Blood pressure and CAVI/ABI were well controlled throughout the study period. RHI did not show any significant improvement during the initial six months, and only slightly improved by the third month (p = 0.063). Even after the rest phase and resumption of stretching, RHI remained stable. Conclusions: The compliance of the stretching program we used, evaluated by the exercise implementation rate for the entire period, was 90% or more; therefore, easy to perform and continue by hypertensive patients. However, we did not observe a significant positive effect on arteriosclerosis index or blood pressure in this study.Background: Treatment of high blood pressure is a combination of lifestyle changes and medications, and appropriateexercise therapy is recommended as one of the lifestyle-related changes. Recently, stretching, a low-intensity exercise, was reported to be antihypertensive and effective for improving arteriosclerosis, in addition to aerobic exercise. The present study investigated the short-term effects of continuous stretching and rest-induced rebound on vascular endothelial function in hypertensive patients. Methods: This study was conducted as a single-arm prospective interventional study including patients between 30 and 70 years of age undergoing treatment for hypertension from October 2019 until May 2021. The intervention consisted of six months of daily stretching, one month of rest, and another three months of stretching. We measured arteriosclerosis indices such as cardio ankle vascular index (CAVI), ankle brachial pressure index (ABI) and reactive hyperemia index (RHI), and flexibility at the baseline and one, three, six, seven, and ten months from the baseline. Results: We included a total of ten patients  with an average age of 60.10 ± 6.05 years. The exercise rate for the entire period was 90% or more, and the anteflexion measurement value improved significantly before and after the intervention ( Due to global population growth and aging, the number of hypertensive patients has doubled from approximately 650 million in 1990 to approximately 1.28 billion in 2019. Whereas the prevalence of hypertension is mainly declining in high-income countries, it is rising in low- and middle-income countries, and this trend is expected to continue [Increased physical activity not only lowers blood pressure , and an While the antihypertensive effect of aerobic exercise has been established, it has also recently been reported that stretching, which is a low-intensity exercise, also produced an improvement in arteriosclerosis and an antihypertensive effect ,11. DailThis study was conducted with a single-arm, prospective interventional study design at two internal medicine out-patient clinics in Niigata city, Japan, between October 2019 and May 2021, and was carried out with the approval of the Institutional Review Board of Niigata University (#2018-0025).Participants, who were receiving treatment for hypertension, were included. The inclusion criteria for this study were age between 30 and 70 years and a diagnosis of essential hypertension. Exclusion criteria were secondary hypertension, organic heart disease, having quit smoking, and those who were judged inappropriate by doctors. Patients in the hospital were recruited for the study by posting posters in the facility and handing out leaflets. The patients who wished to participate were given both written and verbal information before providing their informed consent. Ten participants were included.The intervention consisted of six months of daily stretching, followed by one month of rest, and then another three months of stretching. The researchers explained the content and precautions of the stretches and that they should be done daily from the next day before measuring blood pressure at home. The researchers measured the arteriosclerosis index and flexibility in the subjects at the baseline and one, three, six, seven, and ten months from the baseline .https://www.mhlw.go.jp/www1/topics/kenko21_11/b2.html, accessed on 31 January 2022). The stretching program we used this time consists of 10 elements: calf, back of the thigh, front of the thigh, inside of thigh, waist, upper back, neck, shoulder, upper arm, and wrist. One series took about 10 min and was a low-intensity static stretch exercise that could be easily performed during breaks at home or work . We used three factors as the arteriosclerosis-related indicators in the present study: reactive hyperemia index (RHI), cardio ankle vascular index (CAVI), and ankle brachial pressure index (ABI).RHI, which indicates the endothelial function, was measured by digital reactive hyperemic peripheral arterial pressure measurement (RH-PAT) using the Endo-PAT2000 device . This is a non-invasive technique that can use a pneumatic probe to record the pulse wave amplitude of the finger artery and capture a pulsatile plethysmograph. Prior to the measurement, it was confirmed that patients had fasted for at least four hours and refrained from caffeine, which can affect vascular tone, for at least eight hours. It was performed in a quiet and dim room at 25 ± 1 °C to reduce fluctuations in vascular tone . After cThe CAVI and the ABI were measured with the Vasera VS-1500 Vascular Screening System  to record participants in the supine position. ABI was measured at the same time as CAVI. ECG electrodes were placed on both wrists, a microphone to detect heart sounds was attached to the sternum, and the cuffs were wrapped around both arms and ankles. After automatic measurement, the left and right mean values were used for CAVI and ABI analysis . CAVI isFor the evaluation of stretching, measurements were taken while bending forward. The forward bending was measured according to the method of the Japanese Ministry of Education, Culture, Sports, Science, and Technology. In brief, participants were asked to sit with their feet together, slowly bend forward and slide the box placed in front of them forward and as straight as possible to measure the distance the box moved. The measurement was taken twice, and the better value was recorded.The exercise implementation rate was calculated by dividing the number of days the stretching was performed in a month by the number of days in that particular month.During the experimental period, all participants self-measured their blood pressure at home twice daily, in the morning and the evening. Blood pressure was measured before breakfast in the morning and at a calm time after dinner. After the intervention was started, the average blood pressure was calculated for the measurement day ± three days of each month.We recorded basic information . Participants with exercise habits were defined as “people who exercised for 30 min or more at a time, on two days or more a week, and during one year or more.” Drinking habits were recorded based on the current drinking situation.Using CAVI as the primary endpoint, the required sample size, 34 participants, was calculated under the condition of a decrease in CAVI value due to stretch intervention as 0.3 with the standard deviation of 0.4, α error of 5%, and the power as 80%. The changes in arteriosclerosis-related indicators from baseline to six months were analyzed using the Friedman test, and the Wilcoxon signed-rank sum test analyzed the differences from six to seven months and seven to ten months. Repeated measures analysis of variance (ANOVA) was used for changes in blood pressure during the ten-month duration and changes in flexibility. Easy R (EZR) version 1.55 was used for statistical analysis, and the significance level was judged with a risk rate of less than 5%.2. Four participants (40%) had exercise habits, and six participants (60%) did not. Of the former, three participants walked regularly, and one participant practiced kendo . Five participants (50%) drank alcohol, and five participants (50%) did not  of the participants was 60.1 ± 6.1 years. The body weight (mean ± SD) of the participants was 61.4 ± 6.4 (kg), and the body mass index (BMI) (mean ± SD) was 24.5 ± 2.6 kg/m did not . The ave did not .The exercise implementation rate was used to evaluate the compliance of the stretching program implemented in the current study. The exercise implementation rate for the entire period, excluding the rest period, was almost 90%. The overall average was 87.9%, and the monthly average for eight participants was over 80% for all periods, and for two participants, it was close to 50% .p < 0.001; The changes in body flexibility associated with stretching were evaluated using anteflexion measurements. The anteflexion measurement before the intervention (mean ± SD) was 35.7 ± 13.9 cm. The average value was 43.9 ± 13.0 cm in the sixth month and 46.1 ± 14.7 cm in the seventh month, and the flexibility was maintained for one month even when the stretching was paused. In the tenth month, anteflexion measurement was 47.3 ± 14.3 cm, displaying a significant improvement compared to the pre-intervention value  during the study period. A recent systematic review based on 16 studies has reported that arterial stretching has a significant effect on reducing arterial stiffness . HoweverThe present study has several limitations. First, the number of participants was not sufficient. We initially calculated the required sample size as 34 people using CAVI as the primary endpoint. However, while recruiting patients, the COVID-19 pandemic occurred worldwide, including in Japan; therefore, the enrollment of participants had to be terminated by 10 patients. The small sample size may have concealed a significant improvement in vascular endothelial function. Second, the intervention was applied to participants already taking oral antihypertensive treatment. Therefore, blood pressure and arteriosclerosis indicators were stable throughout the study period, and it is possible that the effects of stretching were underestimated. Third, confounding factors such as the dosage of anti-hypertensive medication, the intensity of other exercises performed, and stress may affect these results. However, we enrolled patients with relatively controlled blood pressure who were not on large doses of antihypertensive drugs. Therefore, it was assumed that the dose of the antihypertensive drug had no effect. In addition, we asked the patients whether they were doing other exercises or were stressed at the time of entry and each measurement timing. With regard to the other exercises, 3 people reported that they walked for 30 min twice a week. We assumed that it did not affect the result of this study as none of the patients complained of stress levels high enough to affect their blood pressure.Finally, the stretching protocol adopted in this study significantly improved flexibility but did not affect arteriosclerosis indicators. However, the findings indicate that blood pressure and the arteriosclerosis index were well controlled during the intervention. In the future, it might be worthwhile to verify the effect of stretching on vascular endothelial function by increasing the sample size and including hypertensive patients who are not on antihypertensive medications. The stretching program adopted in this study can be completed in about 10 min and, therefore, can easily be implemented by hypertensive patients who are busy with work, etc. Although this study design includes a one-month rest period, stretching exercises over a period of 10 months showed good compliance, as indicated by the high implementation rate.The stretching program used in this study was carried out by patients who attended the clinics. Since the short-time protocol could be easy to perform by hypertensive and pre-hypertensive patients, we think that this stretching program can be easily introduced to many clinic settings.The compliance of the stretching protocol we used, evaluated by the exercise implementation rate for the entire period, was 90% or more; therefore, easy to perform and continue by hypertensive patients. However, we did not observe a significant positive effect of the stretching intervention on arteriosclerosis index or blood pressure in this study.


Although asthma and chronic obstructive pulmonary disease (COPD) are two well-defined and distinct diseases, some patients present combined clinical features of both asthma and COPD, particularly in smokers and the elderly, a condition termed as asthma-COPD overlap (ACO). However, the definition of ACO is yet to be established and clinical guidelines to identify and manage ACO remain controversial. Therefore, in this study, inflammatory biomarkers were established to distinguish asthma, ACO, and COPD, and their relationship with the severity of patients’ symptoms and pulmonary function were explored.n = 38), ACO (n = 44), and COPD (n = 96) between January 2021 to June 2022, were enrolled in this study. The patients’ pulmonary function was examined and routine blood samples were taken for the analysis of inflammatory indexes. Logistic regression analysis was used to establish inflammatory biomarkers for distinguishing asthma, ACO, and COPD; linear regression analysis was used to analyze the relationship between inflammatory indexes and symptom severity and pulmonary function.A total of 178 patients, diagnosed with asthma (1/FVC) and FEV1 percent predicted (% pred), and EBR was positively correlated with FEV1% pred.The results showed that, compared with ACO, the higher the indexes of platelet, neutrophil-lymphocyte ratio (NLR) and eosinophil-basophil ratio (EBR), the more likely the possibility of asthma and COPD in patients, while the higher the eosinophils, the less likely the possibility of asthma and COPD. Hemoglobin and lymphocyte-monocyte ratio (LMR) were negatively correlated with the severity of patients’ symptoms, while platelet-lymphocyte ratio (PLR) was negatively correlated with forced expiratory volume in the 1 s/forced vital capacity (FEVInflammatory indexes are biomarkers for distinguishing asthma, ACO, and COPD, which are of clinical significance in therapeutic strategies and prognosis evaluation. Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases characterized by chronic airway and/or lung diseases. Chronic respiratory diseases (CRD) were the third leading cause of death in the world, of which COPD was the most common cause of death, followed by asthma, and the number of deaths from COPD was eight times that of asthma , 2. AlthThe characteristics of asthma and COPD can coexist in a given patient, who are diagnosed with asthma-COPD overlap (ACO), especially in smokers and the elderly . HoweverAsthma and COPD are two common CRD of chronic airway inflammatory . Asthma The purposes of this study are: (1) to compare the inflammatory indexes of asthma, ACO, and COPD, in order to understand their pathological characteristics; (2) to explore biomarkers that can distinguish three groups of CRD, in order to assist clinical differential diagnosis; and (3) to analyze the relationship between inflammatory indexes and the severity of patients’ symptoms and pulmonary function, in order to guide clinical treatment and evaluate the prognosis of the disease.This study was a single-center, retrospective observational study. In this study, participants diagnosed with asthma , ACO 2222, and CIn this study, patients with stable CRD diagnosed for the first time were recruited from Xijing Hospital of Air Force Medical University from January 2021 to June 2022. They were divided into asthma, ACO, and COPD according to physician diagnosis and spirometry. Individuals were excluded if they: (1) were hospitalized; (2) had used systemic corticosteroids and/or antibiotics in the past month; (3) had pneumonia, tuberculosis, and other respiratory diseases; (4) had malignant tumors, autoimmune diseases, systemic infectious diseases, and important organ dysfunction; and (5) had other reasons that are not suitable for the study.Pulmonary function test (PFT): PFT was conducted with spirometer  following the American Thoracic Society/European Respiratory Society (ATS/ERS) standards . ParticiRoutine blood test: 2–5 ml of peripheral venous blood was drawn into ethylenediamine tetraacetic acid (EDTA) anticoagulant blood tubes according to the standard procedure of venipuncture . All samP-value was <0.05.The software SPSS 26.0  was used for statistical analysis. The results are described as median interquartile range (IQR). The differences between more than two groups were analyzed by Kruskal–Wallis test according to the distribution of data points. Logistic regression analysis was used to predict the biomarkers that could distinguish the three diseases. Linear regression analysis was used to analyze the relationship between inflammatory indexes and symptom severity and pulmonary function. Statistical significance was accepted if the n = 38), ACO (n = 44), and COPD (n = 96). Statistical analysis showed significant differences in sex, age, smoking status, and pulmonary function between patients with asthma and patients with ACO and COPD, but there were no significant differences between ACO and COPD patients. Since the wide range of pulmonary function in patients with COPD, they were divided it into GOLD1-2 (n = 50) and GOLD3-4 (n = 46) for inter-group comparison in this study. The baseline characteristics of these patients are shown in A total of 178 patients who met the criteria were included in this study, including asthma , and SIRI between patients with asthma, ACO, and COPD . PatientThis study used multinomial logistic regression to analyze the differences in inflammatory levels among patients with asthma, ACO, and COPD . We founSince the symptoms of asthma patients are not obvious in the stable period, we used the COPD assessment test (CAT) score to evaluate the symptoms of ACO and COPD patients. Through the correlation analysis of CAT score and inflammatory indexes, it was found that hemoglobin and LMR were negatively correlated with the severity of patients’ symptoms . In othe1/FVC and FEV1% pred, respectively; age was negatively correlated with FEV1/FVC; body mass index (BMI) was positively correlated with FEV1/FVC; and EBR was positively correlated with FEV1% pred.The relationship between inflammatory indexes and pulmonary function was analyzed by multiple linear regression . We founChronic respiratory disease is a heterogeneous group of disorders characterized by airway inflammation and airway obstruction, in which asthma and COPD are the most common disease entities . AlthougOur study analyzed the inflammatory indexes of asthma, ACO, and COPD, and found that the higher the indexes of platelet, NLR, and EBR, the greater the risk of asthma and COPD compared with ACO. That may be related to the pathological mechanism of the disease, including the inflammatory process and the increase of inflammation in the aggravation period. Some researchers have found that in addition to playing a critical role in hemostasis and thrombosis, platelets are also considered immune cells participated in various immune related processes . In patiThe reason why high eosinophil is less likely the possibility of asthma and COPD compared with ACO, may be that the exacerbation frequency of ACO is higher than that of asthma or COPD alone , 31. A lWe also found that hemoglobin was negatively correlated with the severity of patients’ symptoms. Although it is traditionally considered that COPD is associated with polycythemia, a large number of studies have shown that anemia in COPD is more prevalent than expected . Anemia 1% pred. Although there is a line of evidence to show that eosinophil is related to exacerbation of patients  and/or long-acting muscarinic antagonists (LAMA) alone (without ICS) as the initial treatment for COPD; but contraindicated for asthma and ACO due to the risk of serious deterioration and death  to better understand CRD in many aspects. Thirdly, since there is no universally recognized definition of ACO currently, our diagnosis was based on the comprehensively assessment of clinical characteristics as well as the result of pulmonary function. Therefore, there may be some differences in the results of different diagnostic criteria. Finally, this study was designed as a cross-sectional study without long-term follow-up of patients, so it was difficult to evaluate the relationship between inflammatory indexes and patient outcomes. Despite these many limitations, we believe that our study shows that inflammatory indexes have clinical application value to a certain extent.Although our research shows that inflammatory biomarkers can distinguish CRD, the clinical application value is still in the exploration stage. We mainly differentiate CRD according to diagnostic criteria and some clinical indicators that can reflect the characteristics of the disease  –50. InflThe results of this study show that patients with CRD can be distinguished by inflammatory indexes. In addition, it was also found that different inflammatory indexes have different effects. Platelet, NLR, and EBR can distinguish asthma, ACO, and COPD; hemoglobin and LMR were correlated with the severity of patients’ symptoms; PLR and EBR were related to pulmonary function. In clinical application, we can use different indexes to achieve different purposes, providing a new direction for accurate identification and individualized treatment in the future.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Xijing Hospital of Air Force Medical University (No. KY20212201-C-1). The patients/participants provided their written informed consent to participate in this study.XT, SQ, and HM participated in the study design. LY, XZ, and XX tested the samples. LL, YZ, and XG contributed to the data collection. SW provided administrative support. HM conducted data analysis and wrote the manuscript. XT and SQ revised the manuscript. All authors have read and approved the final manuscript.


Objective: To explore the effect of a low-dose hydrogen–oxygen (H2-O2) mixture inhalation in midlife/older adults with hypertension.Methods: This randomized, placebo-controlled trial included 60 participants with hypertension aged 50–70 years who were randomly divided into Air group  or H2-O2 group [inhaled H2-O2 mixture (66% H2/33% O2)]. Participants in both groups were treated 4 h per day for 2 weeks. Four-limb blood pressure and 24-h ambulatory blood pressure were monitored before and after the intervention, and levels of plasma hormones related to hypertension were determined.Results: A total of 56 patients completed the study (27 in the Air group and 29 in the H2-O2 group). The right and left arm systolic blood pressure (SBP) were significantly decreased in H2-O2 group compared with the baseline levels . Meanwhile, the H2-O2 intervention significantly decreased diastolic nighttime ambulatory blood pressure by 2.7 ± 6.5 mmHg (p < 0.05). All blood pressures were unaffected in placebo group . When stratified by age (aged 50–59 years versus aged 60–70 years), participants in the older H2-O2 group showed a larger reduction in right arm SBP compared with that in the younger group (p < 0.05). In addition, the angiotensin II, aldosterone, and cortisol levels as well as the aldosterone-to-renin ratio in plasma were significantly lower in H2-O2 group compared with baseline (p < 0.05). No significant differences were observed in the Air group before and after the intervention.Conclusion: Inhalation of a low-dose H2-O2 mixture exerts a favorable effect on blood pressure, and reduces the plasma levels of hormones associated with hypertension on renin-angiotensin-aldosterone system and stress in midlife/older adults with hypertension. Hypertension is a long-term medical condition that increases the risk of serious problems including heart attacks and strokes. Globally, hypertension is estimated to affect 1.4 billion people  and its Lifestyle adjustments, including physical exercise, dietary changes, quitting smoking and restricting alcohol, are generally effective in lowering blood pressure. When lifestyle changes alone cannot achieve the desired result, specific medications are needed. Current drugs for hypertension include angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, beta blockers, and renin inhibitors. The majority of patients with hypertension require a combination of at least two blood pressure lowering medications to achieve recommended goals . However2) has been regarded as a novel gaseous signaling molecule with cardiovascular therapeutic potential. A previous study indicated that 1 h of daily exposure to a low dose H2  for 4 weeks exerted an antihypertensive effect in rats with hypertension induced by 5/6 nephrectomy  mixture (66% H2/33% O2) supplied via inhalation at a flow rate of approximately 6 L/min or 3 L/min via nasal cannula has been demonstrated to relieve dyspnea and other respiratory symptoms in patients with coronavirus disease 2019  have gained increasing interest in recent years. Therefore, we performed a randomized, placebo-controlled trial in hypertensive patients aged 50–70 with baseline right arm SBP ≥120 mmHg to test the efficacy of a low-dose H2-O2 mixture inhalation in patients with hypertension.A high dose of hydrogen–oxygen  and was registered at China Clinical Trial Registry (CHiCTR2100049865). All procedures were conducted in accordance with the principles of the Declaration of Helsinki.This study comprised a 2-week randomized, placebo-controlled, single-center, single-blind, parallel-design clinical trial that was conducted from November 2021 to January 2022. After obtaining informed consent, all participants were randomly allocated to a control Air group or HPotential participants were recruited from community residents aged 50–70 years diagnosed with hypertension and with established health records at Fenghuang Community Health Service Station in Tai’an, Shandong, China. Participants with right arm SBP of ≥120 mmHg by four-limb blood pressure measurement were enrolled. Individuals taking ≥3 kinds of antihypertensive drugs or with a history of major diseases and surgery, such as heart failure, malignant tumor, or organ resection, were excluded. The discontinuation criteria were withdrawal of consent, lack of compliance, or other medical reasons that required the intervention to be terminated. Participants were randomized by computer-based stratification (1:1), which was determined by age  and gender. Allocation was concealed in opaque envelopes until the beginning of the intervention.n = 52) was calculated using the power analysis  0.8, allocation ratio N2/N1 1) for the primary treatment outcome (G-power 3.1.9.7). To accommodate for a 15% attrition rate, we planned to recruit a total of 60 patients.An appropriate sample size . The flow rate was approximately 30–60 ml/min, and the H2 concentration inhaled by the participants during breathing was about 0.2%–0.4%. The Air group inhaled normal air from a machine with the same appearance. Participants were asked to record the intervention time every day.All participants were asked to maintain their usual diet, lifestyle, and medication. Participants in the HThe primary outcome in this study was the right arm SBP, and the secondary outcomes were other blood pressure variables and related blood indexes.via an arteriosclerosis detector  with participants in the supine position after resting for more than 5 min. A trained technician placed the pressure cuffs on both arms and both ankles for two consecutive measurements at 1-min interval, and the average value of the two results was recorded.The values of four-limb blood pressure were automatically and simultaneously measured in an air-conditioned room at the temperature of 22–26°C Assessment of the 24-h ambulatory blood pressure (ABP) monitoring was performed by an ABP detector . Participants were instructed to perform their habitual daily activities. The cuff was of proper size and worn on the right upper limb. ABP measurements were recorded every 30 min during the day (7:00 a.m.–10:00 p.m.) and every 60 min at night (10:00 p.m.–7:00 a.m.). The criteria for valid ABP recordings included at least 70% valid readings and at least one valid reading per hour for 21 h.Blood samples after overnight fasting were collected into tubes containing EDTA at the beginning and end of the study. Plasma was isolated immediately by centrifugation at 3,000 × g for 15 min at 4°C and stored at −80°C until further analysis. Plasma creatinine, uric acid, total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, homocysteine, high sensitivity C-reactive protein (hsCRP), and lipoprotein associated phospholipase A2 (LP-PLA2) levels were determined using an automated chemistry analyzer . Plasma cortisol, angiotensin Ⅱ, aldosterone, and renin levels were analyzed using an automatic chemiluminescence immunoanalyzer . Superoxide dismutase (SOD) activity was measured with an assay kit .t-test and paired t-test were used to detect inter and intra group differences, respectively. Data not conforming to the normal distribution are represented by median (Quantile 1 and Quantile 3); comparisons between groups were made using Mann–Whitney U-test (unpaired) and Wilcoxon signed rank test (paired). Differences were considered significant when p < 0.05. All analyses were performed using SPSS 26.0 software .Data were tested for normal distribution by the Shapiro–Wilk test. Those data conforming to the normal distribution are expressed by mean ± standard deviation (mean ± SD), and the unpaired n = 30) or H2-O2 group (n = 30). During the follow-up, three participants in the Air group and one participant in the H2-O2 group withdrew from the study. Finally, 27 subjects in the Air group and 29 subjects in the H2-O2 group completed the 2-week follow-up study  but was unchanged in the Air group (p > 0.05)  . A similp > 0.05, 2-O2 group , gender , and body mass index (BMI) (BMI < 26 versus BMI ≥26). The older H2-O2 group showed a larger reduction in right arm SBP compared with that of the younger group , but there was no significant change in the Air group . The levels of renin showed no statistically significant changes after the either intervention . The H2-O2 group showed no significant changes in the plasma lipid levels of total cholesterol, triglyceride, HDL cholesterol, or LDL cholesterol; renal function indicators of urea, creatinine, or uric acid; oxidative marker of SOD activity; inflammatory indicators of hsCRP and LP-PLA2; plasma glucose; or homocysteine level . However, these changes did not reach significant differences in each group  is a major hormonal cascade in the control of blood pressure. As shown in 2/33% O2 mixture on the blood pressure of midlife/older adults with hypertension. We found that the 2-week H2-O2 intervention reduced right arm SBP, and the reduction in participants aged 60–70 years was significantly larger compared with that of those aged 50–59. In addition, the H2-O2 intervention improved the plasma hormone levels of cortisol, angiotensin Ⅱ, aldosterone, and reduced the aldosterone-to-renin ratio compared with the baseline levels.The current study conducted a randomized, controlled, parallel-design trial to evaluate the effect of a low-dose 66% H2 has been traditionally regarded as a biologically inert gas. However, in 2007, scholars discovered that H2 can exert antioxidant properties and prevent ischemia-reperfusion injury in a rat model  such as hydroxyl radicals and peroxynitrite anions to exert therapeutic antioxidant activity . Thus, H2 may be used for the prevention and treatment of various aging-related diseases.It is worth noting that the plasma levels of LDL cholesterol, creatinine, and LP-PLA2 increased in the Air group after 2 weeks, however the Hwith age . H2, as r adults . Our pre2 can be administered to humans via different routes, such as H2 gas inhalation  provided better effects than those of 4% H2 inhalation . The dodicators . In anothalation . In the 2/33% O2 mixture played a contributing role in reducing blood pressure, the optimal concentration for H2 inhalation in improving hypertension deserves further investigation. Third, the sample size of the study was relatively small, and we lacked delayed follow-up data . The strengths of our study include its randomized, blinded, placebo-controlled design, the use of four-limb and 24-h blood pressure measurements, and the high compliance rate.There are several limitations of our study. First, the daily intervention times were set by the participants; thus, we were unable to identify the optimal timing. Second, although the low-dose 66% H2/33% O2 mixture exerts a favorable effect on improving blood pressure in midlife/older adults with hypertension. According to the age stratification, the intervention was more effective among patients aged 60–70 years than among those aged 50–59 years. Possible mechanisms of H2 in regulating blood pressure may be the inhibitory effect on the RAAS and stress. The current findings will provide important insight into the application of H2 inhalation as an effective and acceptable method for patients with hypertension.In conclusion, inhalation of a low-dose 66% H


Attention Deficit Hyperactivity Disorder (ADHD) in adults is a growing clinical problem and its prevalence among patients being referred to the General Adult Psychiatry clinic is rapidly increasing. The treatment of ADHD involves the use of medications such as methylphenidate, atomoxetine and lisdexamfetamine. These medications can cause significant adverse effects including arrhythmias, hypertension and appetite suppression. NICE guidelines stipulate that individuals on such medications should have weight, blood pressure and heart rate monitored every 6 months. The aim of this closed-loop audit was to assess if weight, heart rate and blood pressure are being monitored in line with current NICE guidelines in those who are on medication to treat ADHD in a Community Mental Health Team in Glasgow.Patients with an ADHD diagnosis were identified through a search of electronic case records. Electronic records were reviewed for each patient identified to assess if weight, heart rate and blood pressure had been recorded in the last 6 months. The results of the first cycle of this audit was presented at a local meeting in May 2021 with relevant clinicians present. The patient cohort identified was subsequently re-audited in December 2021 to assess if there had been an improvement in the monitoring of these medications.30 patients were identified who had an ADHD diagnosis. 15 male and 15 female patients were identified. Patient age ranged from 18–50. 10 patients did not engage with services and were so subsequently excluded from our analyses. There was a substantial improvement in the monitoring of weight, heart rate and blood pressure in the second cycle compared with the first cycle of this audit. 45% of patients had their weight recorded (previously 15%), 40% had their heart rate recorded (previously 8%) and 50% had their blood pressure monitored (previously 19%).There has been a significant improvement in monitoring heart rate, blood pressure and weight every 6 months in line with NICE guidelines in the second cycle compared with the first cycle of this audit. However, we are still not currently meeting NICE guidelines. This is of particular clinical significance given the increasing prevalence of patients with an ADHD diagnosis and subsequent increase in the use of these medications. The COVID-19 pandemic and the reduction in face-to-face reviews has likely had an impact on our ability to monitor these medications.


Background and Objectives: The purpose of this study was to investigate the effects of a 12-week concurrent training (CT)  on short–term blood pressure variability (BPV) and BP values in hypertensive patients with non-dippper BP nocturnal pattern and underlying coronary artery disease. Material and Methods: The study included 72 consecutive patients who were divided into two groups according to the nocturnal BP pattern: dipping pattern (33 pts) and non-dipping (39 pts). Before starting CT and at 12 weeks, patients underwent the six minute walk test, ergometric test, assessment of 1-repetiton maximum (1 RM), and 24/h BP monitoring (24-h ABPM). Results: After CT, exercise capacity increased in both groups in a similar fashion. Twenty-four/h systolic BPV and daytime systolic BPV decreased significantly in the dipping group while they were unchanged in the non-dipping group . Twenty-four/h systolic BP and daytime systolic BP decreased significantly in the dipping group while they were unchanged in the non-dipping group . Nighttime systolic BP and BPV was unchanged in both groups. Twenty-four/h diastolic BP presented small but not significant changes in both groups. Conclusions: The effects of CT on BPV and BP were blunted in hypertensive subjects with a non-dipping BP pattern. Short-term blood pressure variability (BPV), as assessed by 24-h ambulatory blood pressure (BP) monitoring (ABPM), is a well-established prognostic indicator in hypertensive subjects, being a marker of target organ damage and cardiovascular events ,2 indepePopulation:We evaluated a total of 72 consecutive patients, 52 males and 20 females, with a diagnosis of hypertension , who were assessed to be enrolled in a cardiac rehabilitation program at the rehabilitation center San Raffaele Pisana IRCCS ofRome. Exclusion criteria were resting BP levels exceeding 160/100 mmHg; significant heart valve diseases; hypertrophic cardiomyopathy; signs and/or symptoms of myocardial ischemia during the preliminary ergometric test; uncontrolled arrhythmias; neurological and/or orthopedic conditions contraindicating or limiting exercises; significant chronic obstructive pulmonary disease (FEV1 < 50%); symptomatic peripheral arterial disease (Fontain stages 2–4). Moreover, patients experiencing BP rises requiring changes in their pharmacological treatment during the study period were also excluded. The nighttime to daytime systolic BP ratio was defined as the mean nighttime systolic BP divided by the mean daytime systolic BP. Patients were categorized into two BP patterns based on the nighttime to daytime SBP ratio: dipping pattern (≤0.90), non-dipping pattern (>0.90 to ≤1.00).n = 27/21). All patients gave written informed consent to participate in the study, which conformed to the principles outlined in the Declaration of Helsinki. All patients underwent a baseline evaluation that included clinical and pharmacological history and assessment of body mass index (BMI). Thereafter, patients underwent a six minute walk test (6MWT) and an ergometric test. The 6MWT was performed according to standardized procedures [Study design: The flow-chart of the study is reported in ocedures  and was ocedures . On the Twenty-four hour ambulatory blood pressure monitoring. ABPM was performed with a validated oscillometric device  with the BP cuff placed on the non-dominant arm. The recording was programmed to obtain BP readings at 15 min intervals from 6.00 a.m. to 10.00 p.m. and 20 min intervals from 10.00 p.m. to 6.00 a.m. BP readings considered for data analysis included only those obtained from 8:00 a.m. to 8:00 p.m. (daytime) and from midnight to 6:00 a.m. (nighttime) to exclude transition periods from daytime and nighttime. On the day of the ABPM, patients were instructed to maintain their usual activities and medications. All ABPMs were performed on working days. Thirty-nine out of 72 (54.1%) participants were retired workers and were not engaged in high-intensity activities during the working days in which they performed ABPM. All active workers at the time of the study were office employers and were not engaged in physically demanding jobs; in the days of ABPM, they spent 6–8 h at work, mostly seated behind a desk; regarding the rest of the hours, they were asked to refrain from intense physical activity.Data from ABPM were accepted if at least 75% of the measurements were obtained successfully. The following parameters were considered: 24 h systolic BP, daytime systolic BP, nighttime systolic BP, 24 h diastolic BP, daytime diastolic BP, nighttime diastolic BP, and their respective time-related variability (BPV). BPV was evaluated by means of the average real variability (ARV), according to the formula reported by Mena et al. .Exercise training protocol.Exercise training sessions were performed in the rehabilitation gym at our hospital. Each session lasted 60 min and was preceded by 10 min of warm-up, followed by 10 min of cool-down. In each session, the subjects performed aerobic exercises before resistance exercises. Exercise sessions were scheduled three times/week and were planned as follows: 40 min of aerobic training on a treadmill; 20 min of resistance training . The intensity of the aerobic component over the whole training program was established by means of the RPE method with an intensity target of 13–14 (somewhat hard) during the whole study. Patients were free to change the treadmill set-up during subsequent sessions in order to maintain the same level of effort. The RPE method was chosen to permit updating the exercise prescriptions as the fitness levels changed. The resistance component of the training sessions consisted of the following exercises: leg press, leg extension, shoulder press, chest press, low row, and vertical traction. The intensity of each resistance exercise was established through the assessment of the corresponding 1-RM: for each exercise, patients performed a warm-up set (8–0 repetitions) at 50–60% of their perceived 1-RM. Then, they were asked to perform one repetition at their maximal effort. This latter was carried out three times, with 2–3 min rest between efforts, and the highest value of strength recorded was used as 1-RM . For eacp < 0.05. Data were analyzed using SPSS software . In order to establish whether the nocturnal BP pattern was independently related to the lack of changes of BPV after the exercise protocol, a multivariate linear regression analysis was carried out in which age, BMI, and OSAS were included as covariates.The dependent variable was given by changes (12-week-baseline) of systolic BPV.Data are expressed as mean ± SD. The assumption of normality was checked using the Shapiro–Wilks hypothesis test. All variables recorded in this study were normally-distributed.Between-group comparisons of each variable was assessed using a repeated measure two-way ANOVA, with Bonferroni corrections for post hoc testing. The level of significance was set at p = 0.02 and p = 0.006, respectively). Nighttime systolic BPV was unchanged in both groups. Twenty-four/h systolic BP and daytime systolic BP decreased significantly in the dipping group while they were unchanged in the non-dipping group . Nighttime systolic BP was unchanged in both groups. Twenty-four/h diastolic BP presented small but not significant changes in both groups .No changes in the daytime and nighttime diastolic BP were observed in both groups.Six out of 35 (17.1%) of the individuals who met the criteria for non-dipping BP status at the baseline were reclassified as dippers after the exercise intervention (p = 0.152).No changes in the opposite direction were observed among dippers, however, the ratio between the mean nighttime BP and mean daytime BP increased (from 0.854 to 0.902). In the multivariate regression model, in which age, BMI, OSAS, and nocturnal BP pattern were included, only this latter resulted in being significantly related to changes observed in systolic BPV (p = 0.02)  had a non-dipping pattern. Three patients presenting with an extreme dipping pattern (≤0.80) were included in the dipping group. In the examined population, there were no patients with an inverted BP pattern (>1.00). Sixty-four out of 72 patients completed the protocol and were included in the final analyses. Six patients (three of the dipping group and three of the non-dipping group) dropped out during the training program, because they were unwilling to continue the study. Two patients (one of the dipping group and one of the non-dipping group) were ruled out because a sustained increase in BP values during the training program that required pharmacological intervention. Overall, the exercise protocol was well tolerated and no adverse events occurred. The baseline features of patients are summarized in  = 0.02) .p = 0.02)  . Our datAt the same time, our results might also indicate the need for further studies with different exercise modalities and intensities in order to find a more appropriate exercise protocol and doses for reducing BPV in hypertensive patients, particularly in those with a non-dipping pattern.Our results on BP values are consistent with previous research utilizing aerobic training. Nami et al.  showed aThe nocturnal non-dipping BP pattern is often observed in patients with more severe, resistant, and long-standing type of hypertension and it reflects an inadequacy of the mechanisms regulating BP. Baroreflex and/or autonomic dysfunction, nocturnal volume overload, and abnormal sodium handling have all been documented in non-dipper hypertensive patients . Though More than 50% of patients recruited in this study were non-dippers. These findings are consistent with previous observations in the general population of hypertensive subjects ,33 and iLimitations: This study included middle-age/elderly subjects with already diagnosed CAD, therefore, its results cannot be extended to the entire population of hypertensive patients.This study lasted 12 weeks and we cannot rule out the possibility that a longer exercise training intervention would had been more effective in reducing short-term BPV and BP values. Our results were obtained in subjects undergoing concurrent exercise and cannot be generalized to different exercise modalities. We cannot exclude that the failure to reduce night-time systolic BP could have been dependent on the time of day in which the exercise sessions were performed, that is, the morning. Indeed, Park et al.  reportedWe showed that the impact of a 12-week CT program on 24-h BPV and BP values in hypertensive patients with CAD was blunted in those subjects presenting a non-dipping BP pattern. Efforts should be made to reverse the non-dipping BP pattern, which appears to be the main determinant of the lack of effects of CT on BPV. Further studies are also needed in order to discover the best exercise training modalities in terms of the format and dose for hypertensive patients presenting a non-dipping pattern.


The respective cut-off point values used to classify participants as a beneficiary of HIIT intervention concerning SBP were SMI = 7.84 and MFR = 2.43 in males, and for SMI = 10.12 and MFR = 1.94 in females. Body composition indices based on skeletal muscle  were more likely to predict positive changes in SBP after HIIT intervention in adolescents. PP, MBP, and MAP did not reflect the detecting power of SMI and MFR. However, these thresholds’ utility is limited to adolescents of 16 years of age.This study aimed to investigate the prognostic potential of body composition indices in predicting the improvement in resting blood pressure after 10 weeks of high-intensity interval training (HIIT) implemented in physical education lessons. The participants were 141 adolescents aged 16 years. Independent variables were body mass index (BMI), fat mass index (FMI), muscle mass index (SMI), and mass to fat ratio (MFR); dependent variables were systolic and diastolic blood pressure  and its indices: pulse pressure (PP), mid-blood pressure (MBP), and mean arterial pressure (MAP). The receiver operating curve (ROC) method was employed. SMI and MFR are body composition indices with prognostic potential to predict positive changes in SBP in males (SMI: AUC = 0.82;  Appropriate systolic blood pressure (SBP) is 120 mmHg, and diastolic blood pressure is 80 mmHg in adults, with a slight difference in childhood and adolescence. A person with SBP over 140 mmHg and/or DBP over 90 mmHg is diagnosed with hypertension. Blood pressure exceeding the normal range is a serious medical problem that significantly increases the risk of many diseases, e.g., metabolic syndrome, cardiovascular diseases, and heart diseases ,4. More The worldwide prevalence of obesity in the early stage of life is already well-documented ,8,9. ManFatness can be considered as a distribution in different body locations (measured among others with waist-to-hip ratio (WHR)) or quantity of fat mass in the whole body (body fat mass (BFM) in kilograms or percentages (BFP)) in different parts of the body . Even though the measurements are interpreted differently, they are related to health. Excessive adipose tissue (adiposity) is a reason for adverse endocrine responses provoking cardiovascular diseases . FurtherEvidence that excessive fatty tissue and inadequate muscle mass–fat mass proportions are the risk factors of blood pressure disturbances obliges us to examine different body weight indices as predictors of elevated blood pressure or hypertension. Body mass index (BMI) and waist-to-hip ratio (WHR) is the most often used. However, they have limitations concerning specific groups of people  ,21. TherAn emerging alternative for assessing fat tissue in relation to height or muscle mass is the fat mass index (FMI), skeletal muscle index (SMI), and muscle-to-fat ratio (MFR) . All of Among the instruments for fighting with excessive fat tissue and elevated blood pressure, physical activity comes to the fore. The great value of physical activity, which leads to normal body mass and normotensive blood pressure, has been proved many times ,31,32. THowever, current Polish studies on associations between body weight and its components with resting blood pressure are limited mainly to the assessment of the simple relationship between the weight-to-height ratios, waist and hip circumferences, and body fat with resting blood pressure but do not include the analysis of various fat mass indices . Moreover, to the best knowledge of the authors, to date, there is no assessment of the predicting usefulness of the body composition indices in detecting positive changes in resting blood pressure after high-intensity interval training programs implemented in regular PE lessons. Our study focused on evaluating the various body composition indices based on anthropometric measurements (waist-to-hip ratio (WHR), body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI), and muscle-to-fat ratio (MFR)) as predictors of the cardiovascular state after 10 weeks of regular short-term intensive physical effort in an average adolescent population. Furthermore, the utility of various blood pressure indices (pulse pressure (PP), mid-blood pressure (MBP), and mean arterial pressure (MAP)) were tested apart from systolic (SBP) and diastolic (DBP) blood pressure parameters. Therefore, the study’s primary purpose was to investigate the prognostic potential of these body composition indices in predicting the improvement in resting blood pressure after ten weeks of HIIT implemented in PE lessons in adolescents. Specifically, we aimed to: (1) assess the utility of each index in prediction (based on AUC), and (2) identify the associated thresholds in adolescents.Results in this study were obtained from data received in the project “Physical activity and nutritional education in preventing civilization diseases—theoretical aspects and practical implications for the secondary school physical education program”. The full description of the project and methodology was published elsewhere ,43,44. HThe sample size was calculated before starting the project, based on primary planned analysis—MANOVA—and it was identified that 179 participants should be included. Examinations were conducted in school where there were 187 students in the 1st year of school learning. In total, 46 of them did not finish intervention or were excluded due to various reasons . Thus, the final sample size of the participants comprised 141 adolescents. They were separated randomly into an experimental group (EG) and a control group (CG). High-intensity interval training (HIIT) based on the Tabata protocol (TAP) was conducted for ten weeks. Participants qualified for the experimental group performed the TAP during one weekly PE lesson. A standard PE lesson 45 min) started with a standardized 10 min warm-up. The main activity part was 14 min of TAP, which comprised three sessions, each lasting four minutes  [ min starExercise intensity during the TAP with adolescents’ maximum heart rate was determined with the formula HRmax = 208 − 0.7 × age (16 years) established . High-inMeasurements were taken twice: baseline (preintervention variables) and after the 10-week intervention (postintervention variables). Examinations were conducted one day from 8:00 a.m. to 1:00 p.m. in the same order: anthropometric and body composition measurements and resting blood pressure after 10 min of rest. Body height measurement was taken with an accuracy of 0.1 cm using an anthropometer . Body weight and body fat mass were measured with the InBody230 body composition analyzer . Waist and hip circumferences were measured with the standard anthropometric procedure. The above data were used to calculate indices with the presented formulas:This paper used results of resting blood pressure before and after a 10-week intervention. Automatic Blood Pressure Monitor—Omron BP710 tool was used to measure systolic (SBP (bpm)) and diastolic (DBP (bpm)) blood pressure. Before measurement, participants were asked to sit quietly for 10 min. Readings of resting SBP and DBP were taken three times in 10 min intervals. The mean value of the three measurements was recorded in the database.Based on SBP and DBP blood pressure, various indices were calculated too. The following formulas were used :PP  was conducted to assess the association between positive changes and lack of changes with experiment (EG–CG comparison) and sex . Odds ratios (OR) for assessing the likelihood of the positive changes for groups were calculated too. The numbers of positive changes, as well as the lack of changes, were presented as percentages. Pearson’s chi-square test  method was employed to assess the utility of the body composition indices in predicting positive changes in blood pressure indices. The accuracy of body composition measures to discriminate positive changes in groups of participants was assessed using the area under curve (AUC) parameter with confidence interval (95% CI). AUC statistic measures the model’s goodness of fit and validity based on sensitivity and specificity. Differences between AUC values between each pair of body composition indices were tested using DeLong tests .For statistically significant models, the cut-off points were calculated. It was done using the Youden index, calculated from the formula:The Youden index allows, based on the ROC curve sensitivity and specificity values, the optimal cut-off point to be determined ,26.p-value < 0.05 was considered statistically significant. The calculations were carried out using Statistica 13.0 .A Descriptive statistics of raw measurements and calculated indices (body composition and blood pressure) are presented in Out of 141 students, 87 (61.70%) decreased SBP, and 78 (55.32%) decreased DBP during the period of lasting the program . In consequence, positive changes in blood pressure indices were: PP—74 (52.48%), MPB—87 (61.70%), and MAP—84 (59.57%).2 = 11.59, p < 001; 83.33% EG females vs. 38.30% CG females, χ2 = 18.67, p < 0.001), DBP for females , PP for males , MBP for both sexes  and MAP for females . Calculated odds ratio (OR) showed that males and females who participated in the intervention program were several times more likely to improve blood pressure parameters than peers from control groups. The highest value was observed for SBP ; females: OR = 8.05 (2.95–21.94 95% CI)).Considering subgroups , students from experimental groups noted improvements in blood pressure parameters much more often than peers not included in the program. It was supposed to be linked with the intervention effect. It regards SBP for both sex  and MFR , while in EG females, it was only MFR . Results for CG groups were not significant.The diagnostic accuracy of the cut-off points for predicting positive changes in cardiovascular parameters by indices using skeletal muscle mass in the equation was higher than what would be expected by chance (AUC > 0.5) for all indices except DBP . Body map = 0.041) and FMI (p = 0.014) for SBP and FMI (0.044) for MBP in EG males, and to FMI in EG females (p = 0.050)  . ResultsCut-off point values were calculated only for statistically significant ROC curves. The purpose of the paper was twofold: first, examine the utility of various body composition indices in predicting positive changes in the cardiovascular system (for different blood pressure indices) in adolescents; second, identify cut-off point values for body composition indices best-performing prediction. Regarding the first objective, indices based on skeletal muscle mass , but not BMI and FMI, effectively distinguished between positive changes and lack of changes concerning SBP. Regarding the second objective, thresholds for values of skeletal muscle mass concerning body height (SMI) and body fat (MFR) reflected the chance of positive changes in the cardiovascular system (particularly systolic blood pressure). Interventions based on aerobic and anaerobic exercise are widely used in programs related to human health ,52,53,54A significant reduction of cardiovascular risk after the HIIT program caused by reducing blood pressure was observed in overweight participants . AdditioIt is necessary to emphasize that the HIIT positive effects occur despite the body composition . HoweverThe studies conducted by Ouerghi et al.  and BuchOur study showed that positive changes in blood pressure parameters might be predicted with indices based on muscle mass (SMI and MFR). Therefore, muscle tissue is beneficial to achieving better health results after HIIT. The above study by Korhonen et al.  showed aWe found no previous studies on adolescents that presented the potential of novel body composition indices in predicting the improvement of high-intensity interval training in cardiovascular parameters. Therefore, it is hard to discuss the received cut-off point in our study with other authors. Identifying cut-off point values of the most valuable indices have practical meaning. Therefore, our findings show new directions of examinations and reveal new knowledge in physical activity in physical education lessons. However, due to the lack of similar studies, there is a need to explore this kind of study in wider groups of various ages regarding sex or physical activity. Moreover, there is a need to verify the indicated cut-off values in prospective, longitudinal terms.p = 0.06–0.1). The calculated sample size to receive AUC = 0.73, p < 0.05, and 80% power was 57 participants in EG, while 42 females and 31 males took part in the intervention program.We are aware of the limitations of this study. Limited participants from only one school could have affected the results. Several models were very close to significance. The power of the ROC method was circa 46%. Many models received 0.6–0.7 AUC values  made it possible to assess the value of the short, time-efficient intensive intervention for adolescents participated in regular school classes. Study sample was homogenous, considering similar subjects, which makes our study reliable to this group. We analyzed separately for males and females when sex is crucial to body composition values. Moreover, the results presented in our study are a novelty. To our knowledge, there is a lack of similar research. The high-intensity interval training intervention is an effective program resulting in positive changes in the cardiovascular system in adolescent males and females. Those who participated in the program were eight times more likely to receive positive changes in blood pressure parameters compared to the control group. The study suggested that body composition indices based on skeletal muscle mass in the formula, SMI and MFR, contributed to positive changes in blood pressure parameters but not BMI and FMI. The higher detection power of the positive changes was related to SBP. The blood pressure indices were poor, except for MAP in females. The males with SMI over 7.84 and MFR over 2.43 and females with SMI over 10.12 and MFR over 1.94 were more likely to receive positive changes in SBP. Intentional modification of the proportions between muscle mass and fat mass through the proper diet may support positive effects on the cardiovascular system after HIIT intervention. The time-efficient interval program implemented in PE lessons improves blood pressure parameters, particularly SBP. However, further studies with greater samples and participant age variations are needed.


Patients with Hcy≤10 μmol/L are included in the non-H-type hypertension group (n = 54). Both groups underwent 24-hour ambulatory blood pressure monitoring. Base frequency and allele distribution of MTHFR gene C677 T locus are compared between the two groups, and the relationship between different bases of MTHFR gene C677 T locus and morning blood pressure and Hcy level is analyzed. The risk factors of morning hypertension in patients with H-type hypertension are analyzed by binary logistic regression. Binary logistic regression analysis shows that smoking history, drinking history, high-salt diet, MTHFR gene C677 T genotype, and abnormal 24 h systolic blood pressure are the risk factors for the occurrence of morning hypertension in H-type hypertension patients. The frequency of TT homozygous mutation at the C677 T site of the MTHFR gene is high in patients with H-type hypertension, and the mutation of the C677 T site of the MTHFR gene had an effect on systolic blood pressure and Hcy level.The distribution characteristics of Methylenetetrahydrofolate Reductase (MTHFR) gene C677 T polymorphism and its influence on early morning blood pressure in elderly female patients with H-type hypertension are investigated. A total of 220 elderly female patients with hypertension who received diagnosis and treatment in our hospital from March to September 2021 are selected. All patients received serum index detection in our hospital and are grouped according to blood homocysteine (Hcy) level. Patients with Hcy>10  Existing studies have shown that the high incidence of various cardiovascular and cerebrovascular diseases in clinical practice is closely related to hypertension symptoms . A studyIn this paper, the MTHFR gene C677 T polymorphism, changes in plasma Hcy level and its role in the occurrence of hypertension in elderly female patients with H-type hypertension are studied, aiming to explore the mutation characteristics of MTHFR C677 T in elderly female population, thus, providing reference data for the prevention and treatment of such patients with H-type hypertension and individualized treatment.The rest of this paper is organized as follows: μmol/L) was defined as H-type hypertension, and the guideline for prevention and treatment of hypertension in China (2018 Revision) pointed out that Hc ≥ 10 μmol/L was an important factor affecting the cardiovascular prognosis of hypertensive patients. Hcy is recommended as one of the laboratory examination items for patients with hypertension [Existing studies have confirmed that hypertension and blood Hcy synergistically contribute to the aggravation of the risk of cardiovascular and cerebrovascular adverse events . Some scrtension . MTHFR iChina 201 Revisionβ synthase through the sulfur-conversion pathway with serine, cysteine forms cysteine under the action of cysteine lyase, and finally pyruvate, sulfuric acid, and water [Some scholars have found that there are extensive pathological manifestations of arterial thrombosis and atherosclerosis in the systemic circulation of children who died of hereditary homocystinuria at autopsy, thus, proposing the hypothesis that hyperhomocysteinemia can lead to atherosclerotic vascular disease . Hcy is nd water . Metabolnd water , 12.Previous clinical studies have confirmed that the 677C-T genotype of the MTHFR gene is related to plasma Hcy level, and patients with the 677C-T allele have significantly higher plasma Hcy level, which is an independent risk factor for hypertension, coronary heart disease, and stroke , 14. MorFor elderly women with H-type hypertension, it is important for regular physical examination, early detection, and early treatment. The treatment of high blood pressure in H mainly adopts vitamin folic acid treatment. With the continuous improvement of the H blood pressure ratio in my country, people should pay attention to preventive health care to achieve the healthy development of hypertension prevention and treatment.μmol/L are classified as H-type hypertension and included in H-type hypertension group (n = 166). Patients with Hcy≤10 μmol/L are non-H-type hypertension and are included in the common hypertension group (n = 54). The age range of patients in the H-type hypertension group is 65–80 years, with a mean of (71.75 ± 4.40) years and the duration of hypertension is 3–12 years, with a mean of (7.03 ± 3.24) years. In the common hypertension group, the patients' ages are ranged from 66 to 80 years, with a mean of (71.58 ± 4.51) years and the duration of hypertension was ranged from 3 to 13 years, with a mean of (7.23 ± 3.06) years. There is no statistical difference in age, hypertension course, and other general information between the two groups (P > 0.05), which proves that the comparison between the two groups is scientific and reasonable.A total of 220 elderly female patients with hypertension who received treatment in the Affiliated Hospital of Chengde Medical College from March to December 2021 were selected. All patients are ≥65 years old. All patients receive serum indicators in our hospital, and are grouped according to blood Hcy level. Patients with Hcy>10 There are three inclusion criteria as follows: (1) it meets the diagnostic criteria of hypertension in the 2018 Chinese Guidelines for Prevention and Treatment of Hypertension; (2) the patients are between 65 and 80 years old and all are female; (3) patients with good clinical compliance agree to participate in the study and complete relevant investigations until the end of the study.There are four exclusion criteria as follows: (1) accompanied by cognitive impairment, memory decline, visual spatial impairment and other cognitive impairment; (2) patients with mental diseases; (3) patients with serious organic dysfunction of liver and kidney; (4) patients with acute/chronic infectious diseases or diseases of the blood system.μL, consisting of 10 x PCR buffer 5 μL, 25 mmol/L magnesium chloride solution, 3 μL, 2 mmol/L dNTP mixture 5 μL, 1.25U AmpliTaq DNA polymerase, 0.5 μmol/L primer and 100 μg genomic DNA. Primer sequence of MTHFRC677 T gene: upstream: 5′-CAGTCCCTGTGGTCTCTTCAT-3′, downstream: 5′- CTCACCTGGATGGGAAagat-3′. PCR cycle conditions: pre-denaturation at 95°C for 10 min, denaturation at 94°C for 30s, renaturation at 60°C for 30s, extension at 72°C for 30s, 37 cycles of reaction, and extension at 72°C for 10 min. The amplified primers are detected by 2% agarose gel electrophoresis and stored at 4°C for testing. PCR products are purified and used as sequencing templates. According to the complete sequence provided by the GenBank database, primer design software is used to design PCR primers and corresponding endonuclease for each site.In the morning of the second day after admission, 5 mL of fasting venous blood is taken from all patients, digested by membrane solution/protease K, and genomic DNA is extracted, which is stored at −20°C. Polymerase Chain Reaction(PCR) 50 Clinical data are collected after admission, including age, medical history, and Body Mass Index (BMI). 24-hour ambulatory blood pressure monitoring is performed by the German TM2430EX noninvasive portable dynamic sphygmomanometer. The cuff is tied to the subjects' left upper arm at 8 : 00 a.m., and the measurement interval is set at 15 minutes during the day (6 : 00 ∼ 22 : 00). At night (22 : 00–6:00), the measurement interval is 30 min, and continuous monitoring is conducted for 24 hours. If effective data >80% and blood pressure data missing from 6 : 00 to 8 : 00 in the morning is less than 2, it is regarded as qualified. Otherwise, retest the next day. The mean 24 h, daytime, and nighttime systolic and diastolic blood pressure levels of these subjects are calculated, respectively, and extreme values are removed during the calculation process. The standard deviations and mean values of SBP and diastolic bp at 24 h, daytime and nighttime are calculated. The diagnostic criteria for morning hypertension are as follows: morning hypertension is defined as blood pressure ≥135/85 mmHg within 2 hours after waking up.All subjects are fasted for ≥10h. 5 mL of elbow venous blood is extracted from all patients with an EDTA anticoagulant tube during specimen collection. The blood samples are centrifuged at 3000r/min with a centrifugation radius of 10 cm and a continuous centrifugation time of 15 min. The blood Hcy is determined by chemiluminescence method.morning blood pressure indexes of the two groups are compared;Base frequency and allele distribution of MTHFR gene C677 T locus are compared between the two groups;The relationship between different bases of MTHFR gene C677 T locus and morning blood pressure and Hcy level is analyzed;Binary logistic regression analysis of morning hypertension in H-type hypertension patients.There are four observation indicators as follows:P < 0.05 is considered statistically significant.SPSS26.0 software is used for statistical analysis. A direct counting method is used to calculate the population distribution frequency of the MTHFR C677 T genotype and allele. A chi-square test is used to compare the distribution frequency of gene polymorphism. The risk factors of morning hypertension in H-type hypertension are analyzed by binary logistic regression. Measurement data are expressed by mean ± standard deviation, and P > 0.05), and the morning systolic blood pressure in the H-type hypertension group increases significantly more than in the common hypertension group .P < 0.05).P < 0.05; b is compared with CC, P < 0.05; c is compared with CT, P < 0.05. it can be seen from P > 0.05). The systolic blood pressure level of patients with the TT type is higher than that of patients with the CT type and CC type (P < 0.05). The systolic blood pressure of patients with TT type is higher than that of patients with CC type in the non-H-type hypertension group, and there is no significant difference in systolic blood pressure between patients with TT type and patients with CT type (P > 0.05), suggesting that patients with TT homozygous mutation at C677 T site of MTHFR gene have higher systolic blood pressure. There are no significant differences in diastolic blood pressure levels between CC, CT, and TT type patients , suggesting that TT homozygous mutation at the C677 T site of the MTHFR gene have no significant effect on diastolic blood pressure levels of patients. The Hcy level of CC, CT, and TT patients in the H-type hypertension group is significantly higher than that in non-H-type hypertension group (P < 0.05). In the H-type hypertension group, the level of Hcy in TT type patients is significantly higher than that in CC type and CT type patients . In the non-H-type hypertension group, the Hcy level of TT patients increases significantly more than that of CC patients (P < 0.05), suggesting that the variation of the C677 T locus of the MTHFR gene has a significant impact on the Hcy level of patients.n = 52) and the nonmorning hypertension group (n = 114). The clinical data of the two groups are analyzed by univariate analysis and genotype  and P < 0.05 are included as independent variables. Binary logistic regression analysis shows that smoking history, drinking history, high-salt diet, MTHFR gene C677 T genotype, and 24 h systolic blood pressure elevation are risk factors for the occurrence of morning hypertension in H-type hypertension patients.The distribution characteristics of the MTHFR gene C677 T polymorphism and its influence on early morning blood pressure in elderly female patients with H-type hypertension are investigated. Attention should be paid to Hcy and genotype screening for elderly female hypertensive patients. For carriers of TT homozygous mutation at the C677 T site of the MTHFR gene, attention should be paid to early morning blood pressure, prevention, and treatment plans should be adjusted, and targeted antihypertensive drugs should be applied to effectively control early morning hypertension so as to avoid the occurrence of untimely and cerebrovascular events.


Pearson’s correlation coefficient (PCC) indicated that serum 25(OH) D levels were negatively correlated with left ventricular mass index  and albuminuria . Linear- regression analysis showed that 25(OH) D was a risk factor for left ventricular hypertrophy  and renal damage . In total, our data revealed that serum 25(OH) D was independently associated with hypertensive cardiac and renal damage, meaning that it was a risk factor for LVH and albuminuria in childhood hypertension.Researchers have shown that 25-hydroxyvitamin D (25[OH] D), a kind of active vitamin D in the human body, plays a role in cardiovascular disease (CVD). Low serum 25(OH) D levels have been found to be associated with elevated blood pressure (BP) in adults. However, measurement of 25(OH) D in hypertensive children has not been documented. The aim of this study was to investigate the relationship between 25(OH) D and target organ damage (TOD) in children with essential hypertension. We recruited a total of 346 children with essential hypertension and analyzed the correlation between serum 25(OH) D and TOD. Serum 25(OH) D concentration was significantly lower in the TOD than in the no-TOD group ( In recent years, the incidence of essential hypertension in children and adolescents has increased. From 1991 to 2009, the prevalence of hypertension in children and adolescents ages 6–17 years increased by an average of 0.47% annually in China. By 2009, the prevalence of hypertension in children and adolescents in China reached 13.8% [Hypertension is a disease that seriously threatens human health by causing damage to multiple target organs. Hypertension in children and adolescents can cause target organ damage (TOD) to the cardiovascular (CV) system, kidneys, central nervous system (CNS) and fundus. Studies have found that vitamin D receptors are widely present in organs and tissues such as the heart, kidneys and vascular endothelium, which suggests that in addition to its well-known biological effects on bone, vitamin D might also participate in the regulation of CV metabolism . PreviouThis study was conducted single-center and cross-sectional. We recruited a total of 346 children, including 275 males (79.5%) and 71 females (20.5%), diagnosed with essential hypertension and admitted to the Affiliated Children’s Hospital of Capital Institute of Pediatrics  from June 2016 to March 2021. The research protocol of this study was approved by the Ethics Committee of the CIP. Patients’ parents or guardians of the patients received information about the relevant examinations and signed the written informed consent beforehand.The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents and used the results to diagnose hypertension and perform stage classification [We performed all BP measurements using the auscultation method as recommended in fication . HyperteExclusion criteria for this study were patients >18 years; with secondary hypertension caused by kidney disease, vascular disease, endocrine disease, CNS disease or drugs; or systemic diseases with abnormal calcium and phosphorus metabolism.Pediatric patients fasted overnight for 8 h, In the morning, we collected their venous blood to measure serum sodium, potassium and calcium concentrations; plasma cholesterol; triglyceride; uric acid and other parameters. All biochemical variables were assayed in plasma or serum using standard methods.We determined vitamin D content in serum by detecting 25(OH) D in serum. Venous-blood samples were taken from patients in the morning after 12 h of overnight fasting. After centrifugation for 15 min (2000 g), we collected the samples in tubes and refrigerated them. Concentrations of 25(OH) D were assessed using a chemiluminescence immunoassay . The limit of detection (LoD) for 25(OH) D was 4.8 ng/mL; no samples had concentrations below LoD. All samples were run in duplicate and the values averaged. Total (intra-assay and inter-assay) coefficients of variation for control values of 12.0 and 77.9 ng/mL were 10.0% and 7.6%, respectively.We classified the status of 25(OH) D concentration as deficient (<30 nmol/L), inadequate (30 to <50 nmol/L), or adequate (≥50 nmol/L) per the report released in 2010 by the Institute of Medicine . The timAll patients underwent 24-h ambulatory BP monitoring via a DM Software Ambulatory Blood Pressure (DMS-ABP) device . They received information on the procedure and device beforehand. In order for the device to function properly, patients were told to perform their daily activities normally but to remain immobile during measurements. BP recordings were programmed to occur every 30 min during the day and every 60 min while patients slept. We recorded and adjusted sleep and wake times for each patient to define the nighttime period. Based on these measurements, we determined 24- h systolic BP (24-h SBP), 24-h diastolic BP (24-h DBP), daytime SBP, daytime DBP, nighttime SBP and nighttime DBP. The method was considered reliable if >75% of the measurements were valid.We assessed LVH via echocardiography (ECG). Left ventricular internal dimension (LVIDd), interventricular septal thickness (IVST) and left ventricular posterior-wall thickness (LVPWT) at the end diastole were measured using a Philips iE33 Ultrasound System . Left ventricular mass (LVM) was calculated as follows:Dd3)+0.6 .2.16. Relative left ventricular wall thickness (RWT) was calculated as (IVST + LVPWT)/LVIDd. For the diagnosis of LVH, LVMI ≥ 45 g/m2.16 or RWT > 0.41 was considered abnormal [LVM index (LVMI) was calculated as LVM/heightabnormal , 15.excretion>200 mg/m2/day; urine β2-microglobulin (β2- MG) > 0.3 mg/L or cystatin C (Cys-C) > 1.26 mg/L [We diagnosed patients with renal damage if any of the following conditions was fulfilled: albuminuria  >3 mg/mmol Cr; 24-h urine protein .26 mg/L –19.We grouped patients with essential hypertension by 25(OH) D level: a deficiency group (<30 nmol/L), an inadequacy group (30 to <50 nmol/L), and an adequacy group (≥50 nmol/L). We also grouped patients by presence or absence of TOD; patients in the TOD group were further subdivided into cardiac-damage and renal-damage groups. We then analyzed differences in serum 25(OH) D levels among these groups.t test to compare differences between two groups. Analysis of variance (ANOVA) was used to compare measured differences among multiple groups. Count data are presented as percentages (%). Univariate associations between the indices of 25(OH) D levels, LVMI, and other variables of TOD were assessed using simple linear-regression analyses and Pearson’s correlation coefficient (PCC). P < 0.05 was considered statistically significant.We used SPSS software version 20.0  to process all data in this study. Values of parameters with normal distribution were presented as means ± standard deviations (SDs), whereas values with non-normal distributions were transformed into normal distributions by logarithmic transformation. We used an independent-sample 2. Of these, 253 patients (73.1%) had a BMI exceeding the 95th percentile of children of the same age and gender and were diagnosed as obese. Average 24-h SBP and 24-h DBP of the 346 patients were 126.9 ± 10.3 mmHg and 71.3 ± 6. 9 mmHg, respectively. All 346 were treated at our hospital and had received no previous drug interventions.Among the 346 children with essential hypertension enrolled in this study, there were 275 males (79.5%) and 71 females (20.5%), with a mean age of 12.3 ± 2. 2 years , average height of 16 6.3 ± 13.2 cm, average body weight of 75.2 ± 20.2 kg and average body mass index (BMI) of 26.8 ± 5. 1 kg/mP < 0.001).Demographic and laboratory characteristics and ambulatory BP measurements are shown in Table We evaluated all 346 children for heart and kidney damage. Of all 346 cases, 179 (51.7%) had TOD, including 138 patients with a single organ damaged and 41 patients with two organs damaged.Ninety-four (27.2%) of the 346 patients had LVH. Of these, 81 had increased LVMI and normal RWT, manifesting as eccentric remodeling; 8 had normal LVMI and increased RWT, with concentric remodeling; and 5 had increased LVMI and RWT, manifesting as concentric hypertrophy.One hundred twenty-six (36.4%) of the 346 patients had renal damage, 10 (2.9%) had elevated 24-h urine protein, 60 (17.3%) had albuminuria, 58 (16.8%) had elevated urine β2- MG and 27 (7.8%) had increased Cys-C.vs. 36.99 ± 13. 59 nmol/L; t = 1.048, P = 0.295).Of all 346 patients, 183 (52.9%) had stage 1 hypertension, and 163 (47.1%) had stage 2 hypertension. There was no significant difference in serum 25(OH) D concentrations between these two groups .We compared baseline characteristics between the TOD and no-TOD groups. Of all 346 patients, 179 (51.7%) had TOD, including 148 males (82.7%) and 31 females (17.3%), with a mean age of 12.4 ± 2. 1 years; 167 patients (48.3%) had no TOD, including 127 males (76.0%) and 40 females (24.0%), with a mean age of 12.2 ± 2.4 years. No signifi cant differences in sex or age were found between these two groups . In the TOD group, 138 cases had single- organ damage, while 41 cases had simultaneous two-organs damage. Serum 25(OH) D concentrations of the two groups were lg10, 1.55 ± 0.15 nmol/L and lg10, 1.47 ± 0.10 nmol/L, respectively; serum 25(OH) D levels in the two-organs damage group were significantly lower than in the single organ damage group .Serum 25(OH) D concentration in the TOD group  was significantly lower than in the no-TOD group , and the difference was statistically significant (P < 0.05); further analysis via PCC indicated that these correlations were negative  and renal damage .We analyzed the correlation between serum 25(OH) D levels and TOD in all 346 patients. As shown in Table Essential hypertension is a multi-gene disease in which the genetic components interact with physiological factors. Recent research has shown vitamin D receptors to be widely distributed throughout almost all the organs of the body , and vitSeveral studies have proven a strong relationship between vitamin D deficiency and TOD . VitaminTherefore, serum 25(OH) D concentration correlated negatively with TOD, the incidence of which was higher in children with low serum 25(OH) D levels.Myocardial remodeling in hypertension refers to cardiac hypertrophy and fibrosis. Sustained BP load first and mainly affects the left heart, resulting in LVH. LVMI and RWT are important indices by which to evaluate early LVH. LVH is often the main manifestation of early cardiac damage in children with hypertension. As an intermediate stage of heart damage during the progression from childhood to adulthood, early heart damage is important in evaluations. Not only is LVH related to BP values , but curThe kidney is one of the main target organs in patients with hypertension. Owing to the hidden onset of hypertension and the strong compensatory ability of the kidneys, some hypertensive children with kidney damage show no obvious abnormalities in routine renal-function monitoring indicators. Albuminuria, urine β2-MG and Cys-C are sensitive indicators reflecting early hypertensive renal damage, suggesting impaired glomerular-filtration function and proximal convoluted tubular-reabsorption function . In our In conclusion, 25(OH) D deficiency was a frequent finding in children who had essential hypertension without major CV risk factors. Our results showed that serum 25(OH) D levels were independently associated with hypertensive cardiac and renal damages and that low serum 25(OH) D was a risk factor for LVH and albuminuria in childhood hypertension.Some potential limitations of the present study should be discussed. First, considering that this was a small-scale study from a single center, the generalizability of our data might be limited. The low number of females might also limit its statistical power. Second, carotid intima-media thickness (CIMT) and pulse wave velocity (PWV) are also considered markers of TOD, but we did not assess them in this study, which is another limitation of the study.Third, several studies have shown that serum/plasma levels of PTH are positively associated with increased BP . However