Association between health‐related quality of life and nonadherence to antihypertensive medication

Abstract Aim We aimed to examine the association between nonadherence to antihypertensive medications and Health‐related quality of life. Design A cross‐sectional survey was undertaken. Methods This study was conducted using the data from the Korea National Health and Nutrition Examination Survey. A total of 6493 participants who diagnosed with hypertension, affected by hypertension at the time of survey, and took daily antihypertensive medications or never took this medication were included. Multiple logistic regression analysis was performed to determine the factors that influenced the patients' nonadherence to antihypertensive medications according to sex. Results Our results showed that anxiety/depression was positively associated with antihypertensive medication nonadherence, regardless of sex. According to sex, mobility was negatively associated with antihypertensive medication nonadherence in women. In men, living together was negatively related to antihypertensive medication nonadherence. This study showed the factors associated with antihypertensive medication nonadherence according to sex. HRQoL was associated with antihypertensive medication nonadherence.

Low adherence to antihypertensive medication is a noteworthy barrier in managing hypertension (Holt et al., 2010). Results of the meta-analysis of randomized controlled trials showed that antihypertensive drugs reduced blood pressure and alleviated the risk of cardiovascular diseases (Blood Pressure Lowering Treatment Trialists Collaboration, 2021). Another meta-analysis study reported that antihypertensive medication adherence is associated with various factors, including socioeconomic factors, such as age, civil status, education, and work status; patient-related factors, such as health literacy and awareness, knowledge of hypertension, attitude toward hypertension, self-efficacy, and social support; therapy-related factors, such as drug schedule, drug usage, and alternative medicine; and condition-related factors, such as illness perception and comorbidity (Gutierrez & Sakulbumrungsil, 2021).
Antihypertensive medication adherence was associated with reduced alcohol intake and absence of co-morbidity (Asgedom et al., 2018). Furthermore, other previous studies reported that sex is a significant factor that affects the adherence to antihypertensive drugs (Biffi et al., 2020;Chen et al., 2014).

Among various factors, health-related quality of life (HRQoL)
focuses on the impact of health status on the quality of life as a multidimensional concept, including physical, mental, and social well-being (Yin et al., 2016). HRQoL and treatment adherence are interrelated in patient management and care (Kastien-Hilka et al., 2017). A previous study conducted on patients with tuberculosis in South Africa reported a positive association between treatment adherence and HRQoL (Kastien-Hilka et al., 2017). Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension had an impact on the ability to perform daily activities (Delcroix & Howard, 2015;Ivarsson et al., 2019). In one of the results of the EuroQol 5-Dimension Questionnaire (EQ-5D) survey to evaluate HRQoL, patients with a low EQ-5D index expressed more concerns about their treatment (Ivarsson et al., 2019). In particular, the management of hypertension is closely associated with HRQoL because hypertension is a chronic disease that requires consistent management. Several studies have reported that the treatments for hypertension may worsen the HRQoL (Arslantas et al., 2008;Soni et al., 2010;Xu et al., 2016). However, a low HRQoL is attributed to an individual's awareness of hypertension; thus, having a low HRQoL may also reduce treatment adherence (Xu et al., 2016). Thus, the bidirectional associations between adherence to hypertensive treatment and HRQoL should be considered, and sex differences are an important issue affecting the HRQoL. A study reported a significant sex difference in HRQoL among people with human immunodeficiency virus on antiretroviral treatment (Tesfay et al., 2015). Women with coronary artery disease showed worse HRQoL compared with men (Norris et al., 2008).
Thus, this study aimed to examine the association between nonadherence to antihypertensive medication and HRQoL. The results of this study can serve as a basis for managing HRQoL to improve patients' adherence to antihypertensive medication.

| Data source and participants
This study was conducted using the 5-year data from the 2016- Of the 39,738 respondents, 6493 who diagnosed with hypertension, affected by hypertension at the time of survey, and took daily antihypertensive medications or never took this medication were included in this study ( Figure 1). Patients with missing data were excluded.

| Variables
The following variables were used in this study: age, sex (male or female), education level (elementary school or below, middle school, high school, university, or above), occupation, household income (lowest, lower middle, upper middle, or highest), residential area (urban or rural), drinking (no or yes), smoking (no or yes), body mass index (BMI), cohabitation, EuroQol five-dimensions (EQ-5D) scores, and antihypertensive medication adherence. In terms of occupation, the participants were divided into four groups based on the major classifications of the 6th Korean Standard Classification of Occupations: white-collar workers included managers, professionals, and office workers; pink-collar workers included service and sales workers; blue-collar workers included technicians and device and machine operators; agribusiness and low-level workers included skilled workers in agriculture and fishery and low-level laborers; and the unemployed included homemakers (Kwon et al., 2019). The BMI was classified into four groups: normal (18.5-24.9 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), obesity (≥30.0 kg/m 2) , and underweight (<18.5 kg/m 2 ). Cohabitation was re-categorized as living alone and living with two or more people. The EQ-5D was used to assess the HRQoL. Using this tool, the patients' health status was evaluated on all five dimensions: mobility (EQ1), self-care (EQ2), usual activities (EQ3), pain/discomfort (EQ4), and anxiety/depression (EQ5). Each dimension has three response levels: no problem, some problems, and extreme problems. However, this study only analysed the following two levels: no problem and problems (including some and extreme problems). Adherence to antihypertensive medication was categorized into two groups: taking daily medication and never taking medication. Those participants who only partially took the medication each month were excluded from this study.

| Statistical analysis
All statistical analyses were performed using the IBM SPSS Statistics version 26 (IBM). A chi-square test or t-test was performed to assess the differences in the participants' characteristics according to medication adherence. The categorical variables were expressed as numbers and percentages, while the continuous variables were expressed as means and standard deviations. Furthermore, logistic regression analysis was performed to determine the factors associated with nonadherence to antihypertensive medication according to sex. A p value of <0.05 was considered significant. Table 1 shows the general characteristics of the 6493 hypertensive participants. Among them, 46.2% were men and 53.8% were women. Of the 2997 male participants, 87.8% responded that they lived with two or more people. Approximately 74.5% of women lived with two or more people. Of the male participants, 21.4% responded that they had problems with mobility (EQ1), 6.5% with self-care (EQ2), 11.4% with usual activities (EQ3), 23.1% with pain/discomfort (EQ4), and 8.9% with anxiety/depression (EQ5). Of the female participants, 37.6% responded that they had problems with mobility, 10.2% with self-care, 19.4% with usual activities, 40.0% with pain/ discomfort, and 16.5% with anxiety/depression. Table 2 presents the characteristics of the participants according to adherence to antihypertensive medication in men and women. In men, antihypertensive medication nonadherence showed significant differences in terms of age, education level, occupation, smoking, cohabitation, and anxiety/depression (EQ5). In women, antihypertensive medication nonadherence showed significant differences in terms of age, education, occupation, and mobility (EQ1).

| DISCUSS ION
In this study, we focused on determining the factors related to antihypertensive medication nonadherence according to sex. Our results F I G U R E 1 Flow chart of the study population selection.
showed that anxiety/depression was positively associated with antihypertensive medication nonadherence, regardless of sex. According to sex, mobility was negatively associated with antihypertensive medication nonadherence in women, but not in men. In men, living together was negatively related to antihypertensive medication nonadherence. These results may serve as a basis for selecting the appropriate nurse-based interventions to improve medication adherence.
Health-related quality of life is a multidimensional concept related to physical, psychological, and social functioning that is affected by disease and/or treatment (Megari, 2013). In general, chronic diseases negatively affect the quality of life as long-term treatment and management continue. Hypertension, which is one of the common chronic diseases, is closely associated with the HRQoL (Soni et al., 2010). Hypertension awareness was associated with lower HRQOL in hypertensive patients (Mi et al., 2015). On the contrary, hypertensive patients with poor HRQoL had more concerns about treatment and lower coping ability (Ivarsson et al., 2019).
Lower HRQoL affects medication adherence, which is important for managing hypertension (Holt et al., 2010). Overall, poor HRQoL is related to severe hypertension (Alsaqabi & Rabbani, 2020). The bidirectional associations between hypertension and HRQoL may lead to a vicious cycle. Thus, the HRQoL is important for improving adherence to antihypertensive medication.
EuroQol 5-Dimension Questionnaire, which is used to assess HRQoL, comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, poor adherence to antihypertensive medication was associated with increased levels of anxiety and depression. Nonadherence to medication is a major issue in the treatment of major depressive disorders (Ho et al., 2017). A previous qualitative study reported that the facilitators of antidepressant adherence were insight, perceived health benefits, and regular activities (Ho et al., 2017). These depressive symptoms affect the antihypertensive medication adherence of all participants as they affect cognitive insight and regular activities (Minaeva et al., 2020;Palmer et al., 2015). In this study, poor mobility significantly lowered antihypertensive medication nonadherence in women. Views on sex-based differences in medication adherence vary, but this remains an important issue (Chen et al., 2014;Kitaoka et al., 2016;Mahmoodi et al., 2019;Soni et al., 2010;Xu et al., 2016).
No sex difference was observed in the medication adherence among adolescent kidney transplant recipients, but women showed better medication adherence than men among young adults (Boucquemont et al., 2019). A previous study reported that women with hypertension were more at risk of poor HRQoL than men (Xiao et al., 2019).
Another study reported that women with hypertension had lower general health perceptions, while hypertension was related to higher social functioning in men (Kitaoka et al., 2016). In this study, explaining the relationship between poor mobility in HRQoL and low antihypertensive medication nonadherence in women remains challenging.
However, psychological factors, such as anxiety and depression, act as risk factors for increased hypertensive medication nonadherence, while physical factors, such as poor mobility, act as warning signs to lower hypertensive medication nonadherence.
Another interesting finding is that living together was related to lower antihypertensive medication nonadherence among men.
Medication adherence is closely associated with social support, such as family and friends, in patients with hypertension (Scheurer et al., 2012;Shahin et al., 2021). Another study reported that social support was related to adherence to depression treatment according to gender and race (Gerlach et al., 2017). This study showed that men with hypertension were more susceptible to receiving social support than women with antihypertensive medication nonadherence.

| Implication
In particular, nurse-based interventions are important to improve medication adherence and manage the HRQoL (Chow & Wong, 2010;Dijkstra et al., 2021). The medication adherence support intervention provided by home care nurses increased satisfaction and improved the self-management of medication (Dijkstra et al., 2021). The nurse-based case management program was effective in improving the HRQoL of peritoneal dialysis patients (Chow & Wong, 2010). Thus, the results of this study may serve as a basis for determining the appropriate nursing interventions by understanding the factors associated with antihypertensive medication adherence.

| Limitation
However, our cross-sectional study has limitations in elucidating the association between HRQoL and adherence to

| CON CLUS ION
This study showed the factors associated with antihypertensive medication nonadherence according to sex. HRQoL was associated with antihypertensive medication nonadherence. Understanding the factors associated with medication adherence may help determine the appropriate nursing intervention. Our results can serve as a basis for managing the health-related quality of life to improve adherence to antihypertensive medication.

ACK N O WLE D G E M ENTS
We would like to thank everyone who participated in this study, especially, the author appreciates Gachon University and AMOREPACIFIC Foundation.

FU N D I N G I N FO R M ATI O N
This research has been supported by the AMOREPACIFIC Foundation.

CO N FLI C T O F I NTE R E S T
The authors declare that they have no competing interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data used were from the 2016-2020 Korea National Health and Nutrition Examination Survey conducted by the Division of Health and Nutrition Survey of the Korea Disease Control and Prevention Agency.