High blood pressure (hypertension) is the most frequent cause of morbidity and a major risk factor for cardiovascular complications. The aim here was to describe the prevalence of blood pressure greater than or equal to 140/90 mmHg in the adult Brazilian population and federal states, along with self-reported information about previous medical diagnoses of hypertension, use of medication and medical care for hypertension control. Cross-sectional study analyzing information from the National Health Survey of 2013, relating to Brazil and its federal states. The sample size was estimated as 81,254 households and information was collected from 64,348 households. The survey consisted of interviews, physical and laboratory measurements. Systolic blood pressure was considered to be high when it was ≥ 140 mmHg and diastolic blood pressure, ≥ 90 mmHg. It was found that 22.8% of the population has blood pressure measurements ≥ 140/90 mmHg. The proportion was higher among men than among women: 25.8% versus 20.0%. The frequency increased with age, reaching 47.1% in individuals over 75 years and was highest in the southeast and south. 43.2% reported previous medical diagnoses of hypertension and, of these, 81.4% reported using medication for hypertension and 69.6%, going to the doctor within the past year for pressure monitoring, thus showing regular medical follow-up. These results are important for supporting measures for preventing and treating hypertension in Brazil, with the aim of achieving the World Health Organization's goal of reducing hypertension by 25% over the next decade. Most of them are limited to institutions or municipalities, without national scope. Different methodological approaches have been used, along with different samples, different population groups  and different diagnostic criteria, without any standardization when measuring blood pressure, which makes comparisons difficult.A review study that used blood pressure of 140/90 mmHg as a cutoff indicated prevalence of around 20%, without distinction between the sexes, but with an evident tendency towards increasing pressure with age.,The Longitudinal Study of Adult Health  used a cohort composed of teachers and other employees at six Brazilian universities aged between 35 and 74 years. The study demonstrated that 35.8% of the participants met the predefined criteria for hypertension, which were systolic/diastolic blood pressure greater than or equal to 140/90 mmHg or use of medication prescribed for high blood pressure. Moreover, among the individuals with high blood pressure, 80% were aware that they presented high blood pressure, 78% were undergoing treatment and 56% presented controlled levels.,In 2013, the National Health Survey  included blood pressure measurement among adults, along with questions about high blood pressure diagnosed by doctors, the care provided and use of medications, among other topics.The objective of this study was to describe the prevalence of high blood pressure above 140/90 mmHg among the adult Brazilian population and within each federal state, along with self-reported information about previous medical diagnoses of hypertension, use of medication and medical follow-up for high blood pressure control.,This was a cross-sectional study carried out using secondary data from the PNS, which was a population-based survey conducted by the Brazilian Institute for Geography and Statistics  in 2013, in partnership with the Brazilian Ministry of Health. ,The sample size was estimated in the PNS as 81,357 households, and information was collected from 64,348 of them. Taking into account closed households, the loss rate was 20.8% and the no-response rate was 8.1%.Blood pressure was measured by a trained team using a calibrated digital device. The individuals needed to be at rest and were instructed to empty their bladders, not to smoke or drink during the 30-minute period preceding the measurement and not to do any physical activities during the one-hour period preceding the measurement. The blood pressure measurements were made with the individual in a seated position, having rested for at least five minutes beforehand. The subjects were instructed to keep their back relaxed and supported against the backrest of the chair, not to cross their legs and to leave their left arm free of clothing and resting on a table at the same level as their chest or heart. Three blood pressure measurements were made, with two-minute intervals between them. The measurements were then inserted into a smartphone. The average between the second and third measurements was used for the present study.,A controlled imputation process was used in relation to situations that were deemed to be no-response situations. A set of integrated computational routines were used within a system named CIDAQ . This takes into consideration the combined behavior of all the variables recorded: age, sex, weight, height and family per-capita income. More details can be seen in other published materials.The present study describes the prevalence of individuals with blood pressure ≥ 140/90 mmHg in the Brazilian adult population, according to sex, age group, region of the country and federal state, with the 95% confidence interval (CI). Moreover, the following proportions were also calculated: a) people aged 18 years or over with blood pressure ≥ 140/90 mmHg at the time of the survey, according to any previous medical diagnosis of hypertension (yes or no); b) people aged 18 years or over with blood pressure ≥ 140/90 mmHg who reported having used medications for controlling high blood pressure over the past 15 days (yes or no); and c) people aged 18 years or over with blood pressure ≥ 140/90 mmHg who reported having gone to a doctor because of hypertension over the past year (yes or no).The survey was approved by the National Ethics Commission for Research Involving Human Beings, of the Ministry of Health, under report number 328,159 of June 26, 2013. The free and informed consent statement was signed in the smartphone itself during the PNS.The analysis on high blood pressure at the time of measurement within the PNS in 2013, i.e. systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg, indicated that the prevalence of people with high blood pressure was 22.8%.It was found that 20.0% (95% CI: 19.3-20.8) of the women had high blood pressure, while the prevalence among men was 25.8% (95% CI: 24.8-26.7). The frequency of high blood pressure increased with age, for both sexes, reaching around 47% among people aged 75 years or over. Between the ages of 18 and 74 years, men presented higher blood pressure than women, but the prevalences became equal after the age of 75 years .The frequencies were higher in the southeastern and southern regions of Brazil for both men and women . In all Among the individuals who presented high blood pressure (≥ 140/90 mmHg), 43.2% (95% CI: 41.6-44.8) reported having a previous diagnosis of hypertension, while 56.8% did not know that they had high blood pressure. Among those with a previous medical diagnosis of hypertension, 81.4% (95% CI: 79.5-83.2) were using medication, and 69.6% (95% CI: 67.3-71.8) had visited a doctor during the past year .These percentages differed according to sex. Women presented greater occurrence of previous medical diagnoses of hypertension  than men . Women also used more medication for hypertension  than men  and visited a doctor more often  than men   and 3.This was the first national study indicating results from blood pressure measurements among the Brazilian population. One fourth of the male adult population presented blood pressure ≥ 140/90 mmHg, while high blood pressure affected one fifth of the female adult population. Its frequency increased with age, reaching almost half of the elderly population (over 75 years). Blood pressure levels were higher in the southeastern and southern regions of the country, among both men and women. In all the federal states, blood pressure ≥ 140/90 mmHg occurred more frequently among men. The lowest prevalence was found in the state of Amazonas, while the highest was observed in the state of Rio Grande do Sul. Nearly half of the population reported having previous medical diagnoses of hypertension and, out of this portion, over three quarters reported using medication for high blood pressure and close to two thirds had visited a doctor during the past year for their high blood pressure to be monitored, thus demonstrating that they were receiving regular medical follow-up. Women used more medication than men and went to a doctor more often for their high blood pressure to be monitored.,The PNS provided nationwide blood pressure measurement in Brazil for the first time, using methodology indicated in the literature. Use of digital electronic devices is widely recommended for population-based surveys, given that they reduce measurement errors and make it easier to interpret and standardize the results.A review study involving 35 developing countries identified 204 articles and, similarly to PNS, found greater mean prevalence of hypertension among men, reaching 32.2%, than among women, 30.5%.There are divergences in the results regarding differences between the sexes, which may occur due to factors such as educational level, race/skin color, obesity, seeking of health services and adherence to treatment, among others.,,,The PNS also confirmed what had already been described in the literature, regarding increased prevalence of high blood pressure with age. This higher prevalence is due to the changes inherent to growing older, with greater stiffening of the arteries, greater peripheral vascular resistance and comorbidities among the elderly.The present study showed regional differences according to federal state and region, with greater prevalence in the southeast and south. In addition to demographic factors such as the greater participation of elderly individuals in these regions, other risk factors need to be better studied.The highest frequency among the federal states was in Rio Grande do Sul, followed by Rio de Janeiro, which can be explained because they are states with large proportions of elderly people;,,,,Studies have indicated that detection, treatment and control of high blood pressure are fundamental for reducing the incidence of cardiovascular events.A review studyOther PNS analyses have already indicated that only 3% of individuals in the adult population have never had their blood pressure measured and that, therefore, other opportunities for diagnosing high pressure had previously existed.,,Other indicators such as definitions for hypertensive patients based on correlating high blood pressure and use of medications have been described in the literature.Among the limitations of the present investigation, this was an epidemiological study using a standardized technique to make three sequential measurements using a digital device. The measurements were made by trained interviewers and not doctors, and the stethoscope method of blood pressure measurement was not used.,In 2013, the Global Action Plan for the Prevention and Control of Non-communicable Diseases was approved by the World Health Assembly. The plan included a set of indicators for combating these diseases, and reduction of high blood pressure was among these. The PNS constitutes the baseline for this indicator, which takes into consideration the frequency of the population with blood pressure ≥ 140/90 mmHg.


BackgroundDiabetes mellitus (DM) is a prevalent metabolic disorder characterized by high blood sugar levels. It is classified into type 1 (T1DM) and type 2 (T2DM), which have different mechanisms and complications. The global prevalence of diabetes, particularly T2DM, has increased significantly in recent decades, leading to a need for standardized data collection of macrovascular and microvascular complications to track disease progression and guide treatment options. This study aims to assess and correlate the prevalence and severity of microvascular complications in patients with T2DM.MethodologyThis observational, cross-sectional study was conducted at Poonam Multispeciality Hospital in Ahmedabad, India. A total of 4,123 diabetic patients admitted to the hospital were included. Information on sociodemographics and medical history was collected using standardized forms. Fundus photography and fluorescein angiography were performed to assess diabetic retinopathy, and estimated glomerular filtration rate and albumin-to-creatinine ratio were measured to evaluate renal function. Neurological examinations were conducted to score diabetic neuropathy. Chi-square tests were used to determine associations between medical history with diabetic retinopathy and nephropathy, and t-tests were used to compare diabetic neuropathy scores. Kendall’s Tau correlation was used to determine correlations between diabetic retinopathy and nephropathy. P-values <0.05 were considered statistically significant.ResultsThe overall prevalence of diabetic retinopathy, nephropathy, and neuropathy was 37.5%. Of the patients included, 47.9% had diabetic nephropathy and 28.9% had diabetic neuropathy. A significant association was observed between the severity of diabetic retinopathy and age, body mass index, duration of diabetes, and hemoglobin A1c (HbA1C) levels. Similarly, significant associations were found between these factors and the severity of diabetic nephropathy. Unpaired t-tests revealed significant differences in diabetic neuropathy examination scores based on the duration of diabetes and Hba1C levels. Moreover, correlation analysis indicated a low, positive correlation between diabetic retinopathy and diabetic nephropathy.ConclusionsThis study provides insights into the prevalence, severity, and associations of microvascular complications in patients with T2DM, contributing to the understanding and management of these conditions. Additionally, the research revealed a direct association between diabetic retinopathy and different stages of chronic kidney disease determined by the Kidney Disease Improving Global Outcome guidelines. Diabetes mellitus (DM) is a group of prevalent metabolic disorders that exhibit symptoms of high blood sugar levels. These disorders result from the interplay of various genetic and environmental factors. DM is categorized based on the pathogenic mechanism that triggers high blood sugar levels. The two primary classifications of DM are type 1 (T1DM) and type 2 (T2DM). T1DM arises due to autoimmunity against beta cells, which generate insulin, leading to severely reduced insulin levels. T2DM encompasses a range of disorders characterized by varying levels of insulin resistance, impaired insulin secretion, and heightened glucose production in the liver [DM can affect multiple organs resulting in morbidity and eventual mortality. These complications are categorized as vascular and non-vascular in both types of diabetes. Vascular complications are further divided into macrovascular, such as coronary heart disease, stroke, and peripheral vascular disease, and microvascular, such as retinopathy, peripheral neuropathy, nephropathy, end-stage renal disease, and lower-extremity amputation.In recent decades, the prevalence of diabetes has surged across many developed global regions; currently, approximately 415 million individuals globally are living with diabetes . In 2000Of the global population affected by DM, nearly half exhibit some form of diabetic retinopathy . SystemiDiabetic nephropathy is a significant cause of chronic renal failure; approximately 20% of patients with T2DM develop end-stage renal disease. Diabetic nephropathy is a long-term complication that significantly impacts morbidity and mortality among diabetic patients. While the estimated glomerular filtration rate (eGFR) is the traditional marker for overall kidney function, albuminuria is a key indicator of damage to the glomerular permeability barrier ,8. The cThe prevalence of diabetic peripheral neuropathy ranges from 7% within one year of diagnosis to 50% in individuals who have had diabetes for over 25 years. If individuals with subclinical neuropathic disturbances are included, the prevalence may exceed 90% . DiabetiThis study aimed to determine the prevalence of diabetic retinopathy, nephropathy, and neuropathy in patients with DM, assess the association of various demographic features and medical history with the severity of these microvascular complications, and analyze the correlation between the severity of diabetic retinopathy and diabetic peripheral nephropathy.This observational, cross-sectional study was conducted at Poonam Multispeciality Hospital. Ahmedabad, India, from April 2021 to April 2022, after obtaining approval from the institutional ethical committee . The study was conducted among patients admitted to the hospital’s medicine inpatient unit and intensive care unit. During the study period, a total of 4,123 patients with diabetes were admitted. Patients 18 years of age or above who consented to participate in the study were included. Patients younger than 18 years of age, those who did not consent to participate, pregnant females, and those unable to provide a medical history due to critical conditions were excluded. Thus, excluding the patients who met the exclusion criteria, a total of 3,000 patients were interviewed and included.A standard pre-evaluation form was designed to obtain medical information from participants. It consisted of sociodemographic data, medical history, and personal history. Fundus photography and fluorescein angiography were performed by the ophthalmologist for each participant to assess diabetic retinopathy. Classification of diabetic retinopathy was based on the evidence-based approach of the Early Treatment Diabetic Retinopathy Study . RetinopeGFR and albumin-to-creatinine ratio were measured to assess renal function. Biochemical parameters such as hemoglobin A1c (HbA1c), creatinine, urinary protein, and urinary albumin were also recorded. eGFR was measured using the CKD-EPI equation . Based oTo diagnose the presence of neuropathy and assess severity, a thorough neurological examination was performed for each participant, and neurological signs were scored based on the diabetic neuropathy examination (DNE). This test consists of eight items, which test muscle strength, tendon reflex, and sensations. The maximum score is 16, where >3 is considered abnormal . Table 1Height, weight, and blood pressure were recorded by the investigator and entered into Google Forms. All data were exported to MS Excel  and analyzed using suitable tests for significance by SPSS version 26  and MS Excel. Chi-square, analysis of variance (ANOVA), or t-tests were performed as applicable to compare variables between groups. P-values <0.05 were considered statistically significant. To measure the association of the ordinal variables , Kendall’s tau-c correlation coefficient test was used to determine the probability of concordance minus the probability of discordance pairs. The data were analyzed using SPSS version 21 and stratified based on confounding factors .Of the 3,000 participants, 1,127 (37.5%) were diagnosed with diabetic retinopathy, 1,438 (47.9%) were diagnosed with diabetic nephropathy, and 867 (28.9%) had diabetic neuropathy , duration of DM, and HbA1C (p < 0.05) Table .The chi-square analysis showed a significant association between the severity of diabetic nephropathy and age, BMI, duration of diabetes mellitus, and HbA1C (p < 0.05) Table .An independent t-test was performed to compare the mean DNE scores between males and females. One-way ANOVAs were performed to compare the means of the remaining parameters. A significant difference was observed between the mean DNE score based on the duration of DM (p = 0.03) and HbA1C (p < 0.001) Table .Kendall’s Tau correlation was performed to determine the correlation between diabetic retinopathy and diabetic nephropathy. We found a low, positive correlation between these parameters  Table .Prevalence of microvascular complicationsThis study reported a prevalence of 37.5% of diabetic retinopathy, 47.9% of diabetic nephropathy, and 28.9% of diabetic neuropathy. Ramachandran et al. conducted a study in 1999 and showed that the prevalence of diabetic retinopathy was 23.7% and the prevalence of peripheral neuropathy was 27.5% . A studyDiabetic retinopathyThis study showed a significant association of diabetic retinopathy with age, BMI, duration of DM, and HbA1c levels. The study conducted by Pang et al. in 2012 showed that factors linked to retinopathy in diabetes included the duration of diabetes, blood glucose levels, HbA1C, and albuminuria . Ahmed eDiabetic nephropathyThis study showed a significant association of nephropathy with age, BMI, duration of DM, and HbA1C levels. Ayodele et al. published a study in 2004 and reported that race, genetic susceptibility, hypertension, hyperglycemia, hyperfiltration, smoking, advanced age, male sex, and a high-protein diet were the factors associated with diabetic nephropathy . The stuDiabetic neuropathyWe used the DNE score to compare the means between different groups. A significant difference was observed between the mean DNE score based on the duration of DM and HbA1c. No difference was seen in the mean scores when gender, age, and blood pressure were compared. This indicates that the severity of diabetic neuropathy does not depend on gender, age, and blood pressure. However, more studies are needed to validate this score and compare it with more causal factors. According to a study conducted by Papanas and Ziegler in 2015, the most prevalent neurological symptom in diabetes is distal symmetric sensorimotor polyneuropathy (DSPN), which is primarily influenced by factors such as the duration of DM, high blood sugar levels, and age. Additionally, prediabetes, hypertension, dyslipidemia, and obesity are significant risk factors for developing DSPN . A studyCorrelation between diabetic retinopathy and diabetic neuropathyOur study showed a low, positive correlation between diabetic retinopathy and diabetic nephropathy. This finding was consistent with the study conducted by Anitharani et al. . In a stThe current study relied on the KDIGO classification to derive its findings. Moreover, unlike other studies, the CKD-EPI formula was employed to calculate eGFR. Consequently, the results emphasized a notable connection between various levels of diabetic retinopathy and the severity of CKD based on the KDIGO classification. Furthermore, a decrease in eGFR was associated with the different stages of diabetic retinopathy. The primary strength of the study lies in its ability to compare various levels of CKD using the KDIGO classification, which incorporates both eGFR and albumin levels.The major limitation of the study was the inability to follow up to note the progress of diabetic complications. Conducting a prospective longitudinal study that focuses on comprehensive interventions, considering the risk factors and their association with progression from moderate to higher risk categories, is advisable. Furthermore, more factors should be included in future studies ranging from other laboratory parameters to personal habits and environmental causes to better understand the risk factors and the progression of the complications.This cross-sectional study conducted in a western Indian population with T2DM emphasized the importance of stratifying renal risk using the KDIGO classification rather than solely relying on eGFR or albuminuria. Moreover, the study uncovered a positive correlation between diabetic retinopathy and the various stages of CKD based on the KDIGO classification.


Dyslipidemia is common among patients with heart failure, and it negatively impacts clinical outcomes. Limited data regarding the factors associated with poor lipid control in patients with HF patients. Therefore, this study aimed to evaluate lipid control and to explore the factors associated with poor lipid control in patients with HF.The current cross-sectional study was conducted at outpatient cardiology clinics at two major hospitals in Jordan. Variables including socio-demographics, biomedical variables, in addition to disease and medication characteristics were collected using medical records and custom-designed questionnaire. Medication adherence was assessed using the validated 4-item Medication Adherence Scale. Binary logistic regression analysis was conducted to explore significant and independent predictors of poor lipid control among the study participants.P < 0.05), higher Hb levels , and higher WBC .A total of 428 HF patients participated in the study. Results showed that 78% of the participants had poor lipid control. The predictors that were associated with poor lipid control included uncontrolled BP (OR = 0.552; 95% CI: 0.330–0.923; This study revealed poor lipid control among patients with HF. Future intervention programs should focus on blood pressure control in order to improve health outcomes among HF patients with dyslipidemia. Heart failure (HF) is a complex clinical syndrome with signs and symptoms that are caused by any functional or structural impairment of ventricular filling or ejection of blood . PatientDyslipidemia is a well-established modifiable risk factor for CVDs . ComorbiThe negative impact of dyslipidemia on HF prognosis necessitates exploring the factors associated with poor lipid control in order to be addressed in future intervention programs which aim at improving health outcomes among patients with HF. Earlier studies reported different predictors of uncontrolled lipid profile in patients with dyslipidemia –20. To tIn this cross-sectional study, we interviewed 428 HF patients out of 550 who visited two outpatient cardiology clinics in King Abdullah University Hospital and Al Bashir Hospital in the period from August 2021 through April 2022. Eligible participants were HF patients aged 18 years and older, had HF for at least 6 months, were receiving at least one medication for heart failure management, and consented to participate in the study. Patients were excluded if they had an acute decompensation of HF or an active listing for heart transplantation or cognitive impairment. Patients who were eligible to participate were informed that participation is voluntary, they have the right to withdraw at any time, and their medical care and treatment will not be affected whether they participate or not. The participants were also informed that the collected data will only be used for the research purposes and will be kept at the Principal Investigator's office to ensure confidentiality. An informed consent was obtained from each patient agreed to participate in the study. Each interview with patients took approximately 10–15 min to be completed.During outpatient clinics visits, the researcher pharmacist HH collected participants' sociodemographic data using a custom-designed questionnaire, which included participants' age, gender, body mass index (BMI), marital status, place of residency, living arrangements, education, occupation status, monthly income, smoking status, physical activity, and family history of cardiovascular diseases. The cardiologists established the diagnosis of HF after utilizing the HF diagnostic tests including echocardiography and the elevated pro-NT-BNP. The medical records were used to collect information about medical history including duration of HF, NYHA heart failure classification, the presence and number of other comorbidities such as hypertension, diabetes, ischemic heart disease, chronic kidney disease, dyslipidemias, thyroid dysfunction. The collected information also included the total number of medications, number of heart failure medications, frequency of taking medications, medications side effects, fears of medications side effects, medications satisfaction, and receiving digoxin, anticoagulant and different medications for blood pressure and lipids control among patients with HF. The researcher also used the medical records to obtain biomedical data and laboratory tests including low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TGs), total cholesterol (TC), hemoglobin A1C, random blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), ejection fraction, serum creatinine, white blood cells, red blood cells and hemoglobin. According to the 2018 guideline on the management of blood cholesterol, the patients were considered to have uncontrolled lipid profile if they had any one of the following: LDL-C ≥100 mg/dl (≥70 mg/dl for very high risk patients), TG ≥150 mg/dl or HDL-C <50 mg/dl for females and <40 mg/dl for males . Based ot-test and the Mann–Whitney U-test were applied for normally and non-normally distributed continuous variables. In order to investigate if there is an association between categorical variables and lipid control the Pearson Chi-square test was constructed and the variables with a P < 0.05 were fitted into the binary logistic regression to determine the significant and independent predictors of lipid control.Descriptive and analytical statistics were conducted utilizing the Statistics Package for the Social Sciences (SPSS version 26 from IBM). Continuous and categorical variables were described by means (standard deviations) and frequencies (percentages), respectively. The independent sample The study has been carried out in accordance with the Declaration of Helsinki (1975) for experiments involving human subjects. Ethical approval was obtained from the Institutional Review Board (IRB) of KAUH at Jordan University of Science and Technology (Ref. # 32/141/2021).In total, 428 HF patients agreed to participate in the study. The participants' mean age was 63 ± 12 years. The majority of the participants were males (63.8%), married (94.4%), living with their families (94.6), living in the city (66.8%), did not complete their education (69.4%), unemployed or retired (77.6%), had a monthly income less than 500 JD (67.1%), non-smokers (69.9%), and were not physically active (88.1%). More than half of the patients had no family history of cardiovascular diseases (51.2%). Other demographic characteristics are presented in As shown in Table P < 0.05). Higher Hb levels  and higher WBCs count  increased the odds to be in the uncontrolled lipid group.Results of the univariate analysis showed that monthly income, hypertension control, LDL level, Hb level, WBCs count, and RBCs count were significantly associated with lipid control. Variables that were significantly associated with lipid control in the univariate analysis (<0.05) were included in the binary logistic regression model. As shown in Dyslipidemia is a common disorder and an important risk factor for coronary heart disease and stroke . StatinsLipid control status of the current study patients was far below the expectations, with the majority of them showing uncontrolled lipid status (78.2%). Several previous studies have found inadequate lipid control in patients with different chronic diseases. A study conducted in Spain reported that poor low-density lipoprotein (LDL) cholesterol control was recognized in nearly 60% of the patients with a cardiovascular disease . AnotherPatients with uncontrolled BP in the current study showed significantly poorer lipid control than those with controlled BP. In comparison, a study conducted in Spain reported that the absence of antihypertensive treatment was a significant determinant of poor lipid control in patients with cardiovascular disease participated in the study . AnotherHemoglobin (Hb) is a protein molecule that is found in red blood cells and is involved in carrying oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to the lungs . The curThe current study results showed a significant relationship between white blood count (WBC) and poor lipid profile. A study conducted among 2,873 participants found a significant relationship between white blood cells concentration and plasma lipid levels . A crossThe current study has some limitations, the self-report method used in this study may have affected the accuracy of patients' responses due to social desirability bias. However, this study used a sample size higher than the required which provided a robust findings and unique insights into the predictors of poor lipid control status among Jordanian patients with HF. The dietary pattern and its effect on lipid control was not investigated in this study. Furthermore, dyslipidemia in the present study could be attributed to the lack of physical activity, which was reported by the majority of the study participants, not receiving statin by some patients who were eligible to statin therapy, and the effect of statin dosage regimen-related factors. However, the effect of these factors on lipid control was not evaluated in the present study.via enhancing lifestyle modifications, optimizing blood pressure control medications along with regular patient follow-up. In terms of future research, Hb and WBCs levels should be more involved to help understand the way they affect lipid control and develop appropriate strategies accordingly. Furthermore, the impact of dyslipidemia on morbidity and mortality among patients with HF is deemed necessary in future studies.Overall, findings of the current study can provide valuable insights that can help health care providers and policymakers improve future HF management strategies and develop targeted interventions that address the challenges that prevent achieving an optimal lipid control among patients with HF. Such interventions should focus on improving BP control The current study showed inadequate lipid control in patients with HF. Uncontrolled BP, higher levels of Hb, and higher WBC were significantly and independently associated with poor lipid control in HF patients. Future intervention programs should implement effective strategies that would improve BP control in patients with HF in order to reduce its negative impact on lipid control and other health outcomes among patients with HF.


To detect the widening of the tunnel of the coracoid process after arthroscopic fixation of acute acromioclavicular joint (ACJ) dislocation using the TightRope system and its correlation with loss of reduction and functional scores.From 2016 to 2018, a prospective study was performed on twenty-three patients with acute grade III–V ACJ dislocation. Arthroscopic TightRope repair of the ACJ was performed. Coracoid tunnel widening was measured by CT, and the coracoclavicular distance was measured on the radiographs immediately postoperatively and at 12 months. The Constant Shoulder Score, Oxford Shoulder Score, Nottingham Clavicle Score and Visual analog scale were used as outcome measures at 12 months.p < 0.001). The coracoclavicular (CC) distance showed an increase from a mean of 10.8 ± 1.7 mm to a mean of 11.8 ± 2.5 at 12 months (p < 0.001). There was no correlation between the increase in the coracoclavicular distance and the patients’ functional clinical scores or coracoid tunnel widening.The coracoid tunnel diameter to horizontal coracoid diameter ratio increased from 22.8 ± 3.7% immediately postoperatively to 38.5 ± 5.5% at 12 months (Coracoid tunnel widening and radiological loss of reduction occur after arthroscopic fixation of acute ACJ dislocation with the TightRope system. However, they do not correlate with each other or with the functional scores of the patient.Level IV. Injuries of the ACJ are among the most common injuries of the shoulder girdle, with an estimated incidence of 1.8 per 1000 per year . The RocThe aim of treatment is to achieve anatomical reduction and stable fixation with motion preservation in addition to regaining the preinjury activity and functional state . ArthrosThe concept of arthroscopic-assisted fixation of acute ACJ injury is to use suspensory devices to maintain the coracoclavicular distance and facilitate healing of the CC and AC ligaments , 26. TheThe purpose of this study was to establish whether coracoid tunnel widening dilatation occurs with ACJ stabilization using the TightRope system  and to study whether there is any correlation between this widening and loss of reduction and whether it is clinically significant. The hypothesis was that significant coracoid tunnel widening would occur postoperatively and is a direct cause of loss of reduction.From 2016 to 2018, a prospective study was performed at our institute. Institutional Review Board (IRB) approval was obtained from the faculty of medicine of Cairo University; number I-170518. Twenty-three patients with acute (≤ 3 weeks after injury) Rockwood grade III–V ACJ dislocation were included in the study. Patients with associated coracoid fracture, associated rotator cuff tears or glenohumeral arthritis were excluded. The mean age was 37.5 ± 10.4 years. Out of 23 patients, 21 were males (91.3%), and 2 were females (8.7%). Eleven patients (47.8%) were office-based employees, while twelve patients (52.2%) were manual workers. Six patients (26.1%) had type III ACJ dislocations, 4 patients (17.4%) had type IV dislocations, and 13 (56.5%) patients had type V dislocations. The right side was injured in 14 patients (60.9%), while the left side was involved in 9 patients (39.1%). Eighteen patients (78.3%) were right-hand dominant, while five (21.7%) patients were left-hand dominant. Three patients had associated injuries. Two patients had medial subluxation of the biceps tendon for which biceps tenotomy was performed, and one patient suffered a grade I superior labrum anterior to posterior (SLAP) lesion managed by arthroscopic debridement. All patients were evaluated clinically and radiologically using radiographs  and computed tomography (CT) scans to exclude coracoid fracture. Informed consent was obtained from all participants included in the study.The arthroscopic procedure was performed in a beach-chair position under general anesthesia. After ensuring joint reducibility, a 1 cm vertical incision was made over the lateral end of the clavicle 3 cm medial to the AC joint, and then the deltotrapezial fascia was incised horizontally. Reduction was achieved and then maintained by temporary k-wire under C-arm visualization. Shoulder arthroscopy was then commenced through the standard posterior visualizing portal using a 30° arthroscope. Diagnostic shoulder arthroscopy was performed to exclude associated pathologies. The rotator interval was identified, and an anterolateral working portal was established just above the subscapularis by an outside-in technique preserving the middle glenohumeral ligament (MGHL) and medial biceps pulley. The accessory anterolateral (AAL) portal was established superior and lateral to the previous portal. Then, a radiofrequency probe was used to expose the base of the coracoid. The arthroscope is then switched to the AAL portal.single 4-mm tunnel. The guide pin was removed, leaving the drill bit in place. A flexible looped Nitinol passing wire was passed down the drill bit and retrieved via the anterolateral portal. It was used to shuttle the fiber-wire of the tight rope, bringing the button to rest on the undersurface of the coracoid. The final reduction was confirmed by C-arm followed by securing the washer to the clavicle by tying the fiber-wire free ends together. Closure of the deltotrapezial fascia, subcutaneous tissue and skin was performed in separate layers.A specific C-guide for ACJ  was placed via the anterolateral portal under the base of the coracoid. Care was exercised to ensure that the guide was centered under the coracoid to avoid eccentric drilling or notching. The drill sleeve of the guide was placed over the lateral clavicle approximately 3 cm medial to the AC joint. A guide pin was introduced through the clavicle under arthroscopic visualization until it appeared on the coracoid undersurface. A cannulated drill-bit was used to drill a The arm was immobilized in a broad arm sling allowing only passive range of motion in the supine position for six weeks. From 6 weeks postoperatively onward, active-assisted followed by active range-of-motion (ROM) exercises were allowed. This was followed by a gradual muscle strengthening and coordination program.Immediate postoperative radiographs (Zanca view) were performed at 6 and 12 weeks and one year. The CC distance from the lowest point on the upper surface of the coracoid to the lower margin of the clavicle at a 90-degree angle was measured immediately postoperatively and at 12 months. Any loss of reduction was recorded, while radiological failure was defined as a ≥ 50% increase in the CC distance . Computet test. Correlations between quantitative variables were performed using the Spearman correlation coefficient. The confidence interval was set to 95%, and the margin of error accepted was set to 5%. P values less than 0.05 were considered statistically significant.The sample size was calculated using the G-power program (version 3.1.9.7). The effect size was 0.71 and the power of the test was 80%. The minimum sample size needed for this study was 14 patients, and 9 extra patients were included to avoid any missing data during follow-up. Data were coded and entered using SPSS version 25 . The data are presented as the mean and standard deviation (SD) or as the number and percentage. Comparisons between quantitative variables were performed using the Wilcoxon signed rank test or paired Twenty-three patients with grade III-V ACJ dislocation eligible for arthroscopic fixation using the TightRope System  were included in the study and followed up for 12 months.p < 0.001) ; this signifies loss of reduction over time (Table The CC distance representing reduction showed an increase from a mean of 10.8 ± 1.7 mm immediately postoperatively to a mean of 11.8 ± 2.5 at 12 months (Regarding the correlation between functional scores and CC distance, as illustrated in Table The most important finding in the present study did not fully prove the initial hypothesis. There was significant coracoid tunnel widening and significant increase in CC distance after arthroscopic ACJ fixation using TightRope system. However, there was no correlation between coracoid tunnel widening and loss of reduction and this did not significantly affect functional outcomes, and none of the patients were considered radiological failure. Although loss of reduction did not significantly affect functional outcomes, there were 3 cases who were classified as clinical failure with a Constant score of < 85 at final follow-up.Several open and arthroscopic or arthroscopic-assisted techniques have been described for the treatment of AC joint injuries, each with its advantages and limitations. Restoring the anatomy and stability is the aim of surgery and is key to its success and good functional outcomes. Residual chronic pain and loss of reduction are the most common complications post-ACJ surgery and a major cause of patient dissatisfaction .Arthroscopic techniques have been gaining popularity using smaller wounds to minimize the hospital stay, postoperative pain, and adhesions, which enables quicker recovery. Such techniques allow adequate visualization of the coracoid undersurface and precise tunnel placement when required . They alOne of the most used arthroscopic techniques is using a double tight rope and fiber-wire or fiber-tape for fixation as a brace to allow healing of the ligaments. This technique depends on the drilling of a tunnel into the clavicle and the coracoid .There is concern that tunnel drilling is associated with the risk of coracoid and/or clavicular fractures or tunnel widening. This is hypothesized to be a possible cause of loss of reduction. In a systematic review by Nelson et al. , the pooclavicular tunnel widening and radiological failure. This is similar to this series, where a correlation was not found between coracoid tunnel widening and loss of reduction.Thangaraju et al. have described clavicular tunnel dilatation and have quantified reduction on Zanca radiographs views after a mean follow-up of 6 months with only 13 patients . This stIn another study by Berthold et al. , 24 patiIn their study, Shin et al. reported a 33% loss of reduction. They proposed the use of double tunnels to improve the construct and confer greater stability . HoweverMilewski et al.  studied Drilling of coracoid and clavicular tunnels prior to reduction of the ACJ may be a cause of later tunnel widening and subsequent loss of reduction. In this study, the first step was reduction of the ACJ followed by temporary stabilization with a k-wire, and then an image intensifier was used to check the quality of reduction. This ensures tunnel drilling in a reduced position and minimizes the possibility of tunnels not being in line and posing a risk of tunnel widening.Zhang et al. reported a 25% loss of reduction in their series with lower outcome scores. They explained this with 2 possible reasons: cutting off the fiber-wire against the clavicular cortex and eccentric anterior drilling of the clavicular tunnel .Implant migration is a recognized possible cause of radiological loss of reduction and possible failure. Using the TightRope or EndoButton technique, the most reported complication was hardware migration into the clavicle and/or coracoid. This rate reached 89% in the study of Scheibel et al. However, Scheibel et al. found no correlation between implant migration and loss of reduction or any difference regarding the CC distance on the contralateral side . A similcoracoid tunnel widening using CT. Furthermore, this is the first in vivo study to draw attention to the possible cause of failure and attempt to correlate it to coracoid tunnel widening. An in vitro study by Dalos et al. used micro-CT analysis to assess coracoid and clavicular tunnel widening and compared them across three different repair systems [This study is the first clinical study to quantify  systems . They reThis study has some limitations. The study did not compare tunnel widening with different methods and techniques of fixation, which rely on different drill hole diameters and different suture materials. Recent devices use smaller drill hole diameters, and knowing that the tunnel size affects tunnel widening, in this study, a ratio between tunnel size and the coracoid base diameter was relied on. It is therefore necessary to study tunnel widening, its correlation with loss of reduction and its effect on functional outcomes across different techniques of fixation. In this study, only one measurement of the tunnel diameter was performed, precisely, the widest part. It would be valuable to perform measurements at different cross sections of the tunnel to analyze which portion of the tunnel undergoes the greatest amount of widening. This study highlights the occurrence of coracoid tunnel dilatation after arthroscopic AC stabilization using TightRope system. To minimize the coracoid tunnel widening consequences, it is recommended to use a smaller diameter drill bit and tunnel. It is also recommended to use a single coracoid tunnel rather than double tunnels and to make this tunnel as central as possible in the coracoid.The main findings of this study did not fully prove the initial hypothesis. Both coracoid tunnel widening and radiological loss of reduction significantly occur after arthroscopic fixation of acute ACJ dislocation with the TightRope system. However, they do not correlate with the functional scores of the patient. Furthermore, no significant correlation is established between coracoid tunnel dilatation and loss of reduction.


Background: Electrical stimulation has recently been introduced to treat patients with Obstructive sleep apnoea There are, however, few data on the effects of transcutaneous submental electrical stimulation (TES) on the cardiovascular system. We studied the effect of TES on cardiorespiratory variables in healthy volunteers during head-down-tilt (HDT) induced baroreceptor loading.Method: Cardiorespiratory parameters  were recorded seated, supine, and during head-down-tilt (50) under normoxic, hypercapnic (FiCO2 5%) and poikilocapnic hypoxic (FiO2 12%) conditions. Blood pressure (BP) was measured non-invasively and continuously (Finapres). Gas conditions were applied in random order. All participants were studied twice on different days, once without and once with TES.Results: We studied 13 healthy subjects (age 29 (12) years, six female, body mass index (BMI) 23.23 (1.6) kg·m−2). A three-way ANOVA indicated that BP decreased significantly with TES . Change in gas condition  and different postures  similarly impacted on BP control. When tested for interaction, there were no significant associations between the three different factors electrical stimulation, gas condition, or posture, except for an effect on minute ventilation (gas condition/posture p = 0.0369).Conclusion: Transcutaneous electrical stimulation has a substantial impact on the blood pressure. Similarly, postural changes and variations in inspired gas impact on blood pressure control. Finally, there was an interaction between posture and inspired gases that affects minute ventilation. These observations have implications on our understanding of integrated cardiorespiratory control, and may prove beneficial for patients with SDB who are assessed for treatment with electrical stimulation. Obstructive sleep apnoea (OSA) is a highly prevalent condition that affects about one billion people worldwide . In patiTreatment of OSA includes continuous positive airway pressure (CPAP), and mandibular advancement devices (MAD) . PrimaryCPAP therapy remains the most common treatment for moderate-to-severe OSA, while for milder cases of OSA, MADs can also be effective . HoweverRecently, electrical stimulation invasively applied using hypoglossal nerve stimulation (HNS)  or transWe hypothesize that acute application of transcutaneous electrical stimulation of the submental area will influence cardiovascular control in healthy, awake subjects. In the current study, we sought to describe the effect of transcutaneous electrical stimulation of the submental area on the cardiorespiratory control, for this particular purpose, we recorded beat-by-beat blood pressure with other cardiopulmonary variables when exposed to room air, hypoxic and hypercapnic gas mixtures (chemosensitivity) while in seated and supine postures, as well as with 50° HDT (baroreceptor response) while using electrical stimulation of the submental area (TES).The study was approved by the local research ethics committee  and performed in accordance with the Declaration of Helsinki. All participants received an information sheet and provided informed and written consent prior to participation.We included healthy, normal- and slightly overweight subjects of both sexes over 16 years of age. All participants were non-smokers and free of cardiorespiratory and other significant acute or chronic illness and had normal blood pressure. Participants visited the respiratory physiology laboratory on two occasions at least 1 week apart, with one visit acting as control without electrical stimulation and the other during which TES was used during in all postures and gas conditions.2, non-smoker, and clinically stable in the last 28 days.Subjects for the study met all the following criteria: age >16 years, body-mass index (BMI) > 18.5 and <30 kg/m2) or cachexia (BMI<18.5 kg/m2), and vertigo.Subjects were excluded from the study if any of the following conditions were met: history of cardiovascular, respiratory, or neuromuscular disease, cardiac pacemaker, active seizures, current smokers, acute illness, allergy to skin patches, oobesity (BMI>30 kg/mThe primary outcome of the study was the change in the diastolic blood pressure (BP) with electrical stimulation, affecting baro- and chemoreceptor response. Secondary outcomes were changes in other cardiovascular  and respiratory variables  during electrical stimulation.Following the baseline visit without electrical stimulation the participants were continuously stimulated using electrical current in the submental area , at a frequency of 30 Hz and a pulse width of 250 microseconds during the second visit. Intensity of the electrical current was titrated according to individual comfort using a TENS machine  and associated differential pressure transducer . The distal end of the pneumotachograph was attached to a two way non-rebreathing valve  with inspired and expired gases measured continuously using a gas analyser , connected to a side port on the pneumotachograph via a fine-bore catheter. Blood oxygen saturation (SpO2) was measured using a pulse oximeter  attached to the subject’s finger. All data were acquired  with 1 Khz sampling and displayed . Tidal volume was obtained by digital integration of flow by the acquisition software.Respiratory flow was measured via a low volume (2.5 L) reservoir bag. The inspired gas could be enriched with 100% nitrogen or 100% carbon dioxide from cylinders  to provide the appropriate inspired gas concentration. Three inspired gas mixtures were used; medical air , poikilokapnic hypoxia  and normoxic hypercapnia . Symptoms of breathlessness were scored using the modified Borg scale in each posture .An open circuit  was usedAn electrically operated tilt table  which could be adjusted from 0° (flat) to 50°HDT was used to change posture.The following parameters were recorded at baseline: Demographic data , clinical history, and medications. The neck, hips, and waist were measured along with vital signs (heart rate and blood pressure).2, EtCO2), and oxygen saturations were recorded throughout. The tilt table procedure was repeated three times with the subject breathing in random order (2) dropped below 80%. To account for equilibration for change in posture and different gas mixtures, the final 2 min of recording for each posture and each gas mixture were analysed and an average reported for each variable.Measurements were first recorded in the seated position with the subject exposed to 5 min of each gas mixture, randomly assigned, before moving to the tilt table with measurements commencing in the supine position. Subjects were secured to the tilt table using a foam mattress and a foot strap across the ankles. Participants were familiarized with the 50°HDT procedure prior to the experiment commencing. After an initial period of stabilisation (at least 5 min) in the supine position, a period of 5 min resting breathing was recorded. The table was then tilted to the 50°HDT for 10 min. At the end of the 50°HDT, the subject was returned to the supine position for a further 5 min. Spontaneous ventilation and end-tidal gases  with an analog-to-digital conversion at a sampling of 1 kHz. Data were exported and assigned key time periods for further analysis. Each variable was averaged over the last 2 min in seated, supine, and HDT positions. Respiratory variables  and respiratory rate (RR)) were extracted and multiplied to calculate minute ventilation (VE). Systolic (SBP), diastolic (DBP), and pulse blood pressure (pBP) was computed as pBP = SBP-DBP, and mean arterial pressure (MAP) was calculated as MAP = 1/3 SBP + 2/3 DBP. Heart Rate was derived from the 3-lead ECG, and SpOBased on the sample size of 13 subjects, the study detected a treatment difference at a two-sided significance level of 0.025 if the true mean difference in diastolic blood pressure  was at least 8.049 mmHg (SD 10.6) with 80% power. The variable calculated was the minimal detectable difference in mean diastolic blood pressure, based on previous data .p < 0.05.Following testing for normality, data were presented as mean (SD) unless otherwise indicated. Data were analysed using a three-way analysis of variance (ANOVA)) followed by a Tukey’s test using the ‘anovan’ and ‘multcompare’ function of MATLAB  to evaluate overall effects of three factors: a) TES (on/off), b) posture , and c) inspired gas ; furthermore, baroreflex and chemoreflex interaction was tested with the combination of these three factors. A level of significance was defined as 2, waist: hip (W: H) ratio 0.87 (0.05)) . Two more volunteers were unable to participate in the second visit and had incomplete datasets recorded for the primary outcome, these were not included in the analysis. Subjects used an electrical current of 8 (2) mA, which had been titrated to a comfortable and tolerable level of skin sensation. There were no adverse events, and no participant required electrical stimulation to be stopped.We studied 13 healthy subjects (age 29 (12) years, six female, BMI 23 (1.6) kg/m (0.05)) . Two moA marked reduction in systolic blood pressure during electrical stimulation was observed under hypoxic conditions in the HDT posture; there was also a trend towards reduction in other postures. .A marked reduction in both diastolic and mean arterial blood pressures were also observed during electrical stimulation in supine and HDT postures. There was also a tendency towards a reduction in diastolic blood pressure during electrical stimulation when seated under hypoxic conditions, and during HDT both under hypercapnic and room air conditions. , 3.There was no significant change to the pulse pressure when applying electrical stimulation, independent of different postures and gas mixtures. .The heart rate did not significantly change with electrical stimulation, and this observation was independent of posture or gas mixture. .There was no change in the respiratory rate with electrical stimulation in any of the three postures studied. .There was a trend towards increased tidal volume in the supine posture under hypercapnic conditions with electrical stimulation, although this did not reach significance.  Addition2 during electrical stimulation in seated, supine or HDT posture were observed when breathing room air, under hypoxic or hypercapnic conditions. The SpO2 did not change when comparing electrical stimulation to baseline in any posture or gas condition studied.No changes in EtCOThere was no significant change in the breathlessness scores when applying electrical stimulation, independent of posture and gas mixture. .p = 4.3E-06, diastolic: p = 3.01E-09, mean: p = 3.26E-08). Change in gas condition  and different postures  similarly impacted on BP control. There were no significant interactions between the three different factors: electrical stimulation, gas condition, or posture, except for an effect on minute ventilation  activation and baroreceptor (posture) loading demonstrates marked effects on cardiovascular control, with a modest effect on the respiratory control. Electrical stimulation appears to sensitise the arterial baroreceptor response resulting in decreased diastolic blood pressure, by 19%–25%, under hypoxic conditions (chemoreceptor) supine and with HDT (baroreceptor). The effect of electrical current on the systolic blood pressure was slightly less consistent, albeit a reduction of 16% was observed in HDT position under hypoxic conditions. There were no significant differences in the heart rate or the pulse pressure with electrical current; this was independent of posture or gas mixture used. Respiratory variables did not change significantly with electrical stimulation, except for the minute ventilation.via hypoxia and that affects the baroreflex response, as suggested by our observations. It has been described previously that stimulation of the chemoreceptors can lead to an increased heart rate and a change in the blood pressure  in humans , and counteracts their diminished neuromuscular state-dependent tone which promotes upper airway collapsibility . Both thThis prospective physiological study had a relatively small sample size and certain interactions could become more significant with a larger sample size, for example the effect of the three factors on minute ventilation. The effects of TES on the primary outcome variable, diastolic blood pressure, were highly consistently observed in all subjects with a large effect size. Longer steady state periods could have had further advantages over quasi-steady state achieved during the 5 min baseline periods used. The choice of this was pragmatic to allow for completion of what was a lengthy protocol and return of the healthy volunteers for a demanding second session. We were also limited with making causal inferences due to the observational nature of the design of the study. Despite a complex experimental setup, some parameters such as neural respiratory drive, blood gases, and perfusion could have provided helpful additional insights into the interaction between the cardiovascular, the respiratory, the peripheral autonomic and the central nervous system but were not measured on this occasion. In addition, this study focused on healthy subjects with normal blood pressure. Thus, further studies in subjects with hypertension and sleep-disordered breathing need to provide a comprehensive dataset on how electrical stimulation affects the chemo- and baroreceptor response in these clinically relevant cohorts. However, these points do not negate the insightful setup of a highly complex physiological experiment in human beings with a large effect size that enables to derive useful information for future clinical applications.Electrical stimulation of the submental area affects the chemo- and the baroreceptor response in normal healthy volunteers resulting in substantially lower levels of blood pressure. Similarly, inspired gas and posture impact on blood pressure regulation. Furthermore, electrical stimulation might modulate the cardiovascular risk in patients with hypertension and sleep-disordered breathing, a hypothesis that warrants further investigation in the respective clinical cohorts.


The management of cardiotoxicity concerning the use of oral antineoplastic agents (OAAs) is a challenge for healthcare professionals. Our objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic adverse events (AEs) to assist healthcare professionals when prescribing OAAs.® were reviewed. Cardiotoxic AEs were recorded, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected.A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted. In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). For each drug, the latest summary of product characteristics (SPC) approved by the EMA and the tertiary data source Lexicomp®. Eight OAAs (9.68%) have reported a decrease in LVEF, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations. Almost half (49.5%) of currently approved OAAs can potentially alter blood pressure; 34 (36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. Tachycardia and/or bradycardia are associated with 22.6% and 8.6% of the evaluated drugs, respectively. Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE.In all, 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism. A total of 27 (29.0%) OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in LexicompMore than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units. Oral antineoplastic agents (OAAs) currently represent a large percentage of these new treatments. Most OAAs act specifically against specific molecular targets, increasing their effectiveness. However, OAAs have a narrow therapeutic range, making them high-risk drugs that, without proper dosing and follow-up, have severe consequences .OAAs present class adverse effects (AEs) that can lead to treatment interruption or, in the most severe cases, to the patient’s death. The most frequent AEs related to OAAs are gastrointestinal, hematological, and skin effects . The patDespite increased recognition and consensus of cardiotoxicity from cancer therapy  and receOur objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic AEs to assist healthcare professionals in oncology and hematology when prescribing these drugs.2A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted.In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). We considered as OAAs those drugs for oral administration divided into the following groups of drugs according to their Anatomical Therapeutic Chemical (ATC) : plant a®. Adverse events considered as cardiotoxicity and gathered for each OAA from both data sources were included, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Due to their relationship with cardiovascular risk, alterations in lipid metabolism (hypertriglyceridemia and hypercholesterolemia) were also evaluated. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected.For each drug, the latest summary of product characteristics (SPC) approved by the EMA was reviewed. In cases where different prescription drugs with the same active ingredient were available , the SPC for the originally registered product was consulted. Besides, we reviewed the information available in the toxicity section for each different OAA at the tertiary data source LexicompThe severity of each AE was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0 classification) . The CTC3At the time of the study (January 2023), 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism Table 1.®  OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in LexicompRegarding the decrease in LVEF, eight OAAs (9.7%) have reported this cardiotoxic effect, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations Table 2.® recommendations for each OAA in case of imbalances in blood pressure. First-line antihypertensive treatment should be ACE-I or ARB, as they also prevent LVEF decrease and are the first line of treatment for general hypertension. For cases with high levels (systolic HTN over 160 mmHg), the addition of a dihydropyrimidine calcium channel blocker can help to achieve faster control of HTN levels due to the combined effect of RASS inhibition and arterial vasodilation, counteracting endothelial toxicity of most of the TKIs  of currently approved OAAs can potentially alter blood pressure control; 34 36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. .6% of th.5% of cuTachycardia and/or bradycardia are associated with 22.58% and 8.6% of the evaluated drugs, respectively. Nilotinib and regorafenib are the only active substances that are known to cause both adverse effects Table 4.Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE Table 5.A total of 10 OAAs have been associated with hypertriglyceridemia and hypercholesterolemia; we found that 3  out of 10 have a specific dose adjustment management Table 6.4®.To the best of our knowledge, this is the first guide to summarize the updated recommendations concerning the use of OAAs with their cardiotoxic effects and posology adjustments according to the EMA and LexicompThe fast inclusion in the clinical practice of OAAs, their significant adverse events, and the scarce experience with some groups of patients that were not included in clinical trials make it extremely important that careful management of OAAs is implemented. The mechanism and frequency of cardiotoxicity brought on by targeted molecular therapy are mainly unclear and probably underestimated. Healthcare professionals play a crucial role in patient education, assisting in identifying and managing AEs and drug interactions. Recently, the European Society of Cardiology (ESC) issued its first guideline, providing guidance on the definitions, diagnosis, treatment, and prevention of cancer therapy-related CV toxicity, and the management of CV disease caused directly or indirectly by cancer . HoweverOur review presents a comprehensive guide of available recommendations concerning the dose and posology of OAAs when cardiotoxic events appear. We aimed to compile these recommendations to help clinicians to decide when to change the dose, end treatment, or take another action when a cardiac AE is detected. Considering the limitations of the information used to establish the safety profile of drugs during the premarketing period, there is a need for continuous safety surveillance after approval. As many of these therapeutic agents are approved through expedited procedures, the number of SPC changes in the postmarketing phase due to safety issues has increased. Likewise, it should be noted that specific information on dose adjustment recommendations in cases of adverse effects is reduced so that, in many cases, the recommendations are general for each side effect and not specific for each drug.4.1Torsades de Pointes)  . AlthougPointes) .Several risk factors may increase the risk of QT prolongation. Among the non-cardiac risk factors are being from the female sex and hypothyroidism. Among the cardiac risk factors are congenital long QT syndrome, left ventricular dysfunction, and myocardial ischemia. In addition to QT prolongation, risk factors also increase the risk of concomitant treatments  and AEs associated with cancer therapy  . Before 4.2Left ventricular dysfunction and heart failure may occur due to mitochondrial damage, alterations in cardiac energy balance, and contractile protein dysfunction . The inhVarious studies demonstrated heart failure with reduced ejection fraction or other cardiomyopathies induced by OAAs, such as encorafenib, lorlatinib, osimertinib, or sunitinib –17. Pate4.3Hypertension is one of the most common comorbidities in cancer survivors and patients with active cancer. Its incidence varies according to age, history of hypertension, cancer type, and treatment. A retrospective large cohort study was conducted to estimate the incidence rates of new-onset hypertension in adult cancer patients. New-onset hypertension was observed in approximately one-third of the 25,090 patients with various types of cancer. The incidence rates of severe and crisis-level hypertension were highest in patients with gastric and ovarian cancer . Across The mechanism by which OAAs induce hypertension is not entirely understood but can be directly related to the inhibition of vascular endothelial growth factor (VEGF) signaling via tyrosine kinase . The VEG4.4The pathogenesis of hypertriglyceridemia associated with mTOR agent use, such as everolimus, is poorly understood but may be related to the reduced degradation of apolipoprotein B100 . ApolipoScreening for lipid levels is recommended for individuals without cardiovascular disease (CVD), especially for those with risk factors such as hypertension, family history of premature CVD, diabetes, and smoking. Lifestyle interventions, including smoking cessation, a Mediterranean diet, and exercise, should be discussed with all patients. For secondary prevention patients, high-intensity statin therapy is strongly encouraged, while for primary prevention patients, the decision to initiate moderate- or high-intensity statins should be based on individual CVD risk. Statin therapy is generally not recommended for primary prevention patients over 75 years, but exceptions can be made based on individual patient factors. Patients who cannot tolerate specific statin regimens may be offered lower-intensity options or alternate dosing schedules. Non-statin lipid-lowering drugs are not recommended as first-line monotherapy in primary prevention. Adherence to statin therapy should be reinforced, and monitoring of CK and ALT levels should be reserved for symptomatic or higher-risk patients as determined by the attending clinician .4.5Regarding the thrombotic effect, some studies emphasized the importance of the ribosomal S6 kinase family, as it determines cardiomyocyte survival by inhibiting the phosphorylation of apoptosis-activating factors . By inteIn terms of study limitations, we have not found in the sources consulted any recommendations for the management of some OAAs, despite their cardiotoxicity. Therefore, the application of this guide would help to identify them as cardiotoxic drugs, but not help in their management. Second, we have focused this review on OAAs, but it should be taken into account that other cancer treatments, such as parenteral chemotherapy, immunotherapy, or monoclonal antibodies, can also produce cardiotoxic effects. In addition, it should be noted that continued research and approval of new OAAs are being developed. Finally, data were obtained from EMA and Lexicomp; thus, in cases with limited information, other sources, such as data from clinical trials, can be consulted to supplement the available information. Having the EMA and Lexicomp recommendations in the same Table could confuse some healthcare professionals as to which recommendation to follow. However, the objective is to have more information available, which can be useful in different situations. For example, a European professional could follow the EMA recommendations, or if another professional has doubts, it may be useful to consult both sources.In conclusion, more than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units, especially in high-risk patients such as those with pre-existing bradycardia, those taking anti-arrhythmic medicines or other drugs known to prolong QT intervals, and patients with previous heart disease or developed cardiotoxicity.We suggest that this review can serve as a reference guide for the professionals involved in managing patients with cancer since it provides an easy way to identify the cardiotoxic effects of OAAs and the need for dosage adjustments.The original contributions presented in the study are included in the article/VE-V, RC-B, and CV-B defined the research question and objectives. VE-V, RC-B, CV-B, JR-H, SP-R, and EZ-N defined the methodology of the study. ER-R, PR-B, VE-V, XG-G, and SI-G conducted a search for information for the preparation of the guide. VE-V, AH, and MS were responsible for the research activity plan and its execution. ER-R and VE-V wrote the first draft. All authors contributed to the article and approved the submitted version.


Introduction: Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality in Malaysia and worldwide. This is mainly due to an increase in the prevalence of CVD risk factors such as hypertension, dyslipidemia, smoking, and obesity. Increased physical activity has been recommended as a modality to improve CVD risk. Pulse wave velocity (PWVCF), augmentation index (AI), and finger photoplethysmography fitness (PPGF) index have been introduced to assess the vascular functions related to CVD risk factors. The effects of long-term exercise on PPGF index are not established.Materials and Methods: A total of 70 young men who were sedentary with two or more cardiovascular risk factors were recruited. Subjects were randomly assigned to a control group (CG)  and pedometer group (PG) . PWVCF and AI were measured via the Vicorder system. The PPGF index was obtained via the finger photoplethysmography method. All parameters were measured at baseline and after 6 and 12 weeks.Results: After intervention, the PG had significant increased step count from 4,996 ± 805 to 10,128 ± 511 steps/day (p < 0.001). The PG showed significant improvement in anthropometric variables, lipid, PWVCF, AI, and PPGF index (time and group effect p < 0.001). No changes were observed in CG.Conclusion: This signifies that pedometer-based walking program is beneficial in improving markers of vascular functions among young working sedentary men with CVD risk factors. Pedometer-based exercise should be encouraged to improve cardiovascular health. Aerobic exercise has been recognized as a modality for improving cardiovascular health . This tyvia several mechanisms such endothelial dysfunction, increased inflammation, increased oxidative stress, and insulin resistance, leading to fat accumulation in the arterial wall and atherosclerosis  represents the speed at which the pressure wave travels along the aorta, while the augmentation index (AI) represents the relative contribution of the wave reflections to the amplitude of the aortic pulse wave (pulse pressure) . As the heart contracts, the pressure that is generated travels along the aorta and reaches the peripheral artery. If the stiffness of the aorta increases, the aortic pressure  will increase, and at the same time, the pulse wave pressure travels faster . Part ofressure) . Severalressure) .via optical techniques in accordance with the contraction and relaxation of the heart. PPG values are affected by several parameters, such as arterial stiffness, resistance, pressure, and blood viscosity   .PPG is used to determine the effects of acute aerobic exercise on vascular aging . The stuThe current study was conducted to investigate the effects of pedometer-based exercise among young sedentary men on markers of vascular function. The assessment of vascular functions due to walking may expand the knowledge about the benefit of exercise toward the CVD risk.The study was approved by the Research and Ethics Committee of Universiti Kebangsaan, Malaysia. All measurements were conducted in Universiti Kebangsaan Malaysia Medical Center, Cheras. Subjects were recruited from Institute of Vocational Skills for Youth (IKBN Hulu Langat). The subjects were young men aged 20–40 years with at least two or more CVD risk factors and were randomly divided into the pedometer group  and control group . The sample size calculation was 66 people, where one group contained 33 people .Total sample size:Here, with c = 7.9 for 80% power.Calculation, c = 7.9,μ2-μ1 = 0.7 mmHg,*Values were based on the CRP level that need the highest sample size and obtained from the study that had been conducted by the previous researcher with more or less the same topic and the results of the study were significant .All subjects selected were sedentary, which was defined as having daily steps < 5,000 steps. Exclusion criteria were those with chronic diseases such as diabetes mellitus, CVD, inflammatory disease, peripheral vascular disease, lung disease, and liver disease.Hypertension was defined as systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg or on antihypertensive medication . DiabeteInitially, the PG groups had to increase their daily steps gradually to a minimum of 8,000 steps/day in 4 weeks’ time. Then, they underwent a 12-week pedometer-based walking. The number of steps included from wake-up to bed time every day (five days per week) and was recorded in a standardized diary book. Subjects belonged to the CG were asked to maintain their habitual lifestyle and not to change their daily activity during this program. The parameter assessments were conducted at baseline and after 6-week and 12-week intervention .2 (m2).Height was measured using a wall-mounted stadiometer , and weight was measured using a digital scale . Body mass index was then calculated as weight (kg)/heightvia particle-enhanced turbidimetric assay. This laboratory obtained the approval of International Organization of Standardization (ISO: MS ISO 15189) in compliance with the standard quality.A volume of 5 ml of blood was withdrawn from the antecubital vein after fasting for a minimum of 8 h. Blood samples were analyzed by Gribbles Pathology Laboratory . Serum TG, HDL cholesterol, and TC were measured by using enzymatic methods . The blood glucose was measured by using the enzymatic method using hexokinase and glucose-6-phosphate dehydrogenase enzymes . High-sensitivity C-reactive protein (hs-CRP) was measured via the Vicorder system . A blood pressure cuff was placed on to the right arm of the subject, which allowed the measurements of the brachial systolic and diastolic BP (SBP/DBP) via the oscillometric method and recording of the brachial waveforms. The brachial waveforms were then transformed to the aortic pressure waveforms by using a brachial-to-aortic generalized transfer function. AI was measured by analyzing the aortic pressure waveform using the following formula: augmentation pressure (AP)/pulse pressure x 100 .Measurements were obtained using the Vicorder system. The subject laid on the bed elevated at 45°. A blood pressure cuff was positioned around the upper thigh to record the femoral pulse. Another 30-mm partial cuff was placed around the neck at the level of the carotid artery. Both cuffs were inflated to 65 mmHg, and the pressure waveforms from the carotid and femoral were recorded simultaneously for 30 s by using a volume displacement method. The foot-to-foot transit time (∆t), which is the delay between the two recorded waves, was obtained The measurement was conducted in a quiet room with controlled temperature between 20 and 25°C. The subject was in the supine position. After resting for 5 min, the PPG probe was attached to the left index finger of the subject, and measurement was performed for 120 s. The signals were acquired through the serial port of pulse-oximeter modules . The system was connected to a personal computer running the application developed by the manufacturer of NiVaRiX 1.0. The sampling rate was 100 Hz, and the resolution was 16 bits. The PPGF index was derived from an AC component of the PPG morphological changes and compared with a 19-year-old healthy reference (gender-specific) who was identified from the population. The details of the formula could be found in the previous study .p-value of <0.05 was considered significant.The normality of the data was determined based on inspection of the histogram (plotted as the distribution frequencies) with the acceptable level of skewness (-1 to 1) and kurtosis (-1 to 1). All the data were normally distributed. The unpaired t-test or chi-squared test was used to compare quantitative data or qualitative data for baseline parameters between groups. Pearson’s correlation was conducted to determine the associations between PPGF index and other relevant parameters at baseline. The differences in all the parameters between groups after the intervention were compared using the general linear model (GLM) for repeated measures. A r = 0.37), systolic BP (SBP) (r = -0.32), heart rate (r = -0.30), and PWV (r = -0.34). Log hs-CRP was associated significantly with AI (r = 0.26) (data not shown). After the intervention, there was a significant reduction in BMI, resting BP, resting HR, PWV, AI, and hs-CRP and increase in the PPGF index in the PG when compared to CG, and most of the changes were observed as early as 6 weeks and continued to improve by 12th week  have successfully increased their number of steps to match the active group , which linked to improved cardiovascular risk factors . This reCF is still within the normal range of less than 10 m/s, however, there was a significant decrease in the subjects in the pedometer group. This also applies to the value of AI which also experienced a significant decrease in the pedometer group from 6 weeks of intervention with a sustained downtrend pattern to the end of the intervention. Increased levels of physical activities through walking in this study have also slowed down the process of losing elasticity of arteries and arterial compliance. In the latest European guidelines, PWVCF remains the gold standard for detecting macrovascular stiffness and a value > 10 m/s implies significant pathological macroangiopathy . Other than PWV, this study found that the PPGF index has a significant negative correlation with SBP and HR. Raised SBP and HR show increased stiffness and peripheral arterial resistance, indicative of deteriorated vascular health.The PPGF value in this study was found to correlate significantly with PWV, a standard measurement to evaluate arterial stiffness. This result was also in accordance with the research conducted by Limited studies have been carried out on the chronic effects of exercise on the PPG wave previously. In conclusion, this pedometer-based walking exercise program that has been specifically designed for the working group has successfully proven its effectiveness to reduce CVD risk factors which can be seen as early as 6 weeks after intervention. Walking exercise also managed to improve the central and peripheral vascular functions as evidenced by the reduction in PWV and AI and increase in the PPGF index. Pedometer-based exercise should be encouraged among young working subjects with CVD risk factors.First, this research only comprises young male subjects, which cannot represent the more significant population of younger and older generation people or female subjects. Second, no measurements were conducted to assess their physical activity, diet, or sleep pattern during intervention in both groups, which may affect the finding. Third, this research only focused on pedometer-based exercise. Future studies should be conducted to observe vascular function changes in various other conditions.