Over 70 million Americans are diagnosed with hypertension. Adherence to current AHA/ACC 2017 hypertension guidelines and appropriate antihypertensive therapy is important for optimal treatment outcomes. This study investigates prescribing patterns for ambulatory care patients with hypertension and adherence to these guidelines. Data from the 2015 National Ambulatory Medical Care Survey (NAMCS) were used in the study. Patients with primary diagnoses of essential hypertension were extracted from the data using ICD-9 code “401”. A total of 595 patients were identified. Correlation among demographic variables, source of payment and prescriber specialty were examined. Chi-square and descriptive analysis were performed. 51.4% of the prescriptions were non-first-line medications. Primary care physicians and cardiologists adhered to the guidelines more, when compared to the other specialties. There was a significant difference between various geographic regions, as it relates to guidelines adherence. This study concluded that prescribers do not always adhere to the AHA/ACC 2017 hypertension guidelines. It is recommended to adhere to the guidelines if there are no contraindications. The study’s findings were limited to the ambulatory patients visiting providers in 2015 and by the operational definitions of the study.  About 74 million Americans, or one in three adults, have high blood pressure. Hypertension is a silent disease that does not show symptoms until it has caused permanent damage to the heart, brain, kidneys or eyes ,2. UnforControl of hypertension is one of the most important health care priorities and is expected to increase with an aging population and increasing burden of obesity and other risk factors related to lifestyle. Hypertension is primarily managed in ambulatory settings accounting for an estimated 79% of primary care visits . Better Appropriate antihypertensive therapy in outpatient care is important for optimal treatment outcomes. According to recent guidelines, there are different blood pressure goals using an age cutoff of 50 years. National Ambulatory Medical Care Survey (NAMCS) data analysis for the years 2003–2010 revealed antihypertensive medication prescription increased from 69.2% in 2003–2004 to 78.8% in 2009–2010 (P = 0.001) with increased blood pressure control from 39.1% to 48.8% (P < 0.001). The trend was consistent in patients younger, as well as older than 60. Prescription for beta-blocker has increased from 25.4% to 34.7% while ARB prescription increased 17% to 22.1. African American patients, those with other comorbidities, insufficient insurance coverage and younger patients are less likely to control their blood pressure. Adults aged 18–39 have the lowest hypertension control rates among adults with hypertension in the US . SurprisThe goal of this study is to determine prescribing pattern for patients with hypertension for the year of 2015 and determine if they are being prescribed first-line therapy and evaluate the adherence of prescribers to current guidelines. Non-adherence to first-line therapy is one of the drivers for economic implications as it may lead to treatment failure, disease progression and more complex treatments, resulting in increased cost of treatment. According to AHA, the estimated direct and indirect cost of hypertension in the US was 76.6 billion dollars in 2010 . The dirData from 2015 NAMCS were used in the study. Patients data with primary diagnoses of essential hypertension were extracted by using ICD-9 code “401”. The National Ambulatory Medical Care Survey (NAMCS) is designed to meet the need for objective, reliable information about the provision and use of ambulatory medical care services in the United States. A total of 595 patients were found which represented the study sample. Patient age, sex, race, as well as the source of payment, and the provider type were among the operational factors used in data analysis. Sources of payment were defined as coverage through either private insurance, Medicaid, Medicare, or other state-based programs, self-pay, work compensation, and charity. All variables were categorized as “patient” or “physician” factors. Geographic region was the only variable categorized as both patient and physician.Data analysis was performed using SPSS software for descriptive data analyses and statistical coding. Various demographic variables were analyzed using frequencies, means and other descriptive statistics. The data was further analyzed using chi-square to compare proportions between groups. The extracted data set was checked for integrity, equality and distribution of a number of records in every phase of analysis. The hypothesis focused on physician variables to determine whether the number of non-first-line antihypertensive agents prescribed was related to physician’s specialty, geographic region and other demographic variables, such as age, gender, race and payment type. The definition of prescribing appropriateness was determined by 2017 AHA/ACC guidelines. Thiazides, ACE inhibitors, ARBs and CCBs were defined as first-line and appropriate treatment agents, whereas loop diuretics, beta-blockers, direct renin inhibitor, alpha-1 blockers, direct vasodilators, central alpha-1 agonists and other centrally acting drugs were defined as non-first line agents. Females and white patients represented over half of the sample. Patients aged 65 and older represented half of the sample, followed by those aged 45. Majority of the patients had Medicare as primary insurance (64.45%), and 39.3% were private insurance holders. General doctors (34.8%), cardiovascular specialists (32.1%) and internal medicine physicians (21.8%) were the majority. Most of the visits occurred in the South (36.5%) and Midwest (26.9%) . After a2 = 0.376) and those aged 65 and older (X2 = 0.073) received more non-first-line agents. White, African American patients (X2 = 0.208), as well as Medicare and private insurance holders (X2 = 0.145) were prescribed more non-first-line antihypertensive agents. Chi-square analysis showed that South and Midwest received more non-adherent prescriptions (X2 = 0.023). Cardiovascular specialists, family doctors and internal medicine specialists prescribed more non-first-line agents (X2 = 0.222)  .2 = 0.023). This corresponds to data from other studies about the South being one of the geographical areas with poor health and wellness. This study reveals not only significant differences in antihypertensive drug utilization among various demographics and physician specialties but also lack of adherence to the prescribing guidelines. Female and white patients, representing the majority of the sample, were prescribed more non-first-line treatments, as was the case with patients 65 and older. Since this population represented half of the sample, they also represented the subgroup having Medicare. South and West had more cases of non-first-line prescribing pattern due to being the majority  hypertension is diagnosed in the absence of an identifiable secondary cause. It is characterized by severe headache, fatigue or confusion, vision problems, difficulty breathing among other symptoms. The rise in antihypertensive drug utilization represents a potentially favorable development in terms of increased numbers of patients undergoing drug treatment. Cardiovascular specialists and general doctors who were the most common provider seen by the patients, were also one of the provider specialties prescribing the majority of non-first-line agents, which corresponds to hypertension being a cardiovascular condition. The data analysis showed that half of the antihypertensive prescriptions are not first-line agents, which can imply less effective drug therapy and worse clinical outcomes. This is where the issue of medication non-adherence comes into play to ensure the effectiveness of first-line therapy if there are no contraindications, to avoid side effects associated with non-first-line agents, such as beta-blockers and loop diuretics and to reach a better blood pressure control. Over 25% of people prescribed antihypertensive medications stop taking them 6 months after initiation of therapy. Medication adherence is influenced by physician communication and medical management skills, even though they can be improved by educational and practice interventions . The risConn et al. suggest that habit-focused interventions reduce blood pressure more effectively because they examine participants’ daily routines and incorporate medication administration to routine events. Such interventions improve clinical outcomes by improving adherence. Habit-based interventions can also be tailored into a patient’s daily routine to enhance a healthy lifestyle, which in turn will positively impact blood pressure control. Interventions delivered by pharmacists were found to be most effective, as patients see them as experts in medication therapy and are very receptive to their recommendations . The study was limited by the operational definitions of the study variables and the data collection period. Another limitation was the number of ambulatory care visits during the year of 2015. The variable selection was based on the available NAMCS database. In addition, the patients were assumed to have an initial diagnosis of hypertension, rather than a recurrent visit. Another limitation of the study was that the 2015 guidelines include beta-blockers along with ACE inhibitors or ARBs, and thiazide or thiazide-like diuretics in the first-line treatment in those with a history of MI. The 2017 ACC/AHA guidelines did not indicate beta-blockers as first-line treatments. Although the analysis criteria for this study were for essential hypertension, there may have been few patients who were prescribed only a beta-blocker and were considered as non-first line therapy. No allergy information was available, and the patients not given the first-line agent because of the allergy were not identified. Lastly, treatments consisted of agents other than ACEI, thiazides, CCBs, ARB or a combination of any of the above agents along with the treatments with a primary diagnosis of hypertension and not receiving any therapy were considered non-first-line. Large differences in the utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE inhibitors is unjustifiable. Therefore, more attention should be paid to their implementation in order to improve health gains. Clinicians may use these findings to tailor antihypertensive therapy to the needs of each patient.


The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes  were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness. In the last quarter century, the incidence and prevalence of chronic kidney disease (CKD) have increased significantly, by 89% and 87%, respectively; more importantly, death due to CKD has risen sharply by 98%, with an increment of disability-adjusted life years of 92% . These cNotably, incidence rates of major cardiovascular (CV) diabetic complications, that is, acute myocardial infarction, stroke, and lower-extremity amputation, markedly declined between 1990 and 2010, while only a small decline was observed in the occurrence of end-stage kidney disease (ESKD) . SimilarNovel therapeutic strategies aimed at improving renal prognosis in diabetic patients are therefore urgently needed. This claim becomes even more crucial when considering the high incidence (40%) of new-onset CKD among individuals with type 2 DM (DM2) ,10, as wUnder conditions of normoglycemia or mild hyperglycemia, the renal proximal tubules reabsorb almost the whole amount of filtered glucose by sodium-glucose cotransporters ,16. SGLTSeveral biological mechanisms could explain the nephroprotective effects of SGLT2 inhibitors (SGLT2-i). Improvement of glycemic control is only one determinant of nephroprotection correlated with the use of SGLT2-i. A major mechanism independent of glycemia is the restoration of normal tubulo-glomerular feedback (TGF) . Indeed,The “physiological goal” of TGF is to limit salt dispersion (and dependent volume depletion) in the presence of high blood pressure, perfusion in the renal artery, or reduced proximal tubular reabsorption. This mechanism is constantly active, with the extent of the effect (increased tone of afferent arteriole due to adenosine release) being dependent on the delivery of sodium chloride to the macula densa. In diabetes, SGLT2-dependent higher sodium reabsorption (which reduces sodium delivery to macula densa) leads to afferent vasodilation and dependent glomerular hyperfiltration. SGLT2-i, by limiting the abnormal reabsorption of sodium chloride in the proximal tubule, restores a normal TGF activity and glomerular filtration .per se, that is, even in the absence of diabetes, leads to insulin resistance; in fact, CKD is state of heightened inflammation with elevated levels of pro-inflammatory cytokines, and it is also associated with metabolic acidosis, excessive aldosterone and angiotensin II levels, accumulation of urea and uremic toxin, that is, all factors that promote insulin resistance [In addition to the effects mediated by intrarenal hemodynamic changes, SGLT2-i also have direct anti-inflammatory and antifibrotic nephroprotective effects. Indeed, SGLT2-i suppress the production of reactive oxygen species, lessening glomerulosclerosis and tubulo-interstitial fibrosis ,30. Finasistance .Three large trials have shown improvement in CV outcome, and renal prognosis as secondary outcome, in over 34,000 participants with DM2 at high CV risk ,38,39,40P < 0.001) compared to placebo [EMPA-REG, CANVAS and DECLARE trials consistently demonstrated a significant reduction of CV risk in the SGLT2-i arm, in particular in terms of lower rates of hospitalization for heart failure (HF). Renal events, tested as secondary endpoints, were also generally lowered by these drugs. Reduction in albuminuria and preservation of estimated Glomerular Filtration Rate (eGFR) appear to be a class-effect of SGLT2-i. In EMPA-REG, empaglifozin reduced the progression to severely increased albuminuria by 38% compared with placebo . Similar placebo . Further placebo . In term placebo ,42,43,44Although the findings from EMPA-REG, CANVAS and DECLARE have provided signals on the nephroprotective properties of SGLT2-i in DKD, clinical trials primarily designed to evaluate outcomes in large CKD population are still awaited. Interestingly, two trials will evaluate the effect of SGLT2-i on renal outcome of patients with non-diabetic CKD: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With CKD , and The Study of Heart and Kidney Protection With Empagliflozin .2 for 30 days, doubling of the serum creatinine for at least 30 days, or death from renal or cardiovascular disease). Some key comments must be made on the nephroprotective efficacy of canaglifozin shown in CREDENCE. First, the nephroprotective effect was maintained also in the subgroup with more advanced CKD ; this observation is especially important for nephrologists that treat more severe renal disease. The second aspect to be highlighted is the effect of canaglifozin on a solid marker of progression to dialysis, namely the doubling of serum creatinine; for this endpoint, the HR was even more reduced  with respect to the primary combined endpoint. Third, the nephroprotective effect was anticipated by the sustained 31% reduction in albuminuria in the canaglifozin arm, in evidence from the 6-month control visit after randomization, thus confirming the well-known predictive value of albuminuria change on long-term renal outcome. Fourth, a slower decline in eGFR, with a between-group difference of 1.52 mL/min/1.73 m2 per year versus standard treatment, was maintained throughout the follow-up period, and this is coherent with a reduction of renal damage sustained over time. Last but not least, the nephroprotective effect was obtained in patients under optimal anti-RAS therapy and it was actually of greater extent when compared with the findings in the historical trials testing anti-RAS in similar patients with DKD [Data specific to the diabetic population with CKD  have been provided for the first time by the CREDENCE trial  . CREDENCIn terms of CV protection, the CREDENCE trial extended to diabetic patients with low renal function the remarkable efficacy on the prevention of heart failure , which is a SGLT2-i class effect. More important, CREDENCE trial also documented the efficacy of canaglifozin in preventing atherosclerotic events with a 20% lower risk of CV death, myocardial infarction, or stroke. This finding is similar to that reported in the CANVAS, but it is at variance with results obtained in EMPAREG and DECLARE. Whether this discrepancy is related to the drug or merely due to different patient population remains to be elucidated.Emerging evidence suggest that SLT2-i could exert beneficial effects on CV system through a significant reduction in epicardial adipose tissue, a novel, early, non-invasive biomarker and indicator of CV outcome  46,47,4,49,50. TSGLT2-i are associated with adverse events, including genital, and to lesser extent urinary tract, infections , acute kSGLT2-i increased by 3 times the risk of genital infections in a large population-based study, particularly in elderly subjects . This fiIt is still unclear whether SGLT2-i increase the risk of lower limb amputation. In CANVAS, canagliflozin was associated with 2-fold higher risk of amputations  as compared with placebo  . ConversCANVAS has also prompted attention on the risk of fractures  by reporIn a recent post-hoc analysis of a small trial in 34 patients, dapagliflozin (10 mg/d) was shown to significantly increase (by 11%) serum phosphate at 6-weeks after the start of treatment . SimilarEuglycemic diabetic ketoacidosis (euDKA) can be associated with SGLT2-i in diabetes type 1 (more frequently) and type 2 (less frequently). Potential contributors are concurrent mild infections, decreased calories intake with insulin dose reduction or withdrawal, surgery. The overall risk for developing euDKA, initially described in a case series including 15 patients , is stilAKI may be due to volume depletion not recognized during therapy with SGLT2-i. The FDA recommends monitoring kidney function before and after drug initiation, especially if SGLT2-i are used with other medications potentially linked to AKI, such as anti-RAS, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs); however, SGLT2-i trials do not describe AKI as a consistent adverse event despite most patients had concomitant treatment with anti-RAS drugs and diuretics. Alternatively, SGLT2-i may be linked directly or indirectly to acute nephrotoxicity. SGLT2-i increase uricosuria because of glucose exchange with uric acid in the proximal tubule . TherefoUse of SGLT2-i has recently been associated with Fournier gangrene (FG), a rare urologic emergency characterized by necrotizing infection of the external genitalia, perineum, and perianal region. The FDA identified 55 unique cases of FG in patients receiving SGLT2 inhibitors between 2013 and 2019, with all patients treated by surgical debridement and severely ill. Even if there are no data to establish causality or incidence, physicians should be aware of this complication and to recognize it in its early stages .CREDENCE trial adds knowledge of the safety of canaglifozin in the CKD setting . A novelSGLT2-i show great promise for prevention and treatment of DKD and it is likely that ongoing trials will confirm the high expectations of nephrologists as of other specialists involved in the care of diabetic patients. Available trials, and in particular the most recent CREDENCE study, have demonstrated a reduction in all-cause and CV mortality in DKD patients with DM2 and nephroprotective efficacy with a significant reduction of albuminuria and slowing of CKD progression. Intriguingly, SGLT-2-i may play a role in attenuating insulin resistance, a main CV risk factor, in diabetic as non-diabetic CKD. On the other hand, the safety profile of this drug class indicates that referral to a nephrologist is needed to monitor volemic status and to prevent AKI. Further studies are needed to verify efficacy and safety of the combination of SGLT2-i with other anti-diabetic nephroprotective drugs, namely DPP-4 inhibitors and GLP1 receptor agonists ,75,76.


In the two visits sK was 4.8 ± 0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalaemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis  evidenced that new onset  and persistent  hyperkalaemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalaemia status is common (37%) and predicts per se higher ESKD risk but not mortality.Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits  in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia  by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of end stage kidney disease (ESKD) and death after visit 2. Age was 65 ± 15 years, eGFR 35 ± 17 mL/min/1.73 m Chronic hyperkalaemia is common in non-dialysis chronic kidney disease (ND-CKD). Recent observational studies have reported a greater prevalence of high serum potassium (sK) in this population than in general population; however, the reported rates have been extremely variable—from 1% to 50%—being mainly dependent on GFR and comorbidities of included patients, as on the number of sK measurements ,4,5,6,7.More important, an additional lack of solid information on hyperkalaemia burden in CKD is the prognostic role. Indeed, while in unselected population hyperkalaemia poses a risk excess of mortality for even moderate increases of sK (≥5.0 mEq/L) ,11,12,13To date, no detailed study has evaluated the effect of hyperkalaemia on ESKD in outpatient nephrology clinics. On the contrary, this evaluation is critical for several reasons. First, this is the reference of care for high-risk CKD patients. Second, in patients referred to nephrology ESKD overcomes mortality at variance with unselected CKD population ,24. ThirTo fill this important gap of knowledge, we studied a large prospective cohort of ND-CKD patients under stable nephrology care to verify in outpatient CKD clinics (I) the prevalence of hyperkalaemia at referral and after 12 months, (II) the hyperkalaemia-related risk of ESKD and all-cause death in the subsequent period of follow up. To gain a proper analysis of the effect of sK on kidney survival, the effect of exposure was evaluated by competing risk analysis to take into account the potential occurrence of death before ESKD. Analyses were adjusted for major confounders, including RASI prescription and eGFR change in the first year of nephrology care.This is a multicentre prospective study pooling data from four established cohorts . 2 or proteinuria >0.15 g/24 h) under stable care in Italian outpatients nephrology clinics to gain information on clinical features and outcome of referred CKD. Methodological details are described in the published papers [Cohorts included ND-CKD patients , hyperkalaemia only at visit 1 (resolving), or only at visit 2 (new onset), or at both visits (persistent). Similar categories were created for RASI prescription: both visits, only visit 1, only visit 2, neither visit. Endpoints of the study were ESKD, that is, start of chronic dialysis therapy (>30 days) or kidney transplantation and all-cause death before ESKD, as derived by national registries. For survival analyses, patients were followed from visit 2 up to ESKD, all-cause death, or 31 December 2015 and censored on the date of the last control visit.Continuous variables are reported as either mean ± standard deviation (SD) or median and interquartile (IQR) range based on their distribution. Comparison among hyperkalaemia categories was assessed by ANOVA or Kruskal-Wallis test, while changes in each category across two visits were performed by paired Student’s t-test or paired Wilcoxon test. Categorical variables are reported as percentage and were analysed using a Chi-square test or McNemar test to evaluate changes across two visits. Follow-up for survival analyses started at visit 2 and median follow-up value was estimated by inverse Kaplan-Meier approach. Incidence rates of ESKD and death before ESKD were reported as number of events/person-time and 95% confidence interval (CI) calculated assuming a Poisson distribution. Risk of ESRD versus death in whole population was compared according to Kochar et al. .Competing risk approach was used in the survival analysis because in ND-CKD, ESKD and death before ESKD are competing events, that is, occurrence of death prevents ESKD. The competing risk analysis must be considered when the absolute percentage of competing event is >10% ; in our In the univariate analysis we built and compared cumulative incidence curves among categories by using Gray test , while mModels were stratified by cohort to consider potential differences in the basal risks across the four cohorts and were adjusted for the following potential risk factors of ESKD recorded at visit 2: age, gender, diabetes, body mass index (BMI), systolic blood pressure, cardiovascular (CV) disease history, haemoglobin, eGFR, 24-h proteinuria, categories of RASI, as well as the eGFR change between baseline (visit 1) and 12-month control (visit 2). To take into account the non-normal distribution of 24-h proteinuria and the non-linear association with outcomes, this covariate was log-transformed. Non-linear association of sK as continuous variable with outcomes was tested adding in the model the quadratic value of sK and retained if the coefficient was significant. P value < 0.05 was considered significant. Data were analysed using STATA version 14  and Cmprsk, CrrSC packages of R software 3.3.1 .A two-tailed The whole cohort was originally composed by 2813 patients referred to 46 outpatient CKD clinics in Italy. According to exclusion criteria, we studied 2443 patients . As compIncluded patients still had a high-risk profile, as testified by the high prevalence of diabetes and CV disease, the low eGFR value and the high BMI and blood pressure levels . p = 0.266), and it was dependent on CKD stage . Prevalence of hyperkalemia was similar at visit 1  and visit 2  , while haemoglobin and eGFR decreased (p < 0.001). The higher proteinuria levels in new onset and persistent categories was probably due to higher prevalence of diabetic kidney disease (p < 0.001). RASI prescription in the hyperkalaemia categories is reported in p < 0.001) from visit 1 to 2. Conversely, anti-aldosterone drugs were prescribed in <1% at either visit. The nephrologist intervention also led to increased prescription of statin (from 32% to 38%) and epoetin (from 13% to 18%) (p < 0.001 for both), while intervention aimed at controlling extracellular volume , was observed in 71% patients at visit 1 and decreased to 56% at visit 2 (p < 0.001), likely due to improved BP control , we registered 567 ESKD and 349 all-cause death before ESKD, with incidence rate per 100 patient/years being 6.4 (95% CI 5.8–6.9) and 3.9 (95% CI 3.5–4.3), respectively.p-value < 0.001)  . When examining the four groups, incidence of ESKD was similarly higher in new onset and persistent hyperkalaemia versus absent and resolving group, while mortality did not differ .p = 0.014) with no effect on mortality . The association between sK and outcomes was linear as testified by the non-significant effect of quadratic sK on ESKD (p = 0.79) and death (p = 0.52). Similarly, the sK change (mEq/L) in the two visits significantly predicted ESKD  with a neutral effect on mortality . The multivariable survival analysis examining the independent role of sK as continuous variable showed that 1 mEq/L higher sK at visit 2 was associated with 20% higher risk of ESKD . Also mortality risk related to sK at visit 1 was not significant . These results persisted when adding the 370 patients initially excluded because of missed visit 2  is (I) common with 37% patients showing new-onset or persistent hyperkalaemia over two visits with 12-month interval and (II) portends


Blood pressure measurement is the first step in preventing and controlling hypertension. The objective of this study is to examine the rural–urban difference towards blood pressure measurement among elderly with hypertension.A total of 2007 elderly (65+) were selected from the fifth Health Service Survey of Shandong Province in 2013. A standardized questionnaire was used to investigate the demographic characters, socioeconomic status, self-rated health, and blood pressure related index. Three logistic regression models were used to examine the difference in blood pressure measurement between rural and urban elderly. Unadjusted and adjusted logistic regression models were used to explore the associated factors of blood pressure measurement in both rural areas and urban areas.The prevalence of weekly blood pressure measurement in urban elderly was higher than that in rural elderly (63.9% vs 34.3%). The rural elderly had an odds ratio (OR) for weekly blood pressure measurement of 0.467 (95%CI = 0.380–0.575) compared with urban elderly. Binary logistic regression analysis showed that medication frequency and accepting health care professionals’ guidance were common associated factors of blood pressure measurement among both rural and urban elderly; personal income was unique associated factor of blood pressure measurement among rural elderly; marital status, education level, self-rated health, and blood pressure level currently were unique associated factors of blood pressure measurement among urban elderly.There is a big difference in blood pressure measurement between rural and urban elderly. Interventions targeting identified at-risk subgroups, especially for those rural elderly, should be made to reduce such a gap. Hypertension is one of the most common risk factors for cardiovascular disease . It alreA population-based screening project in 2017 that enrolled around 1.7 million adults from all 31 provinces in mainland China showed that 44.7% of the sample had hypertension .Fortunately, hypertension can be prevented. Detecting high blood pressure is the first step in preventing and controlling it. Acting Director of the WHO Department for Management of Noncommunicable Diseases, Dr. Shanthi Mendis, said that “Early detecting of high blood pressure and lowering heart attack and stroke risk is clearly far less expensive for individuals and governments than heart surgery, stroke care, dialysis, and other interventions that may be needed later if high blood pressure is left unchecked and uncontrolled.” WHO called on all adults around the world to measure their blood pressure to make people know the blood pressure level and take steps to control it on World Health Day 2013 . Some stUnfortunately, the rate of BP measurement is not optimistic. There are many studies about the current situation of BP measurement. An investigation in Italy found that about 56.9% of hypertensive patients performed one or more BP measurement weekly . In ChinSince our population is aging, and hypertension affects most elderly people, these individuals are more likely to have organ damage or clinical cardiovascular disease (CVD). In China, the percentage of 65 and older people is 10.1% in 2015, and it predict to reach 26.8% in 2050 . The preIn the present study, we focused on the elderly with hypertension in Shandong Province. Shandong Province has the second largest population in China, and the percentage of its elderly population (65+) has reached 13.15% by 2016. What is more, the prevalence of hypertension in Shandong Province was high. In 2013 in Shandong Province, the prevalence of hypertension is 24.33%, higher than most of other provinces . TherefoData were drawn from the fifth Health Service Survey of Shandong Province, which was part of China’s fifth National Health Service Survey (NHSS), conducted in 2013. NHSS is a national representative survey organized and directed by the Ministry of Health of China every 5 years.To achieve representation of the whole population, a four-stage, stratified, random sampling method was adopted in both years. In the first stage, 20 counties (districts) were randomly selected in Shandong Province. The second stage sampled townships: 100 townships were selected in sampled counties or districts. In the third stage, 200 villages (communities) were selected in sampled townships. In the fourth stage, 12,000 households were identified. For each household, a face-to-face interview was conducted using a structured household questionnaire which was developed by the Center for Health Statistics and Information of the Ministry of Health of China –21.n = 2104). After data cleaning , a study sample of 2007 hypertensive patients were adopted for analysis.Among a total of 33,070 respondents, we included hypertensive patients aged ≥65 years old (BP measurement frequency was derived from a question “When was the last time you measured your BP?” They could choose one of the five responses (“within a week” “within a month” “within three months” “within six months” “more than six months”). According to Chinese guidelines for the management of hypertension in 2010, patients with controlled BP should measure BP at least once a week . TherefoAge, gender, and marital status were used as demographic characteristics. Age was categorized as 65 to 69, 70 to 74, 74 to 79, and 80 years or more. Marital status was classified as married and single, latter one includes unmarried, divorced, and widowed. Socioeconomic status was measured separately via education level and personal income level. Education level was classified into three categories: no formal education, primary education, secondary, or above. Personal income was calculated by household income and household size, and classified into 5 levels: 0 to 2500, 2500~5000, 5000~10,000, 10,000~20,000, ≥ 20,000 Yuan, RMB per year. Self-rated health score was categorized as bad, moderate, and good.BP-related variables included medication frequency, blood pressure level currently, and accepting health care professionals’ guidance. Medication frequency was classified as on time, occasional, and never. BP level currently was categorized as normal and others . The entry “accepting health care professionals’ guidance” was defined by an affirmative response to the question “In recent three months, have you ever been guided by health care professionals in the prevention and treatment of hypertension?”Data analyses were conducted using SPSS 24.0. Descriptive statistics, including frequency and percentage, were used to describe the social-demographic and BP management characteristics of the patients. Chi-square tests were used to explore the relationships between age, gender, marital status, education level, personal income, self-rated health, BP-related variables, and measurement frequency.P value of less than 0.05 was considered statistically significant for the test.Binary logistic regression models were used to examine the rural–urban difference of measurement frequency. Model 1: univariate model. Model 2: binary logistic regression model, adjusted for demographic characteristics , socioeconomic status , and self-rated health. Model 3: in addition to the factors in model 2, BP-related variables  were included. Univariate models and adjusted binary logistic regression models were used to explore the risk factors of measurement frequency among both rural and urban elderly. Because NHSS has a complex sampling design, sampling weights were considered in the logistic regression analyses. A Among these 2007 participants, 1107 (55.2%) were rural elderly, 900(44.8%) were urban elderly. The mean age was 72.74 (SD = 6.15), and most of the participants were currently married (72.8%). More than one-third (35%) of the patients had no formal education, and most of them were unemployed (81.1%). As for BP management characteristics, most of the patients took medicine on time (79.1%). More than half of the patients had normal BP currently (58.5%). And approximately two-thirds (69.1%) of them had accepted health care professionals’ guidance. Since weekly BP measurement is more clinically useful, the presentation of results focused on the weekly categories. There was statistically significant difference in the frequency of BP measurement between rural group and urban group. Besides, age, gender, marital status, education level, personal income, self-rated health, medication frequency, BP level currently, and accepting health care professionals’ guidance were also significantly different between rural elderly and urban elderly (Table The result showed that 955(47.6%) elderly patients measured BP weekly and 1052 (52.42%) did not. Among these 955 (47.6%) patients who measured BP weekly, 380 (34.3%) were rural elderly and 575 (63.9%) were urban elderly  or never took medicine  were less likely to practice BP measurement compared to those on time ones. Patients who had not accepted health care professionals’ guidance recently were less likely to engage in timely BP measurement  . Education levels were significantly associated with the frequency of BP measurement among urban elderly. The results showed that individuals who had secondary or above education  were significantly associated with more frequent BP measurement than those individuals who had no formal education. What is more, elderly who reported moderate self-rated health were less likely to measure BP on time than bad ones . Those elderly hypertensive patients who took medicine occasionally  or never took medicine  were less likely to practice BP measurement compared to those who took medicine on time. Besides, patients with normal BP currently were associated with more frequent BP measurement compared to those abnormal/unsure ones . Patients who had not accepted health care professionals’ guidance recently were less likely to engage in timely BP measurement compared to those who had  , and rural–urban difference was significant in BP measurement frequency after controlling age, gender, marital status, education level, income, self-rated health, and BP-related variables. The first reason is that the knowledge about prevention and treatment of hypertension among patients in rural areas were significantly lower than that in urban areas . Most ofExtensive researches showed that BP measurement is the first step of hypertension management, and regular BP measurement contributes to hypertension prevention and control . Our resAmong rural elderly, personal income was significantly positively associated with the frequency of BP measurement. Many studies indicated that personal income was an important influencing factor associated with BP control in rural areas, which was in agreement with the finding of this study , 30. TheIn our study, those married elderly usually practice BP measurement more frequent than single ones in urban area. That may thanks to the reminding of their spouse. What is more, the elderly patients with higher education level engaged in more frequent BP measurement in urban areas. There might be three explanations for this finding. First, patients with high level of education make better use of home sphygmomanometers, which provide convenience for BP measurement . Second,The findings in this report are subject to some limitations. First, the cross-sectional nature of our survey precludes us from assigning cause and effect to our results. Second, the analyses were depended on self-reports, which involves a risk of information bias due to false or inaccurate responses from participants. Third, there is a limitation with assumptions made in converting reported “the last time measure BP” into BP measurement frequency. For example, it is conceivable that a person may measure BP within a week occasionally; however, according to our definition, the person will be classified as engaging in BP measurement weekly. Fortunately, this situation is not common and its impact on the result is not obvious.In conclusion, this study found that the elderly in urban areas performed BP measurement more frequent than the elderly in rural areas. In general, personal income, medication frequency, and accepting health care professionals’ guidance were associated factors of BP measurement frequency among rural elderly. Marital status, education level, self-rated health, medication frequency, BP level currently, and accepting health care professionals’ guidance were associated with the BP measurement frequency among urban elderly. The results of this analysis highlight the rural–urban difference in the use of BP measurement and the necessary to better understand the factors associated with more frequent BP measurement. Therefore, more work will be needed for BP measurement to prevent its consequences in rural areas of China. First, the government should develop targeting health promotion policies to improve health literacy among the elderly. Second, the communities should pay close attention to those identified at-risk subgroups to increase the BP measurement frequency among the elderly.


It is particularly important to utilize appropriate blood pressure measurement methods to evaluate the changes of orthostatic hypertension (OHT) for children, and this study was designed to analyze the blood pressure type in OHT children with 24 h semiautomatic ambulatory blood pressure monitoring.Children who were diagnosed by head-up tilt table test as OHT patients (OHT group) and treated or hospitalized in the syncope specialist outpatient unit of the Second Xiangya Hospital of Central South University mainly for syncope or pre-syncope with unknown causes during the October, 2009 to September, 2013 were recruited in the study. Healthy children that came to the hospital for physical examination at the same time period according to age and sex were matched as control group. Semiautomatic ambulatory blood pressure monitoring of every child was recorded. The differences of daytime systolic (diastolic) pressure and night systolic (diastolic) pressure were calculated, and the average systolic pressure and diastolic pressure of the entire day, daytime and night were also calculated, respectively.There were 23 boys and 17 girls in OHT group, aging (11.5 ± 1.9) years. There were 22 boys and 18 girls in the control group, aged (10.6 ± 2.4) years. The difference of daytime systolic pressure and night systolic pressure of the control group was higher than that of OHT group, while the average systolic pressure of the whole day, the average diastolic pressure of the whole day, the daytime average systolic pressure, the daytime average diastolic pressure, the night average systolic pressure and the night average diastolic pressure were higher than that of the control group (P > 0.05). The difference of daytime diastolic pressure and night diastolic pressure of the control group was higher than that of OHT group (P > 0.05). Most children of the OTH group had non-dipper blood pressure type (72.5%), while most children of the control group had a dipper blood pressure type (55.0%). In addition, the time domain SDNN and SDANN in the OHT group were higher than those in the control group (P < 0.01). And, the indicators including TP, ULF, VLF, and LF/HF were higher in the OHT group, when compared with control group (P < 0.01). Besides, in terms of subgroup analysis within the OHT group, the age difference between boys and girls was not statistically significant (P > 0.05). When compared with grils, the time domain SDNN increased (P = 0.003), and the frequency index TP, ULF, and VLF increased in boy group (P < 0.05).OHT Children’s autonomic nervous system showed dysfunction, and differences of systolic blood pressure between day and night were much lower than those of healthy children, and the main blood type was non-dipper blood pressure with circadian rhythm disappearing. To our best knowledge, orthostatic hypertension (OHT) refers to normal blood pressure (BP) in the supine position, and suddenly raised blood pressure when standing or sitting . As knowThe normal blood pressure measured 10 min after supine in a quiet environment is considered to be basal blood pressure. And the OHT changes were measured 3 min after upright tilt test . If the systolic blood pressure increased ≥ 20 mmHg, and (or) the diastolic blood pressure increased ≥ 10 mmHg (1 mmHg = 0.133 kPa), when compared with basal blood pressure, the patients could be diagnosed with OHT .(1) From October 2009 to September 2013, children at the syncope clinic of our hospital, or hospitalized children with unexplained syncope and premonitory syncope. (2) Patients were diagnosed with OHT via HUTT. (3) Physical examination, blood biochemical examination , conventional electrocardiogram, Holter electrocardiogram, echocardiography, electroencephalogram, cranial CT and MRI were carried out, in order to exclude heart, lung, brain, kidney and thoracic wall diseases.In the same period, healthy children in the Children’s Health Clinic of Xiangya Second Hospital of Central South University were selected into this research, and were matched with the OHT group (one-to-one based on age and sex). The identified patients were divided into two groups, and received basic HUTT (BHUT) and sublingual nitroglycerin tilt test (SNHUT), respectively. The electric tilting bed (ST-711) manufactured by Beijing Juchi Medical Technology Co., Ltd. and the tilting test monitoring software system (SHUT-100) provided by Beijing STADLEY Technology Inc. were utilized in this study. The specific inspection method refers to the guidelines for children’s syncope diagnosis issued by the Chinese Medical Association .During the semiautomatic ambulatory blood pressure monitoring examination, the subjects were home at 24 h. The ABPM 6100 monitor is provided by Welch Allyn in America, and the detailed information is as follows. (1) Select the same wide cuff and the same arm as semiautomatic ambulatory blood pressure monitoring. (2) Use a mercury sphygmomanometer to measure BP for 2 times, and then record BP value. (3) Initialize the BP monitoring and then enter the subject’s personal information. (4) The subjects were required to normatively wear BP monitoring, and manually measure blood pressure for 1 or 2 times. If the difference of systolic blood pressure between mercury sphygmomanometer and electronic sphygmomanometer less than 5 mmHg, the electronic sphygmomanometer could be considered to meet the requirements. Meanwhile, explain to the participants the precautions of wearing BP monitoring, and remind the required work and rest time. (5) After semiautomatic ambulatory blood pressure monitoring for 24 h, the blood pressure information of the subjects was input into the computer . (6) RefWhen concerning the types of blood pressure, the thorough explanations are as follows. Under normal circumstances, the human body’s BP rises throughout the day and falls during the night, which can be described as “long handle spoon” curve . 1) Dip Dip1a. , as shown in Table As shown in Table 2 = 6.600, P = 0.012). No over spoon-shaped BP and inverse spoon-shaped BP could be observed in both OHT and control groups, as shown in Table In the OHT group, non-dipper BP accounted for 72.5% 29/40 cases), and dipper BP accounted for 27.5% (11/40 cases). On the contrary, the non-dipper BP accounted for 45.0% (18/40 cases), and dipper BP accounted for 55.0% (22/40 cases). The BP difference between the two groups was statistically significant . Additionally, the difference of systolic BP between day and night in the control group was greater than in the OHT group (P < 0.05). In brief, on account of autonomic dysfunction, the BP type in children with OHT was mostly non-dipper BP, and the circadian rhythm of BP disappeared.


The odds ratio (95% CI) for a typical patient with an initial systolic blood pressure of 100 mm Hg should be changed from 0.73  to 0.67 , and the odds ratio for a typical patient with a median initial systolic blood pressure of 125 mm Hg should be changed from 1.41 to 1.40. This article was corrected online.1In the Original Investigation titled “Association Between Early Intravenous Fluids Provided by Paramedics and Subsequent In-Hospital Mortality Among Patients With Sepsis,”


Uncontrolled hypertension is a significant health problem in the United States, even though multiple drugs exist to effectively treat this chronic disease.As part of a larger project developing data visualizations to support shared decision making about hypertension treatment, we conducted a series of studies to understand how perceptions of hypertension control were impacted by data variations inherent in the visualization of blood pressure (BP) data.In 3 Web studies, participants (internet sample of patients with hypertension) reviewed a series of vignettes depicting patients with hypertension; each vignette included a graph of a patient’s BP. We examined how data visualizations that varied by BP mean and SD (Study 1), the pattern of change over time (Study 2), and the presence of extreme values (Study 3) affected patients’ judgments about hypertension control and the need for a medication change.Participants’ judgments about hypertension control were significantly influenced by BP mean and SD (Study 1), data trends (whether BP was increasing or decreasing over time—Study 2), and extreme values .Patients’ judgment about hypertension control is influenced both by factors that are important predictors of hypertension related-health outcomes  and factors that are not . This study highlights the importance of developing data visualizations that direct attention toward clinically meaningful information. Uncontrolled hypertension is a significant health problem; there are 75 million adults in the United States alone with diagnosed hypertension -3. HyperIn their hypertension clinical action model, Kerr et al  identifiTo improve hypertension control in the primary care setting, our research team has developed a data visualization tool designed to support shared decision making about hypertension treatment. Our tool is a visual display of the patients’ BP data over the last 2 years that will be embedded in the electronic health record (EHR) and will be jointly viewed by patients and clinicians during a primary care office visit. This tool aims to (1) reduce clinical uncertainty about BP data and hypertension control; and (2) increase patients’ willingness to intensify their medication or comply with standing treatment plans, with the downstream benefit of improving hypertension control.The data visualization tool was developed through a rapid prototyping process in which candidate visualizations were iteratively refined on the basis of regular feedback from patient and physician focus groups . During Three demographically diverse internet samples of patients with hypertension reviewed several brief vignettes describing fictitious patients with hypertension through Web survey; each vignette included a graph of the patients’ BP data. All 3 studies used a within-subjects design, where all participants reviewed all vignettes, presented in random order, and provided judgments about the degree of hypertension control for every patient/vignette. The Web surveys are described below, and the results are reported in accordance with the Checklist for Reporting Results of Internet E-Surveys  . The InsEach vignette described a patient who was being treated for hypertension and included a graph of the patient’s BP data over the past 2 years. In Study 2, 6 vignettes differed in the SBP mean  and pattern of change over time , while holding the SD constant  perceived BP control; (2) need for medication change; (3) subjective risk of heart attack; and (4) subjective risk of stroke for each vignette. Perceived BP control and need for medication change were assessed using agree-disagree Likert scales, while the subjective likelihood of heart attack and stroke were measured using unlikely-likely Likert scales. In addition, we asked participants to estimate the proportion of SBP values out of range for each vignette: “What percentage of the patient’s systolic blood pressure values  would you estimate to be out of the goal range?”After evaluating all vignettes, participants completed the Subjective Numeracy Scale (SNS)  and a SiAll data were collected by open Web surveys developed using Qualtrics survey development software . InformeIn all 3 Web surveys, participants completed one practice vignette that included directions for the practice task and 5 practice items; this section of the Web surveys utilized 3 webpages. Each vignette and its corresponding 5 questionnaire items  added 2 additional pages to each Web survey (per vignette). The SILS and SNS scales added 9 items, and the demographic variables added 7 items to each Web study. Furthermore, we provided a free textbox at the end of the study for participants to share any additional feedback on the data visualizations presented in the Web studies.In Study 1, the Web survey included 9 vignettes; therefore, participants completed 68 total items across 27 total webpages. In Study 2, the Web survey included 6 vignettes; participants completed 53 total items across 21 total webpages. In Study 3, the Web survey included 10 vignettes; participants completed 73 total items across 29 total webpages. The presentation order of the vignettes and their associated outcome measures was randomized within subjects. In addition, the team pilot-tested each Web survey themselves for functionality and usability before the surveys were deployed.Qualtrics identified participants with hypertension through a single self-reported measure: “Has your doctor ever diagnosed you with hypertension, also known as high blood pressure?”; similar self-report items have been used to identify patients with hypertension in other epidemiological studies ,21. InfoWe used Internet Protocol addresses and Qualtrics identification numbers to determine unique site visitors. The survey completion rate was 86% (51/59) for Study 1, 79% (50/63) for Study 2, and 66% (55/83) for Study 3. All completed questionnaires were used in the analyses.a priori using G-Power [f=0.25) at an alpha of .05, with a minimum correlation of .50 between repeated measures. All outcomes were treated as continuous variables. We examined the effects of data variations on primary and secondary outcomes by conducting a series of multivariate analysis of variance tests for repeated measures. Predictors included the level of the mean SBP , SBP SD (Study 1), presence and direction of slope (Study 2), and the number and direction of outliers (Study 3). All tests were conducted in SPSS version 24 and R version 3.5 and were considered statistically significant when P<.05.We planned to recruit 50 patients with hypertension for each of the 3 Web studies. The sample size was determined  G-Power ,23 with Across the 3 experiments, a total of 156 patients with hypertension participated in this research. Participants were majority female  and white , with a mean age of 47.30 (range 19-79) years; In contrast, when the patient had BP that was objectively well controlled (mean 130 mm HG), the variability of the BP data had a significant impact on judgments about hypertension control and related health risks. For example, when the variability was low (SD 5 mm HG), BP was considered reasonably well controlled with little need for a medication change, and there was a much lower perceived risk of heart attack and stroke. In contrast, when variability in BP data was high SD 25 mm HG), the perception of BP control was similar to those patients who had much higher mean (160 mm HG) BP values. This is noteworthy because evidence suggests that BP mean, much more than variability, is predictive of outcomes that matter to patients  mm HG, t. The SD F4,200=8.73; P<.001; generalized η2=0.04; Patients in Study 1 were also asked to recall the percentage of SBP values that were “out of range”  in the graph. The recall was largely inaccurate but varied significantly by the SBP mean and SD , need for medication change , heart attack risk , and stroke risk  to be significantly less well controlled , in greater need of medication change , and at greater 10-year risk for a heart attack  and stroke  than a negative data trend  with the same SBP mean. Consistent with Study 1, participants’ recall of the percentage of SBP measurements out of range was largely inaccurate .In Study 2, we observed that patient ratings of hypertension control, need for medication changes, and 10-year risk of heart attack and stroke were significantly affected by trends visible in the BP data see  and 5 . accurate . AlthougF4, 216=17.98; P<.001; generalized η2=0.14), need for medication change , and perceived risk of heart attack , and stroke  independent of the overall measurement variance. In Study 3, we compared judgments about uniform data patterns  with those with either 1 or 2 outliers. In addition, we systematically varied whether those outliers were above or below the mean BP of the depicted time period. The presence and number of outliers significantly affected judgments of hypertension control  also significantly impacted patients’ judgments about hypertension control, the need for a medication change, and the risks associated with uncontrolled hypertension. Observing even 1 or 2 outliers in BP data leads patients to inappropriately determine that hypertension is not well controlled.The use of data visualization in electronic medical records has the potential to transform clinical encounters. While the technology to develop these tools is available, little is known about how these data displays will influence patients’ judgments about hypertension control and subsequent decisions regarding treatment. These 3 studies have demonstrated that judgments about hypertension control are strongly and inappropriately influenced by the presence of outliers and variability in the data. Outliers and variability mask mean BP values and the presence of data trends—important predictors of BP-related health outcomes  . These fThere are several limitations to these studies that potentially constrain their generalizability. One limitation is the use of internet patient samples. When patients are making decisions about treatment for hypertension, they are typically made in conjunction with their physician during a clinic visit. In addition, while our sample of patients is more demographically diverse than typical internet samples, it is not representative of the population of patients with hypertension. Furthermore, we focused only on patients in these studies; therefore, future work should examine the effect of data visualization on physicians’ judgments about hypertension control, as well as the effect on shared patient-physician decisions. It is possible that physicians will perform similarly to patients because we are examining judgments that stem from common perceptual and cognitive processes ,31. On tHealth information technologies provide an opportunity for patients to become more engaged in decision making about hypertension control. We are endeavoring to design a data visualization tool for BP that can be jointly used by physicians and patients in this decision-making process. This tool aims to make the limited time shared in the exam room more efficient and effective. Defining how data elements, such as trends, variability, and outliers, support or detract from an understanding of the data will aid in the design of data visualizations that highlight meaningful characteristics of the data; this may, in turn, result in shared decisions that are better informed. Areas for future study include understanding how these parameters influence physician judgments about hypertension control and how information acquisition from data visualizations is affected by numeracy, health literacy, and graph literacy of patients and physicians.


This study evaluated the relationship between serum l-carnitine level and peripheral arterial stiffness (PAS) in kidney transplantation (KT). Fasting blood samples were collected from 65 patients who underwent KT. We measured the brachial–ankle pulse wave velocity, and 36 patients (55.4%) had PAS. Patients with PAS had a significantly higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044); higher waist circumference (p = 0.010), systolic blood pressure (p = 0.002), serum triglyceride level (p = 0.040), insulin level (p = 0.002), and homeostasis model assessment of insulin resistance (p = 0.002); lower high-density lipoprotein cholesterol (p = 0.036) and serum l-carnitine levels (p < 0.001); older age (p = 0.041); and a longer KT duration (p = 0.025) than those without PAS. Statistical analysis revealed an independent association between PAS in KT and KT duration : 1.003–1.054, p = 0.029) and serum l-carnitine levels . The area under the receiver operating characteristic curve indicated that the diagnostic power of l-carnitine to predict PAS was 0.789 . Serum-free l-carnitine level is negatively associated with PAS in patients who undergo KT. Cardiovascular disease (CVD) is the primary cause of mortality among patients with end-stage renal disease and those who undergo kidney transplantation (KT) . AtherosArterial stiffness is one of the major modifiable CVD risk factors that are independently related to CVD occurrence in patients who undergo KT ,4 Arteril-carnitine, an essential enzyme co-factor in energy metabolism, is considered to be one of the target molecules of mitochondria [l-octanoylcarnitine level in overweight middle-aged individuals after a three-year follow-up [l-carnitine and PAS by measuring baPWV value in patients who underwent KT. Cardiovascular events are some of the major causes of morbidity and mortality among patients who undergo KT; therefore, the present study aimed to determine the relationship between serum l-carnitine and PAS in patients who undergo KT.chondria . It is achondria ,13. The ollow-up . No prevPatients who underwent KT were recruited in a medical center in eastern Taiwan between April and June of 2013. All patients with an acute infection, pulmonary edema, heart failure, acute myocardial infarction, acute rejection, or malignancy at the time of blood sampling, or having an arterial–venous shunt (fistula or graft) in either limb were excluded from the study. The subjects were also excluded if they had a history of medication usage related to calcium, active vitamin D metabolites, bisphosphonates, teriparatide, or estrogen, or if they refused to sign an informed consent form. All subjects signed informed consent forms before joining the study. Ultimately 65 patients who underwent KT were enrolled in this study for further analysis. The Protection of Human Subjects Institutional Review Board of Tzu-Chi University and the Hospital approved this study, and all study procedures were conducted in accordance with the principles stated in the Declaration of Helsinki (IRB108-96-B).Trained staff checked and recorded all subjects’ anthropometric parameters, including body weight, body height, waist circumference, body mass index, medical history, medication usage, and lifestyles ,16,17.Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by an automatic upper-arm oscillometer device operated by trained staff after subjects rested for at least 10 min. Blood pressure was checked three times via the right brachial artery. A subject was diagnosed to have hypertension if SBP was ≥140 mmHg and DBP was ≥90 mmHg or if the person took antihypertensive medication in the past two weeks. Diabetes mellitus (DM) was defined as fasting plasma glucose ≥126 mg/dL or if the person was using oral or injected diabetic medication.The baPWV was assessed by an automated vascular device  ,16,17, wg for 10 min for further examination. All the chemical analyses of the blood samples except serum intact parathyroid hormone (iPTH) were performed by an autoanalyzer  and completed within one hour of the collection from the recipients. Data measured included total cholesterol (TCH), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting glucose, blood urea nitrogen (BUN), creatinine (Cre), total calcium, phosphorus, and serum intact parathyroid hormone (iPTH). The concentration of serum iPTH was measured via enzyme-linked immunosorbent assays . The estimated glomerular filtration rate (eGFR) was calculated by the modification of diet in renal disease formula.After an 8–10-h overnight fast, blood samples of about 5 mL were obtained from the 65 patients who underwent KT. The blood samples were centrifuged at 3000× l-carnitine level was determined by high-performance liquid chromatography and mass spectrometry (LC–MS). Firstly, 100 µL of serum sample and 50 mM sodium phosphate dibasic heptahydrate solution were mixed in an Eppendorf pipette (1.5 mL). The solution to be analyzed was extracted by Novum Simplified Liquid Extraction  and was eluted in ethyl acetate (1.5 mL). The elute was then evaporated to dryness under nitrogen flow, and the residue was reconstituted in 100 µL of methanol for analysis. The study used the Waters e2695 HPLC system, made up of a single quadrupole mass spectrometer  and equipped with an analytical column (phenomenex Luna® C18(2) ). The setting of the temperature of the column was at 40 °C, the flow was 0.8 mL/min, and the injection volume was 30 µL.The serum-free l-carnitine) ion mode electrospray ionization (ESI). In this positive ion mode, the mass spectrometer was then operated in full scan at the speed of 50–450 m/z. The individual masses of each compound (l-carnitine: 162.1 m/z) were monitored in the single ion recording mode. Data acquisition and processing were performed by the Empower® 3.0 software. The retention time for free l-carnitine was 2.49 min. Quantification of the endogenous compounds was done by measuring peak areas, followed by comparison to a calibration curve of the standard solutions.The LC–MS analyses were performed using a modified method  where thOur study used the definition of metabolic syndrome from the International Diabetes Federation . Particit-test (two-tailed). Non-normal distributed data were expressed as medians and interquartile ranges, and further comparison of data between patients was done using the Mann–Whitney U test. Analysis by chi-square test was done for data expressed as the number of patients. Multivariable logistic regression analysis was used for examination of independence of variables that were significantly associated with PAS in patients who underwent KT. SPSS for Windows  was used for data analysis. A p-value of less than 0.05 was considered statistically significant.The Kolmogorov–Smirnov test was used for the determination of the normal distribution of data. Normal distribution of data was expressed as means ± standard deviation (SD) and further comparison of data between patients were done by an independent Student’s p = 0.041), with longer KT duration (p = 0.025), higher waist circumference (p = 0.010), SBP (p = 0.002), serum TG (p = 0.040), insulin level (p = 0.002), homeostasis model assessment of insulin resistance , while they had lower serum HDL-C (p = 0.036), and l-carnitine levels (p < 0.001) and a higher percentage of diabetes (p = 0.001), hypertension (p = 0.033), and metabolic syndrome (p = 0.044), when compared with the control group (Thirty-six patients who underwent KT (55.4%) had PAS, and they were typically older individuals (ol group .p = 0.029) and serum-free l-carnitine levels  were independently associated with PAS in patients who underwent KT : 1.028, 95% confidence interval (CI): 1.003–1.054, rwent KT .l-carnitine in predicting PAS among patients who underwent KT was 0.789  (The area under the receiver operating characteristic (AUC) curve showed that the diagnostic power of < 0.001) .l-carnitine levels. After multivariable adjustment, serum-free l-carnitine level and KT duration were independently associated with PAS in patients who underwent KT.The primary novel finding of this investigation was that patients who underwent KT and had high PAS had a concomitant higher prevalence of DM, hypertension, and metabolic syndrome, as well as older age, longer KT duration, higher waist circumference, serum TG, insulin level, and HOMA-IR, while they also had lower serum HDL-C and free Metabolic syndrome and its components were associated with baPWV values in 2351 Caucasian subjects . HyperglArterial aging is accompanied by vascular remodeling with vascular elastin degeneration, collagen deposition in the arterial wall, endothelial dysfunction, and increases in arterial stiffness ,24. Duril-carnitine is needed for transportation of long-chain fatty acids into the inner mitochondrial membrane for β-oxidation during fatty-acid metabolism, and it is esterified to form acylcarnitines (ACs) [l-carnitine deficiency induces incomplete fatty-acid oxidation for energy production and impacts gluconeogenesis and increases serum AC levels [l-carnitine can stabilize free radicals via conjugation and prevents the toxic effect of reactive oxygen and nitrogen species, thereby presenting an antioxidant effect [l-carnitine results in better protein balance and improves insulin resistance, anemia, and chronic inflammation status in hemodialysis patients [l-carnitine is associated with a decrease in all-cause mortality compared to placebo for secondary prevention of cardiovascular disease [l-carnitine level was independently associated with PAS after adjusting for other cofounders in patients who underwent KT. Although the clinical effect of administration of l-carnitine in KT recipients remains to be assessed, studies showed that it is related to metabolic and inflammatory processes from the molecular aspect [l-carnitine in vascular diseases, and it is recommended that l-carnitine supplementation could be given to in patients with coronary artery disease with a lower level of l-carnitine [l-carnitine supplementation was not evaluated in the chronic kidney disease group of KT recipients and may need further study for clarification.es (ACs) . l-carniC levels . ElevateC levels . l-carnit effect . Supplempatients ,31,32. A disease . Arteria disease . Vascula disease . Serum m disease . Plasma  disease . Patient disease . Arteria disease . All ther aspect . Most rearnitine . Howeverl-carnitine and PAS in patients who underwent KT. The relationship between serum l-carnitine and oxidative stress was also not examined in this study. In addition, chronic oral l-carnitine supplementation may increase the formation of trimethylamine N-oxide (TMAO) in omnivores, which increases the risk of atherosclerosis [l-carnitine and PAS or oral l-carnitine supplementation and TMAO in patients who undergo KT in the future.There are several limitations to this investigation. Firstly, this was a cross-sectional study, which could not confirm a causal effect between serum clerosis . It is wl-carnitine is an important enzyme co-factor in energy metabolism, and the present investigation demonstrated that the serum fasting l-carnitine level was negatively associated while KT duration was positively associated with PAS in patients who underwent KT. Moreover, we found that the AUC of l-carnitine could predict PAS in patients who underwent KT. Further investigations are required to clarify this relationship.


The cardiovascular and respiratory systems are functionally related to each other, but the underlying physiologic mechanism of cardiorespiratory coupling (CRC) is unclear. Cardiopulmonary phase synchronization is a form of cardiorespiratory coupling. However, it is difficult to study in experimental data which are very often inherently nonstationary and thus contain only quasiperiodic oscillations. So how to enhance cardiopulmonary synchronization and quantify cardiopulmonary synchronization, the changes in cardiac function under the conditions of cardiopulmonary synchronization, and the physiological mechanisms behind them are the main issues to be discussed in this paper.p < 0.001). And the respiratory sinus arrhythmia (RSA) obviously decreased (p < 0.01) in the 2/2 mode and increased (p < 0.001) in the 4/4 mode. During the 2/2 breathing pattern compared with spontaneous breathing, systolic blood pressure (SBP) decreased (p < 0.05), and diastolic blood pressure (DBP), mean arterial blood pressure (MBP), and SV decreased significantly (p < 0.01). During the 4/4 breathing pattern compared to 2/2 breathing patterns, DBP, MBP, and cardiac output (CO) increased (p < 0.05), and stroke volume (SV) increased significantly (p < 0.01). When analyzing the relationships among these parameters, the RSA was found to be associated with the respiration rate in all respiratory patterns.The results showed that the cardiorespiratory synchronization significantly increased when breathing was controlled by heartbeat detection (We demonstrated that voluntary cardiorespiratory synchronization (VCRS) can effectively enhance cardiopulmonary phase synchronization, but cardiopulmonary phase synchronization and RSA represent different aspects of the cardiorespiratory interaction. It is found that cardiac function parameters such as the blood pressure and output per stroke could be affected by the number of heartbeats contained in the exhalation and inspiratory phase regulated through VCRS. So we can study cardiopulmonary phase synchronization by VCRS. It can be used to study in experimental data for the physiological mechanism of cardiopulmonary coupling. It is well known that the heart and lung control systems are coupled with each other. Cardiac and respiratory rhythms in humans are synchronized. However, the underlying physiologic mechanism of cardiopulmonary synchronization is unclear. Research on cardiopulmonary synchronization has a certain guiding significance for the diagnosis and treatment of some diseases and for healthcare. Studies have shown that the cardiopulmonary synchronization of athletes and swimmers is superior to that of ordinary people , 2, and The interaction between the cardiac and the respiratory systems is traditionally identified through the respiratory sinus arrhythmia (RSA), which accounts for the periodic variation of the heart rate within a breathing cycle. With the development of nonlinear dynamics, phase-synchronization analysis technology was used to analyze the relationships in cardiorespiratory coupling , 5–8. MoIn this paper, we investigated the physiological mechanism of cardiopulmonary coupling based on enhancing cardiopulmonary synchronicity using the heartbeat to control breath. The only method of controlling respiratory-induced variation before 1964 was for subjects to hold their breath. In 1964, Schmitt was first put forward controlling breathing using synchronization with an electrocardiogram/vector cardiogram (ECG/VCG), which was called voluntary cardiorespiratory synchronization (VCRS) . VCRS haOur aim is to use VCRS to study respiratory effects on blood pressure, heart rate, stroke volume, and cardiac output, using the phase-synchronization technique to quantify cardiopulmonary synchronization time. On the basis of synchronicity enhancement, we analyzed the effects of cardiopulmonary synchronicity on heart function and discussed the underlying physiologic mechanism of cardiorespiratory coupling.Thirty healthy male subjects (19–27 years old) voluntarily participated in the study. Each subject was given a medical survey questionnaire to ensure that they had no respiratory and cardiovascular diseases. The investigation was performed with the approval of the Xi’an Jiaotong University Ethics Committee, and all subjects signed an approved informed consent after the study procedures had been explained.The experiment was performed in a quiet laboratory between 8 p.m. and 10 p.m. and the temperature was controlled to 22–24 °C. The subjects were asked to avoid alcohol, tea, coffee, and strenuous exercises for 12 h and to get enough sleep the night before the experiment.Participants were seated comfortably. Before measurements were taken, participants rested and remained calm for 10 min. Then, the subjects received instructions for breathing in the sitting position. Three sets of data were tested with a rest period of 10 min between each set of measurements. The first measurement was made with subjects breathing spontaneously for 6 min. The subjects then exercised for 2 to 4 min to breath pace the VCRS, and the researchers made sure there were no problems during the procedure. The researcher was asked to follow the paced breathing VCRS mode for 6 min using a sound pattern from the ECG. This breath controller was developed in our laboratory. It outputs a sound signal by detecting the heartbeat signal and counting the heartbeats. The subject was instructed by the sound to breathe, synchronized with his/her heartbeat. The device signaled the subject when to inhale and exhale based on a fixed number of heart beats for each phase of the respiratory cycle: for example, inspire for the first two heartbeats and expire for the next two heartbeats in a 2/2 pattern. The 2/2 pattern was selected as the second measurement mode for 6 min. Figure Respiration, ECG, and thoracic electric bioimpedance (TEB) signals were acquired online using a multichannel physiology recorder  and software  on a PC (Gateway) and collected at 1000 samples per second. Beat-to-beat arterial blood pressure was logged continuously via a noninvasive finger photoplethysmography . The synchronization method between the two instruments involves attaching the output interface (BNC) of the FMS to an analog input channel of the MP150.The ECG was measured using disposable self-adhesive Ag/AgCl ECG electrodes, which were placed on the subject’s right arm, left leg, and right leg. The connection method was a standard bipolar ECG lead II that the left leg was connected to during the in-phase input of the amplifier, with the right arm connected to reverse-phase input, and the right leg linked to ground wire.The TEB was recorded using NICO100C . The NICO100C noninvasive cardiac output amplifier records the parameters associated with cardiac output measurements. It incorporates a precision high-frequency current source, which injects a very small (400 μA) measurement current through the thoracic volume, which is defined by the placement of a set of current source electrodes.Respiration was recorded with a respiratory effort transducer strain assembly belt TSD201 (Biopac Inc.) that measures thoracic expansion and contraction. Voluntary cardiorespiratory synchronized breathing (VCRS) was controlled with the device that generated a sound to instruct the subject when to inhale and exhale, which was introduced above.Phase synchronization is a kind of cooperative performance between two weakly interacted oscillators. It is classically understood as phase locking and defined as : 1\documm respiratory cycles [The synchrogram is a visualization tool which enables the detection of synchronization epochs in bivariate data. The synchrogram is constructed by plotting the corresponding normalized respiratory phase y cycles :2\documeThe respiratory phase, The method of phase recurrences based on a heuristic approach was used to quantify the cardiorespiratory synchrogram. Detection with phase recurrences offered the best temporal resolution and the highest number of synchronized sequence . GeneralIt is most valuable in cases where one of the signals resembles a point process. The synchrogram is a stroboscopic view of the phase of the respiration signal at the times of R waves. R peaks were detected using the combination of wavelet transforms and thresholding methods . The peaRespiratory Sinus Arrhythmia is used to explore the connection between respiration and changes to heart rate. This RSA index is computed using the peak-valley method . This meThe peaks and troughs of the blood pressure signal were extracted for systolic and diastolic blood pressures by combining them with the ECG signal. The mean arterial blood pressure (MAP) (= (2 × diastolic)/3 + systolic/3) was calculated from systolic and diastolic blood pressures. The method of extracting feature points in the blood pressure signal incorporated into the ECG signal is an advantage of synchronous collection of blood pressure and ECG signals. The maximum and minimum of the blood pressure signal matched the cardiac cycle between two adjacent R wave peaks. Each cardiac cycle includes one systolic blood pressure and one diastolic blood pressure. The algorithm has a high detection rate, as shown in Fig. L is mean distance between inner pair of electrodes (cm), −1), and (The stroke volume (SV) and cardiac output (CO) can be derived from the popular noninvasive method of impedance cardiography. CO is defined as the volume of blood pumped each minute . If the data were normally distributed, paired t tests were used. Otherwise, rank sum tests were used. A p < 0.001 for the 2/2 breathing pattern, p < 0.01 for the 4/4 breathing pattern). RSA obviously decreased (p < 0.01) in the 2/2 mode and increased (p < 0.001) in the 4/4 mode. In contrast, the BR was significantly increased (p < 0.001) during the 2/2 breathing pattern, and it was significantly decreased (p < 0.001) during the 4/4 breathing pattern , and DBP, MBP, and SV decreased significantly (p < 0.01). During the 4/4 breathing pattern compared with spontaneous breathing, all of the parameters showed no obvious change. During the 4/4 breathing pattern compared to the 2/2 breathing pattern, SBP, DBP, MBP, and CO increased (p < 0.05), and SV increased significantly (p < 0.01); no obvious difference was found in SBP and HR.To determine the effect of breath triggered by ECG enhancing cardiopulmonary synchronicity on the cardiovascular system, we analyzed cardiovascular function parameters during the 2/2 and 4/4 breathing patterns relative to those during spontaneous breathing pattern and between the 2/2 and 4/4 breathing patterns . RSA was obviously negatively correlated with DBP and MBP in the 2/2 respiratory mode . No obvious correlation was found in spontaneous breathing and 4/4 breath pattern.To study the mechanism of cardiopulmonary coupling, we analyzed the correlation coefficients among the cardiopulmonary synchronization time and blood pressure, cardiac output, stroke output, and respiration rate. No significant correlation was found. When analyzing the correlation between RSA and these parameters, RSA was found to be associated with the respiration rate and BP in the 2/2 mode Fig. . RSA wasPhase synchronization can be used to analyze cardiopulmonary coupling , 2, 11. In this paper, we used VCRS to study the circulatory system and found that blood pressure and stroke volume were reduced in the 2/2 mode by VCRS. Through analysis, we think that this is related to the number of heartbeats contained in the exhalation and inspiratory phase regulated by VCRS. Compared with spontaneous breathing, the 2/2 respiratory pattern resulted in decreased blood pressure and stroke volume (Table Our results demonstrate that cardiopulmonary phase synchronization and the traditionally studied respiratory sinus arrhythmia represent different aspects of the cardiorespiratory interaction. This is consent to previous studies , 24, 28.Our study demonstrates that VCRS can effectively enhance cardiopulmonary phase synchronization, although phase synchronization is difficult to study in experimental data which are very often inherently nonstationary and thus contain only quasiperiodic oscillations. We can study cardiopulmonary phase synchronization by VCRS. In our experimental data, we found that 2/2 mode can lower blood pressure, and we think that this is related to the number of heartbeats contained in the exhalation and inspiratory phase regulated by VCRS. It may be possible to control the cardiovascular parameters by controlling respiratory rate and the number of heartbeats contained in the exhalation and inspiratory phase of the respiratory cycle through VCRS, thereby regulating cardiac function.


Objectives: The aim of this study was to determine the incidence of metabolic syndrome in patients treated with second-generation antipsychotics (SGAs). Methods: In this retrospective study, we reviewed patients’ electronic medical records (EMRs) of all patients who received one SGA for at least six months, excluding patients who were taking other medications that are associated with significant effect on metabolic syndrome. Relevant clinical information was collected prior to starting the SGA and after six months of continuous use of the same SGA. Results: A total of 91 patients were included in the study. The majority of patients (72%) were diagnosed with schizophrenia. After six months of taking the SGA, 44% of patients experienced elevated systolic pressure, 54.9% had elevated triglyceride, and 31.9% had impaired glucose levels . Prior to initiating SGA therapy, 14.3% of patients had metabolic syndrome, while 37.4% had metabolic syndrome after six months of therapy, and it was more prominent in males compared to female patients . Conclusion: This study found a strong correlation between SGA use and the appearance of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels. These findings highlight the importance of assessing metabolic deregulations to minimize SGA associated metabolic abnormalities. Metabolic syndrome is a phenomenon whereby at least three of five metabolic risk factors coexist, these factors being: elevated blood pressure (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg); elevated fasting glucose (≥110 mg/dL); elevated triglycerides (≥150 mmHg); decreased high density lipoproteins (HDL < 40 mg/dL in men and <50 mg/dL in women); and abdominal obesity (waist circumference ≥102 cm in men and ≥88 cm in women) ,7. PatieA high prevalence of metabolic syndrome factors among psychiatric patients has been reported in several studies. In general, psychiatric patients have been found to have a twofold higher prevalence of DM, hypertension, obesity, and dyslipidemia compared to the general population . PsychiaSGAs may induce cardiometabolic and endocrine side effects, which can be particularly exaggerated in children . The inf3, central 5-HT2C, and D2 receptors. Due to this reported evidence about the impact of antipsychotic drugs on metabolic syndrome parameters, several agencies and associations, such as the American Diabetes Association and the American Psychiatric Association, have released reports (ADA/APA Consensus paper) to bring attention to the metabolic consequences of the chronic use of SGAs, including consequences, such as the possible development of hyperglycemia, hypertriglyceridemia, and weight gain. These agencies also recommend the close monitoring of weight, blood sugar, and triglycerides levels during the chronic use of these medications [Genetic variations, including several single nucleotide polymorphisms (SNPs), have also been identified as non-modifiable risk factors . In suppications . In Jordications . Previouications ,25. HoweThis study is a retrospective study which examined the effect of SGAs on the risk factors of metabolic syndrome. The electronic medical records (EMRs) of patients at King Abdullah University Hospital (KAUH) were reviewed. Approval to conduct this study was obtained from Jordan University of Science and Technology and the Institutional Review Board (IRB) at KAUH. This study was conducted by an ethics approval obtained on 1 March 2018, reference code 9/113/2018.The inclusion criteria for patients were: (1) adults (defined as aged 18 years and older), (2) have been taking one SGA for at least six months, and (3) have electronic documentation for their follow-up visits and laboratory tests. We excluded: (1) patients who were taking other medications associated with having a significant effect on metabolic syndrome clinical indicators , (2) patients taking more than one antipsychotic, and (3) patients with more than 20% of missing values.2 and above indicates central obesity, which is one of the components of metabolic syndrome [Patients were identified using the electronic records at KAUH. Patient demographics and any relevant clinical information (using both EMRs and follow-up charts) were collected. Laboratory test results prior to the initiation of the SGA (time 1) and after six months of continuous use of the same SGA (time 2) were also collected. Laboratory tests included: HDL, triglycerides, fasting blood glucose, and blood pressure. Waist circumference measures were not available; therefore, this parameter was not assessed. However, BMI was assessed as an alternative . Accordisyndrome . In thisDescriptive measures included frequencies and percentages for all categorical variables and mean  ±  standard deviation for continuous measures, respectively. Two-tailed t-test was used to analyze continuous variables, and Chi square test was used for categorical variables. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 25.A total of 91 patient records met the inclusion and exclusion criteria. The mean age was 41.4 (SD 16.13) years, and 51.6% of the records were for male patients . The maj2 had nearly doubled after six months of the initiation of SGA. Prior to initiating SGA, 13 (14.3%) patients, seven (53.8%) of whom were female  mice. Given the fact that dyslipidemia and atherosclerosis are major risk factors for CVDs, this may explain in part the high prevalence of CVDs in psychotic patients on SGAs [In a recent cross-sectional study, prediabetes and metabolic abnormalities were found to be highly prevalent among schizophrenic patients taking clozapine or olanzapine . Interes on SGAs . Further on SGAs . SGA-ind on SGAs ,38. Our  on SGAs . In agre on SGAs . Moreove on SGAs , which sIntriguingly, our current study revealed that the chronic use of SGAs increases both systolic and diastolic blood pressure in male patients only. The female patients seemed to have more stable readings of blood pressure, despite the long-term use of SGAs. Parks et al. reported an acute decrease in blood pressure in patients three days post-initiation of SGA . MoreoveGender based differences in the effects of the long-term use of antipsychotics were noticed in this study; specifically, male patients experienced a significant development of four metabolic syndrome criteria. Genetic- and gender-based differences in the effects of SGAs have previously been reported . Plasma This study is a retrospective study with few limitations. This study design has two possible threats: single group threat  and historical threat  . MoreoveIn conclusion, our study has revealed a strong correlation between the use of SGAs and the development of metabolic alterations, such as weight gain, glucose intolerance, and increased triglyceride levels . Further