A 10-Year Trend Analysis of Heart Failure in the Less Developed Brazil

Background Data on heart failure (HF) epidemiology in less developed areas of Brazil are scarce. Objective Our aim was to determine the HF morbidity and mortality in Paraiba and Brazil and its 10-year trends. Methods A retrospective search was conducted from 2008 to 2017 using the DATASUS database and included patients ≥ 15 years old with a primary diagnosis of HF. Data on in-hospital and population morbidity and mortality were collected and stratified by year, gender and age. Pearson correlation and linear-by-linear association test for trends were calculated, with a level of significance of 5%. Results From 2008 to 2017, HF admissions decreased 62% (p = 0.004) in Paraiba and 34% (p = 0.004) in Brazil. The in-hospital mortality rate increased in Paraiba and Brazil [65.1% (p = 0.006) and 30.1% (p = 0.003), respectively], but the absolute in-hospital mortality had a significant decrease only in Paraiba [37.5% (p = 0.013)], which was maintained after age stratification, except for groups 15-19, 60-69 and > 80 years. It was observed an increase in the hospital stay [44% (p = 0.004) in Paraiba and 12.3% (p = 0.004) in Brazil]. From 2008 to 2015, mortality rate for HF in the population decreased 10.7% (p = 0.047) in Paraiba and 7.7% (p = 0.017) in Brazil. Conclusions Although HF mortality rate has been decreasing in Paraiba and Brazil, an increase in the in-hospital mortality rate and length of stay for HF has been observed. Hospital-based clinical studies should be performed to identify the causes for these trends of increase.


Introduction
Heart Failure (HF) is the main cause of hospitalizations in the United States in patients older than 65 years old, 1,2 and is estimated to affect 26 million people worldwide. 3 Its prevalence has been increasing fast due to aging of the population. 1,4 A higher life expectancy has been achieved with adherence to medical therapy, ventricular assist devices (VADs) and increase in the number of heart transplants. 1 Paraiba is one of the nine states of the Northeast region of Brazil and had an estimated population in 2017 of 4,025,558 inhabitants, corresponding to the 13 th highest population among the 27 federative units of Brazil. The gross domestic product per capita of Paraiba was US$3,594.94 in 2010, corresponding to fourth poorest state in the country, and the human development index in 2014 was 0.701, the 6 th lowest in the country. 5,6 Data regarding the epidemiology of HF in less developed countries are still limited and based mainly in cohorts of hospitalized patients or clinical trials. 2 In Brazil, there is no data about the epidemiology of HF in Paraiba, and only a few reports on HF statistics in the Northeast region of Brazil. 7,8 A better understanding of the HF epidemiology in less developed areas of Brazil, as Paraiba, through a population-based study, could lead to a more effective and appropriate healthcare planning. The aim of this study was to describe and to perform a 10-year trend analysis of the HF morbidity and mortality in the state of Paraiba and in Brazil.

Study model
This is a population-based time series analysis using the Hospital Information System (SIH/SUS), available at DATASUS (Department of Informatics of the Brazilian Unified Health System-SUS) database. 6 DATASUS is responsible for the administration of health and financial information declared by all states and cities, and the federal district of Brazil. This database compiles information regarding health assistance, epidemiology, morbidity and demography.

Study population
The population of interest was composed by Brazilians older than 15 years that used any healthcare services under the primary diagnosis of HF, represented by the code I50 of the International Classification of Diseases 10 th Revision (ICD-10), between 2008 and 2017.

Variables
Epidemiological data on HF were extracted, including absolute and relative mortality of the population, in-hospital mortality (absolute numbers), in-hospital mortality rate, number of hospital admissions and length of hospitalization. Variables were stratified by year, gender and age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 and ≥ 80 years). In-hospital data from the period of 2008 to 2017, and population data from 2008 to 2015 were available. The last population census conducted by the Brazilian Institute of Geography and Statistics (IBGE) 5 in 2010 was also used.

Data analysis
Categorical variables were expressed as frequencies and continuous variables as mean ± standard deviation (SD).
In-hospital mortality rate from HF was obtained by dividing the number of all in-hospital HF deaths in Paraiba or Brazil by the number of hospitalizations for HF in the corresponding year. Population mortality rate from HF was calculated by dividing the number of all HF deaths in Paraiba or Brazil by the respective population in the corresponding year.
The Statistical Package for the Social Sciences (SPSS) version 21.0 (SPPS Inc., Chicago, USA) was used for the analysis. We used the Shapiro-Wilk's test to test the normality of data distribution for further analyses. The Pearson correlation was used to evaluate the correlation between numerical variables with normal distribution. The Chi-square test was performed using a contingency table and the linear-by-linear association test, also known as Mantel-Haenzsel test for trends, which is equivalent to the Cochran-Armitage test for trends available in other statistical packages. 9 The level of significance was set at 5%.

Results
Descriptive statistics of our variables are presented in Table 1.

Hospitalizations
The total number of HF admissions in Paraiba state between 2008 and 2017 was 51,172, representing the leading cause of hospitalizations due to cardiovascular diseases (29.4%), followed by other ischemic diseases of the heart (13%), stroke (11%), primary hypertension (10%) and acute myocardial infarction (5%). During the same period, HF was also the leading cardiovascular cause of hospitalization in Brazil, with 2,380,133 cases (21%). HF was responsible for 2.54% and 2.25% of all causes of hospitalization in Paraiba and in Brazil, respectively.
A downward trend in the absolute number of hospitalizations from HF in Paraiba and Brazil was observed between 2008 and 2017, corresponding to a decrease of 62% (R = -0.970; p = 0.004; Table 2; Figure 1A) and 34% (R = -0.964; p = 0.004; Table 3; Figure 1B), respectively. The frequency of males hospitalized for HF was 52% in Paraiba and 51% in Brazil.
When stratified by age, individuals older than 60 years old corresponded to 71% and 73% of all the cases of HF admissions in Paraiba and Brazil, respectively, with the highest frequency in the age range from 70 to 79 years old.

Absolute mortality of population
The absolute mortality from HF of the population showed a non-significant decline from 2008 to 2015 in Paraiba (R = -0.513; p = 0.175; Table 2) and Brazil (R = -0.412; p = 0.276; Table 3), with no difference by gender. Women represented 53% of deaths in Paraiba and 52% in Brazil. In Paraiba, the decrease in absolute deaths from HF in the population across all age categories was not statistically significant ( Table 2).
Between 2008 and 2015, the highest proportion of deaths from HF occurred at the age group of ≥ 80 years old in both men and women in Paraiba (50% and 59%, respectively) and in Brazil (38% and 52%, respectively). The proportions of deaths from HF at the age ≥ 60 years old in Paraiba was 87% in men and 90% in women and, in Brazil, 83% in men and 89% in women.

Population mortality rate
The mean mortality rate from HF in the population was 19.

Absolute in-hospital mortality
The absolute in-hospital HF mortality, between 2008 and 2017, showed a significant decrease of 37.5% in Paraiba (R = -0.824; p = 0.013; Table 2; Figure 3B) and a non-significant 14.6% decrease in Brazil (R = -0.504; p = 0.131; Table 3; Figure 3B). In the stratified analysis, a significant decrease in the absolute in-hospital deaths from HF was observed for both men and women in Paraiba (R = -0.837; p = 0.012 and R = -0.762; p = 0.022; Table 2); this statistically significant trend by sex was not observed in Brazil (Table 3).
Further data on the absolute number of in-hospital deaths from HF per age range in Brazil are specified in Table 3.

In-hospital mortality rate
The in-hospital HF mortality rate increased significantly by 65.1% in Paraiba (R = 0.917; p = 0.006; Table 2), from 6.6%  Table 3), from 8.3% in 2008 to 10.8% in 2017 ( Figure 3A). The increase in in-hospital mortality rate from HF by gender was also significant for both men and women in Paraiba (R = 0.828; p = 0.013 and R = 0.908; p = 0.006, respectively; Table 2). This trend was also observed for both sex in Brazil, in a similar magnitude of effect (R = 0.985; R = 0.980; p = 0.003; Table 3).
The in-hospital HF mortality rate per age range was highest in individuals older than 80 years old, with a mean of 14.7% in Paraiba and 14.5% in Brazil ( Figure 5) from 2008 to 2017. In this age range, the in-hospital mortality rate from HF per gender in Paraiba was 12.4% in men and 15.2% in women, and in Brazil, 13.7% in men and 14.9% in women.

Length of hospital stay
The average length of hospital stay for HF was 5.9 days (±0.8) in Paraiba and 6.9 days (±0.4) in Brazil, with a significant increase of 44% (R = 0.953; p = 0.004; Table 2) and 12.3% (R = 0.960; p = 0.004; Table 3), respectively, between 2008 and 2017 ( Figure 6). In Table 4, we present the duration of hospital stay per year, and the associated cost, both in Paraiba and Brazil.

Discussion
To our knowledge, this is the first study to describe the trends of HF epidemiology in a less developed region of Brazil. Information regarding the incidence, prevalence, morbidity    2008-2009, which is consistent with our findings of a 34% decrease in the absolute number of hospitalizations for HF in Brazil, and 62% in Paraiba. This observed reduction can be a sign of improvement in the overall management of the risk factors for HF, 4 a decrease in the incidence of ischemic heart disease, 15 and an improvement in HF management. 16 Hospitalizations for HF in Paraiba and Brazil were more common for individuals between the ages of 70 to 79 years old. Individuals older than 60 years old represented 71% and 73% of admissions for HF in Paraiba and Brazil, respectively; this is similar to the frequency (70%) reported in previous studies in LAC and U.S.. 2,4 In Paraiba and in Brazil, the        10,19 In the U.S., Go et al. 20 compared the absolute number of HF deaths from 1995 to 2010, and found a decrease of 2.8% (287,000 vs 279,000), which potentially represents a significant decrease in the mortality rate, given the increase in the US population over 15 years.
Our study reports a mean in-hospital mortality rate for HF in Paraiba of 9.2% between 2008 and 2017. A prospective study performed in 51 centers from all the Brazilian regions, only with patients hospitalized due to acute HF, reported a total of 12.6% deaths in 1,263 hospitalized patients. 8 In the LAC, a meta-analysis of 37 studies revealed a similar in-hospital mortality of 11.7%. 10 Our study demonstrated an increase in the in-hospital mortality rate for HF, both in Paraiba and in Brazil (65% and 30%, respectively), between 2008 and 2017. Godoy

Year Total cost with hospitalizations (US$) Duration of admission (days) Total cost with hospitalizations (US$) Duration of admission (days)
between 1992-1993 and 2008-2009, also reported a 15% increase in the previous 15% in-hospital mortality rate in Brazil. In the U.S., however, the in-hospital mortality rate decreased from 4.5% in 2001 to 2.9% in 2014 according to a study that included patients with a primary diagnosis of HF. 13 The decrease in the number of hospitalizations for HF during the study period, both in Paraiba and Brazil, is the most likely reason for the increased in-hospital mortality rate. Another plausible explanation could be the increased survival of HF patients, leading to a higher number of elderly patients, with more advanced HF and multiple comorbidities, and increased risk of death during hospitalization. Lastly, it is important to consider the lack of advanced therapies in less developed areas, as mechanical devices and heart transplantation, contributing to this trend of increased HF mortality rate in Paraiba, Brazil and LAC.
Although there was an increase in the in-hospital mortality rate, absolute in-hospital mortality showed a significant decrease of 37.5% in Paraiba and 14.6% in Brazil for the same period. In the U.S., Bueno et al. 21 also observed a 50% decrease in the in-hospital mortality for HF in a population of elderly Medicare patients, from 1993 to 2008, and Ni and Xu, 22 a 30% decrease.
Women represented 53% and 52% of the absolute mortality for HF in Paraiba and Brazil, respectively. The in-hospital mortality for HF in Paraiba had a similar proportion of women (50.5%). In the U.S., in 2010, 54.6% of all HF deaths happened in women. 20 Hsich et al. 23 observed no difference in the in-hospital mortality between women and men considering both the reduced and preserved ejection fraction groups.
Between 2008 and 2017, the mean duration of hospitalization for HF was 5.9 (±0.8) days in Paraiba and 6.8 (±0.4) days in Brazil, with an increase of 44% and 12.3%, respectively. In the LAC, Bocchi et al. 2,24 found a mean hospital stay of 5.8 days between 1998 and 2012. Ciapponi et al. 10 reported an average of 7 days in 18 studies, and Godoy et al. 14 found an increase of 25% in the length of stay, from 8.8 In the U.S., the per capita cost with healthcare was greater than the per capita gross domestic product of Paraiba (US$8,364.00 and US$3,594.94, respectively). 24 The lower socioeconomic status in Paraiba may represent a risk factor for the high morbidity and mortality observed in our study, because the population has limited access to effective HF treatment. 24 In the U.S., 52.5% of people with a household income less than US$10,000 suffer from a cardiovascular disease 20,25 and Eapen et al. 26 found that a higher income was associated with lower odds of 30-day mortality after a HF admission.

Limitations
This is a retrospective and observational study, and the lack of patient-level data limited our ability to establish relationship between variables. Since our data was derived from a national database, it is likely that underreporting and misreporting of data have occurred. Also, since readmissions are not considered in the total number of HF hospitalizations, in-hospital mortality rate may have been underestimated.

Conclusions
This is the first study to analyze the epidemiology of HF in Paraiba, a less developed state of Brazil, and to compare the results with national and international data. Over the last 10 years, the increase of the in-hospital mortality rate for HF in Paraiba and in Brazil followed the LAC trend, whereas the increase in the duration of hospitalization for HF is opposite to the decrease seen in the U.S.. In Paraiba and Brazil, we observed a decrease in admission for HF as primary diagnosis as well as in the absolute in-hospital deaths for HF, agreeing with the LAC and U.S.. More than 87% of the HF deaths in Paraiba and Brazil involved patients older than 60 years old. There was a higher frequency of woman admitted for HF, both in Paraiba and Brazil, with similar mortality rates when compared to men. Since women are generally underrepresented in clinical trials, there is a need for more studies focusing on that population. Hospital-based clinical studies should be performed to identify the causes for the trend of increase in in-hospital mortality rate for HF.

Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.

Sources of Funding
There were no external funding sources for this study.

Study Association
This study is not associated with any thesis or dissertation work.

Ethics approval and consent to participate
This article does not contain any studies with human participants or animals performed by any of the authors.