Level of Hypertension Treatment Adherence During COVID-19 Pandemic

Background: Arterial hypertension is prevalent and remains one of the most signicant causes of mortality worldwide. Over 1.7 million Bulgarians (24%) have a blood pressure (BP) value equal to or higher than 140/90 mmHg and therefore are at increased risk of complications. Adherence to antihypertensive medications is the cornerstone for achieving hypertension control. Methods: The aim of this study was to assess whether the patients of both sexes with hypertension exhibit equal adherence to medication during the COVID-19 pandemic and to explore how the pandemic has affected the adherence of patients with high BP to prescribed antihypertensive drugs. This multicentre observational study utilized self-completed questionnaires among patients visiting several healthcare centres, including the cardiology outpatient clinic of a university hospital, a private cardiology practice, general practice oces, and a pharmacy between June and November 2020. Results: nonparametric hypothesis testing, chi-square test for analysis of two-dimensional distributions and association measures (contingency factor). The critical signicance level used was α < 0.05.

Hypertension is prevalent and remains one of the most signi cant causes of mortality worldwide. Every year, it accounts for approximately 7.5 million deaths worldwide and has harmful consequences, especially in countries with poor health policies [3]. Elevated blood pressure (BP) is a major risk factor for coronary artery disease and its complications, including heart failure, stroke, renal insu ciency, and blindness, in diabetic patients. The Global Burden of Disease study estimated that hypertension is now the leading risk factor for disability-adjusted life years worldwide [4]. According to the WHO, over 30% of the world's population suffers from hypertension (high blood pressure). Hypertension is the leading risk factor for myocardial infarction and stroke. Poor blood pressure control is the cause of 62% of all cerebrovascular accidents. Over 1.7 million (24%) Bulgarians have a blood pressure value equal to or higher than 140/90 mmHg and therefore are at increased risk of complications.
Healthy lifestyle choices can prevent or delay the onset of high BP and can reduce cardiovascular risk [5].
The risk of developing hypertension can be reduced by effective medication therapy management and signi cant lifestyle modi cations. Adherence to antihypertensive medications is the cornerstone for achieving hypertension control.
Adherence is de ned as the extent to which a person's behaviours, such as taking a medication, following dietary or lifestyle changes, correspond with agreed recommendations from a healthcare provider [6]. Low adherence is one of the main causes of therapy failure worldwide [7][8][9]. Non-adherence to antihypertensive treatment affects 10-80% of hypertensive patients and is one of the key drivers of suboptimal BP control [10][11][12]. Poor adherence to antihypertensive treatment correlates with the magnitude of BP elevation and is an indicator of poor prognosis in hypertensive patients. The aetiology of non-adherence to antihypertensive treatment is multifactorial and includes the healthcare system, the pharmacological therapy, the disease, the patient and their socioeconomic status.
Concerns have been raised about the cost of non-adherence, medication and resource waste and lack of effective strategies for preventing cardiovascular disease [13].
Self-reported scales are the most commonly used instruments to assess medication adherence in research and in clinical practice [14,15].
The Medication Adherence Report Scale (MARS-5, ©Professor Rob Horne) -a shorter form of MARS-10 -comprises items which describe a range of nonadherent behaviours, with items phrased in a nonthreatening and nonjudgmental way to normalise nonadherence, and a response scale that allows the categorisation of patients in terms of their position along the "adherence dimension" rather than on the basis of a "yes/no" or "high/low" dichotomous response, thus providing more detail and differentiation between individuals. MARS-5 follows the same structure as MARS-10 and asks respondents to rate the frequency with which the ve different medication-taking behaviours occur, scoring each item on a vepoint scale (5 = never, 4 = rarely, 3 = sometimes, 2 = often, 1 = very often), with higher scores indicating higher reported adherence. [16][17] Methods Considering the aforementioned facts, our study sought to test the hypothesis that patients of both sexes with hypertension exhibit equal adherence to medication during the COVID-19 pandemic and to explore how the pandemic has affected the adherence of patients with high BP to prescribed antihypertensive drugs. We believe that the ndings of this study will be bene cial for health care providers who deal with patients suffering from hypertension under the current conditions and will help them aid their patients in achieving good BP control. This multicentre observational study utilized self-completed questionnaires to assess medication adherence among patients visiting several healthcare centres, including the cardiology outpatient clinic of a university hospital, a private cardiology practice, general practice o ces, and a pharmacy between June and November 2020. Patients from the cities Varna and Plovdiv were recruited. Overall, 442 patients were included in the study. The inclusion criteria were patients aged greater than 18 years with hypertension who were undergoing treatment. The Ethics Committee of the Medical University of So a approved the study protocol. All participants provided written informed consent before entering the study, and the answers to all questionnaires were anonymized before evaluation. Primary data was collected through standard interviews, which included 13 questions about demographic data of the respondent, characteristics of the disease, comorbidities, risk factors, and blood pressure values. The likelihood of adherence was assessed using the Medication Adherence Report Scale (MARS-5, ©Professor Rob Horne) -a shorter form of MARS-10 with higher scores indicating higher reported adherence which was created and validated by Horne et al. [16]. The Medication Adherence Report Scale was translated into Bulgarian and standardized by forward translation, backward translation, and a pretest.
Face-to-face interviews with the patients were completed by the research team members.
The data were coded and statistically analysed using the IBM SPSS ver.21.0 software package. Statistical analyses included one-dimensional and two-dimensional frequency distributions; summarization of statistical quantities; the Kolmogorov-Smirnov test, which was used to check the normality of the distribution of measured traits; parametric tests to test hypotheses with respect to mean values (t-test for independent samples and analysis of variance (ANOVA)); nonparametric hypothesis testing, chi-square test for analysis of two-dimensional distributions and association measures (contingency factor). The critical signi cance level used was α < 0.05.

Results
In total, 442 respondents took part in the survey, 57% (252) of whom were from Plovdiv and 43% (190) of whom were from Varna. The sex distribution of the whole sample was 51.1% male and 48.9% female. Two-dimensional distribution by sex and place of residence showed the following: -In Varna, 54.2% of the individuals who participated in the survey were men, and 45.8% were women.
-In the city of Plovdiv, men accounted for 48.8% of the individuals who participated in the survey, and women accounted for 51.2% of these individuals.
The sample included respondents aged 19 to 91 years. The mean age of the respondents was 62.65, and the most common age was 60. The mean age of men was higher than that of women (63.96 vs. 61.27) (t = 2,069, p = 0.039). (Table 1)  The one-dimensional frequency distribution of the grouped age data showed that the respondents from 60 to 69 years of age comprised the largest relative share of the sample, representing almost 1/3 of the entire sample.
One in ve (20.8%) respondents indicated that they were in the rst stage of hypertension, but the majority (62.9%) of respondents did not know the stage of their disease.
More of the patients who knew the stage of their disease were women than men (Pearson chi-square = 4,572, p = 0.033). For example, 32.3% of the surveyed men indicated the stage, while this percentage was 42.1% for women.
Among men who knew the stage of their disease, the percentage of those in the rst stage (46.6%) was the highest. The percentage of patients in the rst stage was also the highest among women who knew the stage of their disease, but this percentage was higher at 63.7%.
The average duration of the disease was 10.15 years, and the most common disease duration was 2 years (12.6% of respondents). The sample included respondents who ranged from being relatively recently diagnosed (1 month) to having the disease for more than 20 years (representing 10% of the sample). Men had a longer duration of the disease (mean 11.35 years) than women, with a mean of 8.91 years (t = 3.119, p = 0.002).
A moderately strong positive correlation was found between the age of the respondent and the duration of the disease (r = 0.567, p = 0.000).
The average duration of the disease varied depending on the stage of disease (chi-square = 59.228, p = 0.000); in the rst stage, the median duration was 3 years, whereas it was 15 years in the third stage (  The average number of drugs taken by the respondents was 2.23 (median and fashion of 2). A total of 21.6% of the respondents accepted 1 drug, 44.7% accepted two, and 25.2% accepted three. Overall, 8.3% accepted more than 3 drugs. In the age groups up to 59 years, the number of drugs the participants admitted to using was lower than the average for the sample, while in those over 70 years, it was higher (F = 7.135, p = 0.000).
A difference in the average number of drugs taken was also found between respondents in different stages of hypertension; the average number of drug products taken those in the rst stage was 1.89 drugs; that taken by patients in the second stage was 2.66, and that taken by patients in the third stage was 3.92 (22,717, p = 0.000).
Respondents with comorbidities received a higher average number of medications than those who noted no comorbidities (2.48 versus 2.05) (t = -4.746, p = 0.000).
Correlation analysis showed a medium-strong positive relationship between the duration of the disease and the number of drugs taken (r = 0.352, p = 0.000).
When asked if they happened to forget to take medication for hypertension, 21.4% of respondents indicated that this happens very often, and 55% indicated that it happens sometimes. Those who noted that they never fail to take medication accounted for 23.6% of the sample. Demographic factors (sex and age) did not in uence forgetting to or not taking medication for hypertension.
Less than half (47.5%) of respondents stopped medication for hypertension when they felt unwell. This behaviour was more typical for men (52.2% of male respondents stopped taking drugs) than for women (42.6%) (contingency coe cient = 0.096, p = 0.043). Discontinuation of intake was also observed for respondents who were older (over 70 years of age), among whom the percentage of respondents who discontinued intake was signi cantly higher than the average value; for example, in 70-79-year-olds, this percentage was 51.9%, and for those over 79, it reached 72.4% (contingency coe cient = 0.234, p = 0.001). The stage of hypertension was unrelated to the respondents' tendency to stop the intake of medication when they felt badly (contingency coe cient = 0.169, p = 0.091).
Less than 1/3 (28.3%) of the respondents stopped taking medication for hypertension when they felt better. As for the previous question, discontinuation of medication was more common for men than for women (35.4% of men versus 20.8% of women) (contingency coe cient = 0.160, p = 0.001). Among adult respondents (over 79 years of age), 51.7% stopped taking medication when they felt better (contingency coe cient = 0.211, p = 0.004) The stage of hypertension was unrelated to the respondents' tendency to stop taking medication when they felt better (contingency coe cient = 0.168, p = 0.092).
A variant of MARS-5 was used in the study. Participants were asked to rate the frequency with which they engaged in each of the adherence-related behaviours on a ve-point scale, where 5 = never, 4 = rarely, 3 = sometimes, 2 = often and 1 = always. Scores for each item were summed to give a total score, with higher scores indicating higher levels of reported adherence. As a result, the responses ranged from 5 to 25 as follows: -values of 5 to 10 meant a high degree of nonadherence to treatment; -values from 10 to 20 indicated average degree of adherence; -values from 20 to 25 indicated a high degree of adherence.
The average MARS score of the sample was 16.81, the median was 4.162, and the most common value was 3 (24.5% of respondents).
Overall, 18.1% had a high degree of adherence to the prescribed therapy, and almost 1/3 of the respondents (32.13%) had a low degree of adherence to the prescribed therapy. Table 3 presents the descriptive characteristics of the patients included. Table 3: MARS degree -descriptive characteristics (n = 442). Table 4 presents two-dimensional frequency distributions of MARS scores and the demographic characteristics of the respondents: women were more likely to adhere to the prescribed treatment than men (15.2% of men versus 21.8% of women); increasing age was associated with a decreased tendency to adhere to treatment (the highest share of low-degree MARS scores was observed in respondents over 60 years of age) Analysis of the degree of MARS, hypertension (stage), the number of drugs taken and the presence of concomitant diseases did not reveal any signi cant differences. The only difference was found in respondents with renal insu ciency (among these respondents, 56.6% had low adherence compared to 30.7% for the whole sample) ( Table 5). . Thus, it can be concluded that the rate of adherence to pharmacological treatment in the present study, which was conducted in two of the largest Bulgarian cities, coincides with the rates reported in the literature. In the present study, there was no association between adherence to pharmacological treatment and comorbidities in the sample. While adherence to treatment was shown to increase as the number of diseases increased in some studies, it was shown to decrease in other studies [19,29,30]. In the study, an increase or decrease in the rate of adherence to treatment may have been due to the presence of comorbid chronic diseases, perceived health status, or differences in giving or receiving health care. COVID pandemic was not assessed as an important factor, in uencing the level of adherence, although the patients stated that they know that the disease can worsen their health status.
While sex was not shown to be a determinant of the rate of adherence to pharmacological treatment in some studies, the adherence rate was shown to be higher in women in other studies [19,22]. In the present study, although not signi cant, the rate of adherence was higher in women, as previously shown in the literature [29]. This can be explained by the fact that men are busier with outdoor activities and forget to look after their health during the workday if they experience no symptoms.

Conclusions
In the present study, approximately one-third of the participants complied with pharmacological treatment. The study suggests that several sociodemographic factors but not the COVID pandemic play a role in treatment adherence. The results suggest that good motivation from health care providers can increase adherence among hypertensive patients. Further studies must regularly follow patients and assess their level of adherence to identify the causes of non-adherence and solve this problem.

Declarations
Ethics approval and consent to participate The Ethics Committee of the Medical University of So a approved the study protocol (May, 2020).

Consent for publication
Not applicable Availability of data and materials The data used to support the ndings of this study are included within the article.

Competing interests
The authors declare that they have no competing interests.

Funding
There is no nancial support used for this study here Authors' contributions V.P. was involved in the data analysis, interpretation and study write up. E.H. was involved in the study design, data collection, interpretation and write up review. M.D. was involved in the study design, data analysis, interpretation and write up review. K.A. was involved in the data analysis, interpretation, write-up and nal review. D.G. was involved in the study design, data collection, interpretation and write up review. A.T. participated in the design of the study. A.Ts. performed the document analysis. All authors read and approved the nal manuscript.