Genome-wide characterization of circulating metabolic biomarkers.

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1-7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8-11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

Relationship between trimethylamine N-oxide and the risk of hypertension in patients with cardiovascular disease: A meta-analysis and dose-response relationship analysis.

BACKGROUND: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized to be one of the risk factors for cardiovascular disease (CVD). However, there is a scarcity of data on the relationship between circulating TMAO levels and hypertension in patients with CVD. Meta analysis and a dose-response relationship were used in this study to assess the relationship between circulating trimethylamine N-oxide levels and the risk of hypertension in patients with CVD. METHODS: CNKI, Wanfang Database, Pubmed, Embase, Cochrane Library, and Web of Science were searched up to June 01, 2023. Meta-analysis and dose-response analysis of relative risk data from prospective cohort studies reporting on the relationship between circulating TMAO levels and hypertension risk in patients with CVD were conducted. RESULTS: Fifteen studies with a total of 15,498 patients were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher risk of hypertension in patients with CVD (RR = 1.14,95%CI (1.08, 1.20)). And the higher the TMAO level, the greater the risk of hypertension. The dose-response analysis revealed a linear dose-response relationship between circulating TMAO levels and the risk of hypertension in patients with CVD. The risk of hypertension increased by 1.014% when the circulating TMAO level increased by 1 µ mol/L. CONCLUSION: In patients with CVD, the level of circulating TMAO is significantly related to the risk of hypertension. The risk of hypertension increased by 1.014% for every 1 µ mol/L increase in circulating TMAO levels.

Corin and Left Atrial Cardiomyopathy, Hypertension, Arrhythmia, and Fibrosis.

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in CORIN, the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.

Triglyceride glucose index and renal function decline in Han Chinese hypertensive patients.

Elevated triglyceride glucose (TyG) index is associated with an increased risk of cardiovascular disease. The current study aimed to investigate whether the TyG index was correlated with renal function decline in patients with hypertension. Han Chinese participants with essential hypertension were included. The TyG index was calculated as ln[fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Renal function decline was defined as >25% decline in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to examine the independent effect of the TyG index on renal events. In total, 548 Han Chinese hypertensive participants with a mean age of 62.1 ± 14.3 years were eligible for enrollment. During a mean follow-up period of 4.7 ± 3.1 years, 97 patients suffered from >25% decline in eGFR. When compared to those without eGFR decline, patients with eGFR decline had higher fasting triglyceride levels (P = .056), fasting glucose levels (P = .014), and TyG indexes (P = .014). The Cox proportional hazard regression model revealed that the TyG index (hazard ratio [HR] = 1.490; 95% confidence interval [CI] = 1.016-2.185, P = .041), office systolic blood pressure (HR = 1.013; 95% CI = 1.000-1.026, P = .047), diabetes mellitus (HR = 1.797, 95% CI = 1.026-3.147, P = .040), and baseline eGFR (HR = 1.015; 95% CI = 1.002-1.028, P = .025) were associated with renal events. In conclusions, an elevated TyG index is independently associated with an increased risk of eGFR decline in hypertensive patients.

Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension.

BACKGROUND: Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension. Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis. METHODS: In this phase 1 study, patients with hypertension were randomly assigned in a 2:1 ratio to receive either a single ascending subcutaneous dose of zilebesiran (10, 25, 50, 100, 200, 400, or 800 mg) or placebo and were followed for 24 weeks (Part A). Part B assessed the effect of the 800-mg dose of zilebesiran on blood pressure under low- or high-salt diet conditions, and Part E the effect of that dose when coadministered with irbesartan. End points included safety, pharmacokinetic and pharmacodynamic characteristics, and the change from baseline in systolic and diastolic blood pressure, as measured by 24-hour ambulatory blood-pressure monitoring. RESULTS: Of 107 patients enrolled, 5 had mild, transient injection-site reactions. There were no reports of hypotension, hyperkalemia, or worsening of renal function resulting in medical intervention. In Part A, patients receiving zilebesiran had decreases in serum angiotensinogen levels that were correlated with the administered dose (r = -0.56 at week 8; 95% confidence interval, -0.69 to -0.39). Single doses of zilebesiran (≥200 mg) were associated with decreases in systolic blood pressure (>10 mm Hg) and diastolic blood pressure (>5 mm Hg) by week 8; these changes were consistent throughout the diurnal cycle and were sustained at 24 weeks. Results from Parts B and E were consistent with attenuation of the effect on blood pressure by a high-salt diet and with an augmented effect through coadministration with irbesartan, respectively. CONCLUSIONS: Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT03934307; EudraCT number, 2019-000129-39.).

Does This Child With High Blood Pressure Have Secondary Hypertension?: The Rational Clinical Examination Systematic Review.

Importance: Guidelines recommend that all children and adolescents with hypertension undergo evaluation for secondary causes. Identifying clinical factors associated with secondary hypertension may decrease unnecessary testing for those with primary hypertension. Objective: To determine the utility of the clinical history, physical examination, and 24-hour ambulatory blood pressure monitoring for differentiating primary hypertension from secondary hypertension in children and adolescents (aged ≤21 years). Data Sources and Study Selection: The databases of MEDLINE, PubMed Central, Embase, Web of Science, and Cochrane Library were searched from inception to January 2022 without language limits. Two authors identified studies describing clinical characteristics in children and adolescents with primary and secondary hypertension. Data Extraction and Synthesis: For each clinical finding in each study, a 2 × 2 table was created that included the number of patients with and without the finding who had primary vs secondary hypertension. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Main Outcomes and Measures: Random-effects modeling was used to calculate sensitivity, specificity, and likelihood ratios (LRs). Results: Of 3254 unique titles and abstracts screened, 30 studies met inclusion criteria for the meta-analysis and 23 (N = 4210 children and adolescents) were used for pooling in the meta-analysis. In the 3 studies conducted at primary care clinics or school-based screening clinics, the prevalence of secondary hypertension was 9.0% (95% CI, 4.5%-15.0%). In the 20 studies conducted at subspecialty clinics, the prevalence of secondary hypertension was 44% (95% CI, 36%-53%). The demographic findings most strongly associated with secondary hypertension were family history of secondary hypertension (sensitivity, 0.46; specificity, 0.90; LR, 4.7 [95% CI, 2.9-7.6]), weight in the 10th percentile or lower for age and sex (sensitivity, 0.27; specificity, 0.94; LR, 4.5 [95% CI, 1.2-18]), history of prematurity (sensitivity range, 0.17-0.33; specificity range, 0.86-0.94; LR range, 2.3-2.8), and age of 6 years or younger (sensitivity range, 0.25-0.36; specificity range, 0.86-0.88; LR range, 2.2-2.6). Laboratory studies most associated with secondary hypertension were microalbuminuria (sensitivity, 0.13; specificity, 0.99; LR, 13 [95% CI, 3.1-53]) and serum uric acid concentration of 5.5 mg/dL or lower (sensitivity range, 0.70-0.73; specificity range, 0.65-0.89; LR range, 2.1-6.3). Increased daytime diastolic blood pressure load combined with increased nocturnal systolic blood pressure load on 24-hour ambulatory blood pressure monitoring was associated with secondary hypertension (sensitivity, 0.40; specificity, 0.82; LR, 4.8 [95% CI, 1.2-20]). Findings associated with a decreased likelihood of secondary hypertension were asymptomatic presentation (LR range, 0.19-0.36), obesity (LR, 0.34 [95% CI, 0.13-0.90]), and family history of any hypertension (LR, 0.42 [95% CI, 0.30-0.57]). Hypertension stage, headache, and left ventricular hypertrophy did not distinguish secondary from primary hypertension. Conclusions and Relevance: Family history of secondary hypertension, younger age, lower body weight, and increased blood pressure load using 24-hour ambulatory blood pressure monitoring were associated with a higher likelihood of secondary hypertension. No individual sign or symptom definitively differentiates secondary hypertension from primary hypertension.

Serum Uric Acid Levels Are Associated With Macula Microvasculature Changes In Hypertensive White Matter Hyperintensity Patients.

PURPOSE: To characterize the macula microvasculature using fractal dimension (FD) in hypertensive white matter hyperintensity (WMH) participants and explore the association between the microvascular changes and serum uric acid levels. METHODS: Thirty-eight WMH participants were dementia and stroke-free, and 37 healthy controls were enrolled. Optical coherence tomographic angiography (OCTA) was used to image the superficial vascular complex (SVC), deep vascular complex (DVC), and inner vascular complex (IVC) in a 2.5-mm diameter concentric circle (excluding the foveal avascular zone FAZ). A commercial algorithm was used to quantify the complexity and density of the three capillary layers by fractal analysis. RESULTS: WMH participants showed significantly lower FD value in the SVC (P = 0.002), DVC (P < 0.001) and IVC (P = 0.012) macula microvasculature compared with control group. After adjusting for risk factors (hypertension, diabetes, age and gender) SVC (P = 0.035) and IVC (P = 0.030) significantly correlated with serum uric acid. CONCLUSION: Serum uric acid levels are associated with microvascular changes in WMH. Fractal dimension based on OCTA imaging could help quantitatively characterize the macula microvasculature changes in WMH and may be a potential screening tool to detect serum uric acid level changes.

Association of serum vitamin D levels and TaqIrs731236 among patients with hypertensive coronary heart disease.

The development of cardiovascular diseases (CVD) is influenced through multiple risk factor and hypertension. It may increase the risk of cardiac events, and has a significant impact when combined with other risk factors including low levels of vitamin D and genetic variations like single nucleotide variations (SNV) (TaqIrs731236) in vitamin D receptor (VDR) gene. Blood samples from 500 study participants gathered including 250 hypertensive coronary heart disease patients, 250 age and gender matched healthy controls. To isolate genomic DNA, conventional salting out procedure used followed by amplification of targeted variations through Amplification Refractory Mutation System- Polymerase Chain Reaction (ARMS-PCR) Assay. The amplicon consists of 148 base pairs which was visualized on 2 % agarose gel electrophoresis and confirmed by DNA sequencing. The compared clinical parameters including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), high density lipoproteins (HDL), low density lipoproteins (LDL), cholesterol, triglycerides found significantly different among patients when compared with controls (P < 0.001). The Vitamin D exhibited insufficient levels at different stages of hypertension which were statistically, found significantly associated among patients with hypertensive coronary heart disease showing compared to controls (P < 0.001). The genotype association SNV (TaqIrs731236) T > C showed significant association with hypertensive coronary heart disease compared to healthy controls (Chi-Square χ2 = 60.75 and P < 0.00001). Further, the odds ratio of allelic association for risk allele (C) showed the strength of association with risk of disease, which increases by 2.02 times(P = 0.01). The results suggest that (TaqIrs731236) T > C as genetic predisposition factor, may contribute to develop the risk of hypertensive coronary heart disease. Hypertension as a risk factor along with insufficient levels of vitamin D and SNV (TaqIrs731236) as genetic variations may have been an important contributor to disease risk of hypertensive coronary heart disease.

The serum irisin response to prolonged physical activity in temperate and hot environments in older men with hypertension or type 2 diabetes.

Current labor demographics are changing, with the number of older adults increasingly engaged in physically demanding occupations expected to continually rise, which are often performed in the heat. Given an age-related decline in whole-body heat loss, older adults are at an elevated risk of developing heat injuries that may be exacerbated by hypertension (HTN) and type 2 diabetes (T2D). Elevated irisin production may play a role in mitigating the excess oxidative stress and acute inflammation associated with physically demanding work in the heat. However, the effects of HTN and T2D on this response remain unclear. Therefore, we evaluated serum irisin before and after 3-h of moderate intensity exercise (metabolic rate: 200 W/m2) and at the end of 60-min of post-exercise recovery in a temperate (wet-bulb globe temperature (WBGT) 16 °C) and high-heat stress (WBGT 32 °C) environment in 12 healthy older men (mean ± SD; 59 ± 4 years), 10 men with HTN (60 ± 4 years), and 9 men with T2D (60 ± 5 years). Core temperature (Tco) was measured continuously. In the heat, total exercise duration was significantly lower in older men with HTN and T2D (both, p ≤ 0.049). Despite Tco not being different between groups, Tco was higher in the hot compared to the temperate condition for all groups (p < 0.001). Similarly, serum irisin concentrations did not differ between groups under either condition but were elevated relative to the temperate condition during post-exercise and end-recovery in the heat (+93.9 pg/mL SEM 26 and + 70.5 pg/mL SEM 38 respectively; both p ≤ 0.014). Thus, our findings indicate similar irisin responses in HTN and T2D compared to healthy, age-matched controls, despite reduced exercise tolerance during prolonged exercise in the heat. Therefore, older workers with HTN and T2D may exhibit greater cellular stress during prolonged exercise in the heat, underlying greater vulnerability to heat-induced cellular injury.

Association between B-type natriuretic peptide and long-term mortality in patients with acute severe hypertension visiting the emergency department.

B-type natriuretic peptide (BNP) is a well-established prognostic factor for cardiovascular disorders. However, the association between BNP levels and mortality in patients with acute severe hypertension remains unclear. This study aimed to investigate the association between BNP levels and long-term mortality in patients with acute severe hypertension visiting the emergency department (ED). This retrospective study included patients aged ≥ 18 years who were admitted to the ED between 2016 and 2019 with acute severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg). Patients were categorized into tertiles according to BNP levels upon admission to the ED. Of the 3099 patients with acute severe hypertension, 6.4% in the first (lowest) tertile, 24.8% in the second tertile, and 44.4% in the third (highest) tertile of BNP died within 3-years. After adjusting for clinically relevant variables, patients in the second tertile of BNP (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.96-3.55), and patients in the third tertile of BNP (adjusted HR 4.18; 95% CI, 3.09-5.64) had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP. Therefore, BNP may be valuable for the initial assessment to identify high-risk patients among those with acute severe hypertension.

Evaluation of the significance of interleukin-6 in the diagnosis of postoperative pneumonia: a prospective study.

BACKGROUND: Postoperative pneumonia (PP) is one of the most common complications after cardiac surgery. This study was designed to access the diagnostic value of interleukin-6 (IL-6) for pneumonia within the first 5 days after cardiac surgery in adults. METHOD: This prospective observational study enrolled 694 patients who admitted to our center from 10 October 2020 to 30 June 2021. Blood samples were collected after admission and on five consecutive days after surgery to measure IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) respectively. Combined with clinical data, we assessed the diagnostic performance of different biomarkers using univariate and multifactorial analyses as well as receiver operating characteristic curves (ROC) and the area under the curve (AUC). RESULT: Finally, 68 patients were diagnosed with PP (PP Group). In addition, 626 cases were assigned to the control group (Non-PP Group). From postoperative day 1 (POD1) to day 5, IL-6 and PCT levels showed higher diagnostic value (P < 0.001, P < 0.05, respectively); meanwhile, there was no difference in white blood cell counts between the two groups; CRP showed some value from POD2 onwards (P < 0.001). Among these biomarkers, IL-6 on POD1 [AUC: 0.78, 95% confidence interval (CI): 0.71-0.83], IL-6 on POD2 (AUC: 0.77, 95% CI: 0.71-0.82) and CRP levels on POD3 (AUC: 0.77, 95% CI: 0.70-0.84) had the highest diagnostic value. Multivariate analysis found that smoking status [odds ratio(OR): 7.79, 95% CI: 3.05, 19.88, p < 0.001], drinking status (OR: 22.68, 95% CI: 9.29, 55.37, p < 0.001) and hypertension (OR: 2.85, 95% CI: 1.28, 6.35, p = 0.011), IL-6 on POD2 (OR: 1.01, 95% CI: 1.00, 1.01, p = 0.018), mechanical ventilation time (OR: 1.03, 95% CI: 1.00, 1.05, p = 0.040) and intensive care unit stay time (OR: 1.01, 95% CI: 1.00, 1.02, p < 0.001) were independent risk factors for postoperative pneumonia. CONCLUSION: Smoking, drinking, hypertension, prolonged duration of mechanical ventilation and intensive care unit stay, and IL-6 on POD2 were independent risk factors for pneumonia after cardiovascular surgery. IL-6 level on POD2 may serve as a promising indicator, better than WBC, PCT and CRP.

Impact of pharmacist participation in the patient care team on value-based health measures.

PURPOSE: To evaluate whether pharmacist engagement on the interdisciplinary team leads to improved performance on diabetes-related quality measures. METHODS: This was a retrospective observational study of patients seen in primary care and specialty clinics from October 2014 to October 2020. Patients were included if they had a visit with a physician, nurse practitioner, physician's assistant, or clinical pharmacist practitioner (CPP) within the study period and had a diagnosis of diabetes. The intervention group included patients with at least one visit with a CPP, while the control group consisted of patients who were exclusively managed by non-CPP providers. The primary outcome of this study was the median change in glycosylated hemoglobin (HbA1c) from baseline to follow-up at 3, 6, and 12 months. The secondary outcome was the probability of achieving the HbA1c targets of <7% and <8% at 3, 6, and 12 months. RESULTS: Patients referred to a CPP had higher HbA1c levels at baseline and were more likely to have concomitant hypertension (P < 0.01). Patients seen by a CPP had 0.31%, 0.41%, and 0.44% greater reductions in HbA1c compared to patients in the control group at 3, 6, and 12 months, respectively (P < 0.01). Patients managed by a CPP were also more likely to achieve the identified HbA1c targets of <7% and <8%. CONCLUSION: Patients referred to a CPP were more complex, but had greater reductions in HbA1c and were more likely to achieve HbA1c goals included in the organization's quality measures. This study demonstrates the value of pharmacists in improving patient care and their role in supporting an organization's achievement of value-based quality measures.

Niveles tensionales en niños y adolescentes con esteatosis hepática / Tensional levels in children and adolescents with hepatic steatosis

Introducción: la enfermedad hepática no alcohólica (EHNA) constituye un desorden multifactorial cuyos elementos de riesgo se pueden aludir a la obesidad, el sedentarismo y el componente genético. Objetivo: evaluar los niveles tensionales en niños y adolescentes con esteatosis hepática por sonografía de 5-18 años en el Hospital Regional Universitario Dr. Arturo Gullón. Métodos y técnicas: se realizó un estudio descriptivo de corte transversal y fuente primaria. La muestra estuvo compuesta por de 106 participantes. Se realizó sonografía abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica abdominal para determinar la presencia de esteatosis hepática y se midió la presión arterial sistólica y diastólica, IMC, talla y pruebas de laboratorio. Para el análisis estadístico se empleó chi-cuadrado. Resultados: el sexo predominante en la tensión arterial sistólica fue el femenino con un 44.9 % en estadio prehipertensión, mientras que el masculino fue el sexo predominante en presión arterial diastólica con un 49.1 %. Se evidenció que los individuos con IMC del percentil 90 se encontraban en estadio prehipertensión en el percentil. El perfil lipídico (colesterol, HDL, LDL, triglicéridos) y las transaminasas (SGOT y SGPT) mostraron relación con niveles tensionales elevados con predominio en la TAD. Los valores elevados de glicemia presentan relación con las cifras aumentadas de la tensión arterial sistólica. Conclusión: el estudio mostró que existe una relación entre la esteatosis hepática no alcohólica y el riesgo de desarrollar hipertensión arterial. Presentando relación estadísticamente significativa entre los niveles tensionales elevados y el perfil bioquímico estudiado, así como al IMC de los pacientes evaluados en la investigación

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a multifactorial disorder whose risks factors can be attributed to obesity, sedentary lifestyle and a genetic component. Objective: To evaluate blood pressure levels in children and adolescent aged 5-18 years old with hepatic steatosis using ultrasound at the Dr. Arturo Grullón Regional University Hospital. Methods and Techniques: A descriptive cross-sectional study of primary source were carried out. The sample of the study consisted in 106 participants. Abdominal ultrasono-graphy was performed to determine the presence of hepatic steatosis and systolic and diastolic blood pressure, BMI, height and laboratory tests were measured. Chi square was used in the statistical analysis of the data. Results: The predominant sex in systolic blood pressure was female with 44.9% in prehypertension stage, while male was the predominant sex in diastolic blood pressure with 49.1%. It was evidenced that individuals with BMI ≥90thpercentile were in the prehypertensive stage at the percentile. The lipid profile (cholesterol, HDL-C, LDL-C, triglycerides) and transaminases (SGOT ad SGPT) showed a relationship with high blood pressure levels with a predo-minance in DBP. Elevated glucose levels are related to an increase in systolic blood pressure. Conclusion: The study showed that there is a relationship between nonalcoholic fatty liver disease and the risk of developing high blood pressure. Presenting a statistically significant relationship between the elevated blood pres-sure levels and the biochemical profile studied, as well the BMI of the patients evaluated in this research

Study of serum miR-518 and its correlation with inflammatory factors in patients with gestational diabetes mellitus complicated with hypertensive disorder complicating pregnancy.

OBJECTIVE: Gestational diabetes mellitus (GDM) and hypertensive disorder complicating pregnancy (HDCP) are common complications during pregnancy. This study estimated the correlation of serum miR-518 and inflammatory factors in GDM complicated with HDCP patients (GDM&HDCP). METHODS: Total 240 pregnant women were enrolled, including 118 cases with GDM alone, 57 cases with GDM&HDCP, and 65 healthy pregnant women. The expressions of serum miR-518 and PPARα were detected by RT-qPCR. The clinical diagnostic efficacy of miR-518 for GDM and GDM&HDCP was analyzed via ROC curve. Pearson coefficient was used to analyze the correlation between miR-518 and serum inflammatory factors (hs-CRP, IL-6, and TNF-α), and the relevance between peroxisome proliferator-activated receptor α (PPARα) and serum inflammatory factors. The targeted binding of miR-518 and PPARα was verified using dual-luciferase assay. RESULTS: Serum miR-518 was highly-expressed in GDM and GDM&HDCP patients, but far higher in GDM&HDCP patients. Serum miR-518 level > 1.815 could assist the diagnosis of GDM (81.53% sensitivity and 100% specificity). Serum miR-518 expression was positively-correlated with serum inflammatory factors. miR-518 targeted PPARα and PPARα was lowly-expressed in the serum of GDM and GDM&HDCP patients. PPARα was negatively-linked with serum inflammatory factors. CONCLUSION: High expression of miR-518 assists the diagnosis of GDM and GDM&HDCP, and miR-518 regulates the serum inflammatory factors by inhibiting PPARα.

Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial.

Aim: Study aim was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. Methods: In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. Primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed. Results: Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs. Conclusions: Study results showed that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

The Impact of Sex and Gender on Stroke.

Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

High Remnant Cholesterol Level Potentiates the Development of Hypertension.

Background: Emerging evidence suggests an association between remnant cholesterol (RC) and vascular damage and hypertension. However, this association has not been explored in a large-scale population in China, and a temporal relationship between RC and hypertension also needs to be investigated. Methods: We conducted a retrospective cross-sectional study in 2,199,366 individuals and a longitudinal study in 24,252 individuals with repeated measurements of lipid profile and blood pressure in at least a 3-year follow-up. The logistic model was used to explore the association between lipid components and hypertension in the cross-sectional analysis. The Cox model was used to analyze the association between high RC (HRC) at baseline and the subsequent incidence of hypertension or the association between hypertension at baseline and incidence of HRC. The cross-lagged panel model was applied to analyze the temporal relationship between RC and hypertension. Results: RC level as a continuous variable had the highest correlation with hypertension among lipid profiles, including RC, low-density lipoprotein cholesterol, total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, with an odds ratio of 1.59 (95% confidence interval: 1.58-1.59). In the longitudinal cohort, HRC at baseline was associated with incident hypertension. We further explored the temporal relationship between RC and hypertension using the cross-lagged analysis, and the results showed that RC increase preceded the development of hypertension, rather than vice versa. Conclusions: RC had an unexpected high correlation with the prevalence and incidence of hypertension. Moreover, RC increase might precede the development of hypertension, suggesting the potential role of RC in the development of hypertension.

Endothelial MicroRNA-483-3p Is Hypertension-Protective.

Hypertension is a high-risk factor for developing coronary heart disease and stroke. Endothelial dysfunction and arterial remodeling can lead to increased vascular wall thickness and arterial stiffness. Previous studies showed that microRNA-483 (miR-483) enhances endothelial cell (EC) function. Here, we investigated the protective role of miR-483 in hypertension. Data collected from two patient cohorts showed that the serum miR-483-3p level was associated with the progression of hypertension and positively correlated with vascular function. In cultured ECs, miR-483 targets a number of endothelial dysfunction-related genes, such as transforming growth factor-ß (TGF-ß), connective tissue growth factor (CTGF), angiotensin-converting enzyme 1 (ACE1), and endothelin-1 (ET-1). Overexpression of miR-483-3p in ECs inhibited Ang II-induced endothelial dysfunction, revealed by the decreased expression of TGF-ß, CTGF, ACE1, and ET-1. Furthermore, miR-483-3p secreted from ECs was taken up by smooth muscle cells (SMCs) via the exosome pathway, which also decreased these genes in SMCs. Additionally, telmisartan could increase the aortic and serum levels of miR-483-3p in hypertension patients and spontaneous hypertension rats (SHR). These findings suggest that miR-483-3p exerts a protective effect on EC function during the onset of hypertension and thus may be considered a potential therapeutic target for hypertension-related cardiovascular diseases.

Expression ratio of circular to linear ANRIL in hypertensive patients with coronary artery disease.

Atherosclerotic lesions of the coronary arteries are still in charge of significant annual morbidity and mortality despite intense therapeutic advancements. Genome-born elements contribute substantially to the atherosclerosis process. ANRIL is one of the long non-coding RNAs with outstanding functions particularly regulation of genes involved in atherosclerosis development. In this study, we measured ANRIL expression (circular-, linear-, and circular/linear ratio) in hypertensive patients with coronary artery disease (CAD) compared with peers without CAD. Among hypertensive patients who were candidates of angiography, 25 subjects with CAD and the equal number without CAD were considered as the case and control groups, respectively. Different categories of data were recorded through a predefined questionnaire. Before angiography, blood samples were obtained. After RNA extraction and cDNA synthesis, quantitative PCR was performed using specific primers for circular and linear ANRIL. Age and gender were not different between the groups. Most of the parameters of the lipid profile besides creatinine and blood urea nitrogen were remarkably worse in the case group. Circular ANRIL was significantly lower in the case group while linear counterparts were significantly higher in this group. Circular/linear ratio was also significantly lower in the case group. To overcome growing devastating trend of CAD, scrutinizing different factors involved in the initiation and development of atherosclerosis is a must. Atheroprotective role of circular ANRIL and atheroprogressive role of linear ANRIL were shown in our patients with hypertension.

Fibrosis-4 index: a new marker to predict non-dipper blood pressure pattern in patients with newly diagnosed hypertension / Índice de fibrosis-4: un nuevo marcador para predecir el patrón de presión arterial no dipper en pacientes con hipertensión recién diagnosticada

Introduction: Epicardial fat tissue (EFT) is a significant risk factor for cardiovascular diseases. This study aimed to investigate whether there is a relationship between the fibrosis-4 index (FIB-4 index) and EFT in newly-diagnosed hypertensive patients and explore the usability of the FIB-4 index in predicting non-dipper blood pressure (BP) pattern. Materials and methods: Our case–control study consisted of 210 patients in 3 groups according to BP values, namely normotensive, dipper, and non-dipper groups. Transthoracic echocardiography and 24-h ambulatory BP monitoring were performed in all patients. Results: The median FIB-4 index was higher in the non-dipper group [1.56 (1.10-2)] than in the dipper [1 (0.71-1.32)] and normotensive groups [0.96 (0.69-1.32)] (p < 0.001, for both). A positive correlation was observed between EFT and the FIB-4 index (r=0.389, p<0.001). In multivariate logistic regression analysis, EFT (odds ratio (OR): 0.506, 95% confidence interval (CI): 1.288-2.135; p<0.001) and FIB-4 index (OR: 1.099, 95% CI: 1.621–5.556; p<0.001) were found to be independent predictors of non-dipper BP. In the receiver operating characteristic curve analysis, the FIB-4 index had 68% sensitivity and 72% specificity at a value >1.25 (area under the curve: 0.751, 95%CI: 0.679-0.823, p<0.001). Conclusions: In newly-diagnosed hypertensive people, the FIB-4 index is related to non-dipper BP patterns. FIB-4 index appears to be a helpful tool in assessing risk associated with cardiovascular disease (AU)

Introducción: El tejido graso epicárdico (TGE) es un importante factor de riesgo de enfermedades cardiovasculares. Este estudio tuvo como objetivo investigar si existe una relación entre el índice de fibrosis-4 (índice FIB-4) y TGE en pacientes hipertensos recién diagnosticados y explorar la utilidad del índice FIB-4 para predecir la presión arterial (PA) no dipper. patrón. Materiales y métodos: Nuestro estudio de casos y controles consistió en 210 pacientes en 3 grupos según los valores de PA, a saber, grupos normotensos, dipper y no dipper. A todos los pacientes se les realizó ecocardiografía transtorácica y monitorización ambulatoria de la PA de 24 h. Resultados: La mediana del índice FIB-4 fue mayor en el grupo no dipper [1,56 (1,10-2)] que en los grupos dipper [1 (0,71-1,32)] y normotensos [0,96 (0,69-1,32)] (p<0.001, para ambos). Se observó una correlación positiva entre TGE y el índice FIB-4 (r = 0,389, p < 0,001). En análisis de regresión logística multivariante, EFT (odds ratio (OR): 0,506, intervalo de confianza (IC) 95%: 1,288-2,135; p<0,001) e índice FIB-4 (OR: 1,099, IC95%: 1,621-5,556; p<0,001) resultaron ser predictores independientes de PA no dipper. En el análisis de la curva característica operativa del receptor, el índice FIB-4 tuvo una sensibilidad del 68 % y una especificidad del 72 % a un valor >1,25 (área bajo la curva: 0,751, IC95%: 0,679-0,823, p<0,001). Conclusiones: En hipertensos de nuevo diagnóstico, el índice FIB-4 se relaciona con patrones de PA no dipper. El índice FIB-4 parece ser una herramienta útil para evaluar el riesgo asociado con la enfermedad cardiovascular (AU)