Cerebrovascular disease is the second leading cause of death worldwide1 and the leading cause of death in China.2 Ischemic stroke accounts for 70% of cerebrovascular disease cases, and 70% of patients who have had an ischemic stroke also have hypertension.3 Ischemic stroke remains a global health problem and has become a huge burden on Chinese society,4 because most patients are permanently disabled after stroke.5,6 Hypertension is the most important risk factor for ischemic stroke.3,7 In the United States, approximately 77% of patients who have had a first-time stroke have high blood pressure (BP).1 Similarly, the hypertension diagnosis rate is up to 70% among patients who have had an ischemic stroke in China.3 Increased systolic BP and high pulse pressure (PP) have been demonstrated to accelerate ischemic stroke onset, mainly via damage of the vascular endothelium, formation of atherosclerotic plaques, and angiostenosis.8 Antihypertensive drugs are crucial for the secondary prevention of hypertensive stroke.9 Lowering systolic BP by 5 mm Hg or diastolic BP by 2.5 mm Hg could reduce stroke incidence by 15% to 20%,10 but the awareness of hypertension is not ideal according to published reports. For instance, 17.2% of American adults did not realize they had hypertension.11 In less developed regions, hypertension awareness status is even lower, with 26.5% of adults in Lebanon12 and 38% in Nepal13 unaware of current clinical hypertension. Risk factors related to poor awareness include sex, age, family history, and education level. The antihypertensive medication adherence rate of patients with hypertension varies greatly among countries. In China, multiple investigations have found medication adherence rates of only 33.9% to 42.1%,14 lower than those in the United States (75.7%)11 and South Korea (68.8%)15 and even some developing regions, namely, 62.9% in southern India16 and 72.8% in Brazil.17 The low rate of adherence in China has become a huge challenge to hypertensive stroke healthcare.
Whereas numerous authors have examined hypertensive BP and medication adherence, few have focused on the influence of prestroke medication adherence on admission BP in patients who have had an ischemic stroke. The relationship between medication adherence and admission BP, and the barriers to adherence remain unclear. Therefore, this study with a sample from the Chinese population was conducted to explore the influence of medication nonadherence on admission BP in patients with hypertension who have had an ischemic stroke and to describe the reasons for medication nonadherence. The results of this study will assist in the design of health education programs for patients with hypertension to promote medication adherence and control BP, so as to prevent stroke onset.
Study Design and Participants
This was a cross-sectional descriptive study. A total of 301 patients with hypertension who have had an ischemic stroke were consecutively recruited from departments of neurology of 3 hospitals in Guangzhou, China. The 4-item Medication Adherence Scale was used to investigate prestroke medication adherence. Sociodemographic data were collected via questionnaire. Blood pressure was measured at admission. Logistic regression analysis was used to identify risk factors associated with nonadherence.
The inclusion criteria were as follows: (a) diagnosis of primary hypertension, (b) confirmed diagnosis of ischemic stroke by computerized tomography or magnetic resonance imaging, and (c) ability to communicate through talking or reading and provide informed consent. We excluded patients because of (a) cerebral hemorrhage, (b) aphasia, or (c) having a history of mental health issues.
Sample size calculation was based on the requirement of the logistic regression model, which should be 5 to 10 times the number of independent variables.18 In this study, there were 9 independent variables, including sex, age, education level, employment status, household income, duration of hypertension, medication adherence or nonadherence, and health behaviors (physical activity and nutrition). The results of the calculation indicated that, to achieve a power of 0.80 with a 2-tailed α of .05, 45 to 90 patients were required.
This study was part of the study that was funded by Guangdong Science and Technology Department, the Guangdong Special Program for Scientific Development (no. 2016A020215039). Ethical approval was provided by the hospital (2014ZSLYEC-032).
Sociodemographic and Disease-specific Data
A questionnaire was used to record patient sex, age, marital status, education level, household income, duration of hypertension, modified Rankin Scale,19 incidence of stroke (first or recurrent), and reasons for nonadherence, among other parameters. The modified Rankin Scale is a well validated 6-item scale of disability scored from 0 to 5 as follows: 0, no symptoms at all; 1, no significant disability; 2, slight disability; 3, moderate disability; 4, moderately severe disability; and 5, severe disability.
Health Behavior Scale
Health behaviors were assessed using the Health-Promoting Lifestyle Profile II (HPLP II) designed by Walker et al.20 The HPLP II consists of 52 items grouped into 6 subcategories: physical activity, health responsibility, nutrition, spiritual growth, interpersonal relationships, and stress management. The answer to each item is based on a 4-point ordinal response: 1, “never”; 2, “sometimes”; 3, “often”; and 4, “routinely.” According to the responses, a score for each subcategory can be calculated with higher scores indicating better health behaviors. In this study, 2 subscales of the HPLP II Chinese version21 were used to measure health behaviors, physical activity (8 items), and nutrition (9 items) of patients who have had a stroke. In a pilot study of 30 patients, physical activity and nutrition subscales had Cronbach α values of .827 and .752, respectively.
Four-Item Medication Adherence Scale
The 4-item Medication Adherence Scale by Morisky et al22 was used to evaluate patient medication adherence. The 4 items are as follows: (1) Have you ever forgotten to take medicine? (2) Have you sometimes been unaware of taking medicine? (3) Have you stopped taking medicine if you felt better? (4) Have you stopped taking medicine if you felt worse? Items are answered with either “yes” (0 point) or “no” (1 point), with a total score ranging from 0 to 4. A score of 4 (all answers reported “no”) indicates medication adherence, whereas a score of 0 to 3 points (one or more “yes” answers) indicates medication nonadherence. Li et al14 used this scale to analyze 837 patients with hypertension, and the results showed that the Cronbach α was .760 and the split-half reliability was 0.751. In the current study, 30 eligible patients were chosen for Cronbach α calculation, which yield an α value of .790. Patients who have had a stroke were told to answer these 4 items based on their use of antihypertensive medications 1 month before stroke onset. In the meantime, we also investigated reasons for patients' nonadherence with the following choices: (1) forgot to take medicine on time, (2) believed that long-term antihypertensive medicine was not necessary, (3) not aware of the importance of long-term medication, (4) economic burdens, (5) side effects, and (6) others. All questionnaires were explained by the researchers and completed by patients individually. Questionnaires took approximately 10 minutes to complete.
Admission Blood Pressure Measurement
All 301 patients' BPs were measured when they first came to the hospital, either in the department of neurology or in the emergency room. Three readings of the sphygmomanometer were taken by 2 trained nurses, one in the department of neurology and one in the emergency room, at intervals of 2 minutes. The mean of the closest 2 readings was recorded as the admission BP. A reading of systolic BP/diastolic BP of 140/90 mm Hg or greater was regarded as uncontrolled BP or poor BP control. A BP range of 140 to 159/90 to 99 mm Hg was categorized as type I hypertension; 160 to 179/100 to 109 mm Hg, as type II hypertension; and 180/110 mm Hg or greater, as type III hypertension.23 For patients with hemiparesis, BP should be measured from the healthy arm; for those without hemiparesis, a higher BP measured from 2 arms should be recorded, and the arm with the higher BP should be used for further measurement. When measuring BP, patients should stay in the recumbent position using the same sphygmomanometer for reproducibility and comparability across subjects.9
All data were analyzed using SPSS 20.0 software. Quantitative data were compared using the χ2 test. Continuous data with a normal distribution were compared using t test, whereas nonnormally distributed data were compared using the Mann-Whitney U test. We subdivided the 301 subjects into 2 groups, hypertension unknown and known, including adherent and nonadherent subgroups, and compared sociodemographic and disease-specific lifestyle characteristics. Statistical analysis was used to describe the proportion of admissions in each guideline-recommended BP category. The difference in admission BP between medication-nonadherent and medication-adherent groups was analyzed by the t-test or χ2 test, as appropriate. In addition, we explored the relationship between admission BP meeting the control target (≤140/90 mm Hg) and medication adherence using a logistic regression model by the ENTER model including the following variables: sex, age, education level, employment status, household income, duration of hypertension, medication nonadherence, physical activity, and nutrition.
A total of 301 patients with hypertension who have had an ischemic stroke who met the inclusion criteria were recruited. Patient mean (SD) age was 63.24 (11.21) years, 57.81% were older than 60 years, and 91.36% were married. The median duration of hypertension was 8.26 years, and 48.84% had hypertension for more than 5 years. A substantial minority (30.90%) presented with recurrent stroke, with some patients up to 5 times. Of these recurrent patients, 76.34% were nonadherent. There were no significant differences in sociodemographic and disease-specific characteristics (P > .05) between the nonadherent group and the adherent group. All participant data are shown in Table 1. In addition, there were no significant differences in physical activity and nutrition levels (P > .05) between the nonadherent and adherent groups.
Of the 301 patients, 80 (26.58%) had not been diagnosed with hypertension before stroke onset. Of the 221 patients aware of their hypertension, 23 (10.41%) had never used antihypertensive medications. Of the remaining 198 patients who had a history of medication use, only 55 self-reported medication adherence. In total, 166 patients were nonadherent, for a medication nonadherence rate of 75.11% (Table 2).
Admission Blood Pressure
As shown in Table 3, the overall mean (SD) admission systolic BP for the 301 patients was 156.80 (21.42) mm Hg, mean (SD) diastolic BP was 87.88 (14.08) mm Hg, and mean (SD) PP was 68.92 (17.44) mm Hg. In total, 80.73% of the patients had admission BP higher than the target (>140/90 mm Hg), of which 78.07% exhibited systolic BP of 140 mm Hg or greater, 42.86% exhibited diastolic BP of 90 mm Hg or greater, and 97.68% exhibited PP greater than 40 mm Hg. Of the 221 patients aware of their hypertension, mean (SD) admission systolic BP was 158.98 (21.79) mm Hg in the nonadherent group and 146.02 (16.51) mm Hg in the adherent group (Table 4). Compared with the medication-adherent group, systolic BP (P < .001), diastolic BP (P < .01), and PP (P < .05) were significantly higher in the medication-nonadherent group, and the BP control rate was significantly lower (67.27% vs 83.13%, P < .05).
Influence of Medication Nonadherence on Admission Blood Pressure
We analyzed the relationship between “medication adherence” (independent variable, yes/no) and “BP control” (dependent variable, BP ≥ 140/90 mm Hg or < 140/90 mm Hg) among the 221 patients aware of their hypertension using a binary logistic regression model and a multivariable logistic regression model including sociodemographic parameters, disease-specific characteristics, and health behaviors. Medication nonadherence was significantly associated with elevated admission BP by both binary logistic regression (odds ratio [OR], 2.398; P = .014) and multivariate logistic regression (OR, 2.854; 95% confidence interval, 1.357–6.005; P = .006). No other factors were associated with admission BP (Table 5).
Reasons for Prestroke Medication Nonadherence
Of the 198 patients aware of their hypertension and reporting a history of antihypertensive medication use, 58.08% were nonadherent because of forgetfulness. Male patients exhibited a 1.5-fold greater rate of forgetfulness than female patients. In addition, 61.13% were older (≥60 years old), 27.27% believed that there was no need to maintain long-term antihypertensive medication use and so had stopped, and 24.75% were not aware of the importance of long-term medication use, among which 28.57% were recurrent patients. Other reasons for nonadherence such as economic burden and fear of side effects accounted for smaller proportions of the total nonadherent group (2.53% and 7.58%, respectively).
In this study cohort of patients with hypertension who have had an ischemic stroke, 10.41% of those aware of their diagnosis had never used antihypertensive medications, and overall medication adherence rate was only 24.89%. This rate is in accord with a cross-sectional study of rural patients with hypertension in northern China (21.3%)24 but considerably lower than that in Hong Kong (53.4%).25 These differences may be ascribed to the lower socioeconomic status of patients in rural China and Guangzhou compared with those in Hong Kong because medical cost is an important factor influencing patient adherence to antihypertensive drugs.26 Alternatively, the Hong Kong study patients were all from an outpatient clinic as opposed to a hospital emergency ward. Multiple factors may contribute to medication adherence depending on region and patient type. Furthermore, social, emotional, and disease-related factors such as hypertension duration and hypertension severity may contribute to low medication adherence.27,28 Nonetheless, the authors of this study present additional evidence that medication adherence rates are low in mainland China. However, there may be many contributing factors that remain unknown, so a large-sample meta-analysis is warranted to identify common factors useful for the development of effective strategies against poor adherence in China.
The pathogenic effects of uncontrolled BP (high systolic BP and PP) are well documented.29–31 Increased systolic BP and high PP are important risk factors for ischemic stroke,29,31 and we found that the admission BP control rate was only 19.27% in patients who have had an ischemic stroke. Moreover, 30.9% of patients enrolled were recurrent. Mustanoja et al30 also reported that patients with a recurrent stroke had higher the admission BP than those without a recurrent stroke, but their study focused on a younger population. In a retrospective study of 749 patients who have had an acute ischemic stroke in Norway, 82.9% had uncontrolled BP at admission, and there was an association between admission BP and ischemic stroke severity.32 Collectively, these results indicate a strong association between patient admission BP and stroke onset and imply that stroke prevention should target medication adherence and BP control. Furthermore, reduced admission BP may improve the prognosis of patients who have had an ischemic stroke. Indeed, nonadherence to antihypertensive medication has been associated with stroke incidence, clinical outcome, and prognosis.33,34
The influence of medication nonadherence on poststroke BP has been confirmed,35,36 but the related factors and significance of admission BP are unknown. Authors of a multicenter cluster-randomized study in Spain found that nonadherent patients were at a greater risk for poor BP control than adherent patients.37 Numerous authors of cross-sectional studies have investigated the influence of abnormal admission BP as a risk factor for ischemic stroke severity and prognosis, but most focused on poststroke outcome instead of prestroke adherence. Although admission BP is an important risk factor of stroke outcome, a causal association of adherence and admission BP remains unclear. After analyzing numerous possible factors, we found that only medication nonadherence had an independent negative influence on admission BP (OR, 2.854), indicating that adherence is a predominant factor for admission BP control. This finding implies that improved prestroke medication adherence is crucial to enhance admission BP control and promote ischemic stroke prevention.
In this study, the main reason for patient nonadherence was forgetting, consistent with a mixed method study conducted in the United States.38 For patients with hypertension, especially elderly patients, there are a variety of barriers to sustained medication adherence.39 It may be necessary to use reminders, such as short messaging services, telephone follow-up calls, and family support, to improve patient medication adherence.40 Other reasons cited included believing that there was no need to take antihypertensive medicines over the long term, no awareness of the importance of long-term medication, drug side effects, and economic burden. These are similar to the reasons reported by Allen et al38 in the United States. Patient-centered, provider-focused, and system-based factors may be the main barriers to treatment service for patients who have had a stroke. Programs for improving the medication adherence of patients with hypertension should focus on the importance of regular and lifelong adherence, as well as the development of a social support network. In addition, patients should be provided with adequate information on how to solve problems that may reduce adherence, such as drug side effects.
Although adherence is critical for BP control, 67.27% of the patients categorized as adherent in this study still had uncontrolled admission BP. Furthermore, 23.92% of the patients did not have a sphygmomanometer at home, including those who have had a recurrent stroke. Pan and colleagues,35 in their study of patients in northwest China, drew a similar conclusion. Patients with hypertension face multiple challenges for BP control and stroke management in China, and these have resulted in poor medication adherence,41 even among patients who have had a recurrent stroke. This situation must be addressed to reduce stroke incidence, recurrence, and the associated burdens on patients, families, and the healthcare system. Primary healthcare centers should advocate the importance of BP monitoring, treatment persistence, and healthy lifestyle choices through lectures; encourage regular physical examinations; and offer home visits to discharged patients. Further research is needed to determine other possible factors associated with medication nonadherence. An advanced program to improve patient medication adherence must be aggressively pursued. There were mainly 2 limitations to this study. First, a self-reported scale was used to measure patient medication adherence. Therefore, recall bias could not be avoided, although we assigned trained researchers to conduct the survey and confirm the findings. Second, the study was performed in only 3 major hospitals, and all patients were ethnic Chinese, limiting generalizability.
Conclusions and Implications
Medication nonadherence is a vexing problem for hypertension management, particularly in developing countries. In China, patients with hypertension who have had an ischemic stroke showed low adherence, even after previous ischemic events. Medication nonadherence is a significant risk factor for uncontrolled admission BP. Reasons for medication nonadherence among patients with hypertension who have had an ischemic stroke include forgetting and little awareness that sustained adherence is essential for BP maintenance and stroke prevention. Therefore, all stroke prevention measures should aim to improve patient BP medication adherence. By implementing the findings, face-to-face health education by physicians and nurses for patients in hospitals would be helpful to strengthen patients' knowledge about medications and awareness of secondary prevention.
What's New and Important
- Medication adherence is key to the successful management of hypertension and the prevention of hypertensive ischemic stroke.
- Admission BP of patients with hypertension who have had an ischemic stroke was associated with medication adherence level before stroke onset. Other factors such as lifestyle were not proved to influence the admission BP. Most frequently, subjects reported that forgetfulness was the reason for not taking medications as prescribed.
- Effective prevention measures should be aimed at how to improve patients' medication adherence and BP control to improve the effect of primary and secondary prevention of ischemic stroke.
The authors thank all patients who participated in their study and the concerned nurses and doctors for their time and enthusiastic participation. They also thank Miao-Miao Mo, Cui-Ling Ou, Zhou-Yuan Peng, Wei-Jing Sui, and Ying Liu for collecting the data. Thanks to Xue-Qin Ju, a master student of Sun Yat-sen University, for her revision of this article.
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Keywords:Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
hypertension; ischemic stroke; medication adherence; nursing