Effects of hyperprotein diet on anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats.

NEW FINDINGS: What is the central question of this study? The consumption of a high-protein diet has been associated with an anxiogenic factor that can influence anxiety and possible cardiovascular changes: does the consumption of a high-protein diet interfere with anxiety, haemodynamics and morphofunctional aspects of the heart of Wistar rats? What is the main finding and its importance? Our study showed that the high-protein diet did not interfere with anxiety and haemodynamics. The animals in the hyperproteic group showed positive heart adaptations characterized by less work and lower heart rate without impairing ejection fraction and systemic blood pressure. ABSTRACT: Anxiety is a mechanism preparatory to a response in situations of threat and danger, involving behavioural, affective and physiological factors. Protein-based foods have a high concentration of amino acids which perform multiple functions, including in the biosynthesis of excitatory transmitters for the central nervous system. In recent years, adherence to high-protein diets has been gaining ground in society, on the basis that it brings benefits to the musculoskeletal system and cardiovascular health. The aim of the present study was to investigate the effect of a high-protein diet in a state of anxiety and to investigate morphofunctional cardiovascular effects of a high-protein diet in Wistar rats. The experiment lasted 8 weeks and two groups of male rats were submitted to either a normoproteic or a hyperproteic diet. Anxiety was assessed using the plus maze test and cardiovascular morphofunctional aspects using transthoracic echocardiography and invasive measurements of femoral blood pressure. There was no statistically significant difference in the anxiety test, but the hyperproteic group was more agitated, with greater displacement during the test. Changes were found in systolic and end-diastolic volume, left ventricular diameter in systole and heart rate, which were significantly lower in the hyperproteic group, and there was an increase in the thickness of the interventricular septum in diastole. The results showed no influence of the higher protein diet on the animals' anxiety, body weight and haemodynamics.

Effect of exercise on epicardial adipose tissue in adults: a systematic review and meta-analyses.

According to previous epidemiological studies, we can reduce the thickness of epicardial fat and improve cardiovascular risk factors through exercise, and the changes may depend on the form of exercise. We systemically reviewed published studies that evaluated exercise intervention on epicardial adipose tissue (EAT) levels. We included randomized controlled trials (RCTs) comparing one exercise with another exercise or diet for the treatment to reduce EAT. We used fixed effects models for meta-analyses; effects of exercise on outcomes were described as mean differences (MD) or standardized difference of means (SMD) was used, their 95% confidence intervals (CI). Five RCTs were included (n = 299), 156 in exercise group and 143 in the control. In comparison to the control group, exercise significantly reduced EAT (SMD - 0.57, 95%CI - 0.97 to - 0.18) and waist circumference (MD - 2.95 cm, 95%CI - 4.93 to - 0.97). Exercise did not have an effect on BMI (MD - 0.23 kg/m2, 95%CI - 0.73 to 0.27), weight (MD - 0.06 kg, 95%CI - 1.46 to 1.34), or HDL (SMD 0.26, 95%CI - 0.06 to 0.57).VO2 was significantly increased by exercise (SMD 1.58, 95%CI 1.17 to 1.99). Risk of bias was high for 3 studies, and GRADE quality of evidence was very low to moderate. Exercise reduced epicardial adipose tissue and waist circumference, and did not have effect on weight, BMI, or HDL. Newer trials with better design and methods are necessary to improve the quality of the evidence. PROSPERO registration number (CRD42018096581).

Epidemiological profile, cardiopulmonary fitness and health-related quality of life of patients with heart failure: a longitudinal study.

BACKGROUND: Heart failure (HF) is a severe and self-limiting syndrome. Its signs and symptoms are believed to predict poorer health-related quality of life scores, which are mainly influenced by deterioration in physical capacity. In the present study we try to analyze the influence of clinical and socioeconomic characteristics and physical capacity on the quality of life of people with HF diagnosis. METHODS: A longitudinal study was conducted over 2 years with patients diagnosed with HF. To evaluate the patients the method of face-to-face visit and telephone monitoring was used. In the evaluations were applied: the Clinical and Socioeconomic Characterization Questionnaire, the Minnesota Living With Heart Failure Questionnaire (MLHFQ) for quality of life evaluation and the Veterans Specific Activity Questionnaire (VSAQ) for cardiopulmonary fitness analysis. Measures of central tendency, proportion, normality test, confidence intervals, comparison of data through paired Student t test and Wilcoxon or Mann Whitney test were performed and correlations were verified through Spearman coefficient. RESULTS: The study included 108 patients, most of them female (50.90%) and mean age of 66.62 ± 11.33 years. The median time of HF diagnosis was 5 ± 6 years, being Chagas' disease the main etiologic cause for the disease (57.40%). As for the clinical condition, functional classes II (44.40%) and III (48.10%) of the New York Heart Association (NYHA) were the most frequent. There was a low cardiopulmonary fitness, with loss of capacity to perform daily activities (3 ± 1 to 3 ± 3) over the time of clinical follow-up. There was an increase in the MLHFQ instrument scores, from 50.98 ± 15.52 to 61.76 ± 19.95, over the analysis time. The analysis of correlations demonstrated that variables such as schooling, NYHA class, echocardiographic alterations and the drug profile have a significant relationship with the constructs of quality of life and physical fitness. CONCLUSION: Individuals in HF have significant impairment of cardiorespiratory capacity and tend to present worsening of QL along the evolution of the disease.

Human Immunodeficiency Virus Infection, Antiretroviral Therapy, and Statin: a Clinical Update.

PURPOSE OF REVIEW: This clinical update is intended to focus in relationship between HIV infection and use of antiretroviral therapy (ART) and statin. RECENT FINDINGS: Though ART significantly changed the course of HIV infection, it is related to numerous side effects principally to the lipid profile. In this way, statins became one of the most used lipid-lowering therapies in this population. In our clinical update, we evaluated studies that demonstrate the relationship and molecular mechanisms that HIV infection and ART use trigger dyslipidemia and also the use of statin to reduce this condition. We have demonstrated that use of statin can be used in dyslipidemic HIV-infected people as long as there is no drug interaction with ART. Recently, studies using rosuvastatin have shown greater effects when compared to the other statins.

How Heart Rate Should Be Controlled in Patients with Atherosclerosis and Heart Failure.

PURPOSE OF REVIEW: Resting heart rate is an independent risk factor for all-cause and cardiovascular mortality in patients with heart failure. The main objectives are to discuss the prognosis of heart rate, its association with coronary atherosclerosis, and the modalities of control of the heart rate in sinus rhythm and in the rhythm of atrial fibrillation in patients with chronic heart failure. RECENT FINDINGS: As a therapeutic option for control heart rate, medications such as beta-blockers, digoxin, and finally ivabradine have been studied. Non-dihydropyridine calcium channel blockers are contraindicated in patients with heart failure and reduced ejection fraction. The influence of the magnitude of heart rate reduction and beta-blocker dose on morbidity and mortality will be discussed. Regarding the patients with heart failure and atrial fibrillation, there are different findings in heart rate control with the use of a beta-blocker. Patients eligible for ivabradine have clinical benefits and increased ejection fraction. Vagal nerve stimulation has low efficacy for the control of heart rate. Complementary therapies such as tai chi and yoga showed no effect on heart rate. In this review, we discuss the main therapeutic options for the control of heart rate in patients with atherosclerosis and heart failure. More research is needed to examine the effects of therapeutic options for heart rate control in different population types, as well as their effects on clinical outcomes and impact on morbidity and mortality.

The Role for Cardiovascular Remodeling in Cardiovascular Outcomes.

PURPOSE OF REVIEW: Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes. RECENT FINDINGS: These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.

Bivariate and multivariate analyses of the influence of blood variables of patients submitted to Roux-en-Y gastric bypass on the stability of erythrocyte membrane against the chaotropic action of ethanol.

The stability of the erythrocyte membrane, which is essential for the maintenance of cell functions, occurs in a critical region of fluidity, which depends largely on its composition and the composition and characteristics of the medium. As the composition of the erythrocyte membrane is influenced by several blood variables, the stability of the erythrocyte membrane must have relations with them. The present study aimed to evaluate, by bivariate and multivariate statistical analyses, the correlations and causal relationships between hematologic and biochemical variables and the stability of the erythrocyte membrane against the chaotropic action of ethanol. The validity of this type of analysis depends on the homogeneity of the population and on the variability of the studied parameters, conditions that can be filled by patients who undergo bariatric surgery by the technique of Roux-en-Y gastric bypass since they will suffer feeding restrictions that have great impact on their blood composition. Pathway analysis revealed that an increase in hemoglobin leads to decreased stability of the cell, probably through a process mediated by an increase in mean corpuscular volume. Furthermore, an increase in the mean corpuscular hemoglobin (MCH) leads to an increase in erythrocyte membrane stability, probably because higher values of MCH are associated with smaller quantities of red blood cells and a larger contact area between the cell membrane and ethanol present in the medium.

Implementation of the Lean Healthcare System in the Emergency Room of the Clinical Hospital of the Federal University of Uberlândia: A Case Study.

The objective of this study was to analyze the effectiveness of the implementation of the lean healthcare system at the emergency room of the Clinical Hospital of the Federal University of Uberlândia, based on a comparison of hospital indicators obtained over the three phases corresponding to the period of one year before the implementation (T1), the year during the implementation (T2) and one year after implementation (T3). The methodology applied through this study can be classified as a case study that is exploratory and descriptive and developed in stages. Based herein on the search for hospital indicators, as occurred in the implementation of a lean process at the Clinical Hospital Emergency Department, along with a description of the implemented lean system. During the collection period of data relevant to the National Emergency Department Overcrowding Score and Length of Stay Indicator, the motivation of the teams grew, but with a notable tension between municipal management and hospital management. It was found that, despite the fluctuations, the patient length of stay in the Emergency Room remained high. With the exception of the variable of female deaths before 24 h of hospitalization, all other variables showed percentage increases before and after the intervention. This study reported the difficulties encountered by HC-UFU in implementing the lean project in an emergency room, thus ensuring that other institutions that intend to implement this project do not make the same types of mistakes.

Effects of an L-Leucine-Rich Diet on Liver and Kidneys in a Doxorubicin Toxicity Model.

Supplements and diets containing L-leucine, a branched-chain amino acid, have been considered beneficial for controlling oxidative stress and maintaining cardiac tissue in toxicity models using doxorubicin, a drug widely used in cancer treatment. However, there is a lack of studies in the literature that assess the effects of this diet on other organs and tissues, such as the liver and kidneys. Therefore, this study aimed to evaluate the effects of a leucine-rich diet on the liver and kidneys of healthy rats submitted to the doxorubicin toxicity model by analyzing biomarkers of oxidative stress and histological parameters. The animals were divided into four groups: naive, doxorubicin, L-leucine, and doxorubicin + L-leucine, and the diet was standardized with 5% L-leucine and a dose of 7.5 mg/kg of doxorubicin. We evaluated tissue injury parameters and biomarkers of oxidative stress, including enzymes, antioxidant profile, and oxidized molecules, in the liver and kidneys. Although some studies have indicated benefits of a diet rich in L-leucine for the muscle tissue of animals that received doxorubicin, our results showed that the liver was the most affected organ by the L-leucine-rich diet since the diet reduced its antioxidant defenses and increased the deposit of collagen and fat in the hepatic tissue. In the kidneys, the main alteration was the reduction in the number of glomeruli. These results contribute to the scientific literature and encourage further studies to evaluate the effects of an L-leucine-rich diet or its supplementation, alone or combined with doxorubicin using an animal model of cancer. Therefore, our study concludes that the leucine-rich diet itself was harmful and, when co-administered with doxorubicin, was not able to maintain the antioxidant defenses and tissue structure of the evaluated organs.

Cardioprotective Effects of the 4-Week Aerobic Running Exercises Before Treatment with Doxorubicin in Rats.

Doxorubicin is associated with cardiotoxicity, and physical exercise seeks to minimize the toxic effects of doxorubicin through physiological cardiac remodeling, as well as the reduction of oxidative stress, evidenced by previous studies. This study aimed to analyze whether running training before treatment with doxorubicin influences tolerance to physical exertion and cardiotoxicity. Thirty-nine male Wistar rats, aged 90 days and weighing between 250 and 300 g, were divided into 4 groups: Control (C), Doxorubicin (D), Trained (T), and Trained + Doxorubicin (TD). Animals in groups T and DT were submitted to treadmill running for 3 weeks, 5 times a week at 18 m/min for 20-30 min before treatment with doxorubicin. Animals in groups D and DT received intraperitoneal injections of doxorubicin hydrochloride three times a week for two weeks, reaching a total cumulative dose of 7.50 mg/kg. Our results show an increase in total collagen fibers in the D group (p = 0.01), but no increase in the TD group, in addition to the attenuation of the number of cardiac mast cells in the animals in the TD group (p = 0.05). The animals in the TD group showed maintenance of tolerance to exertion compared to group D. Therefore, running training attenuated the cardiac damage caused by the treatment with doxorubicin, in addition to maintaining the tolerance to exertion in the rats.

Improving patient access to specialized health care: the Telehealth Network of Minas Gerais, Brazil.

PROBLEM: The Brazilian population lacks equitable access to specialized health care and diagnostic tests, especially in remote municipalities, where health professionals often feel isolated and staff turnover is high. Telehealth has the potential to improve patients' access to specialized health care, but little is known about it in terms of cost-effectiveness, access to services or user satisfaction. APPROACH: In 2005, the State Government of Minas Gerais, Brazil, funded the establishment of the Telehealth Network, intended to connect university hospitals with the state's remote municipal health departments; support professionals in providing tele-assistance; and perform tele-electrocardiography and teleconsultations. The network uses low-cost equipment and has employed various strategies to overcome the barriers to telehealth use. LOCAL SETTING: The Telehealth Network connects specialists in state university hospitals with primary health-care professionals in 608 municipalities of the large state of Minas Gerais, many of them in remote areas. RELEVANT CHANGES: From June 2006 to October 2011, 782,773 electrocardiograms and 30 883 teleconsultations were performed through the network, and 6000 health professionals were trained in its use. Most of these professionals (97%) were satisfied with the system, which was cost-effective, economically viable and averted 81% of potential case referrals to distant centres. LESSONS LEARNT: To succeed, a telehealth service must be part of a collaborative network, meet the real needs of local health professionals, use simple technology and have at least some face-to-face components. If applied to health problems for which care is in high demand, this type of service can be economically viable and can help to improve patient access to specialized health care.

Association Between Epicardial Adipose Tissue and Stroke.

Epicardial adipose tissue (EAT) is correlated with endothelial dysfunction, metabolic syndrome, increased mortality and recent studies showed a possible association with the increased risk of stroke. We performed a systematic review of studies evaluating the association between EAT and stroke. Eighty studies met the inclusion criteria and were consequently analyzed. The review had Five main findings. First, the increased epicardial fat thickness (EFT) may be associated with the stroke episode. Second, regardless of the imaging method (echocardiography, MRI, and CT) this association remains. Third, the association of metabolic syndrome and atrial fibrillation seems to increase the risk of stroke. Fourth, this systematic review was considered as low risk of bias. Despite being unable to establish a clear association between EAT and stroke, we have organized and assessed all the research papers on this topic, analyzing their limitations, suggesting improvements in future pieces of research and pointing out gaps in the literature. Furthermore, the mechanistic links between increased EAT and stroke incidence remains unclear, thus, further research is warranted.

Effects of Exercise Training and Statin Use in People Living with Human Immunodeficiency Virus with Dyslipidemia.

PURPOSE: To evaluate the effects of the combination of exercise training (ET) and statins in people living with human immunodeficiency virus. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial. Eighty-three people living with human immunodeficiency virus were assigned to either placebo (PL), statins (STA), PL + ET (PLET) or STA + ET (STAET) groups. Volunteers assigned to STA and STAET groups were administered 10 mg of rosuvastatin, whereas the PL and PLET groups were administered a placebo. The PLET and STAET groups performed ET three times a week. Before and after the 12-wk follow-up, the volunteers underwent to anthropometric assessment and blood collection to evaluate lipid profile, cardiovascular markers, inflammatory profile; a Doppler ultrasound examination, muscle strength (MS) and cardiorespiratory fitness (CF) tests were performed. RESULTS: There was a decrease in total cholesterol, triglycerides, low-density lipoprotein, C-reactive protein, fibrinogen, interleukin (IL)-1ß and right carotid intima-media thickness in the STA, PLET, and STAET groups compared with PL group (P < 0.001). Furthermore, there was a decrease in total cholesterol, triglycerides, low-density lipoprotein, IL-1ß, IL-6, and IL-8 levels and in left and right carotid intima-media thickness and an increase in HDL-c levels in the STAET groups compared with the STA (P ≤ 0.001) and PLET groups (P ≤ 0.001). There was an increase in IL-10 levels, peak-systolic velocity, end-diastolic velocity, wall shear rate in the PLET and STAET groups compared with the PL (P ≤ 0.001) and STA groups (P ≤ 0.001). The PLET and STAET groups reduced body fat mass, body fat percentage and increased lean body mass, MS and CF compared with PL (P ≤ 0.001) and STA (P ≤ 0.001) groups. CONCLUSIONS: The combination of ET and statins is useful to enhance lipid and inflammatory profiles, reduce cardiovascular disease markers, and improve Doppler ultrasound findings, MS and CF in people living with HIV.

Development and Evaluation of a Mobile Decision Support System for Hypertension Management in the Primary Care Setting in Brazil: Mixed-Methods Field Study on Usability, Feasibility, and Utility.

BACKGROUND: Despite being an important cardiovascular risk factor, hypertension has low control levels worldwide. Computerized clinical decision support systems (CDSSs) might be effective in reducing blood pressure with a potential impact in reducing cardiovascular risk. OBJECTIVE: The goal of the research was to evaluate the feasibility, usability, and utility of a CDSS, TeleHAS (tele-hipertensão arterial sistêmica, or arterial hypertension system), in the care of patients with hypertension in the context of a primary care setting in a middle-income country. METHODS: The TeleHAS app consists of a platform integrating clinical and laboratory data on a particular patient, from which it performs cardiovascular risk calculation and provides evidence-based recommendations derived from Brazilian and international guidelines for the management of hypertension and cardiovascular risk. Ten family physicians from different primary care units in the city of Montes Claros, Brazil, were randomly selected to use the CDSS for the care of hypertensive patients for 6 months. After 3 and 6 months, the feasibility, usability, and utility of the CDSS in the routine care of the health team was evaluated through a standardized questionnaire and semistructured interviews. RESULTS: Throughout the study, clinicians registered 535 patients with hypertension, at an average of 1.24 consultations per patient. Women accounted for 80% (8/10) of participant doctors, median age was 31.5 years (interquartile range 27 to 59 years). As for feasibility, 100% of medical users claimed it was possible to use the app in the primary care setting, and for 80% (8/10) of them it was easy to incorporate its use into the daily routine and home visits. Nevertheless, 70% (7/10) of physicians claimed that the time taken to fill out the CDSS causes significant delays in service. Clinicians evaluated TeleHAS as good (8/10, 80% of users), with easy completion and friendly interface (10/10, 100%) and the potential to improve patients' treatment (10/10, 100%). A total of 90% (9/10) of physicians had access to new knowledge about cardiovascular risk and hypertension through the app recommendations and found it useful to promote prevention and optimize treatment. CONCLUSIONS: In this study, a CDSS developed to assist the management of patients with hypertension was feasible in the context of a primary health care setting in a middle-income country, with good user satisfaction and the potential to improve adherence to evidence-based practices.

Correlations of the glycemic variability with oxidative stress and erythrocytes membrane stability in patients with type 1 diabetes under intensive treatment.

OBJECTIVES: This study aimed to evaluate the correlations of glycemic variability with erythrocyte membrane stability parameters and oxidative stress markers in patients with type 1 diabetes mellitus (T1DM) under intensive treatment. MATERIAL AND METHODS: 90 patients with T1DM and under intensive treatment of the disease were evaluated in relation to anthropometric indices, records of glycemic averages and parameters of glycemic variability, biochemical dosages (glucose, uric acid, lipidogram, glycated hemoglobin, microalbuminuria, creatinine and iron) reticulocyte count, erythrocyte membrane stability parameters and oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and glutathione reductase, GR). RESULTS: Indicators of glycemic variability in the short and long term showed correlations with parameters of membrane stability and markers of oxidative stress (GR). In addition, the comparison of these same parameters between the subgroups consisting of quartiles of GV or glycemic control also showed significant differences. CONCLUSION: In the T1DM patients studied here, glycemic variability showed correlations with oxidative stress and erythrocyte membrane stability variables. This corroborates the hypothesis that glycemic fluctuations interfere with lipid peroxidation and cell membrane behavior, emphasizing its participation in mechanisms related to the development of chronic complications of diabetes.

Leucine Supplementation Improves Effort Tolerance of Rats With Hyperthyroidism.

Leucine is a regulator of protein metabolism in vivo and information on its action on effort tolerance of both animals and humans with hyperthyroidism is scarce. The objective of the present study was to verify the influence of leucine supplementation on the effort tolerance of Wistar rats with experimental hyperthyroidism. 40 animals were divided into four groups of ten: control (C), hormone (H), leucine (L), and hormone + leucine (HL). Hyperthyroidism was induced by daily administration of 20 µâ‹…g100 g-1 of levothyroxine sodium in aqueous suspension by gavage. Leucine was supplemented by adding 5% of the amino acid to the conventional feed. The animals' blood was collected by cardiac puncture to analyze TSH, T4, and T3 levels. The effort tolerance was determined by the swimming test with a 7% load attached to animals' tails. Statistical analysis was performed using the Shapiro-Wilk normality test, followed by the analysis of variance (ANOVA) of repeated measures of two factors (treatment × time) and Tukey post hoc, with a significance level of p < 0.05. Administering thyroid hormone increased the swimming performance of rats after 14 and 21 days, but with a drop in performance at 28 days. The HL group, on the other hand, had a significantly higher swimming performance compared to the other groups after 28 days of treatment. Leucine supplementation associated with the experimental model of hyperthyroidism improved the performance of rats in a swimming test after 28 days of treatment.

High-density lipoprotein-cholesterol functionality and metabolic syndrome: Protocol for review and meta-analysis.

INTRODUCTION: The prevalence of metabolic syndrome (MetS) and MetS-related stroke is set to increase dramatically in coming decades. MetS is a complex disease that includes endothelial dysfunction, insulin resistance, diabetes, hypertension, ectopic obesity, and dyslipidaemia and an increased risk of cardiovascular events. One function of high-density lipoprotein (HDL) cholesterol (HDL-C) is the cholesterol-efflux pathway, which is the pathway where cholesterol is removed from macrophages within the arterial walls back into the bloodstream and out to the liver. As one of the key functions of HDL, their hypothesis was that if they could measure HDL-C-efflux capacity, they would have a better handle on the role of HDL in atherosclerosis. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between HDL-C functionality and MetS. The aim of this study is to examine this association of HDL-C functionality with MetS in different ages and sex. METHODS AND ANALYSIS: The update systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (i.e., PubMed, EMBASE, Web of Science, and Google Scholar). Studies that examined the association between HDL-C functionality and MetS; focused on cohort, case-control, and cross-sectional studies; were conducted among in adults aged 40 to 70 years; provided sufficient data for calculating odds ratio or relative risk with a 95% confidence interval; were published as original articles written in English or other languages; and have been published until January 2018 will be included. Study selection, data collection, quality assessment, and statistical syntheses will be conducted based on discussions among investigators. ETHICS AND DISSEMINATION: Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42018083465).