate eccDNAs. Datas at the baseline were collected, including clinical background, biochemical variables, echocardiography and hemodynamic factors. Receiver operating characteristic curve was used to investigate the diagnostic effect of the eccDNA. RESULTS: We identified a total of 21,741 eccDNAs in plasma samples of 3 IPAH patients and 3 individuals in good health, and the expression frequency, GC content, length distribution, and genome distribution of the eccDNAs were thoroughly characterized and analyzed. In the validation cohort, 687 eccDNAs were differentially expressed in patients with IPAH compared with healthy controls (screening threshold: |FC|≥2 and P < 0.05). Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the specific eccDNAs in IPAH were significantly enriched in calcium channel activity, the mitogen-activated protein kinase pathway, and the wnt signaling pathway. Verification queue found that the expression of eccDNA-chr2:131208878-131,424,362 in PAH was considerably higher than that in healthy controls and exhibited a high level of accuracy in predicting PAH with a sensitivity of 86.67% and a specificity of 90%. Furthermore, correlation analysis disclosed a significant association between serum eccDNA-chr2:131208878-131,424,362 and mean pulmonary artery pressure (mPAP) (r = 0.396, P = 0.03), 6 min walking distance (6MWD) (r = -0.399, P = 0.029), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (r = 0.685, P < 0.001) and cardiac index (CI) (r = - 0.419, P = 0.021). CONCLUSIONS: This is the first study to identify and characterize eccDNAs in patients with PAH. We revealed that serum eccDNA-chr2:131208878-131,424,362 is significantly overexpressed and can be used in the diagnosis of PAH, indicating its potential as a novel non-invasive biomarker.

Factors associated with discontinuation of treatment for pulmonary arterial hypertension in the United States.

Information on factors leading to pulmonary arterial hypertension (PAH) treatment discontinuation is limited. This study analyzed 12,902 new PAH medication users to identify predictors of treatment discontinuation. Treatment by accredited pulmonary hypertension centers and combination therapy with PAH agents from different classes were less likely to result in discontinuation.

IL-6/gp130 signaling in CD4+ T cells drives the pathogenesis of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.

Early identification of SOX17 deficiency in infants to guide management of heritable pulmonary arterial hypertension using PDA stent to create reverse Potts shunt physiology.

Heritable pulmonary arterial hypertension (HPAH) is a rare progressive condition that includes patients with an identified genetic cause of pulmonary arterial hypertension (PAH). HPAH and idiopathic PAH (IPAH) have an estimated combined incidence of 0.5-0.9 cases per million children-years. Several pathogenic variants have been associated with HPAH in children and adults, including genes BMPR2, TBX4, and ACVRL1, and more rarely with variants in genes such as SOX17. HPAH is often difficult to manage and has poor prognosis despite advances in medical therapy with many patients progressing to lung transplantation, right heart failure and death. Surgical and transcatheter Potts shunt creation can reduce systolic burden and has shown reduction in morbidity and mortality in children. Early genetic testing can provide both diagnostic and prognostic value in managing and counseling children with severe PAH and it can guide transcatheter or surgical management in refractory cases despite maximal medical therapies. We describe a patient with HPAH (SOX17 mutation) who underwent percutaneous patent ductus arteriosus stent for right ventricle decompression at 2 months of age with clinical management guidance by genetic testing results.

Left-Sided Destroyed Lung With Severe Pulmonary Arterial Hypertension as a Consequence of Recurrent Pulmonary Tuberculosis.

Pulmonary tuberculosis is an infection caused by Mycobacterium tuberculosis, which is an obligate aerobic microbe. Tuberculosis is a multisystemic disease that can attack the respiratory system, genitourinary system, central nervous system, gastrointestinal system, and the skeletal framework of the body. However, the most commonly affected system is the respiratory system (pulmonary tuberculosis). Tuberculosis is an ancient infection that affects millions of people every year, and even after adequate treatment, it is associated with significant morbidity and mortality, which can be attributed to reinfections, complications, extrapulmonary spread, and the long-term effects of tuberculosis on the lungs, leading to various restrictive and obstructive diseases. One of the most hazardous sequelae of pulmonary tuberculosis is the destroyed lung, which is predominately seen in the culminating stage of progressive disease or after reactivation of the disease. Here we present the case of a 46-year-old female patient who presented with complaints of breathlessness, cough with expectoration, and chest pain. With a history of recurrent tuberculosis infections and appropriate antituberculosis treatment for 30 years, the primary infection was recognized at 16 years of age. On examination, the patient was suspected to have developed fibrosis of the left lung, which, on radiological investigation, was confirmed to be a case of a destroyed left lung because of a recurrent tuberculosis infection. The patient was given symptomatic treatment along with broad-spectrum antibiotic therapy.

Integrated bioinformatics analysis and experimental animal models identify a robust biomarker and its correlation with the immune microenvironment in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) represents a substantial global risk to human health. This study aims to identify diagnostic biomarkers for PAH and assess their association with the immune microenvironment through the utilization of sophisticated bioinformatics techniques. Methods: Based on two microarray datasets, differentially expressed genes (DEGs) were detected, and hub genes underwent a sequence of machine learning analyses. After pathways associated with PAH were assessed by gene enrichment analysis, the identified genes were validated using external datasets and confirmed in a monocrotaline (MCT)-induced rat model. In addition, three algorithms were employed to estimate the proportions of various immune cell types, and the link between hub genes and immune cells was substantiated. Results: Using SVM, LASSO, and WGCNA, we identified seven hub genes, including (BPIFA1, HBA2, HBB, LOC441081, PI15, S100A9, and WIF1), of which only BPIFA1 remained stable in the external datasets and was validated in an MCT-induced rat model. Furthermore, the results of the functional enrichment analysis established a link between PAH and both metabolism and the immune system. Correlation assessment showed that BPIFA1 expression in the MCP-counter algorithm was negatively associated with various immune cell types, positively correlated with macrophages in the ssGSEA algorithm, and correlated with M1 and M2 macrophages in the CIBERSORT algorithm. Conclusion: BPIFA1 serves as a modulator of PAH, with the potential to impact the immune microenvironment and disease progression, possibly through its regulatory influence on both M1 and M2 macrophages.

Predictors of early mortality after lung transplantation for idiopathic pulmonary arterial hypertension.

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short-term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90-day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR: 3; CI: 1.4-5), pulmonary artery diastolic pressure (OR: 1.3 per 10 mmHg; CI: 1.07-1.56), forced expiratory volume in the first second percent predicted (OR: 0.8 per 10%; CI: 0.7-0.94), recipient total bilirubin >2 mg/dL (OR: 3; CI: 1.4-7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01-2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90-day mortality after lung transplant for IPAH.

Lung-specific interleukin 6 mediated transglutaminase 2 activation and cardiopulmonary fibrogenesis.

Pulmonary hypertension (PH) pathogenesis is driven by inflammatory and metabolic derangements as well as glycolytic reprogramming. Induction of both interleukin 6 (IL6) and transglutaminase 2 (TG2) expression participates in human and experimental cardiovascular diseases. However, little is known about the role of TG2 in these pathologic processes. The current study aimed to investigate the molecular interactions between TG2 and IL6 in mediation of tissue remodeling in PH. A lung-specific IL6 over-expressing transgenic mouse strain showed elevated right ventricular (RV) systolic pressure as well as increased wet and dry tissue weights and tissue fibrosis in both lungs and RVs compared to age-matched wild-type littermates. In addition, IL6 over-expression induced the glycolytic and fibrogenic markers, hypoxia-inducible factor 1α, pyruvate kinase M2 (PKM2), and TG2. Consistent with these findings, IL6 induced the expression of both glycolytic and pro-fibrogenic markers in cultured lung fibroblasts. IL6 also induced TG2 activation and the accumulation of TG2 in the extracellular matrix. Pharmacologic inhibition of the glycolytic enzyme, PKM2 significantly attenuated IL6-induced TG2 activity and fibrogenesis. Thus, we conclude that IL6-induced TG2 activity and cardiopulmonary remodeling associated with tissue fibrosis are under regulatory control of the glycolytic enzyme, PKM2.

Preliminary Mechanism of Glial Maturation Factor ß on Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Recent evidence suggests that glia maturation factor ß (GMFß) is important in the pathogenesis of pulmonary arterial hpertension (PAH), but the underlying mechanism is unknown. To clarify whether GMFß can be involved in pulmonary vascular remodeling and to explore the role of the IL-6-STAT3 pathway in this process, the expression of GMFß in PAH rats is examined and the expression of downstream molecules including periostin (POSTN) and interleukin-6 (IL-6) is measured using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The location and expression of POSTN is also tested in PAH rats using immunofluorescence. It is proved that GMFß is upregulated in the lungs of PAH rats. Knockout GMFß alleviated the MCT-PAH by reducing right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and pulmonary vascular remodeling. Moreover, the inflammation of the pulmonary vasculature is ameliorated in PAH rats with GMFß absent. In addition, the IL-6-STAT3 signaling pathway is activated in PAH; knockout GMFß reduced POSTN and IL-6 production by inhibiting the IL-6-STAT3 signaling pathway. Taken together, these findings suggest that knockout GMFß ameliorates PAH in rats by inhibiting the IL-6-STAT3 signaling pathway.

Research progress on the role of p53 in pulmonary arterial hypertension.

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. At present, the definitive pathology of PAH has not been elucidated and its effective treatment remains lacking. Despite PAHs having multiple pathogeneses, the cancer-like characteristics of cells have been considered the main reason for PAH progression. RECENT FINDINGS: p53 protein, an important tumor suppressor, regulates a multitude of gene expressions to maintain normal cellular functions and suppress the progression of malignant tumors. Recently, p53 has been found to exert multiple biological effects on cardiovascular diseases. Since PAH shares similar metabolic features with cancer cells, the regulatory roles of p53 in PAH are mainly the induction of cell cycle, inhibition of cell proliferation, and promotion of apoptosis. SUMMARY: This paper summarized the advanced findings on the molecular mechanisms and regulatory functions of p53 in PAH, aiming to reveal the potential therapeutic targets for PAH.

Development of Losartan Orally Disintegrating Tablets by Direct Compression: a Cost-Effective Approach to Improve Paediatric Patient's Compliance.

The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

Gaps in evidence in the management of patients with intermediate-risk pulmonary arterial hypertension: Considerations following the ESC/ERS 2022 guidelines.

A comprehensive evaluation of risk, using multiple indices, is necessary to provide reliable prognostic information and guide therapy in pulmonary arterial hypertension (PAH). The current ESC/ERS guidelines suggest using a three-strata model for incident (newly diagnosed) patients and a four-strata model for prevalent patients with PAH. The four-strata model serves as a fundamental risk-stratification tool and relies on a minimal dataset of indicators that must be considered during follow-up. Nevertheless, there are still areas of vagueness and ambiguity when classifying and managing patients in the intermediate-risk category. For these patients, considerations should include right heart imaging, hemodynamics, as well as individual factors such as age, sex, genetic profile, disease type, comorbidities, and kidney function. The aim of this report is to present case studies, with a specific focus on patients ultimately classified as intermediate risk. We aim to emphasize the challenges and complexities encountered in the realms of diagnosis, classification, and treatment for these particular patients.

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Background: Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. Methods: A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Results: Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. Conclusions: This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment.

BACKGROUND: Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. METHODS: We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. RESULTS: Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CONCLUSIONS: CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

Causal association of depression, anxiety, cognitive performance, the brain cortical structure with pulmonary arterial hypertension: A Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. METHODS: PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. RESULTS: PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. LIMITATIONS: The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. CONCLUSION: Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms.

[Efficacy of manual correction of cervical spine osteochondrosis in the treatment of arterial hypertension syndrome and prediabetes]. / Effektivnost' manual'noi korrektsii osteokhondroza sheinogo otdela pozvonochnika v terapii sindroma arterial'noi gipertenzii i prediabeta.

Cardiovascular diseases and diabetes mellitus, debuting as arterial hypertension (AH) syndrome and prediabetes, are common types of chronic non-communicable processes, that are the leading cause of death in the world. The main treatment method for above mentioned disorders, according to the current guidelines, is pharmacotherapy. However, it is possible to effectively apply non-pharmacological correction methods, aimed at the probable etiological factor and inversive mechanism involved in AH maintenance, in the early stages when no permanent changes are maintaining a high level of blood hypertension (BH) and glycemia. Frequently, this mechanism is hypoxia in the vertebral arteries system due to cervical spine osteochondrosis. OBJECTIVE: To evaluate the therapeutic effect of non-pharmacological methods of restoring brainstem blood supply in patients with AH and prediabetes. MATERIAL AND METHODS: The number of patients equal 125 (57 men and 68 women, mean age 63.3±11.5 and 65.4±11.8 y.o., respectively) with prediabetes and 1st degree of AH without target organs damage, among whom 102 patients with prehypertension or 1st degree of hypertension and 24 ones with 2nd degree of hypertension, were examined. The original method of manually restoring brainstem blood supply developed in the Shishonin's Clinic was applied to all patients. The control group included patients with the same disorder, who did not receive manipulations. Blood pressure (BP) measurement, ultrasound and triplex ultrasonography of vertebral arteries, biochemical blood test, and estimation of glycemia and glycated hemoglobin were performed. RESULTS: All patients of the study group had decreased levels of systolic BP (by 23.8±10.7 mm Hg for men and 32.8±11.9 mm Hg for women), an increase of flow velocity in vertebral arteries (by 20.6±7.5 and 21.5±7.2 cm/s, respectively), a decrease of glycated hemoglobin concentration (by 0.32±0.51 and 0.34±0.41%, respectively). In the comparison group, there were no patients with improvement in these indicators. CONCLUSION: The effectiveness of the author's manual method of cervical spine osteochondrosis correction in the reduction of BP and glycemia levels in the early stages of the disease is shown.