Meta-analyses have demonstrated that isometric handgrip training (IHT) decreases blood pressure in hypertensive individuals. Nonetheless, most studies were conducted in laboratory settings and its effects in real-world settings remain unclear.To analyze the eﬀects of IHT on office and ambulatory blood pressure in hypertensive patients attended within primary healthcare.Randomized controlled trial conducted in primary healthcare units within the Family Health Program, Petrolina, Pernambuco, Brazil.63 hypertensive patients  were randomly allocated into IHT or control groups. IHT was performed three times per week . Before and after the 12-week training period, office and ambulatory blood pressure and heart rate variability were obtained. The signiﬁcance level was set at P < 0.05 (two-tailed testing) for all analyses.IHT signiﬁcantly decreased office systolic blood pressure , whereas there was no effect on diastolic blood pressure . Heart rate variability and ambulatory blood pressure were not altered by the interventions .IHT reduced office systolic blood pressure in hypertensive patients attended within primary care. However, there were effects regarding diastolic blood pressure, ambulatory blood pressure or heart rate variability.NCT03216317. Interestingly, the effects of IHT on ambulatory BP, which is more related to cardiovascular events than office BP, have not been demonstrated. In fact, in three previous studies, despite significant reductions in office BP, no effects on ambulatory BP were shown among hypertensive individuals after IHT, thus suggesting that there was a need for further studies.14 or in home settings.15 The potential effectiveness of this type of training at primary healthcare units is therefore unknown. Primary healthcare is the first point of contact that people have with the healthcare system when they have a health problem. The healthcare services provided within primary care include treatment of health conditions and support for managing long-term healthcare, including chronic conditions such as hypertension, at lower cost than in hospital settings.The benefits of IHT comprise its ease of application and the short time needed for doing the exercise. Therefore, it is ideal for application within primary care, in non-laboratory settings. However, all clinical trials studies analyzing the effects of IHT on BP were conducted either in laboratoryIn this study, we analyzed the effects of IHT on office and ambulatory BP in hypertensive patients attended at a primary healthcare unit. Our hypothesis was that IHT would reduce BP similarly in non-laboratory settings.A randomized controlled trial was used to investigate the effects of IHT on office and ambulatory BP among hypertensive patients attended at a primary healthcare unit. Medicated hypertensive patients were randomly assigned to either the IHT group or the control group. Ambulatory BP, office BP and heart rate variability parameters were measured before and after the 12-week intervention period by researchers blinded to the group allocations.www.clinicaltrials.gov database under the registration number NCT03216317 and formed part of the ISOPRESS network.17 The study methods were approved by the Institutional Review Board of Universidade Federal do Vale do São Francisco  in conformity with the national research ethics system guidelines and with the Helsinki Declaration of 1975 (revised in 1983). Before participation, subjects provided written informed consent.18This randomized controlled trial followed the Consolidated Standards of Reporting Trials (CONSORT) and was registered in the We invited medicated hypertensive patients at primary care units within the Family Health Program in the city of Petrolina, state of Pernambuco, northeastern Brazil, to participate in this study. These primary care units form part of the Brazilian public healthcare system, which serves the population in places near patients’ homes. The eligibility criteria for the study were that the subjects needed to: i) be using anti-hypertensive medications; ii) be over the age of 18 years old; iii) have no presence of diabetes or cardiovascular disease (other than hypertension); iv) have no limitations on undergoing isometric handgrip training; and v) not be engaged in any systematic exercise programs assessed through the International Physical Activity Questionnaire. The exclusion criteria were any of the following situations: (a) changes to the type or dose of blood pressure control medicine; (b) engaging in another exercise program; or (c) taking part in less than 80% of the isometric handgrip training sessions.https://www.randomizer.org), with stratiﬁcation according to sex and baseline office systolic BP (done by a researcher who did not participate in the subject recruitment or data collection), into two groups: IHT group and control group. The allocation information was concealed from the researchers performing the measurements.The participants were block-randomized using a random number table , done through a handgrip dynamometer  at 30% of each patient's maximal voluntary contraction, which was established at the start of each session via the handgrip dynamometer. The Zona Plus dynamometer was developed specifically for isometric handgrip training. The screen in the device provides instantaneous feedback of the amount of force and indicates whether the amount of force applied is sufficient for the intensity selected. In addition, the device has a timer that provides information regarding the duration of the exercise and the rest intervals. Patients allocated to the control group were encouraged to increase their level of physical activity, but with no particular guidance on physical activity.Cardiovascular variables were measured at the baseline and at a follow-up (12 weeks later). The participants received the following instructions for what they should do before the cardiovascular evaluations: (a) have a light meal prior to arrival at the laboratory; (b) refrain from moderate-to-vigorous physical activity for at least 24 h before to the visit; and (c) refrain from smoking or alcohol or caﬀeine consumption for at least 12 h. Researchers who were blinded to the group allocations collected the data. The post-intervention evaluation was performed at least 72 hours after the last exercise session.19 The intraclass correlation coeﬃcient for systolic BP was 0.85, and for diastolic BP it was 0.92.20The office BP was measured through the Omron HEM 742 device . After 10 minutes of supine rest, at least three consecutive measurements with one-minute intervals between them were assessed. The measurements were made on the right arm, with an appropriate cuﬀ size for the arm circumference.21 Also, patients were counseled to report crucial everyday activities, such as meals, movement from one place to another and medications.The ambulatory BP was obtained through an oscillometric device  that had previously been set up for performing BP assessments every 15 minutes during the daytime period and every 30 minutes during the nighttime, based on previously reported procedures.22 All heart rate variability analysis procedures followed previously described guidelines.23 The Kubios HRV software  was used for the analysis. The time  and frequency  domain variables were obtained.The heart rate variability was evaluated from the RR intervals, measured through a heart rate monitor  in the supine position for 10 minutes. At least five minutes of stationary R-R interval data were analyzed. All analyses were carried out by a single experienced evaluator who was blind to the group allocations. The intraclass correlation coefficient for this evaluator spanned from 0.990 to 0.993.24 Given an expected reduction of 6.0 ± 4.6 mmHg and α of 0.05 and β of 0.20, an estimated sample size of 28 participants (14 per group) was deemed sufficient.To determine the sample size, we used previously demonstrated data on the mean reduction and standard deviation (SD) of office systolic BP following IHT.Normality and homogeneity of variances were verified by means of the Shapiro-Wilk test and the Levene test, respectively. Clinical characteristics were compared between the groups using the t test, chi-square test and Fisher test. To analyze the effects of isometric handgrip training on BP, generalized estimating equations were used, along with post-hoc pairwise comparison using the Bonferroni correction for multiple comparisons. Effect size (ES) was used to stipulate the magnitude of differences in the same group. Intention-to-treat analysis was used to estimate overall effects, among all the randomized patients while ignoring noncompliance and dropouts, and the data were imputed with linear regression weighted according to group. The signiﬁcance level was set at P < 0.05 (two-tailed testing) for all analyses. The data were presented as means and standard errors or as 95% confidence intervals. Categorical variables were summarized as relative frequencies.The recruitment and intervention periods encompassed July 2017 July to July 2018. The study ﬂowchart is shown in The dropout rates were 51.6% in the isometric handgrip training group and 53.1% in the control group. Through comparing the characteristics of the patients who were included and the dropouts in the isometric handgrip training group , only a The intent-to-treat analysis did not reveal any significant effect from the IHT program on any of the outcome variables measured (data not shown).The main results of this study in a primary healthcare unit were the following: (i) IHT reduced office systolic BP among medicated hypertensive individuals; (ii) no effects were observed in relation to office diastolic BP, heart rate variability or ambulatory BP in medicated hypertensive patients.15 The magnitude of the reduction in office systolic BP was approximately 8 mmHg, which was similar to findings from previous clinical trial studies conducted in laboratory or home settings.25 Moreover, the analysis on individual responses indicated that 63% of the patients showed reductions in systolic BP of more than 5 mmHg, which may represent a reduction of at least 7% in the risks of stroke, coronary disease and death.26 Thus, IHT may be incorporated as alternative strategy for controlling office systolic BP in medicated hypertensive individuals who are treated in a primary care unit.The main novelty of this study was that the IHT program was conducted in a primary healthcare unit, which is a real-world setting for supervised training. We demonstrated that there was a reduction in office systolic BP in medicated hypertensive individuals, which corroborates previous studies conducted in laboratory or home settings.7 After six weeks of IHT in a laboratory setting, Peters et al. did not observe any reduction in office diastolic BP, although they observed a reduction in office systolic BP.27 Similarly, Taylor et al. demonstrated that there was a decrease in office systolic BP, but not in diastolic BP, after 10 weeks in a laboratory setting.28 Lastly, after 12 weeks of IHT in a laboratory or home setting, Gordon et al. did not find any reduction in diastolic BP.15On the other hand, 12 weeks of IHT performed in a primary healthcare unit did not change office diastolic BP in these medicated hypertensive individuals. Although this result contrasts with the findings from some studies, there are other studies that also reported that there was no reduction in diastolic BP after IHT, among hypertensive patients.29It is not clear why office systolic BP, but not diastolic BP, was found to have decreased after the 12-week training period. One possible explanation is that the patients included in the present study presented well-controlled values for diastolic BP in the pre-intervention period  and, as such, may have had a lower capacity for BP reduction through IHT. In fact, a previous study reported that individuals with higher pre-training resting BP had a greater post-training hypotensive response.13 In contrast, Taylor et al. found improvements in high-frequency spectral power among uncontrolled hypertensive individuals after supervised isometric handgrip training. Interestingly, in Taylor's study, the baseline BP values were higher than those of the present study (156 versus 129 mmHg). This indicates that isometric handgrip training might lead to improvements in autonomic cardiac modulation in individuals with uncontrolled BP.28 Therefore, it is possible that other mechanisms are involved in the reduction of BP after IHT.30In the present study, 12 weeks of IHT in hypertensive individuals did not have the capacity to promote improvement in cardiac autonomic modulation to the heart. Farah et al. did not find any improvements after 12 weeks of supervised or home-based isometric handgrip training in hypertensive individuals who were using medications. Similarly, Stiller-Moldovan et al. did not find any changes in cardiac autonomic modulation after 8 weeks of isometric handgrip training in hypertensive patients.31 that a reduction in arterial stiffness occurs in hypertensive individuals who are responsive to isometric handgrip training. In addition, Peters et al. showed that there was enhancement of oxidative stress after six weeks of training and McGowan et al. observed improvement in endothelial function after eight weeks of IHT.32Recently, our group demonstrated33 Our results indicated that there was no reduction in any of the ambulatory BP measurements after 12 weeks of IHT performed in a primary healthcare unit and are in agreement with previous studies.13 A study conducted by Stiller-Moldovan et al. did not observe any reduction in ambulatory BP after eight weeks of isometric exercise training performed at 30% of maximal voluntary contraction.13 Moreover, Pagonas et al. also showed that there was no reduction in ambulatory BP after 12 weeks of handgrip exercise training performed five times per week at 30% of maximal voluntary contraction, in a hypertensive population.12 Therefore, these results indicate that isometric handgrip training presents only a transient effect on BP that is only observed in office BP and is not prolonged during ambulatory activities.Ambulatory BP has been considered more important than office BP, in terms of clinical perspective, since it presents better prediction of target organ damage and cardiovascular mortality.10 The benefits of this type of training comprise its ease of application and the short time that needs to be dedicated to implementing the exercise, such that it is ideal for application in primary care and in non-laboratory settings. In fact, three sessions per week and 12 minutes per session (i.e. 36 minutes per week) is less time than the current recommendations35 for physical exercise (150 minutes per week), which therefore enables avoidance of important barriers to physical activity practice among patients with cardiovascular diseases.37The American Heart Association and American College of Cardiology have recommended isometric handgrip training as a potential alternative strategy for lowering BP in the hypertensive population.In the present study, we demonstrated that isometric handgrip training reduces office systolic BP in medicated hypertensive patients who were attended in primary healthcare settings. However, we failed to show that this has any efficacy with regard to office diastolic BP, ambulatory BP or heart rate variability parameters. In addition, our dropout rate was higher than in previous studies conducted in laboratory or home settings, which suggests that caution is required in implementing isometric handgrip training in primary care settings.38The present study presents limitations that should be considered. The sample size did not allow for stratiﬁed analysis according to the medication used. This might have enabled comprehension of the mechanism(s) of BP lowering after isometric handgrip training. Generalizations of these findings to other populations (either those with advanced hypertension or other populations) must be made with care. The dropout rate in this study was higher than that we would have liked. It is not possible to assume that similar results would be observed among patients who dropped out of the program, and these data should be considered with caution. In addition, we did not do intention-to-treat analyses. Although without any statistically significant difference, the control group was heavier than the IHT group, and this needs to be taken into account. Lack of control regarding physical activity in both groups was also a limitation, although none of the patients engaged in any exercise programs. Lastly, other mechanisms for BP lowering after isometric handgrip training, such as baroreﬂex sensitivity, vascular measures or use of biomarkers, were not assessed.Isometric handgrip training performed in a primary care setting reduced office systolic BP in hypertensive patients, whereas no effects were observed in relation to office diastolic BP, ambulatory BP or heart rate variability.


Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures , two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47–2.52)] or TNFR1 [HR 5.38 (95%CI 5.26–5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors. Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) in Japan , 2. It iProgranulin (PGRN), also known as granulin-epithelin precursor (GEP), proepithelin, acrogranin, and GP88, is a growth factor composed of 593 amino acids and is abundantly expressed in a broad range of tissues and cell types. As a unique pleiotropic factor, PGRN is involved in many cellular processes and diseases such as embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration, and lysosome function (via its competitive binding to tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2)  , Alzheimd TNFR2)  and inteWe found that circulating levels of TNFR were robust predictors of GFR decline in patients with various stages of both type 1 and 2 diabetes , 15. Sin2 of body-surface area, more than 2 years of follow-up, and ability and willingness of the subject to cooperate with the study protocol. The final sample size included 201 participants. This study was approved by the Institutional Review Board of Juntendo University, Tokyo, Japan (document no. 778). All participants provided written informed consent, and this study complies with the ethical principles of the Declaration of Helsinki.Between November 2011 and December 2020, we enrolled 264 patients with type 2 diabetes mellitus who were ≥ 20 years of age at Juntendo University Hospital in Tokyo, Japan. They were required to have eGFR, as calculated by the equation defined by the Japanese Society of Nephrology, of ≥30 ml/minute/1.73 mBlood samples were obtained at the time of registration and rapidly centrifuged at 4°C. Supernatants were transferred to RNase-free tubes and stored at a temperature of −80°C until utilized in subsequent assays. We used an enzyme-linked immunosorbent assay (ELISA) to measure PGRN and TNFR1  following a previously described method –23.2). The secondary outcome was all-cause death.The primary renal composite outcome of this study was the first occurrence of any of the following: a decline of at least 57% in eGFR from baseline , or the onset of ESRD .All variables were expressed as percentages for categorical data, and as the means ± standard deviation (SD) or median and interquartile ranges for continuous data with or without a normal distribution, respectively. Patients were stratified according to their quartile PGRN and TNFR1 levels for analytical purposes. The event cumulative risk was derived from the Kaplan–Meier method. The Cox proportional hazards model was used to identify independent predictors for developing a primary or secondary endpoint. The hazard ratio (HR) for the risk of a composite with 1 SD increase of logarithmic transformation of each protein was computed by Cox regression after adjusting for age, sex, body mass index (BMI), baseline eGFR, and the urine albumin-to-creatinine ratio (UACR). Pearson’s correlation coefficient was employed to test the correlations between different variables. Before testing the correlations, all non-normally distributed values were log-transformed to better approximate normal distributions. Next, stepwise multiple linear regression was performed to determine the factor that affects the serum PGRN level. A 2; the median eGFR was 73 ml per minute per 1.73 m2; and the median UACR was 23, with albumin measured in milligrams and creatinine in grams. The median follow-up was 7.6 years . A total of 120 (59.7%) and 67 (33.3%) patients were treated with renin-angiotensin system (RAS) blockers and insulin therapy, respectively.The baseline characteristics of the study patients are presented in The median serum PGRN was 59 (52–68) ng/mL in all samples. Stratifying by the PGRN median in two groups, patients with above the median of PGRN were more likely to be associated with low eGFR, high UACR, and high C-reactive protein (CRP).The associations of clinical parameters with serum PGRN or TNFR1 levels are presented in During follow-up, 21 out of 201 patients reached the primary kidney composite outcome and only 5 patients died before reaching the primary outcome. No one reaches ESRD before 57% eGFR decline from the baseline. Univariate analysis showed that the BMI, eGFR, UACR, TNFR1, and PGRN were significantly associated with the risk for renal composite outcome Table 4.As shown in In the present study, we investigated the role of PGRN as a prognostic biomarker of kidney function decline in Japanese patients with type 2 diabetes. This study demonstrated that high levels of serum PGRN are associated with eGFR decline independently of baseline eGFR and albuminuria. However, these associations were no longer statistically significant after further adjustment for TNFR1, probably due to the small size of the study sample.Tang et al.  demonstrin vitro and in vivo and may be involved in the development of obesity-associated insulin resistance, while deficiency of PGRN provides protective action in this condition  grant number 20K08617 to TG.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Introduction: Over the last decades, several scores have been developed to aid clinicians in assessing prognosis in patients with heart failure (HF) based on clinical data, medications and, ultimately, biomarkers. Lung ultrasound (LUS) has emerged as a promising prognostic tool for patients when assessed at discharge after a HF hospitalization. We hypothesized that contemporary HF risk scores can be improved upon by the inclusion of the number of B-lines detected by LUS at discharge to predict death, urgent visit, or HF readmission at 6- month follow-up.Methods: We evaluated the discrimination improvement of adding the number of B-lines to 4 contemporary HF risk scores  by comparing the change in the area under the receiver operating curve (AUC), the net reclassification index (NRI), and the integrated discrimination improvement (IDI). The population of the study was constituted by the 123 patients enrolled in the LUS-HF trial, adjusting the analyses by the intervention.Results: The AUC of the GWTG score increased from 0.682 to 0.789 (p = 0.02), resulting in a NRI of 0.608 and an IDI of 0.136 (p < 0.05). Similar results were observed when adding the number of B-lines to the MAGGIC score, with an AUC that increased from 0.705 to 0.787 (p < 0.05). This increase translated into a NRI of 0.608 and an IDI of 0.038 (p < 0.05). Regarding Redin-SCORE at 1-month and 1-year, the AUC increased from 0.714 to 0.773 and from 0.681 to 0.757, although it did not reach statistical significance (p = 0.08 and p = 0.06 respectively). Both IDI and NRI were significantly improved . Lastly, the AUC for the BCN Bio-HF score increased from 0.733 to 0.772, which was statistically non-significant, with a NRI value of 0.363 (p = 0.06) and an IDI of 0.092 (p < 0.05).Conclusion: Adding the results of LUS evaluated at discharge improved the predictive value of most of the contemporary HF risk scores. As it is a simple, fast, and non-invasive test it may be recommended to assess prognosis at discharge in HF patients. Risk prediction in heart failure (HF) remains essential to identify those patients who may benefit from a closer management. Since the turn of the century, several scores have been proposed and externally validated . Most caAs HF treatment has dramatically evolved during the last decades, existing prognostic scores, have been continuously updated adding emerging data from both newer therapeutic and diagnostic tools . ParticuThus, we hypothesized that contemporary risk scores can be improved by incorporating the number of B-lines detected by LUS at HF discharge to predict death or hospital readmission at 6- month follow-up.This is a sub-analysis including 123 patients enrolled in the LUS-HF trial, whose study design and primary results have been previously reported . In brieThe primary endpoint was a composite of urgent visit, hospitalization for worsening HF, and death at 6 months. Urgent visits for worsening HF were defined as visits to the emergency department or un-scheduled visits to the HF unit as a result of signs and/or symptoms of worsening HF that required intravenous diuretic treatment or diuretic increase with a hospital stay of <24 h. Hospitalization for worsening HF was defined as a stay in hospital for >24 h mainly as a result of signs and/or symptoms of worsening HF. The reported events were reviewed by an independent panel of investigators.The protocol was approved by the ethics committee and the study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients prior to study participation.According to current expert recommendations , LUS wasFor this post-hoc analysis, the number of B-lines detected by LUS at discharge was analysed.We selected 4 contemporary scores: Get with the Guidelines, MAGGIC, Redin-SCORE and BCN Bio-HF.The GWTG-HF score incorporates 9 variables , body mass index (BMI), total cholesterol, high-density lipoprotein cholesterol, QRS duration, smoking status, use of antihypertensive medication, use of diabetes medication) to predict the risk of in-hospital mortality for patients hospitalized with HF.The MAGGIC score was derived from a metanalysis of 30 studies to predict mortality rates in patients with HF, and includes 13 predictors: age, lower ejection fraction (EF), New York Heart Association (NYHA) class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower BMI, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed angiotensin converter enzyme inhibitors (ACEi) or angiotensin-receptor blockers.The Redin-SCORE is a risk score developed to predict short-term (1 month) and long-term (1 year) risk of HF in ambulatory patients. Predictors of 1-month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate (eGFR) < 60 ml/min/m2. Predictors of 1-year readmission were elevated natriuretic peptides, anaemia, left atrial size >26 mm/m2, heart rate >70 beats per minute (bpm), LV HF signs, and eGFR <60 ml/min/m2.The first version of the BCN Bio-HF included clinical variables, medications, conventional laboratory analytes , and NT-proBNP, high-sensitivity troponin T (hs-TnT), and interleukin-1 receptor-like-1 (known as ST2). It was updated in 2018 by incorporating the use of angiotensin receptor neprylisin inhibitor (ARNI), cardiac resynchronization therapy (CRT), and implantable cardioverter defibrillator (ICD).Continuous variables are expressed as mean (standard deviation) or as median (interquartile range) whenever appropriate. Differences in continuous variables were tested by the analysis of variance (ANOVA), Student’s t-test, or Wilcoxon signed rank test for independent samples. Categorical variables were presented as frequency and percentage. Differences in the categorical variables were assessed by the χ2 test or by Fisher’s exact test.p < 0.05 was considered significant.Discrimination, calibration and reclassification methods are recommended when evaluating candidate variables in prognostic studies . Thus, wClinical characteristics of the LUS-HF population and LUS data at discharge are shown in Regarding reclassification indexes, both NRI and IDI after adding the number of B-lines showed a significant improvement with all scores, except for NRI in BCN Bio-HF score. As Our work shows that the predictive value of contemporary HF risk scores can be improved by integrating LUS.Prior research  has alreLUS has emerged in the last decade as a simple, fast, and non-invasive test for lung congestion quantification. Several studies have shown that it might be a better tool for detecting subclinical pulmonary congestion than clinical assessment  and it hAs NT-proBNP, it has also been reported that the presence of B-lines in HF patients is an independent prognostic factor  althoughMoreover, the number of B-lines is not only a prognostic marker but has shown to be also a therapeutic target in HF patients improving their prognosis when monitored during follow-up, mainly due to a reduction of HF decompensations . As it iRisk stratification remains essential in HF to make medical decisions based on life expectancy and develop appropriate treatment plans, but the accuracy of available prognostic risk scores in patients with HF is still limited. Our study contributes on this important issue by integrating in existing contemporary HF risk scores LUS and allowing for a significant improvement in their predictive value in the majority of cases.Some variables included in the pre-existing predictive HF models are not frequently obtained in the clinical care of HF, but LUS can be performed quickly and easily at bedside, and has already become an add-on to lung auscultation for the evaluation of pulmonary congestion.As a semi-quantitative measure of pulmonary congestion, LUS adds new and valuable information to the scores. Due to its dynamic behaviour, it can be used as a monitoring tool allowing reassessment of patient’s status whenever clinical situation changes, and also as a therapeutic target. Several studies had proved a LUS-guided therapy reduces acute decompensation events in the follow-up , which eOur study has some limitations. First, we tested prognostic scores which were specifically designed for ambulatory HF patients in a sample that was comprised by HF patients discharged from hospital. Second, LUS-HF was designed for a 6-month follow-up which may have determined an underestimation of the number of events, since some scores were originally designed to predict longer time points. Also, this is a retrospective (not pre-specified) analysis of the LUS-HF. Finally, our analysis accounts for a composite endpoint consisting in HF hospitalizations, urgent visits for worsening heart failure and all-cause mortality so it may not be generalized to prognostic risk scores specifically designed for other outcomes.We consider our study as hypothesis generating and acknowledge the need of testing the hypothesis in other HF larger cohorts, especially multicentric and with a longer follow-up.Adding the results of LUS evaluated at discharge improved the predictive value of most of the contemporary HF risk scores. As it is a simple, fast, and non-invasive test it may be recommended to assess prognosis at discharge in HF patients.


Liquid biomarkers have shown increasing utility in the clinical management of airway diseases. Salivary and blood samples are particularly amenable to point-of-care (POC) testing due to simple specimen collection and processing. However, very few POC tests have successfully progressed to clinical application due to the uncertainty and unpredictability surrounding their diagnostic accuracy.To review liquid biomarkers of airway diseases with well-established diagnostic accuracies and discuss their prospects for future POC applications.A literature review of publications indexed in Medline or Embase was performed to evaluate the diagnostic accuracy of liquid biomarkers for chronic obstructive pulmonary disease (COPD), asthma, laryngopharyngeal reflux (LPR), and COVID-19.Of 3,628 studies, 71 fulfilled the inclusion criteria. Sputum and blood eosinophils were the most frequently investigated biomarkers for the management of asthma and COPD. Salivary pepsin was the only biomarker with a well-documented accuracy for the diagnosis of LPR. Inflammatory blood biomarkers  were found to be useful to predict the severity, complications, and mortality related to COVID-19 infection.Multiple liquid biomarkers have well-established diagnostic accuracies and are thus amenable to POC testing in clinical settings. POC technology allows certain molecular and antigen tests to be performed and analyzed rapidly anywhere in a near-patient setting, such as in patients’ homes or at their bedsides . BiofluiA growing number of liquid biomarkers have been associated with airway diseases. The airway tract is comprised of the organs involved in respiration, speech, and deglutition, including the nose, oral cavity, pharynx, larynx, trachea, bronchi, and lungs . Airway Although biofluid samples can be easily obtained in physicians’ offices or outside of the healthcare setting , POC testing has yet to be made widely available for the management of airway diseases. A long-standing and legitimate barrier to the implementation of POC testing is the uncertainty surrounding the diagnostic accuracy of liquid biomarker measurements . In thisFour common airway and pulmonary conditions, namely asthma, COPD, LPR, and COVID-19, were included in this review. The biomarkers of these four conditions were the most abundantly researched and could be tested through biomarker detection devices available on the market.“biological marker”; “biomarker”; “biologic marker”; “diagnostic accuracy”; “sensitivity and specificity”; “sensitivity”; “specificity”; “laryngopharyngeal reflux”; “proximal reflux”; “hypopharyngeal reflux”; “extra-esophageal reflux”; “reflux laryngitis”; “COVID-19”; “coronavirus disease 2019”; “COPD”; “chronic obstructive lung disease”; “chronic obstructive pulmonary disease”; “emphysema”; “chronic bronchitis”, and “asthma”  framework was used to guide the search and the reporting of the review . Two dat“asthma” .Studies were included if they reported the diagnostic accuracy of at least one liquid biomarker by providing measures of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC). Studies were required to include human adult subjects with a diagnosis of COPD, asthma, laryngopharyngeal reflux, or COVID-19 infection. Only articles written in English were included due to limited resources for the translation of studies.Studies that did not report a complete set of diagnostic accuracy measures  for at least one liquid biomarker were excluded. Studies conducted in animal or pediatric populations were excluded. Articles written in languages other than English were also excluded.Sources were assessed in a two steps-process to determine their relevance to this study’s objectives. The first step (screening) included a review of titles and abstracts to discard sources that did not match the inclusion criteria. The second step (eligibility assessment) consisted of a full-text assessment of all remaining articles against the eligibility criteria.The literature search yielded 3,628 results that were imported into the Covidence systematic review software Version v2625  for screening and eligibility assessment . Nine reChronic obstructive pulmonary disease (COPD) refers to a group of poorly reversible and progressive respiratory conditions, mostly seen in patients with dyspnea, chronic cough, sputum production, and a history of exposure to risk factors of the disease (such as primary or secondary cigarette smoke exposure) , 20. TheVarious COPD classification systems have been proposed over the years, moving away from the classical binary classification of COPD as emphysema and chronic bronchitis . Some ofThe natural history of COPD is punctuated by periods of acute worsening of respiratory symptoms called acute exacerbations (AECOPD), and a gradual decline in lung function, all of which can eventually lead to death . In the Other blood biomarkers have been studied for their ability to diagnose complications among AECOPD patients, such as left and right ventricular failure and pulmonary hypertension –37. CA-1The measurement of COPD exacerbation biomarkers is not yet employed in routine clinical practice. Aside from lung function parameters, very few biomarkers are routinely used for the clinical management of COPD . The 202n = 2 studies assessing diagnostic biomarkers for COPD, n = 2 studies for AECOPD, n = 5 studies for AECOPD complications, n = 4 studies for COPD phenotype, and n = 5 studies for COPD prognostics). The collection of a plethora of detailed genetic and biochemical data from large cohorts (such as COPDGene and SPIROMICS cohorts) have led to an explosion of smaller studies investigating newer biomarkers , which unfortunately often remain with uncertain diagnostic accuracies , and others were proposed for the diagnosis of asthma , 48–50 . For theAsthma is now recognized as a heterogeneous disease characterized by distinctive endotypes and phenotypes. Asthma endotypes can be broadly categorized into T2-high and non-T2 asthma  Airway eAsthma biomarkers have been proposed to classify the disease according to endotypes and phenotypes. Being able to make such classification is notably useful in the health care setting due to their inherent therapeutic and prognostic implications and may provide the basis for personalized medicine . While p(1)Confirm refractory type 2 inflammation (blood or sputum eosinophils).(2)Assess severe asthma phenotypes (blood or sputum eosinophils).(3)Adjust treatment for adults with persisting symptoms and/or exacerbations despite high dose ICS or ICS-LABA in the presence of sputum eosinophilia (>3%).(4)Increase ICS dose independently of the level of symptom control in adults with sputum eosinophilia (>3%).(5)Guide treatment for adults with moderate to severe asthma who are treated or can be referred to centers experienced with sputum induction testing.(6)Confirm type-2 inflammatory phenotype in patients refractory to high dose ICS-LABA before prescribing type-2 biologic targeted therapy, such as anti-IL5, anti-IL5R, or anti-IL4R (must have blood eosinophilia but cut-off points may vary according to location) .Sputum eosinophils are generally considered to be reliable biomarkers of Th2 airway inflammation in asthma . In orde9/L and 0.33×109/L  found in blood could differentiate AERD patients from aspirin-tolerant asthma patients with relatively low sensitivities of 34–65%, but high specificities of 85–93% , 68. RegAsthma biomarkers can also be used to predict response to pharmacological treatments , 70. Spun = 17 studies), they were evaluated for a wide range of clinical purposes ranging from diagnosis of occupational asthma, non-occupational asthma, and asthma phenotype to the prediction of responsiveness to oral steroids, and the monitoring of disease control. This heterogeneity likely contributed to the high degree of variability in diagnostic accuracies reported across the literature.Included studies were highly heterogenous in terms of population studied, with sample sizes ranging from 6 to 562 cases, and studies including patients with various degrees of asthma control and subtypes of disease, e.g., occupational, and non-occupational, eosinophilic, neutrophilic, or AERD asthma phenotypes, etc. Moreover, few studies evaluated the same biomarkers for the exact same purposes. Overall, 23 different biomarkers or biomarker scores were evaluated across 29 studies. While eosinophils were some of the most frequently studied biomarkers  and clinical manifestations (phenotypes). However, these advances have predominantly been made in T2-high asthma, which is reflected in our literature search highlighting mainly type 2 inflammatory biomarkers such as eosinophils, IgE, periostin, T2-ILC, and IL-13. New serum biomarkers such as IL-17, chitinase-3-like protein 1, and ceramide to sphingosine-1-phosphate ratio are also proposed as diagnostic biomarkers for T2-low asthma . Large cvia microfluidic POC platforms with multiplex capability  . The 24-Laryngoscopic examination is more readily available than 24h-HEMII-pH and is considered to be an important screening tool for the diagnosis of LPR . HoweverIt has thus been argued that there is currently no ideal procedure for the diagnosis of LPR, with each existent diagnostic method involving its own limitations . For thiPepsin is a proteinase secreted by the chief cells of the gastric fundus and body . It is fWhen 24-h pH monitoring is used as a gold-standard method to establish the diagnosis of LPR, the sensitivity and specificity of salivary pepsin vary between 42–85% and 28–86%, respectively  Table 3Table 3. Due to the imperfect sensitivities and specificities of the gold-standard diagnostic methods used for comparison in these studies, the true diagnostic accuracy of salivary pepsin is difficult to determine. At the same time, the wide variability of salivary pepsin diagnostic accuracy values reported in the literature may complicate the interpretation of test results and may justify advocating for its use in combination with other biomarkers or diagnostic methods. Other emergent biomarkers, such as carbonic anhydrase type III, e-cadherins, mucins, and interleukins were also suggested as potential diagnostic biomarkers for LPR . HoweverSince the onset of the COVID-19 pandemic in March 2020, nearly 280 million people have contracted the disease and nearly 5.5 million COVID-19-related deaths have been recorded worldwide  . In an eWhile the development of a vast array of diagnostic tests has allowed for increased rapidity and accuracy of diagnosis, significant progress remains to be made when it comes to the risk-stratification of infected patients. COVID-19 is not only a localized respiratory infection, but also a multisystem inflammatory disease involving complex immunological, inflammatory, and coagulative cascades . Of patiVarious peripheral blood biomarkers such as serum CRP, D-dimers, fibrinogen, procalcitonin, cytokines, electrolytes, blood cell counts, and blood cell count ratios have been studied for their ability to predict disease progression from non-severe COVID-19 to more severe forms of the disease –105. D-dOther candidate biomarkers for the prediction of mortality include ferritin, inflammatory cytokines , troponin 1, mid-regional proadrenomedullin, blood cell counts, and blood cell count ratios , 106–117To date, most risk-stratification clinical tools for the prediction of COVID-19 severity have used an imperfect combination of few clinical and biological variables. There is an urgent need for the development of accurate risk-stratification algorithms allowing for the early identification of patients at risk of severe COVID-19 disease, particularly in a context of limited human and material resources. More research on prognosis biomarkers of COVID-19 will allow for better integration of clinical and laboratory data and the creation of comprehensive and accurate risk-stratification algorithms. These risk-stratification systems could play a decisive role in the planning of patient management and future utilization of available resources.As the field of liquid biomarkers continues to advance, novel biomarkers are discovered with uncertain diagnostic accuracies or cohort reproducibility . In the ® to monitor pH levels and pepsin concentration  and lateral flow assays (LFAs) such as the Peptest ntration . Similarntration , 131. Eantration , 133. Adntration –136. Irrntration .To address the limitations of current methods, novel microfluidic detection devices are being actively explored to develop POC testing capable of delivering accurate, rapid, inexpensive diagnoses –142. MicMicrofluidic devices have been proposed to analyze biomarkers present in various biofluids including saliva, sputum, and blood –156. BloBy analyzing specific biomarkers, several devices have been applied for diagnosing asthma, COPD, and COVID-19 , 160. FoThe simplicity of POC technology is critical to promoting its accessibility and devolving testing away from laboratories to help streamline the future of diagnostic technology . As thesPoint-of-care research also aims to diversify the output that a single sample can provide by expanding the multiplex capacity of testing platforms . If multAside from the technical challenges that remain for POC testing, administrative obstacles must be realized and overcome to deploy POC devices to the general public. A top-down approach driven by a limited number of health professionals has proven ineffective in practice . EstabliThe landscape of biomarkers for airway diseases remains extremely vast and highly heterogeneous. Nonetheless, research efforts and financial investments have facilitated the discovery of a variety of promising biomarkers, among which a few have well-circumscribed diagnostic accuracies and can reliably be used clinically. For communicable airway diseases like COVID-19, diagnosis is largely based on direct detection of the viral load whilst supplementary biomarkers are needed for risk stratification and severity prediction. For non-communicable airway diseases, liquid biomarkers have various clinical applications. For instance, sputum and blood eosinophils can be used for the phenotyping and endotyping of asthma, blood eosinophils to guide management of COPD, and salivary pepsin to diagnose LPR.Despite considerable progress, the majority of microfluidic POC devices remain at a pre-clinical, developmental stage. The lack of standardization across device fabrication and the difficulty in incorporating multiple testing components into a single device present obstacle for manufacturing and scaling-up production. From a testing standpoint, the technical complexity and validation challenges remain limiting factors for device translation to clinical settings. That said, the field of diagnostics continues to transition toward detection devices based on ease of use, low sample volume, and rapid results. Given the ongoing drive to develop microfluidic systems that are simple to use and sensitive, microfluidic systems will continue to trend toward becoming an indispensable part of the healthcare industry as a critical element of POC-based disease diagnosis and pathogen detection in airway diseases.VL and NL-J conceived the manuscript. VL, PC, and NL-J wrote the manuscript. VL designed the figures and tables. All authors read and approved the manuscript.The presented content is solely the responsibility of the authors and does not necessarily represent the official views of the above funding agencies.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Hypertension as a major risk factor for cardiovascular diseases is among the leading causes of death worldwide. The relationship between elevated serum levels of liver enzymes and hypertension has been reported in limited studies, and to the best of our knowledge, there are no previous reports in the literature on this issue in the southeast of Iran. Our investigation aimed at evaluating the relation between ALT, AST, GGT, and ALP with hypertension in the Rafsanjan Cohort Study, a city in Kerman Province, Iran.  In this cross-sectional study, we used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in Iran (PERSIAN). The association of the liver enzymes levels with hypertension was investigated using the multivariable logistic regression models.  Among 9930 participants, the mean age (±SD) was 49.94 (±9.56) years, and 46.56% were men. The odds of abnormal blood pressure significantly increased along with the higher levels of ALT, GGT, and ALP which remained significant only for ALP after adjustment for all confounding variables in both males and females . In subjects with normal levels of ALT, AST, GGT, and ALP, dose-response increases were observed for abnormal blood pressure in both genders. Finally, we found that, among liver enzymes, only elevated ALP was significantly correlated with the odds of stage 1 hypertension and stage 2 hypertension for both genders.  In subjects with normal levels of ALT, AST, GGT, and ALP, dose-response increases were observed for abnormal blood pressure in both genders. Increased serum ALP activity was positively associated with increased odds of hypertension in males and females. Therefore, increased ALP could be an early indicator of hypertension. Hypertension is one of the major causes of premature death globally. Estimates suggest that the prevalence of hypertension in low- and middle-income countries 31.5%) was higher than that in high-income countries 28.5%)  as appropriate and categorical variables as the frequency and percentage. Also, baseline characteristics of individuals were compared across the groups of high blood pressure  and serum concentrations of liver enzymes, using the chi-square test for categorical variables and one-way ANOVA test for normally distributed quantitative variables and the Kruskal-Wallis test for nonnormally distributed quantitative variables.P value <0.25 were selected as confounders. First, to investigate the associations using linear regression, the assumption of normality of the distribution of liver enzymes and linear correlation between those factors with blood pressure was tested using normal probability plots (skewness and kurtosis index) and scatter plots, respectively. Due to nonnormal distribution of data and to improve normality and linear correlation, log transformation was done for all liver serum enzymes in all analyses. The assumption of normality and linear correlation was valid for log-transformed variables except for GGT.Associations between blood pressure and liver enzymes were evaluated by crude and adjusted models in the sex-specific regression analysis, and confounder's variables were identified using relevant epidemiological texts and based on subject matter knowledge. Potential confounding variables were sequentially entered into models according to their hypothesized strengths of association with serum concentrations of liver enzymes and high blood pressure. To reach this goal, confounding variables with a The associations between continuous values of blood pressure and log-transformed (except GGT classified by median) of each serum concentration of liver enzymes were evaluated by crude and multiple linear regression analysis. In linear regression models, the collinearity of the variables was examined by calculating the variance inflation factor using multiple linear regression analysis. Findings of the model indicated prominent collinearity between cholesterol and LDL cholesterol, and accordingly, we selected LDL cholesterol in the regression model for further analyses. Data were presented as unstandardized and standardized regression coefficients and 95% confidence intervals (CIs). In addition, we used dichotomous logistics regression analysis to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hypertension and liver enzymes levels. The baseline model is stratified on the status of serum concentrations of liver enzymes. Adjusted model 1 was adjusted for age, gender, education years, and wealth status index. Adjusted model 2 has additional adjustments for cigarette smoking, alcohol drinking, opium consumption, BMI, and physical activity level. Adjusted model 3 has additional adjustments for diabetes, family history of hypertension in first-degree relatives, and family history of hypertension in second-degree relatives. Adjusted model 4 includes all variables considered in adjusted model 3, plus triglycerides, LDL, HDL, taking hepatotoxic drugs, and fatty liver.P values are two-sided, and P values <0.05 and 95% confidence intervals were considered statistically significant.In addition, logistic regression analysis was performed to assess the association between hypertension and the serum levels of liver enzymes within normal ranges. To reach this goal, levels of serum concentrations of liver enzymes were categorized into quartiles within normal ranges and elevated levels to test for possible dose-related response relationships. Finally, we used multinomial logistic regression models to strengthen the relationship between the level of liver enzymes with a stage of high blood pressure . All analyses were performed through State V.12. All n = 5656), elevated BP (n = 297), stage 1 hypertension (n = 1486), and stage 2 hypertension (n = 2491). Among all participants, the prevalence of elevated BP, stage 1 hypertension, and stage 2 hypertension was estimated at 2.99%, 14.96%, and 25.09, respectively. Elevated AST, ALT, GGT, and ALP were observed in %3, %8.94, % 10.24, and %9.79 of subjects, respectively.In this study, 9930 participants in the baseline phase of the Rafsanjan adult cohort study who completed the medical questionnaire were included. From this population, 4623 (46.56%) were male and 5307 (53.44%) were female. P < 0.001) while the mean level of HDL was not a significant variable for hypertension (P > 0.05).Age, gender, education level, physical activity, alcohol and opium consumption, cigarette smoking, BMI, wealth score index, diabetes, family history of hypertension, fatty liver and taking hepatotoxic drugs, the levels of cholesterol, triglycerides, LDL, HDL, FBS, AST, ALT, GGT, and ALP had significant relationships with hypertension . As seen in Additionally, to evaluate the association of the serum levels of liver enzymes with elevated blood pressure, stage 1 hypertension, and stage 2 hypertension according to sex, sex-specific analyses were done e . In the The prevalence of hypertension is increasing globally . Early dThe main finding of this study was that there was a direct association between elevated serum concentrations of ALT, GGT, and ALP and an increased odd of hypertension even after adjusting for some potential confounding variables such as those related to demographic, lifestyle, history of diabetes, and family history of hypertension compared with the individual with normal levels of liver enzymes. When these analyses were adjusted for more confounding variables such as triglyceride, LDL cholesterol, HDL cholesterol levels, hepatotoxic drugs intake, and fatty liver, although no such significant association was observed for ALT and GGT, a positive association was significantly observed between serum ALP and hypertension. This result is consistent with some previous reports that suggest that increased levels of ALP may be associated with the risk of nonhepatic diseases, such as hypertension –12. We aThe association between serum levels of liver enzymes and hypertension has been less reported compared to other medical conditions such as metabolic syndrome and diabetes. A previous study conducted by the United States National Health and Nutrition Examination Survey on 4,155 men and women showed that ALP had a significant association with a higher frequency of hypertension . Yuji ShTehran Lipid and Glucose Study (TLGS) reported that increased levels of ALT, GGT, and ALP were positively associated with hypertension . HoweverA contradiction between the results of our study and the aforementioned studies is possibly due to the fact that more confounders are considered in our study which could be a strength. Furthermore, in the above-mentioned studies, normal blood pressure was defined as an untreated blood pressure less than140/90 mmHg, but in our study, normal blood pressure was defined as an untreated blood pressure less than120/80 mmHg , so baseAlthough the exact mechanism underlying the association between increased serum levels of liver enzymes and risk of hypertension remains unclear , 11, somIn addition, the association between hypertension and serum concentrations of ALT, AST, GGT, and ALP within the normal range was assessed. Our findings showed that, in individuals with normal serum levels of ALT, AST, GGT, and ALP and those with a higher enzyme concentration, odds of high blood pressure was increasing with a dose-response relationship in both males and females. In study of Rahman, the elevated GGT, but not ALT, was associated with the presence of hypertension in males and females. For GGT, in the highest quartile group compared with the lowest quartile, the multivariate-adjusted OR for hypertension was 2.29 1.68–3.14) in males and 1.52 1.27–1.83) in females .14 in ma–12, GGT –1.83 in This study has strengths and limitations. One of the main strengths of our study is its population-based nature with a large sample size, extensive data collection for the exposure of interest (liver enzymes levels), and potential confounders . In the present study, new definitions for blood pressure classification by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline were used which could be another strength. However, the cross-sectional design of the study did not allow deriving any causal inferences and the possible role of elevated liver enzyme levels in hypertension. Accordingly, it is suggested that this relationship be reconsidered in the follow-up phase of this prospective study. Furthermore, we did not have any ideas about the role of specific types of ALP in hypertension, because the ALP's isozymes were not detected in the study.Increased serum ALP activity was positively associated with increased odds of hypertension. Based on the results of the present study, ALP could be helpful for the early detection of hypertension.


Background and Objectives: Blood pressure measurement is essential evidence to establish that the chosen medicine and dosage are appropriate, and also indirectly indicates whether the medicine is being used at all. Therefore, current research compares adherence to the target blood pressure at home and in the hospital between different age groups, using similar combinations of the drugs prescribed by the doctor within ongoing antihypertensive therapy. Moreover, it is very important to develop a method for the determination of amlodipine and its metabolite, which would suitable for clinical applications, when the result is needed as quick as possible. Materials and Methods: This prospective study included patients aged ≥18 years who were diagnosed with hypertension. Subjects were divided into two age groups according to European Society of Cardiology (ESC) hypertension guidelines; older patients (≥65 years) and adult patients (<65 years). Assessment of adherence rate to antihypertensive medications was performed using a measurement of systolic blood pressure and comparing this to ESC hypertension guideline data. A simple liquid chromatography-tandem mass spectrometer (LC-MS/MS) method for determination of amlodipine and dehydroamlodipine was developed and validated according to the European Medicines Agency guideline on bioanalytical method validation at the Latvian Institute of Organic Synthesis. Results: A total of 81 patients with arterial hypertension were enrolled in this study. A significant number of patients were overweight  and obese . To control arterial hypertension, 70 (86.4%) patients used fixed-dose combinations, where one of the components was amlodipine. Practically, 36 (44.4%) hypertensive subjects were not able to comply with target blood pressure. Nonetheless, 38 (46.9%) patients who received fixed-dose combinations were able to comply with target blood pressure. Conclusions: Adherence to ESC hypertension guideline proposed target blood pressure was relatively low among hypertensive subjects even though a significant number of patients were taking fixed-dose combinations. Therefore, optimizing prevention, recognition, and care of hypertensive young adults require intensive educational interventions. Moreover, survey data suggest that therapeutic drug monitoring using the validated simple, sensitive LC-MS/MS method is pivotal for further understanding factors influencing adherence. The prevalence of hypertension continues to rise, making it a leading global health issue. In 2019, the prevalence of hypertension was 34% in men and 32% in women aged 30–79. Hypertension has been identified as a risk factor for the 8.5 million deaths resulting from renal diseases, ischemic heart disease, stroke, and other vascular diseases [In turn, the use of multiple drugs and the possibility of the development of side effects reduces the patient’s adherence and causes further cardiovascular complications. According to the European Society of Cardiology (ESC) hypertension guideline, amlodipine (AML) often predominates as initial treatment as a single tablet or as a component of a fixed-dose combination (FDC) . The druRegardless of the medication prescribed, it is important that the patient is adherent and has regular blood pressure monitoring. A low level of adherence in chronic conditions is associated with poor outcomes and an additional burden on the healthcare systems ,10,11. AFurthermore, people believe that arterial blood pressure gradually increases during aging over time, hence is a normal condition of the body. However, ESC hypertension guidelines endorsed optimal blood pressure <130/80 mm Hg at the age <65 years, and 140/90 mm Hg for individuals older than 65 years. Likewise, ESC hypertension guideline outlines benefits of home blood pressure monitoring, where white-coat and masked hypertension can be identified because measurement in a home setting may be more relaxed than the doctor’s office . Thus, aThis study was an observational, descriptive study that was conducted at Pauls Stradiņš Clinical University Hospital in Latvia. Written informed consent was obtained from all subjects prior to participation and after nature of the study was explained and all questions regarding the study were answered. Subject data were collected through a face-to-face survey during the period of 1 March 2020 to 31 June 2021. The selection criteria were: subject age over 18 years, a patient must be diagnosed with arterial hypertension (primary or secondary) independently of their risk factors, and must take AML for at least six months. The exclusion criteria was severe hepatic impairment. A questionnaire was used to collect environmental and lifestyle data. Seated blood pressure was measured three times using an automated blood pressure device  following a manual procedure of blood pressure measurement. According to the 2018 ESC hypertension guidelines, it is recommended that older patients (≥65 years) and adult patients (<65 years) target blood pressure should be <140/90 mmHg and <130/80 mmHg, respectively [t-test was used to test the difference in age between gender, as data were normally distributed and homogenous as assessed using the Shapiro-Wilk test with normal Q-Q plots and Levene’s test, respectively. The difference of dose of amlodipine between age groups was tested using the Mann-Whitney U test, because data were not normally distributed. Categorical or qualitative variables were characterized as number and percentage. Categorical variables were compared with Pearson χ2 test or Fisher exact test, depending on the violation or satisfaction of the assumption. The statistical analyzes were performed using SPSS 26  and G*Power 3.1.9. software . Differences were considered statistically significant at p < 0.05. Quantitative variables were described with arithmetical mean and standard deviation (SD) or median and the first (Q1) and third (Q3) quartiles, if data were not normally distributed. The independent samples The analytical method was developed and validated according to the European Medicines Agency (EMA) guideline on bioanalytical method validation . Validatp = 0.011, d = 0.60 (medium effect size), power = 0.86). All subjects had been taking AML for at least six months. Characteristics of participants and their AML therapy are shown in A total of 81 patients with hypertension were enrolled in this study. The core task was to establish a target population of patients with possible changes in drug compliance despite the wide range of FDC combinations and in whom it would be useful to determine the concentration of amlodipine in the blood in the case of continuous use of the antihypertensive medication. The mean age of the population was 66.6 ± 9.1 years between 45 to 87. The average age difference between the genders was statistically significant—for men 64.6 ± 9.2 years and women 69.8 ± 8.0 years , power = 0.86). In order to evaluate answers regarding the regular use of the medicine, the average blood pressure values at home were compared to patient’s measured blood pressure in the hospital  and 30 (37.0%) patients used two and three-drug antihypertensive FDCs, where one of the active pharmaceutical ingredients was amlodipine, more often at a dose of 5 mg. Despite widespread use of FDCs, the average dose of amlodipine in patients over 65 years of age was higher; in patients under 65 years of age the dose of amlodipine was 5.4 ± 2.3 mg  and in patients over 65 years of age the dose of amlodipine was 6.9 ± 2.6 mg   subjects among all 36 (44.4%) hypertensive patients, were receiving FDC antihypertensive medications, where one of the components was AML. Most of the patients, 69 (85.2%) were overweight or obese. According to hospital and home systolic blood pressure measurements, patients in age group <65 years  were more careless about their health, and less compliant to target blood pressure as patients in ≥65 years  group. Furthermore, patients in age group ≥65 years were more often reaching target diastolic blood pressure . In addition, 16 (19.8%) patients confirmed that used to forget to take their medicines as prescribed by a doctor. In Data in Results of AML and DAML validation described in As comorbidities and the number of simultaneously used drugs increases with age, FDC is a major solution to improve compliance during arterial hypertension therapy and a tool to reach target blood pressure. Despite the simplified treatment regimen using FDCs, however, individual patient factors tend to influence the use of the drug. Even so, Shuangjiao et al. reported that medication literacy has a positive relationship with medication adherence. Therefore, adequate knowledge obtained from clinical professionals as well as community pharmacists, would improve patient attitude, behavior and adherence to medication therapy toward hypertension treatment .Comparing the results with other studies will help understand the position of different authors regarding the adherence to target systolic blood pressure by comparing the variables such as age or age group, gender, and risks such as being overweight or obese. 2, 46.8%) or obese . Studies recorded similar patient characteristics when compared to the current study, which recorded 85.2% obese cases. Fleig et al. demonstrated that patient age could not influence blood pressure response. The outcome established that 70.6% of patients <65 years attained blood pressure values of <140/90 mm Hg compared to 66.3% among patients ≥65 years [Various authors have explored the relationship between adherence to antihypertensive medication and subgroups. For instance, the results of the current study paralleled Fleig et al., where the authors explored the effect of FDC of perindopril or amlodipine among patients with arterial hypertension. The researchers demonstrated that 80.6% of the patients treated with FCDs of perindopril/amlodipine were either overweight . Therefore, protein precipitation in the current procedure is low cost, requires minimal equipment, and a large number of samples can be prepared in a short time and the time or labor per sample is low during the daily routine.In the present manuscript, we have expanded the linearity range, which is approximately two times higher than those of most LC-MS/MS methods ,42,44,45Overall, the outcome of the current study established that nearby 50% of subjects did not achieve target values of systolic blood pressure and 85% of patients were overweight or obese. Moreover, the results agree partially with the results from other studies regarding adherence to antihypertensive medications. However, the current study disregards the role of subgroups, while previous studies have revealed an important connection between age and gender. Lastly, the age group <65 years reached target SBP and DBP in the hospital more often than at home, which was contrary to the patients in the age group ≥ 65 years. Moreover, further quantification of AML and its metabolite in patient plasma using the proposed simple, timesaving, highly sensitive validated LC-MS/MS method would help to unveil efficacy for improving blood pressure and patient outcomes depending on dosage among patients with elevated BMI, as well as affirm frequency of use of antihypertensive medication and uncover if the drug is not being used at all.


The eosinophil gradient algorithm from ISAR is successfully replicated in the WATCH cohort of difficult asthma.Repeating eosinophil measures in difficult asthma increases the probability of patients being considered likely to have an eosinophilic background.Contemporaneous blood and sputum measurements are proven theragnostic biomarkers. However, they underestimate the presence of underlying eosinophilic disease.To the Editor,Severe asthma is a heterogeneous disease comprising numerous endophenotypes.There are, however, limitations in defining patients as eosinophilic or not, as severe asthma patients have high oral or inhaled corticosteroid burden which may suppress blood eosinophils and mask the underlying eosinophilic nature of the disease. Particularly if this trait is defined by limited timespan assessment in this variable disease.Following our longitudinal analysis of blood eosinophilia in severe asthma, the International Severe Asthma Registry (ISAR) consortium recently presented a novel multidimensional algorithm to determine the probability of an eosinophilic phenotype within a severe asthma population.The ISAR eosinophil gradient algorithm report identified two points that merit further understanding and which could be addressed by our WATCH cohort data: firstly, how longitudinal BEC assessment might consolidate these algorithm‐derived phenotypes; secondly, how the identification of eosinophilic asthma via the ISAR algorithm aligns with the traditional method of sputum analysis.1Wessex AsThma CoHort of difficult asthma is a real‐world study of patients with difficult‐to‐treat/severe asthma attending a tertiary centre . The study had national research ethics committee (REC) approval (reference 14/WM/1226), and all patients provided written informed consent. The WATCH study protocol and methodology has been described previously.2Replication of the ISAR algorithm in 471 patients from the WATCH cohort confirmed the predominance of an eosinophilic status regardless of the BEC observation timeframe applied (Table p = .625), presence of rhinitis (67.1% vs. 63.2% p = .915), asthma control (ACQ6 score 2.5 vs. 2.1 p = .354), or number of annual exacerbations (3.0 vs. 2.5 p = .452). In addition, as seen in ISAR, Grade 2 or higher patients were older (age at enrolment 55.0 vs. 40.0 p = .002), had a higher FeNO (20.3 vs. 11.0 p = .004) and had a later disease onset (age at asthma diagnosis 21.5 vs. 6.5 p=<.0001). Grade 0 patients were less likely than Grade 2 or higher to be male  and had better preserved lung function . Unlike in ISAR, no difference was found in the prevalence of eczema ever (25.5% vs. 30.0% p = .853), atopy (67.6% vs. 68.4% p = .862) or median total IgE (89.7 vs. 50.9 p = .1).As in ISAR, no differences were observed between WATCH patients classified as Grade 2 or higher compared to patients classified as Grade 0 with regard to BMI (29.8 vs. 29.7 n = 130) of WATCH patients with paired sputum analysis: 107 (82.3%) patients were classified as Grade 3 , the ISAR algorithm corroborates that observation by including clinical characteristics, which is particularly relevant when longitudinal BEC data are limited. When present, however, the inclusion of multiple historic BECs, mitigates against granulocyte count instability and treatment effects, in the detection of an underlying eosinophilic phenotype. Our WATCH data thus support Heaney et al's findings and those of others,It is worth noting that while the terms eosinophilic and T2 asthma are often applied interchangeably, the ISAR algorithm does not incorporate measures of atopic predisposition such as total IgE or specific allergen sensitization. Since allergy is a T2‐associated process that omission might raise concerns that the ISAR algorithm could miss a proportion of T2 patients. However, the ISAR algorithm still finds overwhelming prevalence of eosinophilic status. As no differences were identified in eczema, atopy or total IgE between patients considered Grade 2 and above vs. those considered Grade 0 these definitions cannot be considered interchangeable using the ISAR algorithm in the WATCH cohort.Our sputum findings emphasize the value of longitudinal repeat measures in truly understanding the underlying phenotypic propensity and are consistent with a recent publication that also highlighted that single sputum measures underestimate the likelihood of being classified as eosinophilic.Importantly, the presence of an eosinophilic phenotype does not exclude the concomitant existence of additional biology, as 25% of those identified as eosinophilic by sputum measures in WATCH also had neutrophilic airways disease. Such additional biology is not apparent with the use of BEC for phenotypic classification. There thus remains an unmet need for peripheral blood biomarkers that reflect airway biology additional to that linked to eosinophilic inflammation. One such measure is Chitinase 3 Like 1 (CHI3L1/YKL‐40). Liu and colleagues identified higher measures of the T1 biomarker CHI3L1/YKL‐40 in serum of patients with normal sputum eosinophil levels,In conclusion, though the term “non‐eosinophilic asthma” is used to describe severe asthma patients without current evidence of raised eosinophils while on high dose steroids. It is imprecise: many of these patients will have an underlying eosinophilic phenotype. Nevertheless, though, they may underestimate the presence of an eosinophilic phenotype. It is important to reiterate that contemporaneous blood and sputum measurements are proven theragnostic biomarkers, predicting response to anti IL‐5 and steroid treatment for reducing asthma exacerbations.Dr. Hitasha Rupani reports Speaker and consultancy fees from AstraZeneca, GlaxoSmithKline, Teva, Novartis and Chiesi. Professor Peter Howarth reports employment by GSK outside of the submitted work. Clair Barber, Adnan Azim, Colin Newell, Aref Kyyaly, Hans Michael Haitchi and Ramesh Kurukulaaratchy declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.CB, AA, CN, AK, HR, HMH, PH, RJK all contributed to study development, conduct and governance. AA performed the statistical analysis. CB wrote the first draft of the manuscript AA, CN, AK, HR, HMH, PH, RJK all contributed to manuscript development. RJK acts as guarantor for the manuscript. All authors have read and approved the manuscript before submission.


Background and objectivePreeclampsia is a hypertensive disorder that usually arises after 20 weeks of pregnancy. It is considered a major cause of maternal and fetal mortality worldwide. High blood pressure and high proteinuria are the two main characteristics of preeclamptic patients. Preeclampsia leads to either severe or mild conditions, but in both cases, it affects the organs of the mother and fetus. This study was conducted to determine the prevalence of preeclampsia and associated risk factors  and to investigate its fetal and maternal outcomes.MethodologyThis prospective study was conducted at three healthcare units in the Multan district and involved patients with gestational hypertension. Patients were diagnosed on the basis of blood pressure values, urine tests, and through Doppler ultrasound. Further investigations were conducted, including a complete hemogram and a 24-hour test for proteinuria. Results for preeclampsia-related maternal and perinatal outcomes were documented and statistical analysis was performed to analyze the data.ResultsA total of 142 patients were diagnosed with gestational hypertension and preeclampsia during the two-year study period. Our findings showed 8.67% cases of gestational hypertension and 3% of preeclampsia. The majority of the preeclamptic patients were less than 24 years of age (33.3%), belonged to lower socioeconomic classes (44.4%), and had low educational levels (81.1%). A close association of family history (36.67%) with diabetes (15.5%) and chronic hypertension (5.55%) was observed in these patients. Maternal and fetal outcomes were related to maternal blood pressure. A significant incidence of premature births (45.6%) and a majority of cesarean cases (63.4%) with severe complications were observed. Data from preeclamptic patients showed high albuminuria levels (42.2%) with problems like renal infection, pulmonary edema, and severe anemia. During the study period, a neonatal death rate of 11.1% was observed as well as issues like respiratory tract syndrome, asphyxia, and growth retardation.ConclusionThis study showed that poor economic and educational levels are significantly associated with this disease. A high rate of maternal and neonatal morbidity with neonatal mortality was investigated. Mild to severe outcomes were observed in the form of cesarean deliveries and preterm births. Serious complications lead to ICU admissions causing a serious burden on healthcare units. Paying more attention to the healthcare needs of pregnant women helps to identify preeclampsia earlier and also minimizes the complications associated with it. Preeclampsia is a major medical condition associated with maternal and fetal mortality and morbidity. Preeclampsia is spreading worldwide, especially in underdeveloped and developing countries including Pakistan . It is aAn expecting woman has high blood pressure during preeclampsia, which is higher than or equal to 140/90 mmHg of systolic and diastolic blood pressure, as well as albumin protein in the urine. The albumin that is normally present in the blood during kidney damage is released into the urine. More than 30 mg/L of albumin indicates kidney damage and the presence of these two crucial complications at the same time in pregnancy may point to preeclampsia [Preeclampsia entails either severe or mild manifestations. Mild symptoms include pain in the chest, vomiting, high blood pressure, low amount of urine, and obesity whereas severe pain in the abdomen, low breathing, kidney failure, edema, blurred vision, and eye irritation are the symptoms of severe preeclampsia, which can evolve to eclampsia in some cases. Eclampsia is a harmful stage in which premature birth and, occasionally, fetal death occur. Blood pressure is not controlled by medication in eclampsia in some cases, leading to mental abnormalities and for this reason, this complication is also referred to as the last stage of preeclampsia .Preeclampsia is associated with several sociodemographic and environmental factors, which often accelerate the development of the disease, such as a family history of hypertension, heart disease, kidney disease, and diabetes . RegularHypertension is the major factor based on which preeclampsia is diagnosed, and it is controlled by antihypertensive medications in pregnancy. Specialists also recommend magnesium sulfate and corticosteroid medicines to reduce the rate of eclampsia and associated complications that in turn lead to rectifying fetus health and help with the growth of the baby . ObesityPreeclamptic incidents are on the rise worldwide, and the condition's prevalence is greater in developing countries as compared to the developed world . AccordiThe present study was conducted at Seyal Medical Centre, Asghari Tariq Hospital, and Nishtar Hospital in the Multan district in the Punjab province of Pakistan for two consecutive years (2020-2022). The study focused on patients with more than 20 weeks of gestation. To investigate the rate of preeclampsia, risk factors, and neonatal and maternal outcomes, all patients visiting the Obstetrics and Gynecology department during the study period were included in the study, while for studying gestational hypertension, a separate, shorter study was conducted during this time period with a limited number of patients. The research work involved diagnosis, data collection, and case study observations. The selected patients were admitted to the Department of Obstetrics and Gynecology of the referred healthcare units. Admitted patients were consulted directly and through their attendants to collect data on their sociodemographic variables such as age, family history, economic status, educational level, physical activity, any type of social support, and obstetric history including signs and symptoms, number of pregnancies, and other complications. Blood pressure, urine test, and Doppler ultrasounds were performed at local centers in the presence of specialists and technicians for the purpose of disease diagnosis. Further testing was performed, including a complete hemogram, coagulation profile, renal and liver function tests, and a 24-hour proteinuria test. The same protocol was followed for obstetric management at all healthcare units. The details of labor pertaining to whether it was induced or spontaneous along with the mode of delivery were recorded. Maternal complications before and after delivery were observed in detail along with neonatal complications. Patients with severe cases, multiple pregnancies, cardiac disease, kidney failure, and neurological disorders were excluded from the study. Ethical approval  from concerned departments was obtained as well as informed oral consent from the participants to share their data for research purposes. At the end of the study, the results were compiled and analyzed.A total of 52 out of 600 patients were observed to have hypertension during pregnancy; of these, 32.69% were preeclampsia cases. A total of 90 preeclampsia cases were observed among 2,800 patients visiting the Obstetrics and Gynecology departments of the concerned hospitals. Family history, chronic hypertension, gestational diabetes, and patient age were analyzed as associated risk factors for hypertensive patients Tables -2.The data for hypertensive patients were further analyzed and categorized based on elevated blood pressure values and the presence of albumin protein in the urine Table .For maternal and fetal outcomes, a total of 90 patients with preeclampsia were observed in detail. These patients were further investigated for sociodemographic characteristics, clinical features, and maternal and neonatal outcomes. The predominant age group was ≤24 years, and more than half of the subjects (62.2%) were from urban areas. A high percentage of middle-  and low-income  patients were observed to have preeclampsia as compared to patients of high economic status . In this study, 33 (36.67%) women had a family history of preeclampsia. Severe preeclampsia was diagnosed in 20 (22.23%) patients, and 32 (35.56%) had mild stage while 38 (42.22%) subjects were at the normal stage of preeclampsia  had received at least a secondary level of education (excluding those with only primary levels). A high number of the patients n=47, 52.3%) were housewives whereas the life partners of a high number of patients  had private jobs; among the life partners of patients, 41.11% (n=37) had only a primary-level educational  of the preeclamptic subjects were diabetic, 10 (11.1%) were diagnosed with anemia, and obesity was observed in six 6.7%) women. Eight (8.9%) patients had hypocalcemic-complicated pregnancies, four (4.5%) were asthmatic, and three (3.33%) subjects had arrhythmia. Among the remaining patients, five (5.55%) had hypertension at the time of diagnosis. Two women (2.22%) had a hernia, and nine (10.0%) had multiple complications  whereas 28 (31.1%) had preeclampsia without other comorbidities  participants had systolic/diastolic blood pressure of less than or equal to 140/90 mmHg whereas 38 (42.3%) women had a blood pressure of more than 140/90 mmHg; there were six 6.7%) severely hypertensive patients. About 30 (33.3%) subjects had abnormal pulse rates ranging from 91 to 98; 22 patients (24.5%) had a history of abdominal surgery, with higher chances of premature birth. Seven (7.8%) women had a history of abortion, while 13 (14.5%) women had a history of kidney disease, which is a risk factor for preeclampsia. The majority of the patients  had more than 0.3-3 g/L protein levels in the urine based on 24-hour urine testing  had cesarean deliveries as compared to vaginal . Fifty-six (62.2%) patients fully recovered without any severe outcomes after delivery; 17 18.9%) patients had low Hb levels and seven (7.8) had kidney infections. Pulmonary edema was reported in six (6.6%) patients. Four (4.4%) patients faced serious conditions and were hence admitted to ICU for closer observation  births were premature, and 19 (21.1%) of these preterm babies were delivered between 34 and <37 weeks. Six (6.67%) of the babies had extremely premature births. There were 10 (11.1%) neonatal deaths, and four (4.45%) of these deaths were due to low birth weight. Among the total 90 births, 46 (51.1%) had normal birth weights, ranging from 2.5 kg to 4 kg. Among the 80 babies who survived, 32 (35.6%) had breathing problems, eight (8.89%) were growth-retarded, and 12 (13.3%) were mentally abnormal  patients with ≥160 mmHg systolic and 110 mmHg diastolic blood pressure had cesarean deliveries; 27 (30%) patients with greater than 140/90 mmHg to 160/110 mmHg blood pressure had cesareans. However, 22 (24.5%) of women who had vaginal deliveries had ≤140 mmHg systolic and 90 mmHg diastolic values  of newborns had preterm births due to the mother’s blood pressure being ≤140/90 mmHg, and mothers of 23 (25.6%) premature babies had a mild blood pressure of >140/90 mmHg to 160/90 mmHg. However, all women with extremely high blood pressure levels (≤160/90 mmHg) had premature babies  Table .This two-year study was conducted at three healthcare units in the Multan district. This study focused on finding incidences and complications linked with preeclampsia and their effect on maternal and fetal mortality rates. Due to hypertensive disorders during pregnancy, there are high incidences of maternal and fetal mortality in Pakistan. In developing countries, the estimated rate of preeclampsia is 1.8-16.7%. In the current study, it was much lower than the peak value (3%) and also much lower than that found in another study conducted in Pakistan, in the Sukkur district, where it was 5% . A studyEducational level, occupation, and economic standards affect the rise of preeclampsia cases -17. A stIt has been observed that maternal and fetal outcomes are linked to risk factors associated with preeclampsia. Elevated systolic and diastolic values also affect premature birth and mode of delivery. Severe neonatal and maternal complications are related to the onset and severity of disease including zero to varying numbers of both maternal and neonatal death rates as reported in various studies. A study conducted in 2022 by Wassie and Anmut on eclampsia outcomes reported three maternal deaths . This reDuring the study period, various maternal complications were reported, including renal infection, pneumonia, and respiratory problems, with a zero death rate, which is comparable to the study performed in western Kenya. In the present study, cesarean cases were higher (approximately 63.4%) due to complications during pregnancy induced by preeclampsia, while vaginal deliveries amounted to 36.7%, which is comparable to the above-mentioned study, which also reported a high proportion of pregnancies (more than two-thirds) resulting in cesarean sections. These authors also reported 9.4% of fetal deaths associated with severe complications, which is similar to our findings; we noted that 11.1% of neonatal deaths were due to respiratory tract syndrome, low birth weight, and other related complications . In a stThe current study has some limitations. Primarily, our findings cannot be generalized to the whole population as this was a hospital-based study with a limited number of patients. Two different cohorts of populations were used for assessing preeclampsia and hypertensive disorders incidence with a much lower number for the latter one, which was conducted as a supplementary work. Moreover, the present study’s observational design could not provide deeper insights as to which type, how much, and to what extent an educational intervention would help in knowledge improvement regarding preeclampsia or reduce adverse clinical outcomes. Furthermore, more research work in the current field is required to estimate the potential maternal-neonatal benefits of improved dietary intake and home-monitoring interventions for pre- and post-delivery preeclampsia management.For data collection, two different questionnaires were designed for the two conditions (hypertension and preeclampsia) by reviewing past work with related research objectives. The questionnaires were investigator/administration-approved and used for data collection from enrolled participants. The information collected included patient history, sociodemographic characteristics, and clinical characteristics with maternal and neonatal complication/outcome details (see Appendices).In the current study, the incidence of preeclampsia was relatively low. Based on our findings, family history, maternal age, economic status, low education level, severe anemia, chronic hypertension, and gestational diabetes were the major factors associated with disease onset and severity. A high number of cesarean cases were reported in this study, and 41 (45.6%) deliveries were premature. During the study period, no maternal death was observed, although there was a fetal mortality rate of 11.1% as well as major complications like low birth weight, growth retardation, and respiratory tract syndrome. Maternal and fetal outcomes were highly related to elevated blood pressure levels.