Association between polypharmacy and socioeconomic and demographic factors in adults aged 50 years and older by Brazilian macroregions

Purpose: This study aimed to investigate the proportions of polypharmacy in the macroregions of Brazil, considering socioe- conomic and demographic factors and their associations. Methods: A cross-sectional analysis was conducted using data from the second wave (2019–2021) of ELSI-Brazil. The outcome was self-reported polypharmacy. Independent variables included sociodemographic, health, and behavioral factors, such as diabetes and hypertension. Descriptive analyses incorporated sample weights, and Poisson regression was employed to assess associations between polypharmacy and the independent variables. Analyses were stratified by the five macroregions of Brazil: North, Northeast, Southeast, South, and Central-West. Results: Regional disparities in the prevalence of polypharmacy were observed. In the Central-West region, rural residents had a 16% lower prevalence of polypharmacy compared to urban residents (PR = 0.84, 95% CI [0.82–0.85]). In the North, non-white individuals had an 8% higher prevalence compared to white individuals (PR = 1.08, 95% CI [1.02–1.15]), while Black individ- uals had an 8% lower prevalence than white individuals (PR = 0.92, 95% CI [0.88–0.96]). Age also associated the prevalence of polypharmacy. Older adults aged 80 years or more had a 14% higher prevalence in the Southeast (PR = 1.14, 95% CI [1.08–1.19]) and a 17% higher prevalence in the South (PR = 1.17, 95% CI [1.08–1.27]) compared to younger age groups.

This study identified regional disparities in polypharmacy prevalence across Brazil’s macroregions, influenced by factors such as age, chronic conditions, and socioeconomic status. Strengthening primary care, promoting rational medication use, addressing inequalities, and integrating prevention strategies are crucial to mitigating its negative impacts. Title: Association between polypharmacy and socioeconomic and demographic factors in adults aged 50 years and older by Brazilian macroregions Short Title : Polypharmacy in different Brazilian regions Authors: Orlando Luiz do Amaral J´ unior1 (ORCID: 0000-0002-6611-3871) Thiago Andr´ e Carniel2 (ORCID: 0000-0002-5040-2556) Vanessa da Silva Corralo2 (ORCID: 0000-0003-4234-4875) F´ atima Kremer Ferretti2 (ORCID: 0000-0002-0326-2984) Clodoaldo Antˆ onio De S´ a2 (ORCID: 0000-0001-7409-8870) Affiliation: 1 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. 1 Universidade Federal de Santa Maria, Postgraduate Program in Dental Sciences, Santa Maria, Brazil 2 Universidade Comunit´ aria da Regi˜ ao de Chapec´ o, Graduate Program in Health Sciences, Chapec´ o, Brazil Corresponding author: Clodoaldo Antˆ onio De S´ a 295-D, Servid˜ ao Anjo da Guarda Street Zip Code: 89809-900, Efapi, Chapec´ o/SC, Brazil. e-mail: [email protected] Telephone: 55 49 3321-8000

Purpose: This study aimed to investigate the proportions of polypharmacy in the macroregions of Bra- zil, considering socioeconomic and demographic factors and their associations. Methods: A cross-sectional analysis was conducted using data from the second wave (2019–2021) of ELSI-Brazil. The outcome was self- reported polypharmacy. Independent variables included sociodemographic, health, and behavioral factors, such as diabetes and hypertension. Descriptive analyses incorporated sample weights, and Poisson regres- sion was employed to assess associations between polypharmacy and the independent variables. Analyses were stratified by the five macroregions of Brazil: North, Northeast, Southeast, South, and Central-West.

Regional disparities in the prevalence of polypharmacy were observed. In the Central-West region, rural residents had a 16% lower prevalence of polypharmacy compared to urban residents (PR = 0.84, 95% CI [0.82–0.85]). In the North, non-white individuals had an 8% higher prevalence compared to white individuals (PR = 1.08, 95% CI [1.02–1.15]), while Black individuals had an 8% lower prevalence than whi- te individuals (PR = 0.92, 95% CI [0.88–0.96]). Age also associated the prevalence of polypharmacy. Older adults aged 80 years or more had a 14% higher prevalence in the Southeast (PR = 1.14, 95% CI [1.08– 1.19]) and a17% higher prevalence in the South (PR = 1.17, 95% CI [1.08–1.27]) compared to younger age groups. Conclusion: This study identified regional disparities in polypharmacy prevalence across Brazil’s macroregions, influenced by factors such as age, chronic conditions, and socioeconomic status. Strengthe- ning primary care, promoting rational medication use, addressing inequalities, and integrating prevention strategies are crucial to mitigating its negative impacts.

Polypharmacy, Regional disparities, Sociodemographic factors. 11pt, fleqn, a4paper, ]LegrandOrangeBook Key points • Polypharmacy prevalence varies across Brazilian macroregions. • Older adults ( >80 years) showed the highest prevalence of polypharmacy. • Diabetes and hypertension are strong predictors of polypharmacy. • Regional disparities may reflect healthcare access and socioeconomic differences. • Addressing these disparities is essential to improving elderly care. 11pt, fleqn, a4paper, ]LegrandOrangeBook Plain Language Summary This study examined the use of multiple medications, known as polypharmacy, in Brazilian adults aged 50 and older. Using national data from the ELSI-Brazil survey, researchers analyzed differences by region and looked at how factors like age, income, education, and chronic diseases such as diabetes and hypertension were linked to polypharmacy. Results showed that older adults and those with chronic conditions were more likely to use many medications, especially in the South and Southeast regions. People in rural areas and with higher education had lower rates. The study highlights the need to improve access to healthcare, promote rational medicine use, and reduce inequalities in different parts of the country to improve health and safety for older people.

2 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. Population aging presents complex challenges for health systems, particularly in developing countries (1). This demographic shift has led to a growing proportion of older adults with healthcare needs that often require long-term management and specialized care (2). Consequently, there has been a significant rise in chronic disease prevalence, increasing the demand for continuous care and contributing to higher medication use. Health systems must therefore adapt to the expanding need for long-term care, integrated services, and sustainable health policies(3). Polypharmacy is commonly defined as the concurrent use of five or more medications (4). Among older adults, it is particularly concerning due to its high prevalence, often attributed to the increasing incidence and co-occurrence of chronic conditions in this population (5). Although the use of multiple medications may be clinically justified in some cases, it significantly raises the risk of adverse effects and drug interactions, and may compromise treatment adherence, patient safety, and quality of life (6). Moreover, excessive or inappropriate medication use is considered a risk factor for frailty and adverse health outcomes (4,6). The prevalence and profile of polypharmacy vary substantially depending on demographic, socioeconomic, and educational characteristics, as well as self-perceived health status (7). Given the complex interplay among these factors, it is essential for studies to consider regional characteristics and how these variables influence polypharmacy patterns (7,8). This is particularly relevant in Brazil, a country with vast territorial extension and marked geographical, social, economic, and cultural disparities (9). Understanding the multifactorial determinants of polypharmacy, especially across different socioeconomic and geographic contexts, is crucial for the development of effective public health policies aimed at promoting the rational use of medications and minimizing the risks associated with polypharmacy in older adults. Motivated by these considerations, this study aims to investigate factors associated with polypharmacy prevalence across Brazil’s macroregions, using data from the Brazilian Longitudinal Study of Aging (ELSI- Brazil), which includes sociodemographic, economic, and health data from a nationally representative sample of adults aged 50 years and older. .

Study design and population This study is a cross-sectional analysis based on secondary data from the second wave (2019–2021) of the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a study that collects data on the health of Brazilian adults aged 50 and over which (10). ELSI-Brazil follows a similar methodology to other longitudinal studies on ageing around the world, allowing for international comparisons. Sample construction was guided by data from the 2010 Demographic Census provided by the Brazilian Institute of Geography and Statistics (IBGE). Stratified sampling was applied, categorizing municipalities by population size. In municipalities with populations of up to 750,000 residents, selection proceeded in three stages (municipality, census tract, and household); in larger municipalities, a two-stage approach was used (census tract and household). Data were collected from residents across 70 municipalities spanning all Brazilian regions. The final sample of ELSI-Brazil (2019-2021) consisted of 9,849 non-institutionalized individuals aged 50 and older, representing the national population in this age group. 10 The baseline assessment included four components: household and individual interviews, physical measurements and blood sample collection and analysis. Although all four components were assessed, only the household and individual interview components were used for this study. Further information on the sampling design and methodology employed in ELSI–Brazil can be found elsewhere [http://elsi.cpqrr.fiocruz.br/]. The ELSI–Brazil study received approval from the Research Ethics Committee of the Ren´ e Rachou Institute, Oswaldo Cruz Foundation (CAAE: 34649814.3.0000.5091), and all participants provided informed consent prior to their involvement in the study (10,11). Measures Outcome 3 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. The outcome of this study was self–reported polypharmacy, assessed by the following question: ’How many regular or continuous medications have you taken in the last two weeks?’ The variable was categorized into two groups: no medication or up to four medications and the use of five or more drugs. Polypharmacy was defined as the use of five or more drugs in the last two weeks (4). Exposure variables The independent variables included in this study were selected based on the social determinants of health model proposed in previous studies (12, 13). In addition, sociodemographic variables were considered, in- cluding urban/rural residence, sex (male/female), age groups (50-59, 60-69, 70-79, 80 or older), skin color (white, black, and brown), education level (up to 8 years of schooling or more than 8 years of schooling), and per capita income, which was categorized into quintiles. Variables related to health conditions and behavioral factors were also included, such as the diagnosis of diabetes and hypertension, both categorized as ’yes’ or ’no’; health insurance status (yes/no); and the use of medical services in the past 12 months (yes/no). This variable was used in a previous study (14). Statistical analysis Data analysis was performed using STATA 14.0 (Stata Corporation, College Station, TX, USA). A descriptive analysis incorporating sampling weights was carried out, followed by an examination of the associations between polypharmacy and socioeconomic and demographic factors using Poisson regression. To take account of the complex sampling design, the data was weighted, and the design effect was incorporated using Survey Data Analysis in STATA. Moverover, the goodness-of-fit was assessed to ensure a reliable fit of the data to Poisson’s model. Adjusted prevalence ratios (PR) were calculated, with a 5% significance threshold. All analyses were stratified by the five geographic macroregions of Brazil: North, Northeast, Southeast, South, and Central-West. The range of values within brackets presented henceforward represents 95% confidence intervals (95% CI).

The final sample included 6,917 participants who responded to the analyzed outcome. Table 1 shows the descriptive data and the proportions of polypharmacy among Brazilian adults, highlighting variations bet- ween gender, skin color, schooling and chronic conditions such as diabetes and hypertension. The highest proportion of polypharmacy was in individuals with lower levels of education (78.0% with up to 8 years of study) and in those diagnosed with hypertension (74.7%). In contrast, lower proportions were observed in individuals with health insurance (23.8%) and in those who used medical services in the last 12 months (90.3%). Table 2 presents the results of the Poisson regression for socioeconomic and demographic factors, including unadjusted and adjusted analyses. In the adjusted analysis, significant associations were found for the Sou- theast region (PR=2.29, [1.64–3.19]), South region (PR=2.55, [1.76–3.68]), Central-West region (PR=2.08, [1.42–3.05]) and rural area (PR=0.90, [0.81–1.00]). Furthermore, age 70–79 (PR=1.33, [1.18–1.50]), diagno- sis of diabetes (PR=2.08, [1.93–2.24]), diagnosis of hypertension (PR=1.39, [1.20–1.60]) and use of medical services in the last 12 months (PR=1.65, [1.40–1.95]) showed a higher prevalence ratio being associated with polypharmacy. Table 3 presents the proportions of polypharmacy by socioeconomic and demographic factors, stratified by Brazilian macroregions. Rural areas in the Southeast (27.7%, [23.5–32.2]) and South (28.1%, [21.5–35.9]) had the highest proportions of polypharmacy, while urban areas, mainly in the North (5.4%, [1.4–18.6]) and Central-West (4.7%, [-]), had relatively lower proportions. The proportions of polypharmacy were notably higher among individuals aged 80 years or older, particularly in the South (46.8%, [26.9–67.8]) and Southeast (41.8%, [35.0–49.0]). Individuals with diabetes or hypertension had higher proportions of polypharmacy, especially in the Southeast (45.4%, [37.7–53.4] for diabetes and 32.3%, [28.4–36.3] for hypertension) and in the South (46.9%, [36.4–57.7] for diabetes). Higher proportions of polypharmacy were observed among black individuals in the Southeast (33.9%, [24.0–45.4]) and brown individuals in the South (30.7%, [21.9–41.1]). 4 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. Furthermore, individuals with health insurance reported higher proportions of polypharmacy, particularly in the Midwest (31.2%, [23.7–39.9]). Some confidence intervals overlapped, suggesting that the observed differences between groups may not be statistically significant. Table 4 presents Poisson regression analyses with robust variance for the associations between socioeconomic and demographic factors and polypharmacy proportions in the five Brazilian macroregions. The adjusted prevalence ratios (PR) and 95% confidence intervals (CI) are provided. Rural residents in the Central-West region had a significantly lower polypharmacy prevalence ratio (PR = 0.84, [0.82–0.85]) compared to urban residents, suggesting that rural living is associated with a lower likelihood of polypharmacy in this region. In the North region, mixed-race individuals had a higher polypharmacy prevalence ratio (PR = 1.08, [1.02–1.15]) compared to white individuals, while black individuals had a lower prevalence ratio (PR = 0.92, [0.88–0.96]) compared to white individuals. Age was significantly associated with polypharmacy, with individuals aged 80 years or older showing higher prevalence ratios in the Southeast (PR = 1.14, [1.08–1.19]) and South (PR = 1.17, [1.08–1.27]) regions compared to the reference group (50–59 years). Similarly, individuals aged 70–79 years in the Southeast (PR = 1.08, [1.03–1.14]) and South (PR = 1.11, [1.05–1.18]) regions had higher polypharmacy prevalence ratios compared to the reference group. Regarding education level, individuals with more than 8 years of schooling in the Central-West region had a lower polypharmacy prevalence ratio (PR = 0.94, [0.89–0.99]) compared to those with 8 or fewer years of schooling. This indicates that higher education is associated with a lower likelihood of polypharmacy in this region. Diabetes was consistently associated with higher polypharmacy prevalence ratios across all regions. Prevalence rates ranged from (PR = 1.19 [1.13–1.24]) in the North to (PR = 1.22 [1.18–1.27]) in the Central-West region, highlighting a strong and consistent association between diabetes and polypharmacy (Figure 1).

The demographic transition poses significant challenges for health systems at a global and local level as populations age, with an increasing number of individuals living longer and having to live with a greater number of chronic diseases. 1 In Brazil, this trend is particularly pronounced due to the rapid ageing of the population and the concomitant increase in chronic diseases, in addition to infectious and external causes (triple burden of disease), which contribute to the high prevalence of polypharmacy among older adults (15). This study highlights that polypharmacy is especially prevalent among those aged 80 years and older, a group that often deals with chronic conditions such as hypertension and diabetes. These conditions require complex medication regimens, increasing the risks of adverse drug reactions and potentiating drug-drug interactions. Regional disparities in the prevalence of polypharmacy were evident in this study, suggesting the role of sociodemographic factors in clinical outcomes. The Southeast and South regions have the highest rates, particularly among older age groups, while the Central-West region and rural areas have lower prevalence, potentially reflecting barriers to access to health care. Chronic conditions such as diabetes and hypertension emerge as consistent determinants of polypharmacy across all regions. Furthermore, disparities in educational level and income may suggest the role of socioeconomic inequalities in shaping access to medicines and health services. These findings highlight the importance of considering regional and individual determinants for the development of interventions to manage polypharmacy in Brazil (5, 7). Given these disparities, targeted interventions are crucial to ensure equitable access to medications and healthcare services (16). To comprehensively address polypharmacy in the Brazilian context, it is essential to implement evidence-based strategies that consider the specific characteristics of the country’s macro- regions (15,17). Regular prescription review programs and the strengthening of primary healthcare services, focusing on the integrated management of chronic conditions, can play a significant role (18). Additionally, preventive measures and health promotion strategies targeting modifiable risk factors such as unhealthy diets, physical inactivity, and tobacco use are crucial to reducing the burden of chronic diseases that drive polypharmacy (19). Health education initiatives should empower individuals to take greater control of their health by adopting healthier lifestyles and encourage discussions about treatment goals with healthcare providers (20). 5 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. A regionalized approach to the problem of polypharmacy is fundamental for the development of policies suited to the characteristics of each locality, enabling more effective actions, optimizing resource use, and improving older adults care, who are more prone to the adverse effects of medicines and their interactions (21). Training healthcare professionals in deprescribing protocols and shared decision-making models, along with public health campaigns and community programs, taking into account local characteristics, can improve medication management and raise awareness about the risks of polypharmacy, such as drug interactions and adverse reactions, as well as the costs to the healthcare system (22). This issue is particularly urgent in low- and middle-income countries such as Brazil, where disparities in access to health services exacerbate the challenges posed by the growing prevalence of chronic conditions that require complex medication regimens (23). A proactive, multidisciplinary strategy integrating clinical practices, health education, and evidence- based policies is essential to optimize medication place safety, reduce the risks associated with polypharmacy, and improve health outcomes and quality of life for older adults (24). The study has some limitations. The cross-sectional design does not allow for causal inferences between polypharmacy and associated factors. In addition, the reliance on secondary data may limit control over the data collection processes. However, the use of a nationally representative sample increases the generalizability of the study, providing valuable information on the epidemiological characteristics of polypharmacy in Brazil, a country with significant regional diversity. Understanding these dynamics is essential for developing effective strategies to address polypharmacy and its implications for the health of the older adults in Brazil (17). In conclusion, this study suggests significant disparities in polypharmacy between Brazil’s macro-regions, with factors such as age, gender, place of residence, presence of diabetes and hypertension, skin color, and income associated polypharmacy differently across the South, Southeast, Midwest, North, and Northeast regions. Given these disparities, targeted interventions are crucial to ensure equitable access to medications and healthcare services. Efforts should focus on strengthening primary healthcare, promoting the rational use of medicines, and reducing regional inequalities. Integrating health promotion and disease prevention strategies targeting modifiable risk factors can help address the root causes of polypharmacy. By adapting interventions to local needs and fostering collaboration across health sectors, it is possible to mitigate the risks associated with polypharmacy, enhance health outcomes, improve quality of life for older adults, and contribute to a more equitable health system. Conflict of Interest Statement The authors declare no conflict of interest. Data Availability Statement Data will be made available upon request to the corresponding author. 11pt, fleqn, a4paper, ]LegrandOrangeBook Author contributions Conception and design of study: De S´ a, CA; Do Amaral J´ unior, OL;Carniel, TA; Ferretti, FK; Corralo, VS. Analysis and/or interpretation of data: De S´ a, CA;Do Amaral J´ unior, OL;Carniel, TA. Drafting the manuscript: De S´ a, CA; Do Amaral J´ unior, OL; Carniel, TA; Ferretti, FK; Corralo, VS. Approval of the version of the manuscript to be published: De S´ a, CA;Do Amaral J´ unior, OL;Carniel, TA; Ferretti, FK; Corralo, VS.

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Polypharmacy and trajectories of health-related quality of life in older adults: an Australian cohort study.Quality of Life Research . 2022; 31(9):2663-2671. doi:10.1007/s11136-022-03136-9 Figure 1. Prevalence ranking of polypharmacy according to socioeconomic and demographic variables across Brazilian macroregions. The figure illustrates the adjusted prevalence ratios (PR) derived from Poisson regression models, highlighting differences in polypharmacy among subgroups stratified by region. Variables include age group, skin color, educational level, presence of diabetes and hypertension, urban/rural residence, and use of health services. 7 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. Skin (Black)Diabetes (Yes)Income (Q4)Insurance (Yes) Education (>8 years) Age (60-69) Hypertension (Yes)Med. Services (Yes) Sex (Female)Zone (Urban)Skin (White)Sex (Male)Age (50-59)Insurance (No)Income (Q3)Age (70-79)Skin (Brown)Age (>80)Income (Q1) Education (<8 years)Hypertension (No) Income (Q2)Income (Q5)Diabetes (No)Zone (Rural) Med. Services (No) 0 10 20 30 40 50Prevalence [%] North Diabetes (Yes)Age (70-79)Insurance (Yes)Income (Q5)Skin (Black) Education (>8 years)Hypertension (Yes) Zone (Urban)Sex (Female) Med. Services (Yes) Income (Q4)Income (Q3)Skin (Brown)Age (60-69)Insurance (No)Income (Q1) Education (80)Income (Q2)Skin (White)Sex (Male)Zone (Rural)Diabetes (No) Hypertension (No)Med. Services (No) 0 10 20 30 40 50Prevalence [%] Northeast Diabetes (Yes)Insurance (Yes)Income (Q1)Income (Q4) Med. Services (Yes) Age (50-59) Education (80)Skin (Brown)Sex (Male) Insurance (No)Skin (Black) Hypertension (No) Age (60-69) Education (>8 years) Diabetes (No)Income (Q5) Med. Services (No) Zone (Rural) 0 10 20 30 40 50Prevalence [%] Central West Diabetes (Yes) Age (>80)Age (70-79)Skin (Black)Income (Q3) Hypertension (Yes) Income (Q1)Income (Q2) Education (8 years)Hypertension (No)Med. Services (No) 0 10 20 30 40 50Prevalence [%] Southeast Diabetes (Yes) Age (>80)Age (70-79)Skin (Black)Income (Q2)Skin (Brown)Income (Q1) Education (<8 years)Med. Services (Yes) Zone (Urban)Insurance (Yes)Sex (Female) Hypertension (No) Income (Q4)Insurance (No) Hypertension (Yes) Skin (White)Income (Q3)Income (Q5)Sex (Male)Diabetes (No)Age (60-69)Zone (Rural)Age (50-59) Education (>8 years)Med. Services (No) 0 10 20 30 40 50Prevalence [%] South Hosted file pds-25-0441-File003.docx available at https://authorea.com/users/938410/articles/1308570- association-between-polypharmacy-and-socioeconomic-and-demographic-factors-in-adults- aged-50-years-and-older-by-brazilian-macroregions Hosted file pds-25-0441-File004.docx available at https://authorea.com/users/938410/articles/1308570- association-between-polypharmacy-and-socioeconomic-and-demographic-factors-in-adults- aged-50-years-and-older-by-brazilian-macroregions Hosted file 8 Posted on 25 Jun 2025 — The copyright holder is the author/funder. All rights reserved. No reuse without permission. — https://doi.org/10.22541/au.175082604.40096984/v1 — This is a preprint and has not been peer-reviewed. Data may be preliminary. pds-25-0441-File005.docx available at https://authorea.com/users/938410/articles/1308570- association-between-polypharmacy-and-socioeconomic-and-demographic-factors-in-adults- aged-50-years-and-older-by-brazilian-macroregions Hosted file pds-25-0441-File006.docx available at https://authorea.com/users/938410/articles/1308570- association-between-polypharmacy-and-socioeconomic-and-demographic-factors-in-adults- aged-50-years-and-older-by-brazilian-macroregions 9