P = 0.002) through the prevention of cardiac remodeling and the lowering of plasma catecholamine, brain natriuretic peptide, and angiotensin II. These results suggest that the central mechanism plays an important role in the cardioprotective effects of donepezil.Oral administration of donepezil, a centrally acting acetylcholinesterase inhibitor, improves the survival of rats with chronic heart failure (CHF). The mechanisms of cardioprotective effects of donepezil, however, remain totally unknown. To elucidate potential mechanisms, we examined whether central microinfusion of donepezil would exert cardioprotection. Intracerebroventricular microinfusion pumps with cerebroventricular cannula were implanted in rats with myocardial infarction. The rats were randomly divided into central saline treatment (CST) and central donepezil treatment (CDT) groups. We evaluated cardiac remodeling and function after a 6-week treatment and examined the 160-day survival rate. Compared to the CST, the CDT markedly improved the 160-day survival rate (68% vs. 32%,  Despite significant advances in therapies and prevention , chronicThere have been no reports to prove the improved survival of CHF animals other than treated with donepezil. Other peripheral cholinesterase inhibitors seem less effective in improving survival . PyridosThe care of animals and all animal experiments were performed in strict accordance with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health , and the Guiding Principles for the Care and Use of Animals in the Field of Physiological Sciences, which have been approved by the Physiological Society of Japan. All protocols were reviewed and approved by the Animal Subject Committee in the National Cerebral and Cardiovascular Center.n = 32) and survival study (n = 56) described below.As shown in Fig. Permanent MI (infarct size ≥ 40%) was induced by occluding the proximal left coronary artery in 180 male 8-week-old Sprague-Dawley rats  as described previously –14. SligOne week after inducing permanent extensive MI, we implanted blood pressure (BP) transmitters  into the 32 MI-induced CHF rats to monitor their daily mean BP (MBP) and heart rate (HR) in the remodeling study. The Teflon tube portion of the BP transmitter was cannulated into the abdominal aorta. The pressure signal was acquired at a 500-Hz sampling rate, and the calculated MBP and HR data were recorded intermittently (for 5 s every 5 min) in the freely moving animals.® microinfusion pump . In a preliminary test, we checked whether the drug was accurately being injected into the lateral ventricle using a blue dye. Donepezil or vehicle  was administered at a rate of 1.0 μL/h. Donepezil  was dissolved in saline to a dosage of 0.1 mg/kg/day, which is 1/50 of the oral dose used in a previous study  reduction in the relative risk ratio of all-cause death. As shown in Fig. P = 0.399), the CDT markedly improved survival free from pump failure deaths .Fifty extensive MI-induced CHF rats were enrolled in the survival study. There was no difference in body weight between the surviving CST  significantly reduced HR, especially resting HR; (2) suppressed catecholamine, BNP, AVP, and ANG II levels in plasma; (3) prevention of the progression of cardiac remodeling and dysfunction, and (4) improvement of the 160-day survival rate.P < 0.05). The circadian variation of HR progressively increased in the CDT group  compared to the CST group. Both decreased sympathetic drive and increased parasympathetic efferent discharge appear to contribute to HR reduction, based on decreased plasma norepinephrine and epinephrine levels in the CDT group and increased high-frequency HR variability in the CHF rats when treated orally with donepezil [Telemetric HR under non-stressful, conscious state revealed that the average HR reduction in the CDT group relative to the CST group was 40 bpm Fig. a. The HRonepezil . Cardiaconepezil . Even thonepezil , restingonepezil , 29. TheThe bradycardic effect of donepezil may reproduce beneficial and important effects induced by β-blockers in the treatment of patients with CHF. However, because inhibition of β-receptors on cardiac myocytes would suppress myocardial contractility, β-blockers may not be suitable for patients with decompensation or pre-existing myocardial dysfunction. Maintenance of cardiac output in such patients depends partly on increased sympathetic drive . AlthougCurrent treatments also focus on strategies that use selective HR-lowering agents, such as ivabradine, in patients with CHF –33. A prIn the CDT, cardiac remodeling and dysfunction were markedly prevented Fig.  comparedAs per protocol, a primary endpoint of 160-day all-cause death was evaluated  autonomic nervous balance , 43 and In this study, an extensive MI-induced CHF rat model was used in consideration of the precarious clinical condition of patients with severe CHF with MI and requiring hospitalization. However, the experimental animals were young and may have had a reserve of autonomic function that could be adjusted by various therapeutic interventions. In contrast, patients with severe or end-stage CHF may have limited responsive capacity. In addition, because clinical trials are usually conducted in patients of CHF with various pharmacological treatment backgrounds, it would be difficult to determine the performance of single-drug treatment. It may be an important factor in translating this basic study outcome to the clinical studies. Since we did not assess brain tissue to specify the central action site of donepezil, an exact mechanism for the cardioprotective effect of centrally administered donepezil remains unclear. Direct evidence for the increased vagal efferent activity during central donepezil microinfusion awaits further studies.Central microinfusion of donepezil seemingly reproduced the cardioprotective benefits exerted by oral administration that were previously observed in CHF rats. Although the findings of the current study leave far more uncertainty regarding the mechanisms of donepezil’s benefits, it is probable to conclude that pharmacologically increased central ACh levels may restore the balance of autonomic function, which involves the regulation of inflammation. Therefore, we propose that the central modulation of autonomic function by donepezil is a potential novel therapeutic strategy for patients with CHF.


Different definitions have been proposed to categorize hypertension. We aimed to investigate the difference in prevalence of measures associated with hypertension according to the American College of Cardiology/American Heart Association (ACC/AHA) criteria versus Joint National Committee 7 (JNC7) criteria.We analyzed the data of 10,000 participants of Yazd Health Study (YaHS) aged 20–69 years. Blood pressure was measured three times with standard protocol defined by ACC/AHA. Prevalence of high blood pressure measure was compared in both definitions and absolute differences reported.n = 7887), 55.1 and 22.7% had high blood pressure measure by ACC/AHA and JNC-7 guidelines, respectively. From JNC7 to ACC/AHA, the overall difference in unawareness about HTN increased by 32.4%.The prevalence of high blood pressure in our measurement was 61.0% according to ACC/AHA, and 28.9% according to JNC 7. The prevalence of self-reported hypertension was 18.6%. Age and sex standardized prevalence rates of high blood pressure measure indicates a 2.4-fold increase in the prevalence rate (30.1% absolute difference) by the ACC/AHA guideline. While the prevalence increased in all age groups, the age group of 20–29 showed the highest relative increase by 3.6 times (10.6% vs. 38.1%). High blood pressure measure among people with diabetes increased from 45.8 to 75.3% with the ACC/AHA guideline. Of the people who had no past history of diagnosed hypertension (Prevalence of hypertension associated measures increased over two folds by using the ACC/AHA criteria compared to JNC 7. Also, change in the criteria, reduces awareness of the disease and increases uncontrolled hypertension respectively. More research is needed to determine if the new definitions can affect management of hypertension in societies. Considering local priorities and implication of cost effective may improve implementation of new definitions for hypertension in different countries. Hypertension (HTN) is a global public health crisis; it is the most important risk factor for people with cardiovascular disease, which is one of the main causes of death and life lost in the world . The preIn 2017, the American College of Cardiology/American Heart Association (2017 ACC/AHA) guideline introduced a new classification for high blood pressure in adults which was a change in the clinical hypertension guide since 2003. In the ACC/AHA definition, with a decrease of 10 mmHg, the systolic blood pressure ≥ 130 and diastolic ≥80 mmHg are considered hypertension. In this guide, instead of the “pre-hypertension” category, a new group named “elevated hypertension” has been introduced . AccordiDue to the difference in the prevalence of the disease in different regions, this new approach has prompted researchers to update their findings from surveillances of hypertension. Muntner and colleagues show that the prevalence of hypertension among Americans over 20 years of age increases by 14.7%, according to the ACC/AHA definition . AnotherThe purpose of this study was to estimate the prevalence of hypertension associated measures in a large number of adults in an Iranian population according to the new guidelines (ACC/AHA 2017) and compare it with the old definition (JNC 7). The difference between the two guidelines in the prevalence of hypertension associated measures is a guide for health managers to revise intervention programs for disease control accordingly.Yazd Health Study (YaHS) is a prospective cohort study conducted since 2014 to determine determinants of non-communicable disease and related risk factors in Yazd Greater Area which is located in the center of Iran. Details of YaHS have been published elsewhere . Brieflyhttp://www.yahs-ziba.com. At the physical examination, three blood pressures (BP) were measured by trained and certified person at home visit (out-of-office method) using standard method with appropriate cuff sizes for participants’ arm [A valid questionnaire was completed at home visits. In follow-up, the final overall response rate was 98%. The previous history of HTN diagnosis by a physician was documented according to self-report. Self-reported hypertension has been recorded with a positive answer to the question, “have you ever been told by your physician that you have high blood pressure?” An English version of the YaHS questionnaire has been published elsewhere . Also, ints’ arm . Blood pnts’ arm , 18, 19.Measured BP was classified into normal, pre-hypertension, hypertension stage-1, and hypertension stage-2 by Joint National Committee (JNC 7) classification for adults . The 2012 in kg/m2 and was categorized to; underweight, normal, overweight, and obese according to the World Health Organization (WHO) cut-off point’s recommendation [Body Mass Index (BMI) calculated as weight/heightendation .p-value less than 0.05 were considered statistically significant.Mean BP level values ±standard deviations (SD) were calculated by demographic data and past medical history. The prevalence of hypertension associated measures was described as proportions with 95% confidence intervals (CI). Age-standardized prevalence rates were calculated using the direct method according to 2016 Yazd population census. The absolute differences in prevalence of high blood pressure measures according to guidelines were calculated separately. A chi-square test was used to detect the significance of change. All statistical analyses were performed using SPSS version 16 software. A The research proposal was approved by the ethics committee of Shahid Sadoughi University of Medical Science, Yazd, Iran No: IR.SSU.MEDICINE.REC.1396.311. The study was explained to all respondents willing to participate. All participants had the right to withdraw from the study at any time. Informed consent was obtained from each participant before data collection. Participants with new diagnostics of hypertension were advised to refer their health center or physician for the follow-up.n = 7887), 22.7 and 55.1% had high blood pressure by JNC-7 and ACC/AHA 2017 guidelines, respectively who were not aware of their illness and were not being treated.In this study, the blood pressure of 9861 adults was measured three times. Of total, 18.6% had self-reported hypertension. The crude prevalence of high blood pressure associated with HTN according to JNC 7 guideline was 28.9% (CI 95%: 27.9–29.7), and according to the ACC/AHA 2017 was 61.0% (95% CI: 60.1–62.0%); an absolute increase of 32.1%. Age and sex standardized prevalence rates of high blood pressure was 21.6 and 51.7% according to JNC7 guideline and ACC/AHA 2017, respectively. This indicated a 2.4-fold increase in the prevalence rate accordingly (30.1% absolute difference). Of the people who had no past history of hypertension (Two-thirds of men have blood pressure measure in the range of HTN according to ACC/AHA guideline (compared to 32.5% according to the previous classification). This increased absolute prevalence is higher in men compared with women (35.0% vs. 29.5%). With aging, the prevalence of hypertension associated measures increased, but the highest absolute increase was seen in the group 40–49 years old with the ACC/AHA definitions (35%). In the age of 20–29 years, the prevalence of high blood pressure measurement increased approximately 4 times (10.6% vs. 38. 1%).With the ACC/AHA definition, about 69% of obese people have high blood pressure by ACC/AHA 2017 guideline, compared with 38.6% by JNC 7. With the new guideline, three out of four diabetic patients were in the hypertensive group, which shows an absolute increase of 30%  which corresponds to pre-hypertension in the previous definition were associated with hypertension-stage 1. For diastolic blood pressure, this difference was 33.7%.Mean systolic and diastolic BP in the population were 126.5 ± 18.4 mmHg and 80.2 ± 12.5 mmHg, respectively. Men had higher mean systolic and diastolic BP than women in the study participantsTable The 2017 ACC/AHA guideline was associated with an increase in most of the HTN categories in our study. Men had a higher absolute increase in prevalence than women. A similar increase was observed for hypertension stage 1 and 2 for both sexes. But the increase in hypertension-stage 2 was higher in men than in women (22.1% vs. 17.1%). Table About 60% of the study populations had blood pressure associated with HTN according to AHA/ACC guideline, about twice the prevalence by JNC-7 threshold, however the ratio of men to women with hypertension remains almost the same according to either guideline (1.3 vs. 1.2). More than half of the participants with hypertension who did not have any history of diagnosed hypertension will have high blood pressure according to the ACC/AHA guideline. High blood pressure was more prevalent among males and those with lower education and higher BMI.In a study by Esteghamati et al. a similar hypertension prevalence of 25.6% among Iranian adults according to JNC-7 criteria was reported . HoweverAccording to the AHA/ACC guideline, the prevalence of high blood pressure increased in all age groups but the difference was more prominent in younger age groups in our study. This should not be mixed-up with indication to treatment, as the pharmacologic management of hypertension in the elderly population is the main expected change according to the ACC/AHA guideline. Among those 60–69 years old, 78% had high blood pressure according to ACC/AHA guidelines in our study; this was 51% according to JNC-7. The difference between these two figures may indicate the need for mass medications in the population. While JNC-8 guidelines were considered an easier standard for treatment in those older than 60 years compared to JNC-7,  the ACC/The prevalence of high blood pressure among patients with diabetes in our study increased with the ACC/AHA guidelines from 45.8 to 75.3%. However, any benefit from the intervention in a larger population from this new classification remains questionable. The American diabetes association still recommends blood pressure threshold of 140/90 mmHg for initiation of pharmacologic therapy which does not agree with the general target of 130/80 for diabetic patients . While oHigh blood pressure according to the ACC/AHA guideline does not mean an indication for pharmacotherapy. Three months’ trial of lifestyle modification is needed for most of those labeled ‘hypertensive’ according to the new guidelines . AlthougAlthough the AHA/ACC updated its threshold for HTN, many other American and European associations have not updated their guidelines accordingly. European Society of Cardiology and European Society of Hypertension in their updated guidelines defined hypertension the same as JNC-7 . ‘AmericThere is controversy about the negative effects of labeling patients with hypertension. Some studies have reported negative outcomes including distress and higher levels of physical symptoms, increased work absenteeism and lower health-related quality of life, –34 whileIn addition to changing hypertension definition, ACC/AHA guidelines lowered targets for blood pressure management, especially in older population. Pharmacotherapy for lowering blood pressure below 130/80 mmHg is now recommended in general population. This may have significant impact, especially in older population. It should be noted that JNC 8 panel members report increased target of blood pressure therapy in those older than 60 years to 150 mmHg which is 20 mmHg higher than current recommendation.In the past decades, despite an increase in the prevalence of hypertension, control of this condition was improved in the United States . Using tAlthough there is controversy about the new definition of hypertension among medical authorities around the world, the threshold of normal blood pressure and recommendations for medical treatment is much more similar. Different terms for describing hypertension levels such as “elevated”, “pre-hypertension” and “stage 1 hypertension” may cause confusion for providers and patients. The use of similar and equivalent terms can simplify the doctor-patient communication and facilitate the analysis of public health trends over time. Non-medical management of high blood pressure should be tailored to the culture of local communities and not necessarily limited to the specific terms for describing high blood pressure.This is a cross-sectional study with three consequent BP measurements with 5 min’ interval. Although measuring blood pressure in two occasions was recommended to label patients with hypertension, we only measured blood pressure in 1 day for this study due to the large sample size and logistic issues. However, we tried to increase accuracy by repeating the measurement and report the average of the last two times similar to other large epidemiologic studies. Inter-observer differences in measuring blood pressure can lead to misclassification. However, our interviewers were trained in practical courses and digital calibrated sphygmomanometer was used with minimum interpretation by the interviewers.This study shows that the ACC/AHA guideline puts the blood pressure of a significant proportion of adults in the range of hypertension. This public health problem calls for more comprehensive interventions to prevent and control hypertension. Changes in HTN definition may prompt people to change their lifestyles sooner and further investigation into the initiation of medical treatment is warranted. In addition, differences in the prevalence of cardiovascular risk factors, unhealthy lifestyle, and health care systems in countries should be considered in determining cut-off points for initiating treatment. Prospective research is useful to evaluate the effect of this change in the guideline on the rate of uncontrolled high blood pressure complications.


In the past few decades, swimming became one of the most important physical activities within the health system and is considered a practical nonpharmacological approach to managing of type 2 diabetes (T2DM), hyperlipidemia, hypertension (HTN), and obesity. The current study aimed to assess the effect of long-term swimming sessions on glycemic and lipidemic parameters, hemodynamic responses, body fat percent, and body mass index for patients with metabolic risk factors from Palestine.Forty participants from both genders with T2DM and HTN (aged 52.4 ± 5.5 yrs) agreed to participate in this quasi-experimental study and were divided into two groups. The first group included the participants who performed long-term swimming sessions and the second group served as the control. The first group exercised for 2 h, 3 times/week in 29–33 °C swimming pool temperature for 16 weeks. Simultaneously, the control group did not participate in any exercise and advised them to keep on with their everyday lifestyle. All the obtained metabolic syndrome risk factors data were analyzed using a two-way ANOVA analysis of variance (2*2) which was applied to determine the differences according group, time, and interaction.p < 0.05 in the variables of Total Cholesterol (TC), High Density of Lipoprotein (HDL), Low Density of Lipoprotein (LDL), Triglycerides (TG), Blood Glucose (BG), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Body Mass Index (BMI), and body fat percent according to group, time, and interaction for the experimental group.The results showed that there were statistically significant differences at The findings of the current study suggested that the regular 16 weeks of swimming sessions could be considered nonpharmacological approaches in managing T2DM and HTN. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by long-lasting hyperglycemia, which mainly occurs due to disturbances in insulin action, insulin secretion, or both . Long-laHypertension (HTN) is another chronic metabolic disorder, characterized by the elevation of systolic and/or diastolic blood pressure, which can be associated with lethal complications such as heart failure and stroke . The WHOAnother metabolic disease that is threatening humanity is hyperlipidemia, in which lipids, fibrous plaques, calcium, and cholesterol can accumulate on the walls of the blood vessels. Lipid deposits can build up and result in narrowing and hardening of the arteries. Consequently, tissues and organs would not receive enough blood to function correctly. If arteries that supply the heart with blood are affected, this accumulation can narrow the blood vessel and reduce blood flow and oxygen to the heart’s muscle, which can cause angina pectoris . SimultaDue to DM’s harmful complications on blood vessels, HTN may occur in many diabetic patients, especially those suffering from uncontrolled blood glucose levels . TherefoAccordingly, these chronic diseases must be carefully treated, and the related medical conditions require appropriate management because pathological and mental health problems may increase the risk of developing many major public health diseases, which may contribute to premature death. Lifestyle modification and glucose- and blood pressure-lowering medications are provided to keep glucose and atrial blood pressure levels close to normal .One of the essential points for improving lifestyle is the continuous practice of physical exercises that significantly improve blood circulation, metabolic processes, and other physiological functions .Swimming is one of the safest and gratifying methods of aerobic physical exercise . In the Many scientific data described the effects of swimming and other types of aerobic physical fitness on diabetes, cardiovascular, and respiratory systems responses, and their effects on the serum lipid profile, body fat percentage, and muscle mass in subjects with T2DM –23.To the best of our knowledge, investigations that describe the effects of long-term swimming sessions among patients suffering from T2DM and HTN as comorbid in Palestine are missing from the literature. Therefore, more information to evaluate the effects of regular long-term swimming procedures on blood glucose level, blood lipid profile, blood pressure, body mass index, and body fat percent in T2DM and HTN patients is required.Therefore, this study investigates the outcomes of 16 weeks of swimming sessions on blood pressure levels, glycemic responses, lipid profiles, body mass index, and body fat percent in patients with T2DM and HTN compared with a control group suffering from these disorders without swimming sessions.n = 20) were divided equally into two groups, experimental and control, and for women. The first group included the participants who performed long-term swimming sessions and the second group served as the control. The control group did not participate in any exercise and advised them to keep on with their everyday lifestyle.Forty patients (twenty women and twenty men with age 52.35 ± 5.5 yrs) diagnosed with T2DM and HTN from the employees of An-Najah National University were included in the current study. The study was conducted on a purposive sample consisting of two groups , while blood pressure was measured utilizing a mercury sphygmomanometer . Moreover, the researchers calculated the body mass index and fat mass percent before and after finishing the current study. The capillary glycaemia and blood pressure measurements were taken before and after 10 min of each swimming session. All participants provided the researchers with their biochemical laboratory analysis data for TG, TC, LDL, and HDL before starting and after finishing the current experiment. However, these biochemical analyses were performed in accordance with the standard biochemical procedures and protocols. The biochemical analysis was carried out in a certified medical laboratory  by certified and trained laboratory technologists with experience in the use of automated analyzers. For every automated machine, daily quality assurance checks were conducted in accordance with the manufacturer’s recommendations.The study protocols, aims, and the informed consent forms were approved by the Institutional Review Board (IRB) at An-Najah National University (IRB archived number 3.7.2019). The study was conducted in accordance with the requirements of the declarations of Helsinki. A written informed consent obtained from all the participants before they entered in current study. Participants were not offered any incentives and they were able to withdraw from the study at any time. Data obtained was kept confidential.p < 0.05.Means and standard deviations were utilized as descriptive statistics. Two-way ANOVA analysis of variance (2*2) was applied to determine the differences according to group, time, and interaction. The effect size was determined by using partial eta squared. No abnormal distributions were noticed in pretests according to Shapiro- Wilk results for both groups. Data were analyzed by using Statistical Package for the Social Sciences (SPSS) version 20  program, and the level of significance was fixed at p < 0.05 on all of the studied variables according to group, time, and interaction. However, in the case of group , in favor of the experimental group, there were significant differences at p < 0.05 on the posttest of the TC, HDL, LDL, TG, BMI, body fat percent, BG, SBP and DBP variables. On the contrary, no significant differences were found at p < 0.05 on the pretests of all variables between the experimental and control groups. Concerning the comparison between pre- and post-tests, the findings of the present study showed that there were statistically significant differences at p < 0.05 in all of the variables  in favor of posttests in the experimental group. Regarding the control group, no significant differences were found at p < 0.05 between the pre- and post-tests of all variables. In the case of interaction (group* time), there was statistically significant interaction at p < 0.05 for all of studied variables in favor of the post tests for the experimental group.As depicted in Table Regular physical exercises are associated with a decrease in mortality and the risk of developing various cardiovascular diseases. Physical exercises have also been found to slow aging, reduce physiological dysfunctions, and decrease DM complications by improving endurance, metabolism, muscle strength, circulation, and decreasing body fat mass , 25. Besp < 0.05) with effect size of partial eta squared were 43.7, 21.1, 39.8, 55.7, 11.5, 13.2, 12, 15.5, and 14.7%. While, no significant difference was found at p < 0.05 on the pretest of all studied variables compared to the control group.In the current study, the statistical analysis results between groups  showed that the TC, HDL, LDL, TG, BMI, body fat percent, BG, SBP and DBP variables on the posttest were significantly improved (p < 0.05) in all conducted variables  in favor of posttests in the experimental group, as the effects size of partial eta squared were 32.7, 29.6, 31.1, 48.8, 15.8, 22.9, 34.8, 27.3 and 27.9%, respectively. Whereas, no significant differences were found at p < 0.05 between pre- and post-tests of the studied variables in the control group.Moreover, comparing the pre- and post-tests results, the findings of this study showed that there were statistically significant differences (p < 0.05) for all of studied variables. However, the value of HDL in the post test for patients  was significantly the greatest compared to these values of pretest (for patients in both groups) and the post test for patients of the control group, as the effects size of partial eta squared was (27.3%). Furthermore, the values of posttest for the variables  among patients  were significantly the lowest in comparison with these values of pretest for patients in both groups and in the post test for patients (control group), as the effects size of partial eta squared were 35, 32.8, 49.4, 15.1, 20.6, 21.7, 16.7 and 16.5%, respectively.In addition, in the case of interaction (group* time), there was statistically significant interaction , and heart rate monitoring parameters for a more extended with a larger sample size.p < 0.05) between pre and post-tests in blood glucose levels, lipids profiles, BMI, body fat percent, and arterial blood pressure readings for individuals with T2DM and HTN. No significant differences were found at p < 0.05 between pre and post-tests for all studied variables in the control group for both genders. Therefore, this kind of exercise can a useful therapeutic tool for patients with T2DM, HTN, hyperlipidemia, obesity, and overweight. This is a clinically crucial finding since a continuous swimming program can be highly recommended for individuals with HTN and T2DM. Besides, it can be useful for individuals with obesity, overweight, and hyperlipidemia.Sixteen weeks of regular swimming sessions resulted in significant reductions (


Non-dipper blood pressure (NDBP) is one of the important causes of hypertension-related target organ damage and future cardiovascular events. Currently, there is no practical tool to predict NDBP pattern.The aim of this study was to investigate the relationship between aortic arch calcification (AAC) on chest radiography and NDBP pattern.All patients referred for ambulatory BP monitoring test were approached for the study participation. NDBP was defined as the reduction of ≤10% in nighttime systolic BP as compared to the daytime values. AAC was evaluated with chest radiography and inter-observer agreement was analyzed by using kappa statistics. Univariate and multivariate logistic regression analysis was conducted to assess the association of AAC and NDBP pattern. A 2-tailed p-value < 0.05 was considered statistically significant.A total of 406 patients (median age: 51.3) were included. Of these, 261(64%) had NDBP pattern. Overall, the prevalence of AAC was 230 (57%). Non-dipper group had significantly higher prevalence of AAC  as compared to the dipper group. Presence of AAC was a strong and independent predictor of NDBP pattern  in multivariate analysis.Presence of AAC on plain chest radiography is strongly and independently associated with the presence of NDBP pattern. Moreover, ABPM is superior to office BP measurements in predicting cardiovascular risk.6 However, utilization of ABPM to unselected population is not practical and currently, there is no practical tool to predict NDBP pattern.Hypertension (HT) is the most common cardiovascular disease and it is the leading cause of cardiovascular mortality and morbidity. Blood pressure (BP) follows a circadian pattern with a nocturnal decline of %10 or more as compared with daytime BP. Non-dipper BP (NDBP) pattern is defined as the absence of normal nocturnal decline in BP as compared to daytime measurements. NDBP pattern is associated with disease severity, left ventricular hypertrophy (LVH), proteinuria, secondary forms of HT and insulin resistance.8 Vascular calcification plays an important role in the development of arterial stiffness.10 Accordingly, aortic arch calcification (AAC) has been shown to be closely related to arterial stiffness.12 Thus, we hypothesized that AAC on chest radiography predicts NDBP pattern.NDBP pattern has shown to be associated with arterial stiffness.All patients who were referred for ABPM test were approached for the study participation. Indication for ABPM test was left to physician discretion. Following inclusion criteria, we applied: 1) Age ≥ 18-years-old; 2) A valid measurement rate of >85% during the ABPM test. Nighttime workers, patients with inadequate chest x-ray, pregnancy or suspicion of pregnancy, history of moderate to severe cardiac valve disease, malignancy, cardiac or thoracic surgery, coronary artery, cerebrovascular and peripheral vascular disease were excluded from the study. Posterior-anterior (PA) chest radiography and transthoracic echocardiography were performed in all patients. Eligible subjects underwent a comprehensive assessment, including documentation of medical history, physical examination and measurement of laboratory variables. Body mass index was calculated as the weight in kilogram divided by height in square meter. Diabetes was defined as being on treatment with insulin or oral anti-diabetic drugs. HT and hyperlipidemia were defined as the use of anti-hypertensive drugs or lipid-lowering drugs, respectively. The institutional ethics committee approved the study protocol. Patients were divided into two groups according to circadian BP pattern; non-dipper and dipper group.ABPM studies were carried out using a Mobil-O-Graph  monitoring device. The first hour was discarded from the analysis. BP readings were obtained automatically at the 30-min interval and if >85% of the measurements were valid then it was included in the analyses. Daytime, nighttime and 24-hour BP data and the percentage of the decrease in nighttime systolic BP vs. daytime systolic BP were recorded. The default setting for daytime (07:00 to 23:00) and nighttime (23:00 to 07:00) hours were modified appropriately based on the patient’s feedback. NDBP pattern was defined as the reduction of ≤ 10 % in nighttime systolic BP as compared to the daytime systolic BP.13  was acquired with the patient standing up . The focus-patient distance was 150 cm. An automated exposure control with a fixed tube voltage of 117 kV was used. We noted the presence of calcification in the aortic knob. AAC was graded as follows: Grade 0, no visible calcification; Grade 1, small spots of calcification or thin calcification; Grade 2, one or more areas of thickened calcification, and Grade 3, circular calcification on the aortic knob13 . One hun14A venous blood sample was collected from each participant under fasting conditions. Fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and creatinine were measured by standard laboratory methods. Glomerular filtration rate (GFR) was calculated using CKD-EPI Creatinine Equation.3 - LVEDD3)]} + 0.6.15 Left ventricular mass index (LVMI) was calculated by dividing the LVM by body surface area. LVH was defined as LVMI > 115 g/m2 for men and 95 g/m2 for women.16 Based on relative wall thickness (2 x PWT/LVEDD) and the presence or absence of LVH various types of the left ventricular geometrical pattern were defined .All patients were examined in the left lateral decubitus position using by a commercially available system  with a phased-array 3.5-MHz transducer. The conventional M-mode and B-mode parameters were measured in accordance with the American Society of Echocardiography guidelines. Left ventricular end-diastolic (LVEDD) and end-systolic (LVESD) diameters, and posterior (PWT) and septal (IVST) wall thicknesses were measured. Left ventricular ejection fraction was measured by using the Teichholz method. Left ventricular mass (LVM) was calculated using the Devereux equation: LVM = 0.8{1.04[([LVEDD + IVST +PWT]Continuous variables were expressed as mean (standard deviation) or median (interquartile range (IQR)), and categorical variables as number (percentage). The distributions of the continuous variables across the study groups were tested with the Kolmogorov-Smirnov test. Normally distributed data were compared using the Independent Samples t-test and data with non-normal distribution were compared using the Mann-Whitney U test. Categorical data were compared using the chi-square or Fisher’s exact tests when needed.Univariate and multivariate logistic regression analyses were conducted to assess the association of AAC and NDBP pattern. In multivariate regression analysis (Enter method), the effect size was adjusted for variables with a univariate significance level of < 0.1. Adjusted odds ratios (OR), along with their 95%CIs were presented. A 2-tailed p-value < 0.05 was considered statistically significant. All statistical analyses were performed using the IBM SPSS software A total of 406 patients  were included. Two hundred sixty-one (64%) had NDBP pattern and classified as non-dipper group. The remaining 145 (36%) patients who had dipper BP pattern were classified as dipper group. As compared to the dipper group, the non-dipper group was older (p < 0.001), had higher LVMI (p = 0.007), prevalence of LVH (p = 0.013), prevalence of HT (p = 0.049) and higher serum triglyceride level (p = 0.013). GFR was significantly lower in the non-dipper group (p < 0.0001). Groups were similar with respect to the remaining baseline characteristics shown in There was no difference in daytime DBP, 24-hour SBP and 24-h DBP values between non-dipper and dipper groups. However, daytime SBP was lower in non-dipper groups (p = 0.012). In addition, nighttime SBP (p < 0.0001) and DBP (p < 0.0001) values were significantly higher in non-dipper group .Prevalence of AAC was 57% in our study population. Non-dipper group had significantly higher prevalence of AAC (grade ≥ 1) on chest radiography (p < 0.0001) as compared to the dipper group .Age, body mass index, female gender, HT, GFR, LVMI, presence of LVH, LV geometric pattern of concentric hypertrophy and AAC were associated with the presence of NDBP pattern in univariate logistic regression analysis with a p-value of less than 0.1 . Of thes6 In this study, the presence of AAC on chest radiography was a strong and independent predictor of NDBP pattern.NDBP pattern is one of the important causes of HT-related target organ damage and future cardiovascular events.19 Patients with NDBP pattern are at high risk for target organ damage including myocardial infarction, LVH, carotid artery disease, chronic kidney disease and stroke.20 In the Ohasama study, impaired nocturnal BP decline was associated with cardiovascular mortality.21 Each 5% decrease in the decline in nocturnal BP was associated with an approximately 20% greater risk of cardiovascular mortality. Importantly, this association was observed not only in hypertensive, but also in normotensive individuals.21 Moreover, cardiovascular mortality and morbidity can be reduced by achieving a better nocturnal BP control.22 Thus, effective treatment of HT should include nighttime BP control as well. Currently, ABPM remains the only method for the diagnosis of nocturnal BP variations. Unfortunately, it is relatively expensive, inconvenient for routine usage and not widely available tool. Yet, it may not be practical to perform ABPM in every hypertensive patient. A practical and inexpensive tool may help the filtration of the unselected population for ABPM. Here, in this study, we have shown that AAC on plain chest radiography, an inexpensive and widely available tool, has a strong predictive ability for NDBP pattern.Diagnosis of HT is generally based on daytime office BP measurements, and nighttime BP and NDBP are usually overlooked in clinical practice. However, the association of nighttime and NDBP with HT-related target organ damage is more powerful than daytime BP.23 Melatonin plays a pivotal role in the regulation of nocturnal BP.26 Autonomic nervous system activity is involved in the control of the circadian variation of BP28 and impaired sympathovagal balance with increased sympathetic nervous activity and/or decreased vagal activity has been documented in non-dippers.30 Melatonin shifts the balance between the sympathetic and parasympathetic system in favor of the parasympathetic system. It may also reduce nighttime BP by its direct arterial vasodilator effect.25 Accordingly, exogenous melatonin has been shown to reduce nighttime BP.32 Thus, a reduced melatonin secretion during nighttime may significantly impair nocturnal BP decline. Second, AAC is closely related with vascular stiffness and loss of arterial compliance33 which in turn may impair arterial relaxation capacity. An impaired nocturnal decrease in BP was found to be independently associated with aortic stiffness in patients with nocturnal HT.34 Moreover, it has been found that increased arterial stiffness is more associated with nighttime BP load than day time BP.35 Third, the relationship between arterial BP and arterial calcifications is likely a bidirectional phenomenon. Increased arterial BP load may facilitate arterial calcification and vice versa. Non-dippers are exposed to an abnormal the nocturnal BP load which may accelerate arterial calcification and stiffness. Fourth, the underlying clinical profile of the patients with impaired nocturnal BP decline and arterial calcification are similar. Both conditions are associated with age, renal diseases, diabetes, sleep apnea, autonomic dysfunction, malignant HT and coronary artery disease.37There are several possible mechanisms that may explain the relationship between AAC and NDBP pattern. First, AAC was found to be strongly correlated with pineal gland calcification which may reduce melatonin secretion during sleep.NDBP pattern is associated with disease severity and a higher risk of subsequent cardiovascular events. This risk can be reduced by achieving better dipping patterns and nocturnal BP levels. In clinical practice, many patients with controlled daytime BP levels are not evaluated for the nighttime BP levels. Our results may help to improve detection of NDBP pattern and nocturnal HT. Appropriate treatment of these patients by changing antihypertensive medications or administering the antihypertensive medications in the night may eventually help to improve dipping pattern and patient outcomes.40 In this study, we showed that there is also a strong association between AAC and NDBP. Further studies are needed to confirm our findings and to evaluate the potential association of AAC with other hypertensive subforms.Both AAC and NDBP are associated with several HT-related target organ damage and future cardiovascular events in patients with HT.This study has several limitations. The small sample size is the main limitation. Our definition of NDBP pattern was based on systolic BP variations. Although this is the most commonly used definition of NDBP, diastolic BP values may also be used to assess NDBP. We did not study autonomic nervous system activity or vascular stiffness parameters to explain the potential mechanistic link between AAC and NDBP. Finally, we did not study the association of AAC with cardiovascular events.Presence of AAC on plain chest radiography is strongly and independently associated with the presence of NDBP pattern. Routine use of this simple and inexpensive tool in clinical practice may have additional benefits in the detection and control of the nocturnal BP. Moreover, this tool may help to use of ABPM devices more precisely, which may reduce healthcare cost.


Background and objectives: There has been an increasing interest in the role of inflammation in thrombosis complications in chronic heart failure (HF) patients. The incidence of thrombosis in HF has been shown to be the highest in patients classified as NYHA IV (New York Heart association). It is stated that inflammation is regulated by platelet-induced activation of blood leukocytes. We aimed to compare the platelet and cell count readings in chronic HF with reduced ejection fraction (HFrEF) patients according to NYHA functional class and to evaluate the correlation between those readings. Materials and methods: A total of 185 patients were examined. The results of heart echoscopy (TEE) testing; fibrinogen, N-terminal pro b-type natriuretic peptide (NT-proBNP), C reactive protein (CRP), and cortisol concentrations; complete blood counts; and a 6 min walking test were assessed and platelet aggregation was determined. Results: Mean platelet volume (MPV) increased with deterioration of a patient’s state (p < 0.005). Lymphocyte count and percentage were the lowest in the NYHA IV group (p < 0.005). Neutrophil and monocyte percentage and count were the highest (p < 0.045) in the NYHA IV group. Adenosine diphosphate (ADP)- and ADR-induced platelet aggregation was higher in the NYHA III group compared to NYHA II and I groups (p < 0.023). NYHA functional class correlated with mean platelet volume (MPV) , lymphocyte count , monocyte count , and percentage . CRP concentration correlated with NT-proBNP . MPV correlated with fibrinogen concentration . Conclusions: (1) MPV could be considered as an additional reading reflecting a patient’s condition, however the use of MPV to identify patients at risk of hypercoagulable state should be evaluated in more extensive studies; (2) increased neutrophil and monocyte counts could indicate a higher inflammatory state in chronic HFrEF. The inc < 0.01) . Venous  < 0.01) . VTE ris < 0.01) . Increas < 0.01) . DespiteThere has been a growing interest in the role of inflammation in thrombosis complications in CHF. The platelet’s involvement in the interplay between hemostasis, thrombosis and inflammation is important in disease occurrence . ChronicIt has been stated that inflammation processes are regulated by platelet-induced activation of blood leukocytes  . A mean While myocardial damage in heart failure patients with reduced ejection fraction (HFrEF) has been shown to be driven by oxidative stress, inflammation is a recognized factor in disease progression in both HFrEF and HFpEF (heart failure with preserved ejection fraction) . HoweverA total of 356 patients admitted to the Department of Cardiology of Kaunas Clinical Hospital of Lithuanian University of Health Sciences between 1 January 2016 and 1 March 2018 and diagnosed with CHF were screened for inclusion. The data for 185 patients diagnosed with chronic heart failure with reduced ejection fraction (systolic heart failure class I‒IV according to the New York Heart Association (NYHA)) who had not been taking any antiaggregants in the last two weeks and had experienced no other factors affecting platelets and had given written informed consent to participate were included in the study. The diagnosis of CHF was made following the guidelines for the diagnostics and treatment of heart failure approved by the European Society of Cardiology . Patientg for 15 min at room temperature. Platelet-poor plasma was obtained when the rest of blood was centrifuged at 1000× g for 30 min. Platelet aggregation was investigated in platelet-rich plasma using the aggregometer  with the standard Born method [The results of heart echoscopy (TEE) testing, fibrinogen and cortisol concentrations, complete blood counts, and a 6 min walking test were assessed and platelet aggregation was determined after the patients’ admission to the hospital. Blood samples for the complete blood counts and NT-pro BNP testing were taken from the forearm vein with a 20 G needle into 4.5 mL vacuum tubes with ethylendiamintetraacetic acid (EDTA) and for complete blood count testing were put into a COULTER LH 780 hematological analyzer . Blood for NT-pro BNP testing was centrifuged for plasma preparation and analyzed with a Tosoh AIA 2000 instrument . In order to investigate platelet aggregation, blood samples were taken from the forearm vein into 5 mL vacuum tubes with 3.8% sodium citrate. In order to prepare platelet-rich plasma, the blood was centrifuged at 100× n method ,17. BlooAll investigations were approved and conducted in accordance with the guidelines of the local bioethics committee and adhered to the principles of the Declaration of Helsinki and Title 45, U.S. Code of Federal Regulations, Part 46, Protection of Human Subjects . The study was approved by the Regional Bioethics Committee at the Lithuanian University of Health Sciences (No. BE-2-102).p values < 0.05 were accepted as statistically significant.For the statistical analysis, we used the Statistical Package for the Social Sciences (IBM SPSS 20) for Windows. Categorical variables were defined as percentages and comparisons were made using the chi-square test. Quantitative variables are expressed as means ± standard deviations, and for the comparison of variables between the groups Welch’s test (for the parameters showing the nonparametric distribution and to compare more than two groups) was used. The results were assessed using post hoc analysis. Correlation analyses were performed using a Pearson’s correlation test. Here, p < 0.015) patients. The 6 min walking test result decreased with the deterioration of patient state (p < 0.005). The mean BMI value for NYHA IV patients was lower than for NYHA I and II patients (p < 0.029). The SBP value was highest for NYHA I group patients (p < 0.015). The DBP value for NYHA IV patients was lower than in NYHA I group (p = 0.015). There were no differences in medications used by patients (The study population consisted of 185 patients with CHF (with left ventricular ejection fraction (LVEF < 50%)): 26 NYHA I patients, 78 NYHA II patients, 54 NYHA III patients, and 27 pa NYHA IV patients. The baseline characteristics of the CHF patients are shown in the patients . NT-proBp < 0.005). The mean lymphocyte count and percentage were the lowest in NYHA IV group . The neutrophil percentage in NYHA IV was higher than in NYHA III and I groups (p = 0.034). The neutrophil count in NYHA III group was lower than in NYHA IV (p = 0.028). The monocyte percentage and count in NYHA IV group was statistically significantly higher than in NYHA I group .A comparison of cell counts between the groups is shown in m) and evening cortisol (cortisole) concentrations between the patient groups. The cortisol concentration difference between the morning and evening concentrations (cortisolm-e) was statistically significantly lowest in NYHA IV group in comparison with NYHA III and NYHA I groups   .p < 0.023). The result for ADR-induced platelet aggregation was higher in NYHA III group than in NYHA I group , monocyte percentage , and monocyte and lymphocyte counts , lymphocyte count , monocyte count , and monocyte percentage , neutrophil count  and monocyte count  and with NYHA grouping . Monocyte percent correlated with NYHA . MPV correlated with monocyte percent , and monocyte count  (p = 0.00001). BMI correlated with NYHA and lymphocyte count and percentage  and monocyte count , PLT  and conversely correlated with lymphocyte percent and PLT .Data from the all patients were pooled to analyze the correlation between laboratory and clinical cell count readings. Patient age correlated with MPV  . Leucocyr = 0.277, p = 0.001). However, zero-order correlations showed that there was a statistically significant weak correlation between MPV and age , indicating that age had very little influence in controlling for the relationship between MPV and NYHA functional class.Despite the fact that there was no difference in age between the patient groups, age correlated with NYHA and MPV . Therefor = 0.175, p = 0.038 and r = −0.169, p = 0.044, respectively). Zero-order correlations showed that there was a statistically significant weak correlation between MPV and monocyte and lymphocyte counts , indicating that age also had very little influence in controlling for the relationship between MPV and monocyte and lymphocyte counts.A partial correlation was run to determine the relationship between an individual’s MPV and monocyte and lymphocyte counts whilst controlling for age. There was a weak partial correlation between MPV and monocyte and lymphocyte counts whilst controlling for age, which was statistically significant (p = 0.049) and LVEF . Morning cortisol concentration correlated with platelet aggregation, induced with ADR . CRP correlated with NT-proBNP, fibrinogen, and cortisole concentrations , fibrinogen concentration , CRP  , evening cortisol concentration , and CRP . Neutrophil percentage correlated with evening cortisol concentration . Lymphocyte percentage correlated with fibrinogen concentration , CRP , and evening cortisol concentration . Monocyte percentage correlated with fibrinogen concentration . Monocyte count correlated with morning cortisol, fibrinogen concentration , CRP , and PLT , lymphocyte percentage , and lymphocyte count  . NeutropIt was found that PLT, MPV, neutrophil and lymphocyte percentages, and neutrophil and lymphocyte counts weakly correlated with some drug usage .Platelets are presented as cellular mediators of inflammation and atherogenesis via interactions with leukocytes  and the endothelium . A stronWe found that mean MPV was the highest in the NYHA IV group. MPV increases with the deterioration of a patient’s state. Platelet aggregation induced by ADP and ADR was the highest in NYHA III group as compared to NYHA II and I groups. A weak correlation was found between MPV and fibrinogen concentration and a moderate correlation was found between MPV and NYHA grouping.Some studies ,22,23 haIt was shown that MPV results depend on the time elapsed from the venipuncture and should be done within 120 min after venipuncture . We inveIncreased levels of platelet activation markers in HFrEF patients in comparison with healthy controls have been reported in the literature ,25. The p = 0.001) in patients with AHF has been stated in the literature [A moderate correlation between MPV and PLT  in AHF patients [Some authors have found a moderate correlation between MPV and BNP concentrations  [It has been stated that heart failure (HF) patients have increased levels of soluble P-selectin and platelet-derived adhesion molecules , which i< 0.001)  are in ap = 0.036) [n = 27).We failed to find any work about platelet aggregation differences in chronic HFrEF groups according to NYHA. Mostly, platelet activation markers were compared only between all CHF and control groups, but not between NYHA groups. Increased platelet activity in chronic, stable HFrEF was reported in one study, while CD62P was higher in NYHA III–IV in comparison with NYHA I–II (= 0.036) . The aut= 0.036) . This waA strong fibrinogen correlation with PLT was described in coronary heart disease patients . CoagulaAlthough uric acid measurement was not directly the aim of our work, it is necessary to mention that uric acid is stated as being related to inflammation and platelet activation and enhanced pro-thrombotic stimulus in acute coronary syndrome patients . Some reIn conclusion, our results confirm a correlation between MPV and CHF patient condition and support a relationship between increased MPV levels and functional and hemodynamic parameters of disease severity. The correlations between fibrinogen concentration and MPV and between PLT and CRP support the low inflammation in chronic HFrEF patients and its relationship with platelets.Monocytes  and othep = 0.047) [Humans have three types of monocytes: Mon1 85%), Mon2 (6%), and Mon3 (9%). Mon1 has been shown to express cytokines, whereas Mon 2 produces anti-inflammatory IL-10. Mon1 numbers are increased during HF decompensation 5%, Mon2 . Mon3 pr= 0.047) . Patient= 0.047) . We foun= 0.047) ,43,49.p = 0.0002) and negatively correlated with LVEF  [A reason why different studies present conflicting results may be because of different subsets of monocytes being predominant in CHF groups . One wor= 0.022) . We founAdditionally, we found that monocyte count weakly correlated with PLT and moderately correlated with MPV and CRP. These correlations can be assumed as a relationship between inflammation and platelet production. In Charach’s work , it was The neutrophil count serves as an indicator for inflammation . NeutropHigh levels of CRP and of neutrophils have already been described in CHF patients. Levels of myeloperoxidase, which is a product of activated neutrophils, are excessive in CHF patients. It has been reported that myeloperoxidase levels were linked to functional indices of worsening heart failure , similarWe found that the mean neutrophil count and percentage were the greatest in NYHA IV group and moderately correlated with fibrinogen concentration and CRP. Some authors have found that in heart failure patients, the incidence was greater among people with higher neutrophil counts, and that the greater the neutrophil count was, the bigger the hazard ratio . TherefoLow lymphocyte count or low percentage of lymphocytes has been associated with patient mortality in CHF .m-e value was in NYHA IV. Evening cortisol concentration inversely correlated with lymphocyte percent. Cortisolm-e correlated with the lymphocyte count and percentage. All of these results support the knowledge about conditions of greater stress in chronic HFrEF and its influence on lymphocyte counts.In our work, the mean lymphocyte count was the lowest in the NYHA IV group and negatively correlated with NYHA grouping. Lymphocyte percentage negatively correlated with CRP, fibrinogen concentration, and evening cortisol concentration. Other authors have found that circulating lymphocyte subset Treg negatively correlated with BNP, LV chamber remodeling, and CRP , indicatWe found that CRP correlated with NT-proBNP. This finding suggests an association between neurohumoral activation and inflammation in the setting of HFrEF. In conclusion, the lowest lymphocyte count in NYHA IV and its negative correlations with NYHA grouping and evening cortisol concentration indicate a relationship between the disease severity and neurohormonal parameters, which had an influence on lymphocyte count. Therefore, lymphocyte count could be used as an additional marker for evaluation of a patient’s condition.Our study had some limitations. One of them was the small sample size. This might be why we did not observe a correlation between CRP and LVEF and NYHA functional class, or between MPV and PLT, which are described in the literature. The other limitation is the absence of healthy subjects or HFrEF groups that could help in defining pathological links.We did not measure the levels of inflammatory markers, such as TNF-α, IL-6, and others. Therefore, we could not compare those inflammatory factors. Additionally, we did not measure other platelet activation readings, meaning we can evaluate platelet activity only when we have platelet aggregation results.The range of CRP levels at enrollment was wide, and it was unable to adjust for confounding factors such as subclinical infection. Interpretation of the present results is limited because monocytes and lymphocyte phenotypes were not investigated. Different monocyte and lymphocyte subsets have distinct mechanisms. Therefore, their differences in different patient condition groups and relationships with platelet and inflammation markers remain to be investigated. However, the correlations we found may serve as reliable markers in the additional evaluation of chronic HFrEF severity.The main strength of our study was the broad age range of the population, without smoking or diabetes mellitus influencing platelet readings. The influence of medications on blood count and platelet parameters was evaluated too. Blood samples were collected at baseline and measured with standardized tests, allowing comparability with other studies. Standardization is particularly important for MPV measurement.In addition, this was an observational and nonrandomized study; it can be accepted as a prototype of further prospective and randomized studies to compare the effects of the blood cell counts on platelet and inflammatory readings in chronic HFrEF.To the best of our knowledge, this is the first work where blood cell count and platelet readings of MPV are compared between chronic HFrEF patient groups according to NYHA grouping, and in which the correlations between platelet, blood cell count, CRP, NT-proBNP, and cortisol readings were evaluated.We expanded understanding of differences between chronic HFrEF patients groups according to NYHA grouping. Our work revealed differences of platelet readings; platelet aggregation and MPV values; and blood cell monocyte, lymphocyte, and neutrophil counts in those groups, as well as correlations between platelet and inflammation readings. According to these findings we can state that: (1) MPV could be assumed as an additional reading reflecting a patient’s condition and that the idea that MPV values help in identifying patients at risk of hypercoagulable state should be evaluated in more extensive studies; (2) neutrophil and monocyte increases in HFrEF could indicate a higher inflammatory state in chronic HFrEF.


Home blood pressure monitoring has many benefits, even more so, in populations prone to high blood pressure, such as persons with diabetes.The purpose of this research was to validate the QardioArm mobile device in a sample of individuals with noninsulin-dependent type 2 diabetes in accordance with the guidelines of the second International Protocol of the European Society of Hypertension.The sample consisted of 33 patients with type 2 diabetes. To evaluate the validity of QardioArm by comparing its data with that obtained with a digital sphygmomanometer (Omron M3 Intellisense), two nurses collected diastolic blood pressure, systolic blood pressure, and heart rate with both devices.The analysis indicated that the test device QardioArm met all the validation requirements using a sample population with type 2 diabetes.This paper reports the first validation of QardioArm in a population of individuals with noninsulin-dependent type 2 diabetes. QardioArm for home monitoring of blood pressure and heart rate met the requirements of the second International Protocol of the European Society of Hypertension. Ultimately, devices that automatically measure blood pressure have gradually evolved to replace the standard mercury sphygmomanometer, as the risk of mercury toxicity outweighed any potential benefits of its use. Today there are a wide variety of devices capable of measuring blood pressure both in and outside of clinical environments -7.Among the advantages of home blood pressure monitoring are that it helps to detect white coat and masked hypertension; it is highly available at a low price; blood pressure measurements at home are taken in a more natural, relaxed, and domestic environment than when taken in the doctor’s office; patient convenience in blood pressure measurement ensures more commitment; repeated measurements can be easily taken, and it can be used over longer periods to assess the daily variability of blood pressure .But logically, it is a necessary requirement that these devices have been validated by standardized protocols, such as the European Society of Hypertension-International Protocol 2 (ESH-IP2) , the BriIf this validation is essential in the general population, it is even more important in at-risk populations, such as patients with diabetes, where reliability and accurate blood pressure measurement are essential to avoid the disease’s progression. Type 2 diabetes is a prevalent disease and represents a very serious social health problem; it has been seen to occur to a greater extent in older adults ,13. The This atherosclerotic disease is the main cause of morbidity and mortality in people with diabetes, and the one that contributes the most to the direct and indirect costs of diabetes ,17. In aFor all these reasons, correctly and validly measuring blood pressure in a person with diabetes is crucial. On one hand, blood pressure control has been shown to decrease the risk of diabetes-related complications such as microvascular and microvascular pathology ,22-25. OIn that regard, it has been proven that blood pressure control and the prevention of morbidity and related mortality could be improved in persons with diabetes ,8,16. HoOne of the great challenges is to avoid therapeutic inertia, as this would result in an unacceptable burden in terms of human lives, sequelae, and socioeconomic costs ,32.Therefore, we consider it highly relevant to evaluate the validity of automatic blood pressure measurements in persons with diabetes because of the high prevalence of hypertension in this specific population and its significant morbidity and mortality rate.The main goal of this study was to test the validity of the measurements of the QardioArm blood pressure monitoring device in individuals with noninsulin-dependent type 2 diabetes persons, in accordance with ESH-IP2 . We hypoWe performed an observational concordance study to validate the QardioArm device for measurement of heart rate, diastolic blood pressure, and systolic blood pressure, in individuals with noninsulin-dependent type 2 diabetes according to ESH-IP2  and STROThis research study received ethical approval (number 173/2019). This study respected the Helsinki Declaration . All parThe Omron M3 Intellisense  was used as the gold standard instead of a mercury sphygmomanometer, in this study, because it has been validated in the general population according to ESH-IP2 .The Omron M3 Intellisense device records heart rate in the range of 40 to 180 bpm and brachial blood pressure in the range of 0 to 299 mmHg using the oscillometric method; systolic blood pressure, diastolic blood pressure, and heart rate are shown on screen. The inflation system does not require pressure presetting or reinflation because of its technology, and deflation is automatically released by a pressure valve. It weighs approximately 340 g without batteries. The standard cuff fits arm circumferences ranging from 22 to 32 cm; it is also available in a large cuff to fit arm circumferences from 32 to 42 cm.The QardioArm (Atten Electronic Co) is an automatic home blood pressure measurement monitoring device. QardioArm is a blood pressure measurement system intended to assess heart rate, diastolic blood pressure, and systolic blood pressure in an adult population, for pulse rates in the range of 40 to 200 bpm and blood pressure in the range of 40 to 250 mmHg.This device utilizes an inflatable cuff that is wrapped around the upper arm, with circumferences ranging from 22 to 37 cm. The weight of unit is 310 g with batteries and its dimensions, when closed, are 140 mm×68 mm×38 mm. There is a freely downloadable app on the company’s website, Google Play, or the Apple App Store. A smart device with Android 4.4 (KitKat) or later, or Bluetooth 4.0 and iOS 7.0 or later, is required, being compatible with iPhone, iPod, iPad, Apple Watch, tablets, and smartphones. QardioArm also provides graphics to facilitate visual data interpretation on screen. This app may be configured by warnings and reminders, also measurements and progress may be shared in real time with clinicians and other users.All patients were recruited from Fresenius Medical facilities in Plasencia-Extremadura, Spain. The inclusion criteria were age greater than 25 years, gender (at least 10 men and 10 women), and recruitment blood pressure requirements according to the guidelines : 33 partThe exclusion criteria were having an arrhythmia or using insulin as treatment at the time of the study.Two nurses with experience in blood pressure measurement performed all assessments. The assessment room was a comfortable temperature without noise, distractions, or any factors that could have influenced the measurements .Birth date, gender, weight, and height of each participant were recorded, and the arm circumference was measured in order to ensure an adequate cuff size. Body mass index was calculated using the Quetelet index.The same assessment room was used for all participants. Each participant was seated in the assessment room, and the measurements were assessed after a period of 10 to 15 minutes of rest. Measurements by both units were taken on the left arm supported at the heart level, and a total of 9 consecutive measurements  were carried out alternating the Omron M3 Intellisense and the QardioArm in the following order: blood pressure A—entry blood pressure using the Omron M3 as standard device; blood pressure B—entry blood pressure using the Omron M3 as test device; blood pressure 1 by Omron M3; blood pressure 2 by QardioArm; blood pressure 3 by Omron M3; blood pressure 4 by QardioArm; blood pressure 5 by Omron M3; blood pressure 6 by QardioArm; and blood pressure 7 by Omron M3.During measurement, the patient remained quiet and calm, sitting placing the back straight maintaining the feet over the floor in parallel position without crossing their legs as well as resting the arm over a flat surface, with the hand palm upwards and the elbow in a slightly flexed position in order to place his fist at the height of its heart. The interval between one measurement and the next was 30 or 60 seconds .P>.05. Two-tailed independent t tests or Mann–Whitney U tests were used for parametric or nonparametric variables, respectively.Results are described as mean and standard deviation with range. Sociodemographic variables were examined using the Kolmogorov–Smirnov test to assess normality, and data were considered normally distribution if Device accuracy, following the ESH-IP2 , is baseFor each patient, systolic blood pressure measurements obtained from the QardioArm device  were compared with the systolic blood pressure measurements from the Omron device ; the comparisons which were favorable to the device were utilized. The same procedure was followed with diastolic blood pressure and heart rate measurements.Differences were separately classified for diastolic blood pressure and systolic blood pressure, depending on whether the difference was within 5, 10, or 15 mmHg  as well Results were analyzed and detailed according to ESH-IP2 requirements in order to determine if the device passed the validation protocol. Accuracy was determined by the number differences in these ranges for both individual measurements (part 1) and individuals (part 2). To pass, a device must meet the minimum pass requirements.Furthermore, Bland-Altman plots were utilized to quantify agreement between such systolic blood pressure, diastolic blood pressure, and heart rate by constructing limits of agreement .P=.05 with a 95% confidence interval.All analyses were carried out with SPSS statistical software . In all analyses, the threshold for statistical significance was P>.05, All the sociodemographic variables showed a normal distribution P>.05, . A samplParts 1 and 2 of the validation according to the ESH-IP2 for the QardioArm blood pressure are presented in Mean differences between the QardioArm and Omron M3 were 3.37 (SD 3.19) mmHg for diastolic blood pressure and 3.15 (SD 4.67) mmHg for systolic blood pressure.A total of 87/99 differences (89%) for systolic blood pressure and a total of 88/99 differences (89%) for diastolic blood pressure showed an absolute difference within 5 mmHg (ESH-IP2 criteria: at least 65 for diastolic blood pressure and at least 73 for systolic blood pressure). Furthermore, a total of 95/99 comparisons (96%) for systolic blood pressure and a total of 96/99 (97%) for diastolic blood pressure showed an absolute difference within 10 mmHg (ESH-IP2 criteria: at least 81 for diastolic blood pressure and at least 87 for systolic blood pressure). A total of 98/99 differences (99%) for systolic blood pressure and a total of 99/99 differences (100%) for diastolic blood pressure exhibited an absolute difference within 15 mmHg (ESH-IP2 criteria: at least 93 for diastolic blood pressure and at least 96 for systolic blood pressure). Part 1 of the validation was successfully completed since 2 or more of the 3 absolute difference ranges  for systolic blood pressure met the minimum requirements, and 3 out of 3 absolute difference ranges for diastolic blood pressure met the minimum requirements.A total of 32/33 patients (97%) for systolic blood pressure and a total of 29/33 patients (88%) for diastolic blood pressure showed a minimum of 2 out of 3 differences within 5 mmHg (ESH-IP2 criteria: at least 24 out of 33 patients for systolic blood pressure and at least 24 out of 33 patients for diastolic blood pressure). Nevertheless, 1/33 patients (3%) had 3 differences outside 5 mmHg for systolic blood pressure, though 0/33 patients (0%) had 3 differences outside 5 mmHg for diastolic blood pressure  showed an absolute difference within 3 bpm, a total of 96/99 comparisons (97%) showed an absolute difference within 5 bpm, and a total of 99/99 differences (100%) showed an absolute difference within 8 bpm. Thus, part 1 of the device validation was successfully completed for the heart rate.A total of 31/33 participants (94%) had a minimum of 2 of 3 comparisons within 3 bpm difference for heart rate. Nevertheless, a total of 1/33 participants (3%) had 3 differences greater than 3 bpm; therefore, part 2 of the device validation was successfully completed for heart rate, and consequently, part 3 of the QardioArm device validation was passed.Indeed, the QardioArm device met the validation criteria of the ESH-IP2 for heart rate, systolic blood pressure, and diastolic blood pressure for this sample of 33 individuals with noninsulin-dependent type 2 diabetes.The Bland-Altman plots show the differences between QardioArm and Omron M3 measurements for systolic blood pressure , diastolAs far as we know, this is the first study to validate an upper arm oscillometric wireless device connected to an app to measure heart rate and blood pressure in a population with noninsulin-dependent type 2 diabetes. QardioArm was validated in 2017 ,37 in thThe results of this study have shown that QardioArm device passed both parts of the validation  in patieWe have already seen the enormous advantages of home blood pressure monitoring, especially in specific populations prone to hypertension, such as persons with diabetes. Chronic diseases such as diabetes are one of the most common pathologies and have significant physical, psychological, social, and economic impacts ,28,29,32Nevertheless, we found very few studies analyzing the validity of automatic blood pressure monitors in a population with noninsulin-dependent type 2 diabetes, ,45-48, aOnly one study by Chahine et al  was founAnother important fact is that measurements of people with type 2 diabetes involve stiffer arteries; however, in our study this was not assessed, since it was not the main aim of this research.Finally, for future studies, consecutive sampling bias should be considered; a simple random sampling process might be more appropriate.Moreover, we consider that further validations are needed for devices that measure blood pressure in patients with noninsulin-dependent type 2 diabetes. In fact, a future line of research could be to specifically investigate the validation of this QardioArm device in patients with type 2 diabetes who have microarteriopathy as diabetic retinopathy, patients with type 1 diabetes as well as other populations with specific diseases such as pregnant women.QardioArm for home blood pressure monitoring showed validated measures of blood pressure and heart rate in individuals with noninsulin-dependent type 2 diabetes meeting the requirements of ESH-IP2. The findings of the study may be relevant since it is the first validation showing that a device linked to an app to measure blood pressure and heart rate met the requirements of the ESH-IP2 in noninsulin-dependent type 2 diabetes population.


All the selected clinical information and retinal vessel measures were used to develop different discriminative models for QDBS and PSIC using logistic regression. Discriminative efficacy and model performances were evaluated by plotting a receiver operating characteristic curve. As compared to QDBS, the PSIC patients had a lower incidence of insomnia problems  and a higher tortuosity index . Moreover, the area under the curve of the logistic model showed that its discriminative efficacy based on both retinal and clinical characteristics was 86.7%, which was better than the model that employed retinal or clinical characteristics individually. Thus, the discriminative model using AI-assisted retinal characteristic analysis showed statistically significantly better performance in QDBS and PSIC syndrome differentiation among stroke patients. Therefore, we concluded that retinal characteristics added value to the clinical differentiation between QDBS and PSIC.We aimed to investigate the efficacy of an objective method using AI-based retinal characteristic analysis to automatically differentiate between two traditional Chinese syndromes that are associated with ischemic stroke. Inpatient clinical and retinal data were retrospectively retrieved from the archive of our hospital. Patients diagnosed with cerebral infarction in the department of acupuncture and moxibustion between 2014 and 2018 were examined. Of these, the patients with Qi deficiency blood stasis syndrome (QDBS) and phlegm stasis in channels (PSIC) syndrome were selected. Those without retinal photos were excluded. To measure and analyze the patients' retinal vessel characteristics, we applied a patented AI-assisted automated retinal image analysis system developed by the Chinese University of Hong Kong. The demographic, clinical, and retinal information was compared between the QDBS and PSIC patients. The  Since 2012, stroke has been a leading cause of death and disability in China, and its incidence has been increasing at a rate of 8.7% per year . One of According to the “Guidelines for the Diagnosis and Treatment of Common Diseases in the Traditional Chinese Medicine” , the synTCM treatment selection for stroke is based on the TCM syndrome types. Patients with QDBS are characterized by hemiplegia, weakness of limbs, numbness of the body, deviation of the tongue, swelling of hands and feet, pale complexion, shortness of breath, lack of strength, palpitation and spontaneous sweating, deviated and pale tongue with a thin white coating, and a fine gentle pulse, therefore improving Qi and promoting blood circulation is the first principle of treatment . On the An essential component of TCM diagnosis is an overall observation of human symptoms, which is defined as the TCM syndrome. However, due to the lack of standard and objective evaluation criteria, such diagnoses, can be influenced by the doctors' personal experience, which puts the repeatability and reliability of the diagnosis in question . In lieuOne of the critical pathological changes of stroke is cerebral vascular change . AccordiThis study was approved by the Ethics Committee of the Shenzhen Traditional Chinese Medicine Hospital  and was performed in accordance with the guidelines of the Declaration of Helsinki (1964). All patients provided written informed consent for their participation in the study.In the case-control study, a total of 328 ischemic stroke patients from the Shenzhen Traditional Chinese Medicine Hospital were included. Patients were divided into 2 groups according to their TCM syndrome types: the QDBS group and the PSIC group. The patients' demographic and clinical data, including age, sex, medical history, physical examination, laboratory test, and electrocardiography results, were collected by trained doctors.The inclusion criteria were as follows: the subject was in the recovery stage of ischemic stroke, aged between 30–80 and was adequately able to maintain his/her posture while sitting for the duration of the retinal photography procedure. If the subjects were found to be suffering from any of the following conditions, they were excluded from the study: clinically unstable and requiring close monitoring, moribund, had an eye disease that severely affected retinal vessel structures, or was physically or subjectively unable to comply with magnetic resonance (MR) examination. In addition, if the patient was suspected to have cerebral diseases or conditions that may potentially alter retinal vessel morphology, he or she was excluded as well. Eventually, 196 of the 328 patients with ischemic stroke were included in our study .Risk factors related to cerebral infarction, such as hypertension, diabetes, dyslipidemia, high homocysteine, coronary heart disease, atrial fibrillation, smoking history, drinking history, and sleep disorders, were collected in this study. Hypertension was defined as a systolic blood pressure greater than 140 mmHg and a diastolic blood pressure above 90 mmHg or the use of antihypertensive medication for up to 2 weeks prior to the start of the study. According to diagnostic criteria from the National Diabetes Data Group, diabetes mellitus was defined as a fasting serum glucose level of more than 6.99 mmol/L, a nonfasting value of more than 11.1 mmol/L, or a history of treatment for diabetes . Based ond day of hospital admission using the SmartScope Ey4 Camera . To ensure the compatibility of the parameters, all the retinal images were scaled to 1365∗1024 pixels and saved in the jpg format. A patented, fully automatic retinal image analysis was applied to measure the retinal vessel characteristics, including vessel diameter, vessel branching angle and bifurcation measures, vessel tortuosity, and fractal dimensions [Retinal images were taken on the 2mensions –24.t-tests to compare the continuous data and chi-squared tests to compare the categorical data. A p value of <0.05 was considered statistically significant. We used nonparametric test (Mann-Whitney test) if the normality test showed rejection of normality assumption. For categorical data, exact Fisher's test was used if the expected count was less than five. A logistic regression model was used to build classification models. The steps used to establish these models were drawn from the method proposed by Hosmer and Lemeshow [We reported data as mean and standard deviation (mean ± SD) for continuous variables and as proportions for categorical variables. To analyze the manually measured clinical and retinal characteristics, we used 2 sample independent Lemeshow  for selep=0.019), fewer insomnia problem , and a higher tortuosity index syndrome . The drinking status presented a certain difference between the two syndromes with borderline significant difference (p=0.051). On the other hand, no statistically difference was found between the two groups in terms of the other clinical risk factors such as hypertension, diabetes, coronary heart disease (CHD), lipid level, or homocysteine level  and drinking history (p=0.039) were significant. The percentages of correct classification for PSIC and QDBS were 39.5% and 80.8%, respectively. The model that used retinal characteristic variables alone included AVR (p=0.053), bifurcation coefficient of venule (p=0.003), hemorrhage (p=0.025), and arterial occlusion (p=0.033), and a composite score of retinal interactions, showed that the percentages of correct classification were 70.4% and 80.8% for PSIC and QDBS, respectively. A final logistic regression model combined both clinical and retinal variables included insomnia status (p=0.020), AVR (p=0.099), BCV (p=0.006), hemorrhage (p=0.019), arterial occlusion (p=0.030), and a composite score of interactions (p=0.001). The percentages of correct classification were 76.5% and 84.8% in PSIC and QDBS, respectively. The odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) of each of the significant variables are shown in The stepwise logistic regression method was used to build classification models that included only clinical variables, only retinal variables, and combination of both clinical and retinal variables together. For the clinical model, the insomnia status (p=0.004) for model 1 with clinical variables alone, 0.857  for model 2 with retinal variables alone, and 0.867  for model 3 with both clinical and retinal characteristics. Compared with model 1, the AUCs of model 2 and model 3 have statistically significant increased . The increase in AUC from model 2 to model 3 was not statistically significant (The AUCs were 0.624 (95% CI: 0.542–0.706, nificant .In practice, the four clinical TCM diagnosing techniques, that is, observation, auscultation and olfaction, interrogation, and pulse feeling and palpation are combined to identify a specific disease. However, obtaining a correct diagnosis using these techniques is highly dependent on the domain knowledge of the TCM physicians. For instance, most of the diagnostic information is gathered by the naked eye and subjective feeling during assessment of each physician. Therefore, our proposed method of using an objective AI-based retinal characteristic analysis is considered a highly valuable approach in the clinical practice of traditional Chinese medicine.At present, there is a vast difference between the procedure of standardization of the TCM syndrome classification of syndrome type and the method of statistical processing. The clinical methods suitable for standardizing TCM syndrome classification include cluster analysis, factor analysis, principal component analysis, artificial neural networks, regression analysis, and discriminant analysis –28. CollIn recent years, there have been many clinical studies on the correlation between objective indicators and the TCM syndrome types of ischemic stroke, of which the indicators in question have been biochemical indicators, imaging indicators, and scale evaluations –31. In 2Insomnia and alcohol consumption are related to the occurrence ischemic stroke and are considered to be its risk factors. Insomnia is a common symptom that is associated with increased risk of mortality in first-time stroke patients . A high A cross-sectional study based on two community populations in southeastern United States explored the positive relationship between fundic vascular anomalies and cerebral infarction and confirmed it via MRI . This stIn this study, we differentiated between the two TCM syndromes of ischemia stroke using different retinal characteristics. A model that facilitated this differentiation model displayed higher diagnostic efficacy based on both retinal vessel characteristics and clinical variables, rather than being dependent only on clinical variables. In fact, the model based on retinal variables alone is almost as good as the combined model with both clinical and retinal variables. Therefore, the retinal vessel features that were obtained by us could be used for interpretation and guidance of stroke syndromes in TCM clinical practice.Several potential study limitations should be considered. First, all the participants included in this study were recruited in the same hospital. A multicenter clinical study should be designed to fully investigate our results. Second, in addition to QDBS and PSIC, the other five TCM syndrome types should be investigated in future studies. Third, due to the small sample size of our study, a test data was not conducted in this study. Future studies on this topic should include larger sample sizes. However, we have carried out a leave-one-out cross-validation for the final model. The percentages of correct classification for PSIC and QDBS were 77.8% and 74.7%, respectively.In this study, we developed a logistic regression diagnosis model by combining clinical variables and retinal characteristics. We collected information on clinical variables and used the features extracted automatically from retinal images to create an objective method of diagnosis of ischemic stroke. This model is effective for distinguishing between the two TCM syndromes of ischemic stroke. Therefore, we concluded that retinal characteristics are useful for clinically differentiating between QDBS and PSIC.