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PLOS ONE logoLink to PLOS ONE
. 2022 Dec 22;17(12):e0278891. doi: 10.1371/journal.pone.0278891

The direct and indirect costs of cardiovascular diseases in Brazil

Jevuks Matheus de Araújo 1,#, Rômulo Eufrosino de Alencar Rodrigues 1,#, Adélia da Costa Pereira de Arruda Neta 2,#, Flávia Emília Leite Lima Ferreira 2,, Rafaela Lira Formiga Cavalcanti de Lima 2,, Rodrigo Pinheiro de Toledo Vianna 2,, Lucas Vasconcelos Leitão Moreira 3,, José Moreira da Silva Neto 4,, Patrícia Vasconcelos Leitão Moreira 2,*,#
Editor: Pankaj Bahuguna5
PMCID: PMC9778932  PMID: 36548305

Abstract

Objective

To evaluate the direct and indirect costs of cardiovascular diseases (such as coronary heart disease and stroke) by sex and age group, attributed to the excessive consumption of salt, saturated fat and trans fat in Brazil.

Materials and methods

The data for estimating the Population Attributable Fraction (PAF) corresponding to the consumption of salt, saturated fat and trans-fat were obtained from the Household Budget Survey 2017–2018. The calculation of direct costs for cardiovascular diseases (CVD) was made from the accounting sum of costs with hospitalizations and outpatient care found in the National Health System (Hospital Information System and Outpatient Information System), from 2017 to 2019, including the costs of treatment, such as medical consultations, medical procedures, and drugs. Regarding the indirect costs, they were measured by the loss of human capital, given the premature death, resulting in loss of productivity. To define the attributable costs, they were multiplied by the PAF.

Results

Higher burden of CVD attributable to the consumption of salt, saturated fat and trans fat were observed in younger individuals, which progressively decreased with advancing age, but still generated economic costs in the order of US$ 7.18 billion, in addition to 1.53 million productive years of life lost (YLL) to premature death, if considering salt as an inducer. Although attributable burden of CVD is higher among younger individuals, the highest costs are associated with males aged 45 to 74 years old for direct costs and 45 to 64 years old for indirect costs.

Conclusion

The attributable fractions to consumption of salt are the ones that cause the most effects on CVD, followed by saturated fat and trans fat, with direct and indirect costs being higher for males.

Introduction

Cardiovascular diseases (CVD) are one of the key challenges in health globally, since they are the main cause of premature deaths and compromised productivity, reaching a mortality rate in 2019 of around 32% in the total population and 38% in individuals under the age of 70 [13]. Three quarters of the total of these deaths are concentrated in low- and middle-income countries [3], where the population is more vulnerable to the risk factors of these diseases. Furthermore, with the increase in longevity and the considerable reduction of infectious diseases, the aging of the population also contributes to increase the number of CVD [4, 5].

In 2018, the total population of Brazil was 208,494,900 people, of whom 51.08% were women and 69.43% were 15 to 64 years old. Life expectancy at birth was 72.74 years for men and 79.80 years for women [6]. Specifically in Brazil, between 2000 and 2018, crude mortality rates from CVD have been decreasing in adults over 25 years of age, of both sexes, except in men over 85 years of age [7]. Even in this scenario, CVD were responsible for 28% of all deaths that occurred between 2010 and 2015, and 38% of this number occurred in the productive age group (18 to 65 years) [8].

In addition to the irreversible social losses in the family environment, CVD have a considerable weight in public and private financial costs (direct costs) due to hospitalizations, monitoring, treatment, and others, and in the loss of productivity (indirect costs). Health financing in Brazil comes from public and private sources. The model covers the Brazilian National Health System (SUS—Sistema Único de Saúde), supported by taxes and contributions collected at the federal, state and municipal levels, and the Complementary Health System, with resources from companies and individuals, with 71% of the Brazilian population using this system [9].

In Brazil, estimated costs for CVD were around R$37.1 billion in 2015 [7]. Of these estimated CVD costs, 61% were estimated for premature death from CVD, direct costs for hospitalizations and consultations were 22%, and disease-related lost productivity costs were 15% of the total [8]. Therefore, the growth of these recurrent costs represents an important problem for health systems, as well as for their socioeconomic impacts [1012].

Nowadays, Brazilians have been going through gradual changes in eating patterns, evidently perceived on the excessive consumption of nutrients linked to the causes of Non communicable diseases (NCD), such as sodium, sugars, and fats [13]. An increase in the consumption of ultra-processed foods (UPF) by the Brazilian population has been observed [13, 14]. These UPF have high levels of the above mentioned nutrients, with scientific evidence of their relation to obesity [15, 16], diabetes mellitus [17, 18], hypertension [19] and cardiovascular diseases [2022].

Few studies have been carried out with the objective of attributing the effect of nutrient consumption to the cause of CVD and its consequent costs [23, 24]. In Brazil, it was estimated the attributable burden of excessive salt consumption in cardiovascular diseases, showed savings of 9.4% of total hospital costs for CVD, if the average salt intake of Brazilians were reduced to 5 g/d [23]. In this sense, studies that seek to minimize the socioeconomic impacts of this nature can contribute to stimulating the improvement and development of public policies to combat and prevent these diseases.

The Population Attributable Fraction (PAF) is a measure of public health impact that has been widely used by the World Health Organization, based on Global Burden Disease (GBD) data, in order to determine goals, prioritize interventions and build public policies [25, 26]. In addition, the PAF has also been used to provide information on economic costs attributable to some risk factors, such as salt consumption [27].

There are two ways to estimate health costs for a disease. The first is “top-down”, going from the total values at the national level of the set of all diseases and, through a disaggregation process, arriving at the level at which the cost of the disease under analysis is found. The second is “bottom-up”, and through this method, estimates are made for a sample of cases and are extrapolated to the total number of individuals [28].

In Brazil’s context, it is possible to obtain the total direct costs related to a given pathology in the National Health System, which can be disaggregated by level of health care (outpatient and hospital), sex and age groups. Thus, the best approach to be used in Brazil is the top-down approach, from the perspective of public health services, based on health cost data, available in the information systems of the Ministry of Health [28].

Thereby, this study assessed the direct and indirect costs of coronary heart disease (CHD) and stroke by sex and age group, concentrating the etiology of the CVD to the excessive consumption of salt, saturated fat, and trans fat, between 2017 and 2019, in Brazil.

Materials and methods

Data

Several databases were referred to collect and analyse CVD cost related information between 2017 and 2019 for Brazil. For the estimation of the Population Attributable Fraction corresponding to salt, saturated fat and trans fat, data were obtained from the Household Budget Survey (HBS) (Pesquisa de Orçamento Familiar—POF) 2017/2018, from the Brazilian Institute of Geography and Statistics, which provides information on household food consumption [14, 29]. Data for direct costs were focused on expenses with hospital admissions, from the Hospital Information System (Sistema de Informação Hospitalar, SIH/SUS) [30], and outpatient care, from the Outpatient Information System (Sistema de Informação Ambulatorial, SIA/SUS) [30] (including the costs of treatment, such as medical consultations, medical procedures, and drugs), both covering the entire proposed period, collected from the Brazilian National Health System (SUS—Sistema Único de Saúde) database (DATASUS) [30], Ministry of Health of Brazil. DATASUS is an open public domain secondary database that includes a wide range of systems and subsystems that contain time-varying information between them, and a variety of information systems on Brazilians in relation to mortality, hospital care, outpatient care, basic health care, live births, physical structure of hospitals and clinics, professionals included in the SUS, notifications of contamination of epidemiological diseases, among others [31].

Regarding indirect costs, three databases were necessary: the observational characteristics of deceased individuals which were attained from the DATASUS Mortality Information System (SIM, Sistema de Informação de Mortalidade) between 2017 and 2019 [32]; for the characteristics and income of living individuals, data were collected from the Brazilian Institute of Geography and Statistics (IBGE) in the National Household Sample Survey (NHSS), for the year 2015 [33]; finally, the mortality probabilities of the population by age and sex were obtained from the IBGE Complete Mortality Tables (2017, 2018, 2019) [32].

Moreover, in order to filter data on CVD that led to hospitalizations, outpatient care and mortality, these diseases were classified according to the 10th review of the International Classification of Diseases—ICD 10, with the codes I20-I25 for CHD, and I60-I69 for stroke [34]. The age groups were formed following the standard of the Pan American Health Organization for both sexes: 25–34 years old, 35–44 years old, 55–64 years old, 65–74 years old, 75–84 years old and > 85 years old (for indirect costs, the last age evaluated was 65 years).

In addition, all monetary values were corrected using the Index National Price on Expanded Consumers (Índice Nacional de Preços ao Consumidor Amplo, IPCA/IBGE) in Brazilian currency (R$—reais) for 2019 and, subsequently, converted to US dollars ($) at the average exchange rate for 2019, corresponding to 3.944 R$/U$S (0.25345 U$S/R$), made available by the Institute of Applied Economic Research (IPEA) [35].

The research protocol was approved by The Ethics Committee of Federal University of Paraíba with consent number 3.843.739. As these are secondary data made available on public domain sites of the Brazilian Unified Health System, ethics committee waived the requirement for informed consent.

Population Attributable Fraction (PAF)

The proportion of the risk of developing CVD that would be reduced in each period if the consumption of salt, saturated fat and trans fat were reduced to their ideal consumption (TMREL), is called Population Attributable Fraction (PAF), which was defined as:

PAF=0lRR(x)P(x)d(x)RR(x)TMREL0lRR(x)P(x)d(x) (1)

Where P(x) is the distribution of current food consumption, RR(x) is the relative risk of developing CVD at exposure level (x), and (l) is the maximum level of exposure, that is, of consumption of the nutrient. The TMREL is the theoretical minimum risk level, that is the consumption level considered ideal to minimize the risk at the population level. In this study, the TMREL for salt was 5g/day, for saturated fat was 10% of the total daily energy value and for trans fat was 1% of the total daily energy value [10].

O RR(x) is defined to be:

exp(β(xy(x)))ifxy(x)0 (2)

or

1ifxy(x)<0

where β is the change in log relative risk per unit of exposure [10, 36], x is the current exposure level, and y(x) is the TMREL.

Food consumption was measured using food records, applied on non-consecutive days, in which individuals were instructed to record and report in detail the names of the foods consumed, the type of preparation, the measure used, the amount consumed, the time and whether the consumption of the food occurred at home or outside the home, with their serving sizes converted from standard units or household measures, to grams, using a common reference table to HBS [14]. A second measure of food records was performed in a sub-sample of HBS [14]. Habitual nutrient intake was estimated using the Multiple Source Method (MSM). This last method is suitable to estimate the usual individual intake for repeated measurements and a defined period [37].

To verify the distribution that best fits the sample data, the adherence test was performed, which confirmed that the salt consumption data showed a log-normal distribution, while the saturated and trans fat data showed a gamma distribution. Both distributions were used in the PAF calculation.

Direct cost

The total direct costs (TDC) of the CVD were attained by the sum of the costs of the admissions and outpatient care in the National Health System (SUS). Hence, public expenses for CHD and stroke were estimated in both, the Hospital Information System (Sistema de Informação Hospitalar, SIH/SUS) and the Ambulatory Information System (Sistema de Informação Ambulatorial, SIA/SUS). The base equation is presented below:

TDCt,a,b=n=1nSIHij,t,a+k=1kSIAaj,t,a (3)

Where, TDCt,a is the total direct cost of all n hospital admissions, SIHij,t,a, plus k outpatient care, SIAaj,t,a, of individuals (ij) and (aj), in the age group (a), sex (b) at time (t), for CVD diseases (CHD and stroke). To isolate the effect attributable to excessive nutrient intake, we weight Eq 3 by the PAF:

TCDs,st,tf,t,a,b=(n=1nSIHij,t,a,b+k=1kSIAaj,t,a,b)*PAFs,sf,tf (4)

Therefore, PAFs,sf,tf,a,b represents the population attributable fraction by age group and sex, with respect to salt (s), saturated fat (sf), trans-fat (tf), that is, the portion attributable to the costs of excess consumption of these nutrients.

Indirect cost

The main approaches in indirect costs analysis are human capital that is associated with lost productivity and friction costs that estimates the costs of worker replacement. We used the human capital approach and estimated the productivity losses based on wages over the working life of the worker. Observational variables are used that characterize the income of living individuals, correlating with the observational characteristics of individuals who had deaths from CVD under the age of 65 years. Thus, this combination provides the income of the individual who died given the probability of being alive.

The method used in Ywata et al. (2008) [38] was partially followed, where they measured the loss of human capital caused by premature external deaths, such as those caused by homicide and traffic accidents. Using the income data of individuals and crossing these data with information regarding age group, sex, schooling, and geographic location of the residence, it is possible to establish an estimate of the average income for subgroups of the population [33]. To obtain the income stream of these population subgroups we project the estimated income over time. Thus, to understand the loss of productivity, the reduction of income generated by the deaths caused by the CHD and stroke imputed to the subgroups of the dead population the estimated income stream for the same subgroups of the population that maintained their work activities. The estimates of average income and projection of future income follow the methodology described in Ywata et al [38]. To separate the causes, we weighed the income stream of each population subgroup by the PAF.

In this study, irreversible productivity losses due to the premature death of individuals aged 25 to 65 years caused by CVD were considered. For this task, six explanatory variables for income that are available in the NHSS, and SIM databases were considered: state of the country in which the individual resides (residence), age, sex, education level, color/race, and marital status [39].

Since it is impossible to accurately define the future income of deceased people, data from living people contained in the NHSS database, were used to pair the dead individuals with the observational variables from both databases. In other words, the income of individuals contained in the NHSS was used for the dead individuals of the SIM database, looking to match the six selected variables, since the income is found only in the NHSS database. The observations perfectly matched between the bases in 83.8%. For the imperfectly matched combinations, variables were being removed according to their importance for the explanation of income. First, marital status and then, color/race. As it is not possible to define whether the level of education, residence status and marital status of deceased individuals would change over time, only the age was increased. Thus, an individual who died at 25 years of age, in 2019, had his age extended to the following years to 26, 27…, until 65 years of age, in 2049, which is the maximum age of productivity considered, given the probability of survival. Therefore, all other variables values are constant in time. To bring the future income stream to the present, we applied the net present value (NPV) which allows to measure the value of money in time:

TICt,i=X=DiT1(1+d)(xDi)*Pr(Fi>x|FiDi)*Wi (5)

In the occasion that (d) is the annual discount rate of 3%, (Wi) is the expected annual income of the individual (i) present in the SIM. ‘T’ is the maximum productive age, in this case, 65 years. The probability Pr (Fi > x|Fi ≥ Di), is the probability that the individual is alive at age (x), given that he did not die at the age of (Di), that is, the age registered in the SIM. The age of death is indicated by (Fi), given that individual (i) has already died. Finally, TICt,i is the total indirect cost of individual (i) at time (t). Similarly, to the direct costs, to isolate the effect of nutrients on indirect costs, it is:

TICt,i=X=DiT1(1+d)(xDi)*Pr(Fi>x|FiDi)*Wi*PAFs,sf,tf (6)

Hence, for the general total indirect cost and for the general total attributable indirect cost, they are attained by summing up the individual costs and grouping them by age group. In addition, if the individual had not died, the expected years of productive life lost due to premature deaths were calculated accordingly:

YLLt,i,s,sf,tf=x=DiTx*Pr(Fi>x|FiDi)*PAFs,st,tf (7)

In the occasion that YLLt,i,s,sf,tf are the Years of Life Lost (YLL) by the individual due to premature death from CVD attributable to excessive use of salt (s), saturated fat (sf) and trans fat (tf).

This methodological approach to the estimation of indirect costs was considered due to the costs associated with permanent loss of productivity given the premature death from CVD, caused by excessive consumption of nutrients, being, in hypothesis, the highest within this cost modality [38]. In addition, the estimates are more realistic, as real observational variables are used as determinants of the income of deceased individuals, reducing possible bias in the results [38].

Results

Table 1 brings the estimates for the impacts of the excessive consumption of salt, saturated fat and trans-fat by age group and sex. The attributable fractions to salt are the ones that cause the most effects on CVD, followed by saturated fat and trans fat. Among the sexes, males have a greater share related to the excessive consumption of all nutrients associated to CVD, with salt being responsible for the highest value, 99.7% in the 25–34 age group. Likewise, for females, the highest values for nutrients are all in the 25–34 age group: 85.8% for salt, 62.7% for saturated fat and 14.4% for trans fat. Between the sexes, the greatest similarity is found in the PAFtf, with all PAF having an inverse relationship with the age.

Table 1. Population Attributable Fraction (PAF) to salt, saturated fat and trans fat by age and sex.

Age group (Years) Male Female
PAFs* PAFsf** PAFtf*** PAFs* PAFsf** PAFtf***
25–34 0.997 0.749 0.163 0.858 0.627 0.143
35–44 0.953 0.687 0.089 0.690 0.521 0.071
45–54 0.862 0.574 0.057 0.518 0.519 0.064
55–64 0.722 0.361 0.020 0.374 0.329 0.026
65–74 0.485 0.266 0.013 0.241 0.227 0.016
75–84 0.343 0.156 0.003 0.153 0.155 0.013
85 > = 0.145 0.093 0.005 0.068 0.116 0.006

PAFs: Population Attributable Fraction to salt; PAFsf: Population Attributable Fraction to saturated fat; PAFtf: Population Attributable Fraction to trans fat

Moreover, it is significant to highlight that there is an intersection between the consumption of nutrients by the individuals. This means that the individual who consumes salt excessively, also consumes fats, so the sum of PAF exceeds in most cases.

Regarding direct costs, between 2017 and 2019, there were approximately 1.5 million admissions and 21 million visits by Brazilian clinics caused by CVD, most predominantly by males in the 55–64 age group. In this period, hospitalizations and outpatient care resulting from excessive consumption of salt demanded US$ 730.91 million for the public resources, with approximately 77.5% of expenses for males, as shown in Table 2. We observed, for females, that the highest amounts of hospitalizations and outpatient visits were in the 65–74 years age group. Also, the direct costs attributable to salt, saturated fat and trans-fat of, were respectively: US$ 40.44, US$ 38.07 and US$ 2.62 million. Between 2017 and 2019, total direct costs for males increased by 2.1% and for females the growth was 2.6%.

Table 2. Direct costs attributable to excess consumption of nutrients (salt, saturated fat and trans-fat) by sex and age group in US$ per Million.

Sex Age 2017 2018 2019
Salt Sat. Fat * Trans fat Salt Sat. Fat * Trans fat Salt Sat. Fat * Trans fat
Male (M) 25–34 3.56 2.67 0.58 3.54 2.66 0.58 3.41 2.56 0.56
35–44 12.85 9.26 1.20 12.89 9.30 1.21 13.16 9.49 1.23
45–54 42.33 28.19 2.79 40.34 26.87 2.66 40.74 27.13 2.69
55–64 66.66 33.29 1.80 66.51 33.22 1.80 68.43 34.18 1.85
65–74 39.53 21.67 1.10 40.86 22.40 1.13 41.68 22.85 1.16
75–84 12.40 5.64 0.11 12.66 5.76 0.11 13.24 6.03 0.12
85 > = 0.97 0.62 0.03 0.92 0.59 0.03 1.00 0.64 0.03
Total 178.29 101.35 7.62 177.73 100.79 7.52 181.67 102.88 7.63
Age 2017 2018 2019
Salt Sat. Fat* Trans fat Salt Sat. Fat* Trans fat Salt Sat. Fat* Trans fat
Female (F) 25–34 2.43 1.78 0.40 2.29 1.67 0.38 2.28 1.67 0.38
35–44 7.17 5.41 0.74 7.06 5.32 0.73 7.39 5.57 0.76
45–54 15.99 16.02 1.99 15.43 15.45 1.92 15.50 15.53 1.93
55–64 20.49 18.05 1.43 20.19 17.79 1.41 20.66 18.20 1.45
65–74 13.28 12.50 0.86 13.38 12.60 0.87 13.78 12.97 0.89
75–84 4.77 4.83 0.42 4.58 4.64 0.40 4.94 5.00 0.43
85 > = 0.55 0.93 0.05 0.51 0.88 0.04 0.56 0.96 0.05
Total 64.68 59.51 5.89 63.44 58.34 5.75 65.12 59.90 5.89
M + F - 242.96 160.86 13.50 241.17 159.14 13.27 246.78 162.78 13.52
M% - 73.3 63.0 56.3 73.6 63.3 56.6 73.6 63.2 56.5
F% - 26.7 37.0 43.7 26.3 36.7 43.3 26.3 36.7 43.5

*Sat. Fat: Saturated fat

Furthermore, Table 3 provides the data regarding the indirect costs as consequence of the premature deaths from CVD associated to the excessive intake of salt, saturated fat and trans fat. During the studied period of time, a total of 855,370 deaths from CVD were registered in Brazil, of which 62.17% were males, with an average age of 54 years of age. Deaths resulting from excessive salt intake resulted in costs of US$ 6.45 billion to the economy due to premature loss of productivity, to which males accounted for about 80.5% of this value. Also, the age group that presents the highest indirect costs for both sexes and for all nutrients are people from 45 to 54 years old. However, the male participation in these costs is increasing for all years and all nutrients.

Table 3. Indirect costs attributable to excess consumption of nutrients (salt, saturated fat and trans-fat) by sex and age group in US$.

Year Indirect Costs Male (M) M + F
25–34 years 35–44 years 45–54 years 55–65 years Total
2017 Salt Costs 140.156.876 379.619.463 689.564.809 522.422.390 1.731.763.539 2.157.206.808
Sat. Fat* Costs 105.289.015 273.682.097 459.250.077 260.911.322 1.099.132.511 1.472.231.054
Trans-Fat Costs 22.843.454 35.492.147 45.496.694 14.125.903 117.958.197 164.782.112
2018 Salt Costs 133.183.858 370.817.683 700.298.668 523.168.842 1.727.469.050 2.142.931.279
Sat. Fat* Costs 100.050.726 267.336.559 466.398.825 261.284.119 1.095.070.229 1.458.929.613
Trans Fat Costs 21.706.957 34.669.233 46.204.902 14.146.086 116.727.178 162.267.613
2019 Salt Costs 138.312.820 383.595.663 685.977.191 532.698.544 1.740.584.217 2.153.450.921
Sat. Fat* Costs 103.903.718 276.548.691 456.860.723 266.043.500 1.103.356.632 1.464.909.893
Trans Fat Costs 22.542.900 35.863.898 45.259.987 14.403.762 118.070.547 163.303.520
Year Indirect Costs Female (F) M%—F%
25–34 years 35–44 years 45–54 years 55–65 years Total
2017 Salt Costs 46.529.998 112.907.731 162.654.562 103.350.978 425.443.269 80.2% - 19.7%
Sat. Fat* Costs 34.019.473 85.140.776 162.909.522 91.028.771 373.098.543 74.6% - 25.3%
Trans Fat Costs 7.734.167 11.633.291 20.225.925 7.230.532 46.823.914 71.5% - 28.4%
2018 Salt Costs 45.242.926 110.990.110 155.338.898 103.890.295 415.462.229 80.6% - 19.4%
Sat. Fat* Costs 33.078.457 83.694.748 155.582.391 91.503.787 363.859.383 75.1% - 24.9%
Trans Fat Costs 7.520.231 11.435.711 19.316.230 7.268.263 45.540.435 71.9% - 28.1%
2019 Salt Costs 44.789.505 110.516.817 154.114.749 103.445.633 412.866.704 80.8% - 19.2%
Sat. Fat* Costs 32.746.946 83.337.851 154.356.324 91.112.140 361.553.261 75.3% - 24.7%
Trans Fat Costs 7.444.864 11.386.946 19.164.008 7.237.154 45.232.972 72.3% - 27.7%

*Sat. Fat: Saturated fat

Finally, an alternative way to quantify productivity losses that generate indirect costs, is to estimate the expected productive years of life lost due to premature death, as shown in Table 4. Interestingly, as a result of the 855,370 premature deaths between 2017 and 2019, a total of 1.53 million of potential productive years of these individuals were lost (about 72.5% for males), considering the excessive use of salt; for saturated fats a total of 1.09 million years (about 66.6% for males) and in relation to trans fats, a total of 132.41 thousand years (about 63.5% for men), having the 45–54 age group with the highest aggregate loss.

Table 4. Years of Life Lost (YLL) due to premature death by sex and age group.

Sex Age 2017 2018 2019
Salt Sat. Fat * Trans fat Salt Sat. Fat * Trans Fat Salt Sat. Fat * Trans fat
Male 25–34 43.368 32.579 7.068 41.131 30.899 6.704 42.431 31.875 6.916
35–44 99.092 71.439 9.264 96.169 69.332 8.991 97.903 70.582 9.153
45–54 148.116 98.645 9.772 148.503 98.903 9.798 145.658 97.008 9.610
55–65 84.056 41.980 2.273 84.036 41.970 2.272 85.702 42.802 2.317
Total 374.632 244.643 28.378 369.839 241.103 27.765 371.694 242.267 27.997
Age 2017 2018 2019
Salt Sat. Fat* Trans fat Salt Sat. Fat* Trans fat Salt Sat. Fat* Trans fat
Female 25–34 21.089 15.419 3.505 20.957 15.322 3.483 21.003 15.356 3.491
35–44 44.341 33.436 4.569 43.678 32.936 4.500 42.536 32.076 4.383
45–54 53.392 53.476 6.639 50.868 50.948 6.325 50.434 50.513 6.271
55–65 24.318 21.418 1.701 24.335 21.434 1.702 24.383 21.476 1.706
Total 143.140 123.750 16.415 139.837 120.640 16.012 138.357 119.421 15.851
M + F - 517.772 368.393 44.793 509.677 361.743 43.777 510.051 361.688 43.848
M% - 72.3 66.4 63.3 72.5 66.6 63.4 72.8 66.9 63.8
F% - 27.7 33.6 36.7 27.5 33.4 36.6 27.2 33.1 36.2

*Sat. Fat: Saturated fat

Discussion

Study showed that the direct and indirect costs of CVD (such as CHD and stroke) attributed to the consumption of salt, saturated fat and trans fats, by sex and age group, between 2017 and 2019 were in the order of US$ 7.18 billion. The highest burden of CVD attributable were observed in younger individuals, which decrease with advancing age. Considering only salt as an inducer, an estimated 1.53 million expected productive years of life are lost due to premature death. Although attributable burden of CVD is higher among younger individuals, the highest costs are associated with men aged 45 to 74 years old for direct costs and 45 to 64 years old for indirect costs and expected years of productivity incurred because of permanent loss of productivity due to premature deaths.

Although the highest CVD costs attributable to the consumption of salt, saturated fat and trans fats is among the 45–74 age groups, the consumption of these nutrients is inversely proportional to the age. One of the explanations for our findings is that, due to the greater number of CVD cases occurring in these age groups, the risk attributable to the consumption of these nutrients is added to the risk related to the age group, suggesting that preventive measures at younger ages can benefit the entire population in their future.

Despite the continuous decline in crude and adjusted mortality rates for CVD (such as CHD and stroke), especially in the age group 35 to 44 years for both sexes [7], Brazil still has high mortality rates from these diseases and remains the leading cause of death in the country [40]. Unhealthy diet are one of the main causes, with an excess of critical nutrients such as salt, sugar, oils, and fats [27]. The increased consumption of UPFs is directly associated with the growth in consumption of these nutrients [13]. From 2000 to 2013, the traded volume of UPFs grew 43.7% worldwide and 48% in Latin America [15], so the intake of risk factor nutrients also increased [27].

Nilson et al. (2021) [24] estimated the economic effects and impact on health between 2013 and 2032 of the implementation of sodium reduction in processed foods in Brazil. They also reported that during this period, around 110,000 CVD male cases and 70,000 CVD female cases will be prevented. This estimate will result in a total savings of around US $ 220 million in medical costs for the Brazilian National Health System for the treatment of CHD and stroke. Moreover, corroborating our findings, a recent study carried out in Brazil showed that the costs attributable to excessive salt consumption were higher for males when compared to females, corresponding to 62% of the costs associated with hospitalizations and 53% of outpatient’s costs for CVD, attributable to salt consumption [27].

According to Mozaffarian et al. (2006) [41], a 2% increase in trans fat consumption can increase the risk of CHD by up to 23%. Therefore, several countries have sought to regulate policies to limit the industrial use of trans fat [42] and to obligatorily include the content of this nutrient on food labels [43]. Marklund et al. (2020) [44] estimated that the ban on the use of trans fats would prevent 2,294 and 9,931 events of CHD in the first 10 years in Australia. In Argentina, where there was voluntary adherence to the reduction of trans fat in foods by the industry [45], according to Rubinstein et al. (2015) [46], given an annual incidence rate of almost 500 cases per 100,000 individuals over 34 years of age, the zero implementation of trans fats by the industry would prevent between 1.3% and 6.35% of cases of CHD, generating savings of, respectively, US$17 million and US$87 million.

Regarding the consumption of saturated fats, Dall et al. (2009) [47] estimated that if saturated fat intake reached 4g for adults with LDL-C > 100 mg/dL, the savings generated in CVD costs would be US$443.8 per case per year in the United States. In Germany, direct expenditure on these diseases, caused by excessive consumption of saturated fat, amounts to 2.9 billion euros a year [48]. The food replacement of this type of fat by polyunsaturated fats leads to a decrease in the risk of ischemic heart disease [49], therefore, being a possible option to minimize costs and losses in productivity generated, directly and/ or indirectly by illness.

In a study developed in Germany which relates the direct costs with non-communicable diseases [48], the highest expenses were attributed to the consumption of sugar (EUR 8.6 billion), followed by the consumption of salt (EUR 5.3 billion) and saturated fat (EUR 2.9 billion). The same pattern was observed in this study, in relation to salt (US$ 730.91 million) and saturated fat (US$ 482.78), considering that sugar was not analyzed.

In addition to the estimated years of life lost and costs associated with CVD (such as CHD and stroke), premature deaths from these diseases also cause several issues not addressed in this study. For instance, a recent study carried out in Brazil by Camarano (2020) [50], showed that premature loss of elderly victims due to COVID-19, in an extreme situation of this entire population dying, the household income monthly per capita would go from BRL 1,772.2 to BRL 529.2. This means a decrease of almost 75%, affecting 12.1 million people, of which 2.2 million are under 15 years old. Therefore, it can be inferred that the socioeconomic scenario of premature mortality from CVD is even more catastrophic, since the average age of death is 54 years old, with the leading ratio being from 55 to 65 years of age for both sexes. Thus, premature deaths from CVD should leave hundreds of thousands of younger people despondent, with greater vulnerability, due to their dependence on the income of older people. On the other hand, the earlier the death, the greater the individual indirect costs are due to the longer loss of potential productivity and yield of human capital.

In the American Continent, several countries have undergone food regulations. Frontal food labeling is being adopted in Chile, Peru, and Uruguay [51]. Brazil passed a bill for frontal labeling of foods in the year 2020 that should be effective as of October 2022, 24 months later, displaying a warning of the presence of excess added sugar, salt and fat, in addition to including in the table of nutritional composition of industrialized foods the amount of sugar added to the product [52]. This measure is an important step to alert consumers about the nature of the products chosen on the market, making it possible to make healthier choices.

Regarding CVD prevention policies and programs in Brazil, every ten years the Ministry of Health prepares a plan of strategic actions to `ht non-communicable diseases and conditions. The last document concerns the period of 2021 to 2030 and defends the increase of physical activity practice, consumption of healthy foods, reduction of smoking and alcohol consumption in the population [53]. To achieve the goal of promoting healthy eating, it includes the proposal to identify technical-scientific and political subsidies to support the elaboration of regulatory and fiscal measures to reduce the consumption of ultra-processed foods and encourage the consumption of in natura and minimally processed foods [53].

Studies that measure the economic impact attributable to salt, saturated fats, and trans fats, as is the case in the present study, are important to reinforce the importance of policies that enable the reduction intake of these nutrients and minimize their socioeconomic effects without loss of social well-being due to this restriction, between the sexes and the most affected age groups.

Brazil performed only the voluntary regulation of salt in processed foods [54]. One of the limitations of this positioning is not always reaching the defined goals, as well as not reaching all products available on the market. Furthermore, the absence of legal instruments to guarantee the achievement of targets and eventually impose sanctions in case of non-compliance is also an issue that should be taken into consideration [55]. In addition to these two matters, it is still important to consider that, according modeling study developed by Nilson et al. [56], the adoption of official regulatory limits with the lowest global targets could reduce salt consumption by 0.8g/day, compared to a reduction of 0.25g/day that is achieved with the current Brazilian voluntary targets, and could prevent about four times more deaths in ten years than the actual measure.

Furthermore, according to the revision of the Food Guideline for the Brazilian Population [57] there was considerable progress on the quality of food consumed, as well as an increase in the number of gyms at public parks. These are usually referred as Open Air Gyms, which were implemented by city halls all over the country [7], playing a vital role in the health of the population. However, there is a constant need for attention and confrontation of NCD, especially the CVD. This is because of their greater mortality compared to others, which may require specific measures that enable the improvement of the control of dietary risk factors, and others that improve collective health.

This scenario shows that in the case of Brazil, despite the great scientific advance in the recognition of risk factors associated with CVD, as in the case of this and other recent published works, and important official documents such as the aforementioned action plan or the new food guideline, there is no official restriction or taxation action for products with high amounts of salt, fat or sugar. In Mexico, sweetened beverages were taxed [58], and Argentina has already advanced observing regulatory measures to reduce sodium [59].

Countries such as the United Kingdom (UK) and Turkiye had a successful implementation of sodium reformulation policies [60], while the United States finds it difficult to include this type of policy, due to the strong rejection from the industry [61]. The UK showed a different scenario with its salt reduction policy, the implementation of this policy resulted in a 7% reduction of sodium in processed foods [62], while the industry continued to grow [24].

Finally, according to Ezzati et al. (2015) [63], the control of variable risk factors, such as diet, can contribute to a 50% reduction in mortality from CVD. In Brazil, Nilson et al. (2020) [23] estimated in 2017 that if the average daily consumption of sodium was reduced to 2g, 46,651 deaths from CVD would be avoided.

To our knowledge, no study has been previously carried out in Brazil, involving the loads attributable to the consumption of multiple nutrients in relation to cardiovascular diseases. This study brings scientific evidence that make strong arguments for the political decision to promote the consumption of healthy diets, reinforce the importance of food labeling and the taxation policies in relation to ultra-processed foods in the country.

However, there are some limitations of this study that should be highlighted. First, we only collected information’s on public expenditure, we did not observe private health expenditures. We estimate the direct costs adding to the expenses recorded in the two official databases SIH/SUS and SIA/SUS. Although there is a greater participation of private spending in the acquisition of health services in Brazil, public spending represents approximately 40% of the total expenditure. We emphasize that observing only public spending is a limitation of our data. Second, a longitudinal assessment of the direct and indirect costs is essential to better understand the trends related to these expenses and losses.

Another aspect that should be mentioned is the estimation of indirect costs. There is a high probability that those values are being underestimated, for two main reasons: first, due to fact that the variables of the state of the country, marital status and education level remain constant overtime. Therefore, the earlier the death of the individual, the greater the underestimation of their loss of future earnings; and second, 2015 was the year which was used by the NHSS for the individual income, Brazil was experiencing an economic crisis that impacted employment and consequently, the income of the population, which can reflect on the results found in this study. Besides, the fact that other studies use different approaches to calculate the indirect costs makes it difficult to compare the results [12, 64, 65].

Conclusions

Studies of this nature are important for Brazil’s economy and the world society, being a necessary tool for the formulation of public policies that enable the minimization of involvement and effects by NCDs, especially CVD. Firstly, the study provides useful data that measures the impacts on public spending, and the social and productivity losses that negatively reflect on the economy. Additionally, it allows the comparison of pre-public and post-political intervention values for health systems and the socioeconomic response of these measures. This is possible via effective methods of measuring the impact of reducing the consumption of dietary risk factors, such as those analysed in this work.

In conclusion, the attributable fractions to consumption of salt are the ones that cause the most effects on CVD, followed by saturated fat and trans fat, with direct and indirect costs being higher for males.

Data Availability

The microdata used in the study are available in the following public domain and open access databases: - Brazilian Institute of Geography and Statistics: (https://www.ibge.gov.br/estatisticas/sociais/saude/24786-pesquisa-de-orcamentos-familiares-2.html?=&t=microdados); (https://www.ibge.gov.br/estatisticas/sociais/populacao/9127-pesquisa-nacional-por-amostra-de-domicilios.html?=&t=microdados); and (https://www.ibge.gov.br/estatisticas/sociais/populacao/9126-tabuas-completas-de-mortalidade.html?=&t=downloads) - Informatics Department of the Brazilian Unified Health System (DATASUS) for the Outpatient Information System (SIA, specifically, SIA-PA [production subsystem]), Hospital Information System (SIH, specifically, SIA-RD [subsystem of accepted admissions]) and Mortality Information System (SIM, specifically, SIM-DO [death certificate subsystem], all on the same link for access to raw data (https://datasus.saude.gov.br/transferencia-de-arquivos/).

Funding Statement

The National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) supported all the funding received during this study; Grant number 442891/2019-9. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Decision Letter 0

Pankaj Bahuguna

1 Aug 2022

PONE-D-21-41019The direct and indirect costs of cardiovascular diseases in BrazilPLOS ONE

Dear Dr. Moreira,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we suggest a major revision and invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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PLOS ONE

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We will update your Data Availability statement to reflect the information you provide in your cover letter.

Additional Editor Comments:

  • Line 94-95, please provide brief description of 'National Health System Database', Ministry of Health Brazil in terms of what does it covers; since when this data on direct costs is available in dataset; primary source of data in dataset; is it in public domain? etc. This information will be helpful for non-Brazilian readers.

  • I suggest to add brief description of methods used Ywata et al. (2008) for estimating indirect costs to make it reader friendly.

  • At present, authors only give conclusions at the end of discussion. I suggest to add some clear recommendations in relation to public policy.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

**********

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

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Reviewer #1: No

Reviewer #2: No

**********

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Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewer Comments to authors

General comments

Thank you for the opportunity to review this manuscript. Overall, this is an important area of research and imperative to know the costs involved in cardiovascular diseases that are cause of high morbidity and mortality globally. The paper details on the costs involved but lacks clarity on costing methods used and standard terminologies for direct costs, unit costs involved and how authors arrived at them. Focus is more outlined for indirect costs, however both are important in cardiovascular diseases. For the better clarity and understanding of the readers, the language editing is required at multiple places in the current manuscript.

Specific comments

Abstract

Line 26: It would be helpful to mention the study setting in the objective.

Methods: Which of the costing approach was used in the study and what was the perspective of the costing exercise? Please add few details in the methodology.

Results: Please rephrase the line 36 for better clarity.

Line 40: Please add appropriate unit with age group defined.

Introduction

Line 48: Please clarify whether it is mortality rate or a different indicator where authors refer to lethality rate. It is unclear.

Materials and methods

Line 89 is unclear. What is implied by databases have time limits? Did it have any effect on the main analysis and final outcomes? It would be good to clarify here than referring elsewhere.

Which costing approach and perspective was used for costing. Please provide details in the methodology section.

Line 112-113: How was this ideal consumption identified? Please provide supporting reference and the reference standard taken.

Line 120: The authors mention that food consumption was measured on non-consecutive days. Please provide details on choosing this rationale. Could this have introduced any bias and affected the analysis? Why were a sub sample chosen? It is unclear how many measurements and how many times in all at individual level were done to capture food consumption from the current manuscript.

Line 126: It is unclear on whom and how the adherence test was done.

Line 132: It would be good to mention the components of public expenses here for better understanding of the readers.

Line 138-139: Were there any individuals who had both both CHD and stroke? How were these cases if there handled in the cost analysis?

Results:

Line 185-186: Is this the study finding or finding from literature review. It is unclear. If the latter then could be shifted to discussion.

Discussion

In general authors have extensively reviewed about various aspects but this section does not clearly outline key findings and their implications and is quite confusing to read. Few suggestions that could be helpful to authors to strengthen this very important aspect of the paper for better clarity and understanding to readers are:

Introductory paragraph outlining what the study entailed, what was found, and why this is important in place of citing other paper on study design

Summarising key findings of current study

Importance of key findings in terms of what they tell us and implications of findings, in the context of what is already known in the literature and preferably in similar settings, and what is novel.

Study limitations are mentioned. However, the authors mentioned in methods about limited time-limit of databases. Were there any limitations in for the data availability or health information management systems? Were any limitations present in relation to estimation of direct costs?

Future direction/studies (optional)

Reviewer #2: Introduction general comment: Can you specifically outline the policy rationale for undertaking this analysis looking at this specific relationship between nutrients, CVDs and costs

It would be helpful for the reader to understand Brazilian sociodemographic characteristics specifically in terms of the population age characteristics to contextualize results better?

Line 55: Could you please specify what the respective age scenarios are that you are referring to?

Line 58: A brief overview of financing of Brazilian healthcare system along with these statements might be helpful

Line 66: Please consider clearly rephrasing statements when you are referring to author names. Also, it would be helpful to know what these authors have concluded in their respective studies.

Line 67: Grammatical error: ‘others’ should be replaced with ‘other’. Errors in structuring of sentences are quite common throughout the manuscript. It would help you to review these throughout the manuscript and to not use longer complex sentences.

Line 69: ‘the’ needs to be replaced by ‘a’

Line 76: Could you give more evidence and references to back this claim?

Line 79: What is the method generally used to know indirect costs?

Line 81: Premature death cases are only due to CVD? How has this been established?

Materials and Methods general comment: It would be helpful to outline the extent of indirect costs you are considering in the analysis with clear justification for doing so and providing a reason for excluding components of indirect costs that are not analysed in this analysis

Line 89: I am not sure if the limits of databases have been adequately highlighted later in the manuscript or in limitations?

Line 110: Could you please mention the currency exchange rate and its source as a reference?

Line 116: How has individual food consumption been estimated from household food consumption dataset?

Line 124: What is the multiple source method mentioned here?

Line 132: Given that public expenses for CHD and stroke from available data sources are used, and that private expenses do account for healthcare costs in Brazil, how does this justify the projected costs?

Line 148: Are costs only due to premature deaths accounted for? What about the costs due to morbidity/disability? Has this been accounted for in the analysis?

Line 165: It is unclear to me why discounting has been used only for indirect costs given in the corresponding formula?

Table 2: Any specific reason for as to why trans-fat consumption is relatively high in female population as compared to males?

Discussion general comment: The relevance of these findings needs to be better contextualised to relevant policies in Brazil. Please identify and discuss specific aspects of policies that can be addressed given the findings of this study.

Line 309: 110,000 and 70,000 cases of what?

**********

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Reviewer #1: No

Reviewer #2: No

**********

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PLoS One. 2022 Dec 22;17(12):e0278891. doi: 10.1371/journal.pone.0278891.r002

Author response to Decision Letter 0


15 Sep 2022

PLOS ONE

Dear Pankaj Bahuguna, Ph.D.

We would like to thank you and the reviewers for your time to provide feedback on our paper. We have addressed all Journal requirements and the reviewers’ comments below.

Journal Requirements

Comments to the Author:

1. “Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.”

Response: Thank you so much for your directions. Now the manuscript meets the required template styles.

2. “Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.”

Response: Thank you for spotting this omission. Now in the ‘Methods’ section, the full name of the committee is included. In addition, the source of the information was now added, and that the committee also waived the requirement for informed consent in this study.

Lines 132-135:

“The research protocol was approved by The Ethics Committee of Federal University of Paraíba with consent number 3.843.739. As these are secondary data made available on public domain sites of the Brazilian Unified Health System, ethics committee waived the requirement for informed consent.”

3. “In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.”

We will update your Data Availability statement to reflect the information you provide in your cover letter.

Response: Thank you for pointing out this omission. The microdata used in the study are available in public domain and open access databases. These databases were inserted in the text and in the list of references with the respective URLs, as follows:

Brazilian Institute of Geography and Statistics: (https://www.ibge.gov.br/estatisticas/sociais/saude/24786-pesquisa-de-orcamentos-familiares-2.html?=&t=microdados); (https://www.ibge.gov.br/estatisticas/sociais/populacao/9127-pesquisa-nacional-por-amostra-de-domicilios.html?=&t=microdados); and (https://www.ibge.gov.br/estatisticas/sociais/populacao/9126-tabuas-completas-de-mortalidade.html?=&t=downloads.

Informatics Department of the Brazilian Unified Health System (DATASUS) for the Outpatient Information System (SIA, specifically, SIA-PA [production subsystem]), Hospital Information System (SIH, specifically, SIA-RD [subsystem of accepted admissions]) and Mortality Information System (SIM, specifically, SIM-DO [death certificate subsystem], all on the same link for access to raw data (https://datasus.saude.gov.br/transferencia-de-arquivos/).

Additional Editor Comments:

“Line 94-95, please provide brief description of 'National Health System Database', Ministry of Health Brazil in terms of what does it covers; since when this data on direct costs is available in dataset; primary source of data in dataset; is it in public domain? etc. This information will be helpful for non-Brazilian readers.”

Response: Thank you for your suggestion. DATASUS is an open public domain secondary database that includes a wide range of systems and subsystems that contain time-varying information between them. Taking the Outpatient Information System (SIA) as an example, it is subdivided into 12 subsystems, the one used by us was the SIA-PA which deals with information on outpatient production and its values in monetary terms, with data availability 1994. The other two systems used, SIH and SIM, also follow this same model, with data available, respectively, from 1992 and 1979. These details are now contained in the manuscript.

In Lines 109-113, now it says:

“DATASUS is an open public domain secondary database that includes a wide range of systems and subsystems that contain time-varying information between them, and a variety of information systems on Brazilians in relation to mortality, hospital care, outpatient care, basic health care, live births, physical structure of hospitals and clinics, professionals included in the SUS, notifications of contamination of epidemiological diseases, among others [26].”

“I suggest to add brief description of methods used Ywata et al. (2008) for estimating indirect costs to make it reader friendly.”

Response: Thank you for your suggestion. Now, a brief description of the methods in the manuscript was added.

Lines 187-196, now it reads:

“Using the income data of individuals and crossing these data with information regarding age group, sex, schooling, and geographic location of the residence, it is possible to establish an estimate of the average income for subgroups of the population [28]. To obtain the income stream of these population subgroups we project the estimated income over time. Thus, to understand the loss of productivity, the reduction of income generated by the deaths caused by the CHD and stroke imputed to the subgroups of the dead population the estimated income stream for the same subgroups of the population that maintained their work activities. The estimates of average income and projection of future income follow the methodology described in Ywata et al [33]. To separate the causes, we weighed the income stream of each population subgroup by the PAF.”

“At present, authors only give conclusions at the end of discussion. I suggest to add some clear recommendations in relation to public policy.”

Response: Thank you so much for highlighting this point. The entire discussion was reviewed by the authors and specific public policy points were added, as suggested. In Lines 293-423.

Reviewer #1

General comments to the Author:

“Thank you for the opportunity to review this manuscript. Overall, this is an important area of research and imperative to know the costs involved in cardiovascular diseases that are cause of high morbidity and mortality globally. The paper details on the costs involved but lacks clarity on costing methods used and standard terminologies for direct costs, unit costs involved and how authors arrived at them. Focus is more outlined for indirect costs; however both are important in cardiovascular diseases. For the better clarity and understanding of the readers, the language editing is required at multiple places in the current manuscript.”

Response: Thank you so much for taking your time to contribute to the improvement of our manuscript. Your contributions were valuable in bringing greater clarity to the manuscript and in improving its overall quality and organization. The entire text has been revised in its language to facilitate the understanding and for better clarity of the readers.

Specific comments to the Author:

Abstract

“Line 26: It would be helpful to mention the study setting in the objective.

Methods: Which of the costing approach was used in the study and what was the perspective of the costing exercise? Please add few details in the methodology.

Results: Please rephrase the line 36 for better clarity.

Line 40: Please add appropriate unit with age group defined.”

Response: Thank you for the suggestions in relation to the abstract.

Objective:

In Lines 21-23, now it says:

“Objective: To evaluate the direct and indirect costs of cardiovascular diseases (such as coronary heart disease and stroke) by sex and age group, attributed to the excessive consumption of salt, saturated fat and trans fats in Brazil.”

Methods:

In Lines 27-32, now it says:

“Methods: The calculation of direct costs was made from the accounting sum of hospital costs with hospitalizations and outpatient care found in the Hospital Information System and Outpatient Information System. Regarding the indirect costs, they were measured by the loss of human capital, given the premature death, via a non-parametric method of pairing by observational explanatory characteristics for income between the living and the dead. To define the attributable costs, they were multiplied by the PAF.”

Results:

In Lines 33-38, now it says:

“Results: Higher burdens attributable to the consumption of salt, saturated fat and trans fat were observed in younger individuals, which progressively decreased with advancing age, but still generated economic costs in the order of US$ 7.18 billion, in addition to 1.53 million productive years of life lost to premature death, if considering salt as an inducer. Although attributable burdens are higher among younger individuals, the highest costs are associated with men aged 45 to 74 years old for direct costs and 45 to 64 years old for indirect costs.”

Introduction

“Line 48: Please clarify whether it is mortality rate or a different indicator where authors refer to lethality rate. It is unclear.”

Response: Thank you. Now, in Lines 44-47, it says:

“Cardiovascular diseases (CVDs) are one of the great challenges of world health, since they are the main cause of premature deaths and compromised productivity, reaching a mortality rate in 2019 of around 32% in the total population and 38% in individuals under the age of 70 [1–3].”

Materials and methods

“Line 89 is unclear. What is implied by databases have time limits? Did it have any effect on the main analysis and final outcomes? It would be good to clarify here than referring elsewhere.

Which costing approach and perspective was used for costing. Please provide details in the methodology section.”

Response: Thank you for your comment. Our apologies for not being clear about the sentence “some databases have time limits that will be highlighted.” We rewrote the sentence and explained the issue of databases better by talking about the limitations in the discussion section.

Now, in Lines 99-100, it says:

“The analysis of CVD cost information for Brazil was carried out from 2017 to 2019, using several databases that will be highlighted.”

“Line 112-113: How was this ideal consumption identified? Please provide supporting reference and the reference standard taken.”

Response: Thank you for your comment. We added the ideal consumption of each evaluated nutrient, as well as their respective references.

We added the statement:

In Lines 144-146:

“In this study, the TMREL for salt was 5g/day, for saturated fat was 10% of the total daily energy value and for trans-fat was 1% of the total daily energy value [8].”

“Line 120: The authors mention that food consumption was measured on non-consecutive days. Please provide details on choosing this rationale. Could this have introduced any bias and affected the analysis? Why were a sub sample chosen? It is unclear how many measurements and how many times in all at individual level were done to capture food consumption from the current manuscript.”

Response: Thanks for your comment. The Personal Food Consumption Block, HBS 7, was the instrument used to record information on food intake. This instrument was developed with the participation of specialists from all over the country, based on a partnership established between the IBGE and the Ministry of Health. To carry out the food record, the individuals were instructed to record and report in detail the names of the foods consumed, the type of preparation, the measure used, the amount consumed, the time and whether the consumption of the food occurred at home or outside the home. In cases where there was an impediment for the resident to complete the registration, it could be done with the help of another resident or a close person.

Data referring to the personal food consumption module were collected for all residents aged 10 years and over from 20,112 selected households, which corresponded to a subsample of 34.7% of the 57,920 households investigated in the HBS 2017-2018. In this way, information was obtained about the individual food consumption of 34,003 residents. Households that participated in the subsample were randomly selected from among those households that were selected for the original HBS sample.

Although the food record provides for the completion of one day of food consumption, it can be applied in two or more days. A single food record per individual may be sufficient when the objective of the study is to estimate the average consumption of food and/or nutrients for a population group. However, most studies that assess food consumption aim to assess the distribution of individual consumption or investigate the proportion of individuals who inappropriately consume a group of foods or a particular nutrient or even analyze the association of dietary factors with the outcome of health. In all these cases, the interest is to assess the usual food consumption. Thus, a single day of food records is not capable of estimating an individual's eating habits. For this reason, replication of the method is important and necessary. In addition, it is believed that there is a dependence on food consumption on consecutive days, that is, the diet of a given day can influence the dietary consumption of the following day. Therefore, it is suggested to use consecutive days and preferably covering weekdays and weekends (Willett, 2013).

Statistical tools, such as the MSM, have been developed and increasingly improved to correct for intrapersonal variability and estimate habitual consumption from a limited number of food record days. For these tools to be used, it is necessary that the food record be applied in at least two days so that the intra-individual variability is estimated. Some statistical methods allow estimating distributions of habitual food consumption when two days of dietary assessment are obtained in 40 to 60% of the total sample, that is, it is not necessary to obtain two days of food records from all individuals investigated (Verly Jr et al., 2012).

References:

Verly JR E, Castro MA, Firsberg RM, Marchioni DM. Precision of usual food intake estimates according to the percentage of individuals wiht a second dietary measurement. J Acad Nutr Diet. 2012; 112(7):1015-20.

Willett WC. Nature of variation in diet. In: Willett WC. Nutritional epidemiology. 2. ed. New York: Oxford University Press; 2013. p. 34-48.

In Lines 155-160, it now says:

“Food consumption was measured using food records, applied on non-consecutive days, in which individuals were instructed to record and report in detail the names of the foods consumed, the type of preparation, the measure used, the amount consumed, the time and whether the consumption of the food occurred at home or outside the home, with their servings sizes converted from standard units or household measures, to grams, using a common reference table to HBS [14].”

“Line 126: It is unclear on whom and how the adherence test was done.”

Response: One way of trying to verify whether or not a distribution fits well to the sample data is by comparing the sample frequencies with the theoretical frequencies expected by the probabilistic model, that is considered valid to describe the observed data. There are hypothesis tests, called goodness-of-fit tests, which serve to test more general hypotheses about the distribution of data. This means that they assess whether or not the distance from the distribution of observed data is significant in relation to a distribution of reference. In the case of the present study, adherence tests were performed in the R software to verify the distribution of food consumption variables (salt, saturated fat and trans fats).

We changed the text in the manuscript:

Now, it says in Lines 164-167:

“To verify the distribution that best fits the sample data, the adherence test was performed, which confirmed that the salt consumption data showed a log-normal distribution, while the saturated and trans fat data showed a gamma distribution. Both distributions were used in the PAF calculation.”

“Line 132: It would be good to mention the components of public expenses here for better understanding of the readers.”

Response: Thank you for your suggestion. The text has been replaced by an explanation of the approaches commonly used in indirect cost analysis.

Now, in Lines 86-89, it says:

“The main approaches in indirect cost analysis are human capital that is associated with lost productivity and friction costs that estimates the costs of worker replacement. We used the human capital approach and estimated the productivity losses based on wages over the working life of the worker.”

“Line 138-139: Were there any individuals who had both CHD and stroke? How were these cases if there handled in the cost analysis?”

Response: Thank you for your question. In the SUS database, there is no information on the individuals themselves, but on the count of specific morbidities and mortality by sex, age, and region. Therefore, it is not possible to know if the same individual is present in the CHD and Stroke counts simultaneously.

Results:

“Line 185-186: Is this the study finding or finding from literature review. It is unclear. If the latter then could be shifted to discussion.”

Response: Thanks for pointing this out. We removed the part of the text that confuses the interpretation, since we are talking about our results, which are presented in Table 1.

Now, in Lines 241-242, it says:

“The attributable fractions to salt are the ones that cause the most effects on CVDs, followed by saturated fat and trans fats.”

Discussion

“In general authors have extensively reviewed about various aspects but this section does not clearly outline key findings and their implications and is quite confusing to read. Few suggestions that could be helpful to authors to strengthen this very important aspect of the paper for better clarity and understanding to readers are:

Introductory paragraph outlining what the study entailed, what was found, and why this is important in place of citing other paper on study design

Summarizing key findings of current study

Importance of key findings in terms of what they tell us and implications of findings, in the context of what is already known in the literature and preferably in similar settings, and what is novel.

Study limitations are mentioned. However, the authors mentioned in methods about limited time-limit of databases. Were there any limitations in for the data availability or health information management systems? Were any limitations present in relation to estimation of direct costs?

Future direction/studies (optional)”

Response: Thanks for the comments. We have improved our discussion by considering the various points suggested above. We even added details about limitations related to databases. The new thread can be verified between the Lines 293-423.

Reviewer #2

Comments to the Author:

“Introduction general comment: Can you specifically outline the policy rationale for undertaking this analysis looking at this specific relationship between nutrients, CVDs and costs

It would be helpful for the reader to understand Brazilian sociodemographic characteristics specifically in terms of the population age characteristics to contextualize results better?”

Response: Thanks for your comments. The introduction has been rewritten to take your suggestions into account.

“Line 55: Could you please specify what the respective age scenarios are that you are referring to?”

Response: Thank you for spotting this omission, we added the age scenario.

Now, in the Lines 53-57, it says:

“Specifically in Brazil, between 2000 and 2018, crude mortality rates from CVD have been decreasing in adults over 25 years of age, of both sexes, except in men over 85 years of age [7]. Even in this scenario, CVDs were responsible for 28% of all deaths that occurred between 2010 and 2015, and 38% of this number occurred in the productive age group (18 to 65 years) [8].”

“Line 58: A brief overview of financing of Brazilian healthcare system along with these statements might be helpful”

Response: Thank you for your suggestion.

Now, in Lines 58-65, it says:

“In addition to the irreversible social losses in the family environment, CVDs have a considerable weight in public and private financial costs (direct costs) due to hospitalizations, monitoring, treatment, and others, and in the loss of productivity (indirect costs). Health financing in Brazil comes from public and private sources. The model covers the Brazilian National Health System (SUS - Sistema Único de Saúde), supported by taxes and contributions collected at the federal, state and municipal levels, and the Complementary Health System, with resources from companies and individuals, with 71% of the Brazilian population using this system [9].”

“Line 66: Please consider clearly rephrasing statements when you are referring to author names. Also, it would be helpful to know what these authors have concluded in their respective studies.”

Response: Thanks for raising these points. The text was rewritten, and the conclusions of the study were added.

“Line 67: Grammatical error: ‘others’ should be replaced with ‘other’. Errors in structuring of sentences are quite common throughout the manuscript. It would help you to review these throughout the manuscript and to not use longer complex sentences.”

Response: Thanks for raising these points. The manuscript has been extensively revised for grammatical issues.

“Line 69: ‘the’ needs to be replaced by ‘a’”

Response: Thanks for raising these points. The manuscript has been extensively revised for grammatical issues.

“Line 76: Could you give more evidence and references to back this claim?”

Response: Thank you for your suggestion. We added some evidence and references from the literature.

Now, in Line 71-77, it says:

“Nowadays, Brazilians have been going through gradual changes in eating patterns, evidently perceived on the excessive consumption of nutrients linked to the causes of Non communicable diseases (NCDs), such as sodium, sugars, and fats [13]. An increase in the consumption of ultra-processed foods (UPFs) by the Brazilian population has been observed [13,14]. These UPFs have high levels of the above mentioned nutrients, with scientific evidence of their relation to obesity [15,16], diabetes mellitus [17,18], hypertension [19] and cardiovascular diseases [20–22].”

References added below:

13. Louzada ML da C, Martins APB, Canella DS, Baraldi LG, Levy RB, Claro RM, et al. Ultra-processed foods and the nutritional dietary profile in Brazil. Rev Saúde Pública. 2015;49. doi:10.1590/S0034-8910.2015049006132

14. Brazilian Institute of Geography and Statistics. IBGE. Pesquisa de Orçamentos Familiares 2017-2018. Análise do Consumo Alimentar Pessoal no Brasil. IBGE; 2020.

15. Pan American Health Organization. Ultra-processed food and drink products in Latin America: trends, impact on obesity, policy implications. Paho Washington (DC); 2015.

16. Askari M, Heshmati J, Shahinfar H, Tripathi N, Daneshzad E. Ultra-processed food and the risk of overweight and obesity: a systematic review and meta-analysis of observational studies. Int J Obes 2005. 2020;44: 2080–2091. doi:10.1038/s41366-020-00650-z

17. Levy RB, Rauber F, Chang K, Louzada ML da C, Monteiro CA, Millett C, et al. Ultra-processed food consumption and type 2 diabetes incidence: A prospective cohort study. Clin Nutr Edinb Scotl. 2020. doi:10.1016/j.clnu.2020.12.018

18. Srour B, Fezeu LK, Kesse-Guyot E, Allès B, Debras C, Druesne-Pecollo N, et al. Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort. JAMA Intern Med. 2020;180: 283–291. doi:10.1001/jamainternmed.2019.5942

19. He FJ, Tan M, Ma Y, MacGregor GA. Salt Reduction to Prevent Hypertension and Cardiovascular Disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75: 632–647. doi:10.1016/j.jacc.2019.11.055

20. Bonaccio M, Di Castelnuovo A, Costanzo S, De Curtis A, Persichillo M, Sofi F, et al. Ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality in the Moli-sani Study. Am J Clin Nutr. 2021;113: 446–455. doi:10.1093/ajcn/nqaa299

21. Pagliai G, Dinu M, Madarena MP, Bonaccio M, Iacoviello L, Sofi F. Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. Br J Nutr. 2021;125: 308–318. doi:10.1017/S0007114520002688

22. Srour B, Fezeu LK, Kesse-Guyot E, Allès B, Méjean C, Andrianasolo RM, et al. Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé). BMJ. 2019;365: l1451. doi:10.1136/bmj.l1451

“Line 79: What is the method generally used to know indirect costs?”

Response: Thank you for your question. The text was replaced by an explanation of the approaches commonly used in indirect cost analysis.

In Lines 86-89, it now says:

“The main approaches in indirect cost analysis are human capital that is associated with lost productivity and friction costs that estimates the costs of worker replacement. We used the human capital approach and estimated the productivity losses based on wages over the working life of the worker.”

“Line 81: Premature death cases are only due to CVD? How has this been established?”

Response: Thank you. Deaths are filtered for CVD only. The premature deaths considered are those that occur under the age of 65 years, given that individuals have a share attributable to death from excessive consumption of salt, trans fat and saturated fat. In this way, the PAFs of these nutrients work as a weight that is assorts between 0 and 1, where 0 indicates no cost associated with these nutrients and 1 the total cost attributable to them. For clarity, the passage in question has been replaced.

In Lines 90-92, it now says:

“Observational variables are used that characterize the income of living individuals, correlating with the observational characteristics of individuals who had deaths from CVD under the age of 65 years.”

Materials and Methods general comment: “It would be helpful to outline the extent of indirect costs you are considering in the analysis with clear justification for doing so and providing a reason for excluding components of indirect costs that are not analysed in this analysis.”

Response: Thank you for your suggestion. The choice to use the loss of permanent productive capacity given by the mortality came from three conditions: 1) Firstly, because in the indirect costs the individual's productivity resumption is irreversible; 2) Secondly, this way of estimating costs allows more realistic results without introducing possible bias. 3) Thirdly, because it is a very laborious task that takes a considerable amount of time, since the data used are not processed directly by the DATASUS system and, in addition, our approach includes age groups that are not available in it. Therefore, it was necessary to extract raw data and carry out all the processing by the statistical program R, in order to make the connection between the living and the dead, individual by individual. Then, we were able to separate the age groups present in the study and the sum of indirect costs. In this way, we made it impossible to add other indirect costs that could possibly bring bias to the results.

Three other indirect cost approaches were considered, but their limitations led us not to choose them:

- Approach 1: it would be developed using data from the Hospital Information System (SIH), which provides information on the number of days where individuals remained hospitalized, in other words, being unable to work and be productive, generating indirect costs. This approach would follow in a similar way to that found in the study, but without using the probability of death and without a discount rate, as the values would be in the present. However, the SIH does not provide valuable information for determining income, such as education and marital status of individuals (especially schooling, which is a recognized variable in the literature as a proxy for human capital and, consequently, for determining income), which could generate inaccurate information on the income of hospitalized individuals.

- Approach 2: simpler than the others, it would be the identification of permanently disabled and retired living individuals that would generate a direct social security cost, but indirectly due to premature productivity loss. This approach was disregarded because in most cases the amounts paid by social security are the minimum stipulated by law, so it is an exogenously determined income that would bias the results because it is controlled by the government and not by factors inherent to the individual.

- Approach 3: the last approach considered was the inverse of the one present in the study, which would be the attempt to estimate the marginal propensity of individuals to pay to live an additional year given premature death from excessive consumption of salt, trans fat and fat saturated, which is credited in the literature as the “value of life”. This line is used especially in studies on violence, but it has a strong tendency to overestimate indirect costs, which discouraged us, as there are data limitations for this estimation.

In Lines 233-238, it now says:

“This methodological approach to the estimation of indirect costs was considered due to the costs associated with permanent loss of productivity given the premature death from CVD, caused by excessive consumption of nutrients, being, in hypothesis, the highest within this cost modality [33]. In addition, the estimates are more realistic, as real observational variables are used as determinants of the income of deceased individuals, reducing possible bias in the results [33].”

“Line 89: I am not sure if the limits of databases have been adequately highlighted later in the manuscript or in limitations?”

Response: Thank you for pointing out this issue. Now at the end of discussion section, it was added some limitations that occurred in this study.

In Lines 408-423, it now says:

“However, there are some limitations of this study that should be highlighted. First, we only collected information’s on public expenditure, we did not observe private health expenditures. We estimate the direct costs adding to the expenses recorded in the two official databases SIH/SUS and SIA/SUS. Although there is a greater participation of private spending in the acquisition of health services in Brazil, public spending represents approximately 40% of the total expenditure. We emphasize that observing only public spending is a limitation of our data. Second, a longitudinal assessment of the direct and indirect costs is essential to better understand the trends related to these expenses and losses.

Another aspect that should be mentioned is the estimation of indirect costs. There is a high probability that those values are being underestimated, for two main reasons: first, due to fact that the variables of the state of the country, marital status and education level remain constant overtime. Therefore, the earlier the death of the individual, the greater the underestimation of their loss of future earnings; and second, 2015 was the year which was used by the NHSS for the individual income, Brazil was experiencing an economic crisis that impacted employment and consequently, the income of the population, which can reflect on the results found in this study.”

“Line 110: Could you please mention the currency exchange rate and its source as a reference?”

Response: Thank you for spotting this omission. The conversion rate used was 3.94 R$/U$S (0.25345 U$S/R$) which corresponds to the average of the 12 months of the year 2019. These data are available at the Institute of Applied Economic Research (IPEA) < http://www.ipeadata.gov.br/Default.aspx > from Brazil under the heading to access the data link “Exchange rate - R$ / US$ - commercial - purchase - average” by monthly data. The exchange rate information as well as its respective reference are now present in the manuscript.

In Lines 127-131, it now says:

“In addition, all monetary values were corrected using the Index National Price on Expanded Consumers (Índice Nacional de Preços ao Consumidor Amplo, IPCA/IBGE) in Brazilian currency (R$ - reais) for 2019 and, subsequently, converted to US dollars ($) at the average exchange rate for 2019, corresponding to 3.944 R$/U$S (0.25345 U$S/R$), made available by the Institute of Applied Economic Research (IPEA) [30].”

“Line 116: How has individual food consumption been estimated from household food consumption dataset?”

Response: Thank you for your comment. The Personal Food Consumption Block, HBS 7, was the tool used to record the information on food intake. This tool was developed with the participation of specialists from all over the country, based on a partnership established between the IBGE and the Ministry of Health. To carry out the food record, the individuals were instructed to record and to report in detail, the following: the names of the foods consumed, the type of preparation, the measure used, the amount consumed, the time and whether the consumption of the food occurred at home or outside. In cases where there was an impediment for the resident to complete the registration, it could be done with the help of another resident or a close person.

Data referring to the personal food consumption module were collected from 20,112 selected households, for all residents with 10 years of age and over, which corresponded to a subsample of 34.7% of the 57,920 households investigated in the HBS 2017-2018. In this way, information was obtained about the individual food consumption of 34,003 residents. Households that participated in the subsample were randomly selected from among those households that were selected for the original HBS sample.

Although the food record provides for the completion of one day of food consumption, it can be applied in two or more days. A single food record per individual may be sufficient when the objective of the study is to estimate the average consumption of food and/or nutrients for a population group. However, most studies that assess food consumption aim to assess the distribution of individual consumption, or target to investigate the proportion of individuals who inappropriately consume a group of foods or a particular nutrient, or even aim to analyze the association of dietary factors with the outcome of health. In all these cases, the interest is to assess the usual food consumption. Thus, a single day of food records is not capable of estimating an individual's eating habits. For this reason, replication of the method is important and necessary. In addition, it is believed that there is a dependence on food consumption on consecutive days, that is, the diet of a given day can influence the dietary consumption of the following day. Therefore, it is suggested to use consecutive days and preferably covering weekdays and weekends (Willett, 2013).

Reference:

Willett WC. Nature of variation in diet. In: Willett WC. Nutritional epidemiology. 2. ed. New York: Oxford University Press; 2013. p. 34-48.

“Line 124: What is the multiple source method mentioned here?”

Response: Thank you. Statistical tools, such as the Multiple Source Method (MSM), have been developed and increasingly improved, in order to correct for intrapersonal variability and estimate the habitual consumption from a limited number of food record days. Moreover, for these tools to be used, it is necessary that the food record be applied in at least two days so that the intra-individual variability is estimated. Some statistical methods allow estimating distributions of habitual food consumption when two days of dietary assessment are obtained in 40 to 60% of the total sample, that is, it is not necessary to obtain two days of food records from all individuals investigated (Verly Jr et al., 2012). We added the MSM´s reference in the manuscript.

References:

Verly JR E, Castro MA, Firsberg RM, Marchioni DM. Precision of usual food intake estimates according to the percentage of individuals with a second dietary measurement. J Acad Nutr Diet. 2012; 112(7):1015-20.

Harttig, U et al. The MSM program: web-based statistics package for estimating usual dietary intake using the Multiple Source Method. European Journal of Clinical Nutrition, v.65, p. S87–S91, 2011.

The reference was added in the manuscript:

In Lines 161-163, it says:

“Habitual nutrient intake was estimated using the Multiple Source Method (MSM). This last method is suitable to estimate the usual individual intake for repeated measurements and a defined period [32].”

“Line 132: Given that public expenses for CHD and stroke from available data sources are used, and that private expenses do account for healthcare costs in Brazil, how does this justify the projected costs?”

Response: Thank you. In this study, we collected only information’s on public expenditure, we did not observe private health expenditures. We estimate the direct costs adding to the expenses recorded in the two official bases SIH/SUS and SIA/SUS. Although there is a greater participation of private spending in the acquisition of health services in Brazil, public spending represents approximately 40% of the total expenditure. We emphasized that observing only public spending is a limitation of our data.

“Line 148: Are costs only due to premature deaths accounted for? What about the costs due to morbidity/disability? Has this been accounted for in the analysis?”

Response: Thank you for your comment. Yes, only premature death costs are counted. Unfortunately, there is no follow-up data over time for individuals with morbidity, so there is no way to identify how long the individual has had the morbidity or if he or she has ceased to have a state of morbidity.

Furthermore, in addition to the need of data for the calculations, there would possibly be a need for an individual identification variable. For instance, the Individual Taxpayer Registry (CPF), is a unique number assigned to each Brazilian citizen. This would be necessary to avoid double counting of indirect costs. This is not the case for deaths, as each row in the raw database will always represent a death of a person and its observational characteristics. The only exception would be the time which the individual spent hospitalized and, consequently, absent from work, regardless of whether he had to be hospitalized “n” times, with the limitations mentioned above regarding the absence of important variables. In this case, it was only possible to calculate the direct costs that the morbidities generate for the SUS via hospitalizations and outpatient care. Regarding disability, there is the possibility of the individual retiring prematurely. In this condition, there would be data, however, the value would not correspond to the loss of productivity of the individual, but how much he contributed to the social security, which in most cases, results in retirement with a minimum wage stipulated by law. Thus, in both possible cases, it would produce biased results.

“Line 165: It is unclear to me why discounting has been used only for indirect costs given in the corresponding formula?”

Response: Thank you for your comment. Our calculations for indirect costs were related to the permanent loss of productivity resulting from premature death. Calculations start at the current time extending into the future, under the assumption that the individual who dies in year t is alive in year t+1, t+2, until reaching the maximum productive age (considered to be 65 years). Thus, it is necessary to bring the future values t+1, t+2, until completing the entire productive age, to the present value. In this case, the values are calculated for the present values of 2017, 2018 and 2019. As the direct costs are current values for each year considered in the study, there is no need to use the discount rate. Furthermore, the discount rate used in the calculation of indirect costs was the same as in the study by Ywata et al. (2008).

Reference:

Ywata AXC et al. Custos das mortes por causas externas no Brasil. Rev Bras Biom. 2008;26: 23–47.

In Lines 214-218, now it says:

“To bring the future income stream to the present we apply the net present value (NPV) allows you to measure the value of money in time:

TICt,i=∑_(X=Di)^T▒1/〖(1+d)〗^((x-Di)) *Pr⁡(Fi>x│Fi≥Di)*Wi

In the occasion that (d) is the annual discount rate of 3%, (Wi) is the expected annual income of the individual (i) present in the SIM.”

“Table 2: Any specific reason for as to why trans-fat consumption is relatively high in female population as compared to males?”

Response: Thank you for your question. According to Household Budget Survey (POF 217/2018), which was the database for the present study, small differences were observed regarding the participation of the four food groups in the diet of men and women. The consumption of in natura or minimally processed foods was slightly higher in men than in women (54.1% and 52.8% of total calories, respectively) as well as consumption of processed foods (11.8% and 10.8%, respectively). On the other hand, the consumption of processed culinary ingredients was higher among women (16.2% against 15.0% among men) and the consumption of ultra-processed foods (20.3% against 19.1% among men). Therefore, one of the plausible explanations for the high consumption of trans fat among women is due to the consumption of ultra-processed foods, since these are the main sources of trans fat.

Discussion general comment: “The relevance of these findings needs to be better contextualised to relevant policies in Brazil. Please identify and discuss specific aspects of policies that can be addressed given the findings of this study.”

Response: Thank you very much for your considerations. The discussion was reviewed by the authors and relevant policy aspects in Brazil were mentioned. Now it reads in Lines 293-423.

Line 309: 110,000 and 70,000 cases of what?

Response: Thank you for spotting this omission.

In Lines 310-314, it now says:

“Nilson et al. (2021) [36] estimated the economic effects and impact on health between 2013 and 2032 of the implementation of sodium reduction in processed foods in Brazil. They also reported that during this period, around 110,000 CVD male cases and 70,000 CVD female cases will be prevented. This estimate will result in a total savings of around US $ 220 million in medical costs for the Brazilian National Health System for the treatment of CHD and stroke.”

Kind regards,

The author (On behalf of the co-authors)

Attachment

Submitted filename: Response to reviewers.docx

Decision Letter 1

Pankaj Bahuguna

21 Oct 2022

PONE-D-21-41019R1

The direct and indirect costs of cardiovascular diseases in Brazil

PLOS ONE

Dear Dr. Moreira,

Thank you for submitting the revised manuscript to PLOS ONE. The revised manuscript has improved significantly but after careful consideration, we feel there is still scope of further improvement. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Pankaj Bahuguna, Ph.D.

Guest Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

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Reviewer #1: (No Response)

Reviewer #2: (No Response)

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Reviewer #2: Yes

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Reviewer #2: I Don't Know

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Reviewer #2: Yes

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Reviewer #2: Yes

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Reviewer #1: Thank you for revising the manuscript and improving clarity for better understanding of the readers. However, the paper still needs language editing at few places and use of shorter sentences.

Abstract

Line 24-25: It could be useful to know whether the cost mentioned here was overall cost/health system cost/societal cost and specifically for treatment?

Line 27-28: Were these direct medical costs only? Please specify if so.

Line 29-30 can be rephrased to shorter sentences for better clarity.

Results: Line 33: Higher burdens of what attributable to?

Conclusion Line 39: “Studies of this nature….” Is very broad scope and could be rephrased to narrower scope for clarity. Also authors may use shorter sentences in conclusion and should restrict to findings from the study than generic statements.

Introduction

Line 44: This line may be rephrased to “Cardiovascular diseases (CVD) are one of the key challenges in health globally, since……………”

Line 78: Please cite supporting references besides “few studies…….” Or may rephrase.

Line 85-86 looks repetitive in lines 94-96 and may be better placed there.

Lines 87-89 seems better suited to methodology section.

Line 99 could be rephrased to “Several databases were referred to collect and analyse CVD cost related information between 2017 and 2019 for Brazil.”

Line 114: There seems to be incomplete word in here. Whether its three sources or three databases, it is currently unclear to understand “three bases”.

Discussion

Line 293: The sentence could be rephased to “Findings from or study showed………….”

Reviewer #2: Thank you for considering suggestions and revising the manuscript. The manuscript content is structured better and reads more logically now. The authors have addressed grammatical mistakes to a large extent. Policy relevance of this work is highlighted better than the previous version. Following are some of my suggestions/clarifications for the revised manuscript (Line numbers refer to the latest unmarked version):

Consider further grammatical checks: For example, replace burdens with burden (multiple places, replace servings with serving – Line 158, typos on Line 214-215, Replace manuscript with ‘study’ – Line 293, typo error on Line 295, typo on Line 375, consider replacing ‘inadequate diet’ with maybe unhealthy diet if you thing that is more reflective on Line 305. You may consider further similar grammatical checks in the manuscript.

The revised introduction section makes a better read. However, on line 87, you go on to directly explain methods of indirect cost analysis. I would suggest you consider moving this to the methods section. The introduction section could give a brief overview of what all analysis (PAF, direct cost, indirect costs) is being aimed. Similarly, I found it difficult to establish relevance of Line 69-70 in context to the previous statement. What do you mean by recurrent costs here? My understanding is recurrent costs would be those attributed to hospitalisations and consultations (22% of costs)

For lines 137 to 143 – Can you clarify if adjusted relative risk values should be used for PAF calculation instead of relative risk?

For lines 198 to 201 – Can you give any rationale/reasoning/references for choosing the six explanatory variables that have been chosen?

Based on your results, specifically tables 1 and 2, can anything be commented/discussed on relationship between PAF and direct costs that you have observed?

In discussion, can you compare findings of high costs and mortality for males as compared to females with any existing evidence from Brazil to possibly validate your result?

For Table 4 from Line 290 onwards – I do not understand the unit used for your findings. The reported YLL is for what unit of observation? Is it for the entire cohort, per number of cases or what exactly?

In discussion section, can you compare your indirect cost findings to any other relevant literature?

********** 

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2022 Dec 22;17(12):e0278891. doi: 10.1371/journal.pone.0278891.r004

Author response to Decision Letter 1


10 Nov 2022

9th Nov 2022

REBUTTAL LETTER

PONE-D-21-41019: The direct and indirect costs of cardiovascular diseases in Brazil

Dear Pankaj Bahuguna, Ph.D.

We would like to thank you and the reviewers for your time to provide feedback on our paper. We have addressed all Journal requirements and the reviewers’ comments below.

Journal Requirements

Comments to the Author:

1. “Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.”

Response: Thank you for raising this point. We extensively reviewed the reference list and, in this manuscript, we haven’t cited papers retracted.

Reviewer #1

General comments to the Author:

“Thank you for revising the manuscript and improving clarity for better understanding of the readers. However, the paper still needs language editing at few places and use of shorter sentences.”

Response: Thank you for your comments and for the opportunity to further improve our manuscript with your suggestions.

Specific comments to the Author:

Abstract

Line 24-25: It could be useful to know whether the cost mentioned here was overall cost/health system cost/societal cost and specifically for treatment?

Response: Thank you for your suggestion. We added the information that the costs were from health system and related to hospitalizations and outpatient care.

In Lines 26-31, now it says:

“The calculation of direct costs for cardiovascular diseases (CVD) was made from the accounting sum of costs with hospitalizations and outpatient care found in the National Health System (Hospital Information System and Outpatient Information System), from 2017 to 2019, including the costs of treatment, such as medical consultations, medical procedures, and drugs. Regarding the indirect costs, they were measured by the loss of human capital, given the premature death, resulting in loss of productivity.”

Line 27-28: Were these direct medical costs only? Please specify if so.

Response: Thank you for pointing out this omission. We added the costs’ information.

In Lines 29-30, now it says:

“…including the costs of treatment, such as medical consultations, medical procedures, and drugs.”

Line 29-30 can be rephrased to shorter sentences for better clarity.

Response: Thank you. We rephrased the sentence.

In Lines 30-31, now it says:

“Regarding the indirect costs, they were measured by the loss of human capital, given the premature death, resulting in loss of productivity.”

Results: Line 33: Higher burdens of what attributable to?

Response: Thank you. We now rephrased the sentence.

In Line 33, now it says:

“Higher burden of CVD attributable to the consumption of salt,…”

Conclusion Line 39: “Studies of this nature….” Is very broad scope and could be rephrased to narrower scope for clarity. Also authors may use shorter sentences in conclusion and should restrict to findings from the study than generic statements.

Response: Thank you. We now used shorter sentences restricted to our findings.

In Lines 40-42, now it says:

“The attributable fractions to consumption of salt are the ones that cause the most effects on CVD, followed by saturated fat and trans fats, with direct and indirect costs being higher for males.”

Introduction

Line 44: This line may be rephrased to “cardiovascular diseases (CVD) are one of the key challenges in health globally, since……………”

Response: Thank you for your suggestion. We rephrased the text using your suggestion.

Line 78: Please cite supporting references besides “few studies…….” Or may rephrase.

Response: Thank you for raising this point. Now we added two supporting references.

In Lines 78-79, now it says:

“Few studies have been carried out with the objective of attributing the effect of nutrient consumption to the cause of CVD and its consequent costs [23,24].”

Line 85-86 looks repetitive in lines 94-96 and may be better placed there.

Response: Thank you for spotting this. Now we deleted the lines 85-86 and placed only in Lines 100-102.

Lines 87-89 seems better suited to methodology section.

Response: Thank you for spotting this. Now we deleted Lines 87-89 from the Introduction and added to methods section (Lines 193-199).

Line 99 could be rephrased to “Several databases were referred to collect and analyse CVD cost related information between 2017 and 2019 for Brazil.”

Response: Thank you for your suggestion. We rephrased the text using yours (now in Lines 105-106).

Line 114: There seems to be incomplete word in here. Whether its three sources or three databases, it is currently unclear to understand “three bases”.

Response: Thank you for spotting this. We made it clearer in the text that we used three databases to obtain the information needed to calculate indirect costs.

In Line 121, now it says:

“Regarding indirect costs, three databases were necessary…”

Discussion

“Line 293: The sentence could be rephased to “Findings from or study showed………….”

Response: Thank you for your suggestion. We rephrased the text using your suggestion.

Reviewer #2

Comments to the Author:

“Thank you for considering suggestions and revising the manuscript. The manuscript content is structured better and reads more logically now. The authors have addressed grammatical mistakes to a large extent. Policy relevance of this work is highlighted better than the previous version. Following are some of my suggestions/clarifications for the revised manuscript (Line numbers refer to the latest unmarked version):”

Response: we are very grateful for all the considerations. They were very valuable to improve our manuscript.

“Consider further grammatical checks: For example, replace burdens with burden (multiple places, replace servings with serving – Line 158, typos on Line 214-215, Replace manuscript with ‘study’ – Line 293, typo error on Line 295, typo on Line 375, consider replacing ‘inadequate diet’ with maybe unhealthy diet if you thing that is more reflective on Line 305. You may consider further similar grammatical checks in the manuscript.”

Response: Thank you for raising these points. We checked the whole manuscript looking for grammatical errors. Now the corrections are in red words.

“The revised introduction section makes a better read. However, on line 87, you go on to directly explain methods of indirect cost analysis. I would suggest you consider moving this to the methods section. The introduction section could give a brief overview of what all analysis (PAF, direct cost, indirect costs) is being aimed. Similarly, I found it difficult to establish relevance of Line 69-70 in context to the previous statement. What do you mean by recurrent costs here? My understanding is recurrent costs would be those attributed to hospitalisations and consultations (22% of costs)”

Response: Thank you for your comments. We moved the Line 87 and correlated aspects to methods section, and we added three paragraphs (Lines 85-99) with a brief overview of all analysis, as suggested. In Lines 69-70, we are talking about all kind of costs mentioned in previous statement (mortality, hospitalization and years of life lost). To make this information clearer, we have amended the text using “these recurrent costs”.

In Lines 85-99, now it says:

“The Population Attributable Fraction (PAF) is a measure of public health impact that has been widely used by the World Health Organization, based on Global Burden Disease (GBD) data, in order to determine goals, prioritize interventions and build public policies [25,26]. In addition, the PAF has also been used to provide information on economic costs attributable to some risk factors, such as salt consumption [27].

There are two ways to estimate health costs for a disease. The first is “top-down”, going from the total values at the national level of the set of all diseases and, through a disaggregation process, arriving at the level at which the cost of the disease under analysis is found. The second is “bottom-up”, and through this method, estimates are made for a sample of cases and are extrapolated to the total number of individuals [28].

In Brazil’s context, it is possible to obtain the total direct costs related to a given pathology in the National Health System, which can be disaggregated by level of health care (outpatient and hospital), sex and age groups. Thus, the best approach to be used in Brazil is the top-down approach, from the perspective of public health services, based on health cost data, available in the information systems of the Ministry of Health [28].”

In Lines 69-70, now it says:

“Therefore, the growth of these recurrent costs represents an important problem for health systems, as well as for their socioeconomic impacts.”

“For lines 137 to 143 – Can you clarify if adjusted relative risk values should be used for PAF calculation instead of relative risk?”

Response: Thank you for raising this point. To calculate the relative risk (RR) used in the PAF formula, it was calculated according to the distribution of our own variables. For this, we used a relative risk already established in the literature, from review studies or larger studies, such as the Global Burden Disease (GBD). These relative risks are adjusted for, at least, sex and age. Implicit in the way we characterize the RR function are some of the fundamental assumptions we make about relative risk. That is, the relative risk increases exponentially as the distance from the theoretical minimum level of risk exposure (y) increases, that there is no risk associated with exposure beyond the theoretical minimum level of risk exposure, and that both x and the level theoretical minimum risk exposure for an individual at exposure level x are the qth quantile of their respective distributions (the observed exposure distribution and the TMREL, respectively).

Reference:

Micha R, Peñalvo JL, Cudhea F, Imamura F, Rehm CD, Mozaffarian D. Association Between Dietary Factors and Mortality From Heart Disease, Stroke, and Type 2 Diabetes in the United States. JAMA. 2017 Mar 7;317(9):912-924.

“For lines 198 to 201 – Can you give any rationale/reasoning/references for choosing the six explanatory variables that have been chosen?”

Response: Thank you for your comments. The Mincerian equations from the study by Mincer (1974) show that the coefficients of age (proxy for experience), education and sex are significantly relevant to estimate individual income. For Brazil, due to regional/local and color/race disparities, the location variables "individual residence" and "color/race" are also of great importance. We added the reference in the text.

In Lines 212-216, now it says:

“In this study, irreversible productivity losses due to the premature death of individuals aged 25 to 65 years caused by CVDs were considered. For this task, six explanatory variables for income that are available in the NHSS, and SIM databases were considered: state of the country in which the individual resides (residence), age, sex, education level, color/race, and marital status [39].”

“Based on your results, specifically tables 1 and 2, can anything be commented/discussed on relationship between PAF and direct costs that you have observed?”

Response: Thank you for your advice. We added a paragraph in the discussion.

In Lines 323-328, now it says:

“Although the highest CVD costs attributable to the consumption of salt, saturated fat and trans fats is among the 45-74 age groups, the consumption of these nutrients is inversely proportional to the age. One of the explanations for our findings is that, due to the greater number of CVD cases occurring in these age groups, the risk attributable to the consumption of these nutrients is added to the risk related to the age group, suggesting that preventive measures at younger ages can benefit the entire population in their future.”

“In discussion, can you compare findings of high costs and mortality for males as compared to females with any existing evidence from Brazil to possibly validate your result?”

Response: Thank you for spotting this. In discussion, a study that addressed this issue with Brazilian data had already been mentioned. However, to reinforce our findings, we add another recent evidence.

In Lines 337-345, now it says:

“Nilson et al. (2021) [24] estimated the economic effects and impact on health between 2013 and 2032 of the implementation of sodium reduction in processed foods in Brazil. They also reported that during this period, around 110,000 CVD male cases and 70,000 CVD female cases will be prevented. This estimate will result in a total savings of around US $ 220 million in medical costs for the Brazilian National Health System for the treatment of CHD and stroke. Moreover, corroborating our findings, a recent study carried out in Brazil showed that the costs attributable to excessive salt consumption were higher for males when compared to females, corresponding to 62% of the costs associated with hospitalizations and 53% of outpatient’s costs for CVD, attributable to salt consumption [27].”

“For Table 4 from Line 290 onwards – I do not understand the unit used for your findings. The reported YLL is for what unit of observation? Is it for the entire cohort, per number of cases or what exactly?”

Response: Thank you for your question. The Years of Life Lost (YLL) for a cause are essentially calculated as the number of cause-specific deaths multiplied by a loss function, specifying the years lost for deaths as a function of the age at which death occurs. Table 4 shows the total years of life lost attributable to the consumption of nutrients (salt, saturated fat and trans fats) by age group and sex. The unit of measurement is actually "years", as presented in the Global Burden Disease (GBD) and as presented in other publications (please, see the doi https://doi.org/10.1371/journal.pone.0235514.t003, as example).

“In discussion section, can you compare your indirect cost findings to any other relevant literature?”

Response: Thank you for your suggestion. The problem with making comparisons in relation to indirect costs lies precisely in the difference between the methodologies adopted in studies involving this theme. Recent work by Nilson et al (2020), assessed the years of life lost, however, it did not calculate indirect costs. Rasmussen's study (2015), for example, which carried out an analysis of indirect costs, addressed other methodological aspects, such as absenteeism, presenteeism and early retirement. So, we decided to add a few words to the discussion referring to a limitation of comparing these data given these previous explanations.

In Lines 454-455, now it says:

“Besides, the fact that other studies use different approaches to calculate the indirect costs makes it difficult to compare the results [12,64,65].”

Patrícia Moreira

On Behalf of co-authors

Attachment

Submitted filename: Response to reviewers - 2.docx

Decision Letter 2

Pankaj Bahuguna

24 Nov 2022

The direct and indirect costs of cardiovascular diseases in Brazil

PONE-D-21-41019R2

Dear Dr Moreira,

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Reviewers' comments:

Acceptance letter

Pankaj Bahuguna

14 Dec 2022

PONE-D-21-41019R2

The direct and indirect costs of cardiovascular diseases in Brazil

Dear Dr. Moreira:

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Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response to reviewers.docx

    Attachment

    Submitted filename: Response to reviewers - 2.docx

    Data Availability Statement

    The microdata used in the study are available in the following public domain and open access databases: - Brazilian Institute of Geography and Statistics: (https://www.ibge.gov.br/estatisticas/sociais/saude/24786-pesquisa-de-orcamentos-familiares-2.html?=&t=microdados); (https://www.ibge.gov.br/estatisticas/sociais/populacao/9127-pesquisa-nacional-por-amostra-de-domicilios.html?=&t=microdados); and (https://www.ibge.gov.br/estatisticas/sociais/populacao/9126-tabuas-completas-de-mortalidade.html?=&t=downloads) - Informatics Department of the Brazilian Unified Health System (DATASUS) for the Outpatient Information System (SIA, specifically, SIA-PA [production subsystem]), Hospital Information System (SIH, specifically, SIA-RD [subsystem of accepted admissions]) and Mortality Information System (SIM, specifically, SIM-DO [death certificate subsystem], all on the same link for access to raw data (https://datasus.saude.gov.br/transferencia-de-arquivos/).


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