Anthropometric parameters as alternatives to identify visceral fat and cardiovascular risk in hepatitis C patients

Objective: To analyze the anthropometric parameters used as alternatives to identify visceral fat and cardiovascular risk in patients with hepatitis C. Methodology: Study carried out between June to November of 2017, with hepatitis C patients. Social data, lifestyle and biochemical parameters were collected. Anthropometric assessment was carried out, being measured height, weight, waist circumference and hip circumference were measured. Then, body mass index, waist and height ratio, waist-to-hip ratio, visceral adiposity index and Framinghan risk score were calculated. For statistical analysis, chi-square test was applied, and simple and multiple logistic regressions have been performed to explore the correlation between anthropometric parameters and Framingham risk score, adopting a 5% significance level. Statistical Package for Social Science software was used. Results: 55 patients evaluated. It was observed that 56.36% presented cardiovascular risk according to waist circumference and waist-to-hip ratio, 78.18% according to the waist and height ratio, and 74.55% according to the visceral adiposity index. In the relation between Framingham risk score and anthropometric parameters it was observed that waist-to-hip ratio was considered a significant independent predictor (OR=14.7000; CI95% = 3.5360 – 61.1180). Conclusion: For the identification of visceral fat, it Research, Society and Development, v. 11, n. 2, e27011225829, 2022 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25829 2 is suggested to use the waist-to-hip ratio because it indicated a probability for the development of cardiovascular events in individuals with hepatitis C.


Introduction
The hepatitis C virus (HCV) infection allows metabolic alterations that may contribute to the development of metabolic syndrome, and consequently, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) (Negro 2014). Besides, it is believed that the infection may allow chronic inflammation and can be responsible for possible modifications of the vascular endothelium (Badawi et al., 2018). In a study was evidenced that HCV infected patients presented from 2.5% to 3.5% higher chances of developing a cardiovascular problem in 10 years than the ones not infected (Badawi et al., 2018).
It is suggest that HCV can promote atherogenesis and its complications through different biological mechanisms, from which involve the virus' colonization and replication inside the arterial walls, hepatic steatosis and fibrosis, inflammatory cytokines' increased and unbalanced secretions, oxidative stress, cellular and humoral disorders, hyperhomocysteinemia, IR and T2DM (Domont & Cacoub, 2016). According to Petta (2017) a pro-inflammatory and pro-fibrogenic environment increases even more the development of cardiovascular lesions.
Thus, due to metabolic alterations and extrahepatic manifestations observed in patients, it is common to observe overweight in these individuals (Menta et al., 2015). Alves, Schmidt and Benet (2018) evidence that the high percentage of body fat observed in chronic hepatitis C patients is considered as an important risk factor to the appearance of CVD and other associated complications.
According to Gadekar et al. (2020) there is a massive necessity of simple methods, as of easy application, low cost and practices to be used as substitutes to body fat measuring. Therefore, it has been created parameters based in anthropometric data capable of estimating body fat and, consequently, identifying the cardiovascular risk, being able to be considered as good alternatives . Among these, it is highlighted the body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist and height ratio (WHtR) and visceral adiposity index (VAI) Czeczelewski et al., 2020;Amato et al., 2010).
However, until this moment the researches that use such parameters in patients diagnosed with hepatitis C are scarce. Therefore, the present study has as objective analyzing the anthropometric parameters used as alternatives to identify visceral fat and cardiovascular risk in patients with hepatitis C.

Study protocol and patients
Cross-sectional, descriptive and analytical study, because according to Zangirolami-Raimundo et al. (2018), crosssectional studies allow the researcher to observe the variables at a single moment, being the collection of information carried out in a short space of time, without the follow-up of the individuals. As for descriptive studies, the main objective is to describe in a detailed and organized way one or more phenomena, and analytical studies, establish relationships and/or associations between two or more variables (Zangirolami-Raimundo et al., 2018) Data collection was carried out between June and November in 2017. The sample was selected by convenience sampling with non-probabilistic methods. Participated patients from 32 to 74 years old, from both genders, diagnosed with hepatitis C, treated at a Brazilian Eastern Amazon reference center.
The exclusion criteria adopted were: liver disease by other viral agents which are not virus C carriers, pregnant and nursing mothers, edematous patients, ascites presence, clinical intercurrence that made impossible the research formulary and nutritional evaluation application.

Biochemical evaluation, life style, anthropometric assessment and Framingham risk score
It was applied a particular formulary developed by the research team, containing items related to social data (age and gender), biochemical evaluation, clinical characterization, and lifestyle. Data has been collected from the patients' medical record and/or during the interview. Weight and height were measured in anthropometric evaluation, in a platform type weighing scale from Welmy® (Brazil) brand with a 180 kg capacity and 100g precision, with attached stadiometer, according to Lohman protocol (1988). In Research, Society andDevelopment, v. 11, n. 2, e27011225829, 2022 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25829 4 addition, for the BMI calculus the formula used was: weight (kg) / height squared (m 2 ). Parameters from the WHO (2000) and from Lipschitz (1994) were used for classification to adults and elderly, respectively. WC measurement (cm) was performed using an inelastic measuring tape, at the midpoint between the iliac crest and the last rib, as suggested by the WHO (2000). For the cardiovascular risk evaluation, the parameters from WHO (2000) were considered.
Hip circumference (cm) was measured by going around the height of the largest gluteus circumference, with the aid of an inelastic measuring tape and making adjustments to avoid looseness (Rossi et al., 2017).
Then, WHtR was obtained by the formula: WHtR = WC (cm) / height (cm), and the patients were classified according to Ashwell and Hsieh (2005). WHR was obtained by the formula: WHR = WC (cm) / HC (cm), and the results was classified by Heyward and Stolarczyk (2000).
The Framingham risk score (D'Agostino et al., 2008) was calculated considering the variables: age, LDL-c, HDL-c, systemic blood pressure (mm/Hg), T2DM and smoking, for males and females. The results were classified as: low risk (risk less than 10%), moderate risk (values between 10% to 20%) or high risk (risk above 20%).

Statistical analysis and ethical aspects
The data were analyzed by Statistical Package for Social Science software. For analytical analysis, chi-square test was applied, and to explore the association between anthropometric parameters and Framingham risk score, simple and multiple logistic regressions have been performed. Were used adopting the alpha significance level of 5%. The Framingham risk score "moderate risk" and "high risk" categories were grouped into only one category for regression analyses. The Framingham risk score was considered as the dependent variable, and the anthropometric variables (BMI, WC, WRtH, WRH, VAI) were considered as independent.
Regarding ethical aspects, the present study is inserted in the research project "Clinical and nutritional evaluation of subjects diagnosed with viral hepatitis treated at a reference center in the Amazon" approved by the Research Ethics Committee of the reference hospital (number 2.084.522), complying with the legal requirements of Resolution n. 466/12 from the National Health Counsel (Brasil, 2012) according to the Helsinki Declaration. All participants signed an informed consent form. 45.45% (n=25) did not consumed alcoholic beverage and 58.18% (n=32) did not present smoking habits. When the biochemical parameters were evaluated, it was observed that the majority of patients have presented adequate results of total cholesterol (76.36%; n=42; p<0.001) and triglycerides (83.64%; n=46; p<0.001). Regarding the Framingham risk score, it was observed that most participants were classified as low risk (56.37%; n=31) ( Table 1).  when the VAI was evaluated (Table 2). When evaluated the relation between Framingham risk score and BMI, WC, WHtR, WHR and VAI it is observed in Table 3 that there had been significance between the VAI and WHtR and WHR. However, when multivariate analysis was performed, only the WHR remained significant [X 2 (1) = 18.282; p<0.0001, R 2 Negelkerke = 0.379]. Therefore, only the WHR was considered an independent significant predictor (OR=14.7000; IC95% = 3.5360 -61.1180).

Discussion
In this present study was possible analyzed the anthropometric parameters of risk identification to cardiovascular diseases in patients diagnosed with hepatitis C. The majority of patients were female, similarly as observed by Menta et al. (2015) in which 54.0% of hepatitis C patients were female. Regarding the lifestyle evaluation, this present research evidenced a high rate of physical inactivity. Hudson et al. (2015) reported that the practice of physical activity with restrictions is well tolerated in chronic hepatitis C patients, including cirrhotic patients, and the authors also present association with the reduction of the circulating liver enzymes, body fat and insulin resistance. Nonetheless, if the treatment load (intensity, volume, frequency and density) is not adequate to the subject it can show negative effects.
Regarding the alcoholism, results of this present study was differently from observed in the Cortes et al. (2017) study, in which all individuals presented alcohol consumption history, 38.9% of them being classified as alcohol abusers and 56.7% as dependents. It is important to mention that according to the authors alcohol consumption is one of the factors that contribute to the infection progression.
As of smoking, the result was similar to the Beltrão et al. (2015) study in which the authors had as objective to associate the nutritional state with the gravity stage of the chronic hepatic disease, and observed that the majority of the evaluated patients was classified as non-smoker. The authors reported that the stage and the disease's clinical conditions induce the patients to stop such habit, once that nicotine can contribute to fibrogenesis.
In the biochemical parameters it was observed that most patients had adequate levels of TC and TG. Pesset et al. (2020) mention that although an adequate lipid pattern is observed, there is an increase in cardiovascular events associated with HCV infection, due to other pathophysiological mechanisms.
On evaluating the anthropometric parameters, the majority of adult patients was diagnosed with overweight. In the Santis and Silva et al. (2015) study, the majority of hepatitis C patients presented obesity (34%) or overweight (20%) according to BMI. However, Czeczelewski et al. (2020) report that despite being largely used, BMI is not a precise indicator of CV risk identification, once it does not evaluate body fat distribution.
In the Hu et al. (2004) study it has been verified that the HCV infection was the main cause of alterations in the BMI and lipid levels, and was positively associated to T2DM, cardiovascular events and kidney diseases. Besides, according to Badawi (2018), overweight can contribute to the LDL-C levels increase, corroborating with the observed this present study.
Regarding the anthropometric parameters commonly used to estimate the body composition and CV risk, the majority of patients from this present research was diagnosed with CV risk in all employed methods. Furthermore, it is important to highlight that there was not found studies in which such anthropometric indexes were evaluated in hepatitis C patients.
Regarding the WC, according to Czeczelewski et al. (2020) it is the basic clinic indicator employed to evaluate visceral fat and presents as advantage the measurement simplicity, besides not needing an additional calculus in order to obtain results. In the Zhao et al. (2017) study the authors observed that the SAH risk increased significantly with the WC elevation in both genders' subjects in a Chinese population.
As for the WHR, once it is turned towards the visceral adiposity, it is routinely employed in the CV risk prediction, and present a good level of reliability and low cost . In the Medina et al. (2017) study the authors observed that the WHR is associated with a higher risk of cardiovascular events among women, but not in men presenting coronary artery disease. As well as Streng et al. (2018) observed that increased WHR was associated to a higher mortality in women with cardiac insufficiency, but not in men. The authors suggest that the difference found between genders can be due to the body fat distribution, once men accumulate more visceral fat and women store subcutaneous fat in the gluteal-femoral region (Streng et al., 2018).
Regarding the WHtR, it is considered a method which presents advantage over the isolated employment of WC to verify the risk of CVD, that is, it is significantly associated to all risk factors for obesity and metabolic syndrome, presenting better index of dyslipidemia prognosis, SAH and risk of CVD, in both genders, according to Ashwell and Hsieh (2005). Hsieh and Muto (2005) compared in non-obese Japanese the effects of age, BMI, WC and WHtR with coronary risk factors and the sensibilities and specificities of proposed anthropometric indexes, and observed that the WHtR identified more subjects in CV risk and presented more sensibility in identification when compared to the other parameters, in both genders.
On evaluating VAI, Jablonowsk-Lietz et al. (2017) carried out a study in the National Food and Nutrition Institute in Warsaw, and suggested that VAI is a method that can be considered useful in daily clinic practice and in populational studies, and to the evaluation of cardiometabolic risk associated with visceral adiposity, being a substitute marker for the dyslipidemia dysfunction and insulin resistance. According to Czeczelewski et al. (2020) VAI can be considered a useful indicator to trace dyslipidemia, hyperuricemia, hyperglycemia, SAH and CV risk factors associated.
In the Kouli et al. (2017) study, authors had as objective evaluating associations between VAI and the incidence of cardiovascular disease in 10 years, and observed that VAI is independently associated to a elevated risk for CVD, suggesting to be an additional indicator that can be employed to identify CV risk in a long term in Caucasian/Mediterranean men without previous CVD. Bagyura et al. (2020) evaluated the association between VAI and the coronary artery calcium score in asymptomatic Caucasian population, and observed that the method can be a clinical marker of cardiometabolic risk and central obesity mainly in men, it can though present ethnical difference. It highlights the necessity of more studies which evaluate the association of VAI with the risk of CVD development in Brazilian population.
From logistical regression between Framingham risk score with the anthropometric variables to identify the CVD, it was observed that WHR was considered an independent significant predictor. There has not been found studies in hepatitis C patients, but Aparicio et al. (2019) assessed the risk of ischemic stroke associated with BMI, WC, and WHR in a community sample, and observed that higher WHR predicted 10-year risk of ischemic stroke. Therefore, the authors suggest that the WHR is a simple measure of abdominal obesity that should be used in future studies investigating weight loss interventions for stroke prevention. Medina-Inojosa et al. (2018) evaluated whether patients with established coronary artery disease and central obesity, defined as an elevated WHR, have an increased risk of adverse cardiovascular events when compared to patients without central obesity, and observed that WHR is associated with a higher risk of adverse cardiovascular events among women. Streng et al. (2018) evaluated the association between abdominal fat (as measured by WHR), BMI, and all-cause mortality in patients with heart failure, and found that increased WHR values were associated with a higher risk of death in female patients with heart failure. Gadekar et al. (2020) study the authors had as objective to evaluate the correlation between visceral fat area and WHR, WC and BMI in healthy young adults, and observed a strong correlation between visceral fat and the WHR. Thus, authors consider a method that can be used as substitute to measure visceral fat.
Therefore, from the observed results it is suggested that health professionals may employ WHR parameter, for it is practical methods, of low cost, easy measurement and considered useful measuring for the visceral fat identification and, consequently, CV risk. Once the more effective parameters employed for measurement are instruments less accessible due to its high cost, such as bioimpedance, magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DEXA).
Notwithstanding, this present study presents as limitation being a transversal research with non-probabilistic sampling by convenience, exposing the necessity of more research which investigate the relation between such anthropometric parameters in hepatitis C patients. In addition, equipments of high technology were not used, such as bioimpedance, DEXA, MRI or ultrasound, which present with higher precision the individuals body composition, thus our study cannot determine the accuracy of substitute anthropometric parameters for the visceral fat evaluation.

Final Considerations
This study verified the presence of CV risk factors in HCV patients when evaluated the anthropometric parameters. In addition, our result shows that WRH is independently associated with 10-year CVD risk. Therefore, it is suggested the use of WHR because it indicated a probability for the development of cardiovascular events in individuals with hepatitis C.
However, it is important highlighting the research's scarcity that evaluate the anthropometric parameters specifically in patients diagnosed with hepatitis C, more studies being necessary to clarify this relation, once such information are fundamental to the identification of anthropometric measurements that can be used by health professionals in a practical way to precocious identification and consequently prevention of CVD.
Therefore, it is suggested new studies of nutritional intervention that evaluate body composition through anthropometric parameters and more technological equipment, besides investigating the patients' eating habits in order to verify the impact in the hepatitis C patients' nutritional state and thus confirming this study's results.